[0002] Epidemiological studies show an increase in mortality associated with overweight and obesity. Individuals who are obese (body mass index ("BMI") > 30) have a 50-100% increased risk of premature death from all causes compared to individuals with a BMI in the range of 20 to 25. BMI is calculated according to the formula : Weight in pounds (Height in inches) [0003] An estimated 300, 000 deaths a year in the United States may be attributable to obesity. Overweight and obesity are associated with an increased risk for coronary heart disease ; type 2 diabetes ; endometrial, colon, postmenopausal breast, and other cancers ; and certain musculoskeletal disorders, such as knee osteoarthritis.

[0004] Both modest and large weight gains are associated with significantly increased risk of disease. For example, a weight gain of 11 to 18 pounds increases a person's risk of developing type 2 diabetes to twice that of individuals who have not gained weight, while those who gain 44 pounds or more have four times the risk of type 2 diabetes. A gain of approximately 10 to 20 pounds results in an increased risk of coronary heart disease (nonfatal myocardial infarction and death) of 1. 25 times in women and 1. 6 times in men. Higher levels of body weight gain of 22 pounds in men and 44 pounds in women result in an increased coronary heart disease risk of 1. 75 and 2. 65, respectively. In women with a BMI of 34 or greater, the risk of developing endometrial cancer is increased by more than six times. Overweight and obesity are also known to exacerbate many chronic conditions such as hypertension and elevated cholesterol. Overweight and obese individuals also may suffer from social stigmatization, discrimination, and poor body image.

Although obesity-associated morbidities occur most frequently in adults, important consequences of excess weight as well as antecedents of adult disease occur in overweight children and adolescents. Overweight children and adolescents are more likely to become overweight or obese adults ; this concern is greatest among adolescents. Type 2 diabetes, high blood lipids, and hypertension as well as early maturation and orthopedic problems also occur with increased frequency in overweight youth. A common consequence of childhood overweight is psychosocial- specifically discrimination. See The Surgeon General's Call To Action To Prevent and Decrease Overweight and Obesity, U. S.

Dept. of Health and Human Services, 2001. Thus, the need exists for methods of controlling weight and treating obesity.

[0005] Melanin-concentrating hormone (MCH) is a cyclic, 19- amino acid hypothalamic neuropeptide derived from a larger pro- hormone precursor of MCH, Pmch. Pmch-deficient mice are lean, hypophagic, and have an increased metabolic rate. Transgenic mice over-expressing Pmch are hyperphagic and develop mild obesity. Consequently, MCH has been implicated in the regulation of energy homeostasis, through actions on motor activity, metabolism, food intake and neuroendocrine function.

[0006] Two receptors have been identified in MCH, and are designated MCH 1 receptor and MCH 2 receptor. The MCH 1 and MCH 2 receptors are G protein-coupled receptors (GPCRs) believed to be responsible for the actions of MCH. G proteins are heterotrimeric proteins that control cellular responses to stimuli by cycling between a GTP-bound active state, which regulates the activity of a number of effector proteins, and a GDP-bound inactive state. GPCRs accelerate activation of the G protein by increasing the GDP/GTP exchange rate..

[0007] MCH 1 receptor-deficient mice have normal body weights, yet are lean and have reduced fat mass. Surprisingly, MCH 1 receptor-deficient mice are hyperphagic when maintained on regular chow, and their leanness is a consequence of hyperactivity and altered metabolism. Consistent with the hyperactivity, MCH 1 receptor-deficient mice are less susceptible to diet-induced obesity. Importantly, chronic central infusions of MCH induce hyperphagia and mild obesity in wild-type mice, but not in MCH 1 receptor-deficient mice. Marsh et al., Proc. Nat. Acad. Sci., 99 (5), 3241 (2002).

[0008] Because MCH has been shown to be an important regulator of food intake and energy balance, compounds capable of modulating the activity of MCH receptors, particularly MCH 1 receptors, are highly desirable for the treatment of eating disorders and metabolic disorders.

[0009] PCT Publication No. WO 02/04433 describes phenylcycloalkylmethylamino and phenylalkenylamino derivatives as modulators of MCH 1 receptors useful in the treatment of certain metabolic, feeding and sexual disorders.

[0010] U. S. Patent No. 6, 472, 394 describes the use of amide derivatives of 1, 4-disubstituted piperidine as MCH antagonists for the treatment of obesity and diabetes.

Summary of the Invention [0011] Among the several objects of certain embodiments of the present invention, therefore, may be noted the provision of melanin concentrating hormone receptor antagonists ; the provision of pharmaceutical compositions comprising melanin concentrating hormone receptor antagonists ; the provision of methods of treating, preventing, or otherwise ameliorating melanin concentrating hormone-mediated disorders in a subject ; the provision of methods for treating, preventing or otherwise ameliorating obesity in a subject ; and the provision of methods of achieving sustained body weight loss in a subject.

[0012] Briefly therefore, the present invention is directed to a melanin concentrating hormone receptor antagonist of Formula I as defined herein.

[0013] The present invention is also directed to pharmaceutical compositions comprising a compound of Formula I, as defined herein, and a pharmaceutically acceptable carrier, adjuvant, or diluent.

[0014] The present invention is also directed to a method of inhibiting a GPCR, comprising contacting a compound of Formula I, as defined herein, with a GPCR, wherein the compound of Formula I is present at a concentration sufficient to inhibit the binding of a GPCR ligand in vitro. This method includes inhibiting a GPCR in vivo, e. g., in a subject given an amount of a compound of Formula I that would be sufficient to inhibit the binding of a ligand to the GCPR in vitro. Examples of GPCRs which may be inhibited according to the present invention include, but are not limited to the following GPCR families : Acetylcholine muscarinic, Adenosine, adrenergic, adrenergic, alpha-adrenergic, angiotensin, AR, Cannabinoid, DA, dopamine, His, imidazoline, Leukotriene, mAch, MCH, Opioid, serotonergic, serotonin, and Somatostatin.

[0015] Inhibition of the binding of a GPCR ligand to GPCRs is useful in the treatment of numerous disorders, including digestive tract disorders ; mucolytic asthma ; arrhythmia ; ischemia ; reperfusion injury ; bronchospasm associated with asthma, emphysema and chronic bronchitis ; acute and chronic respiratory diseases, including cystic fibrosis ; cardiostimulant ; chronic bronchitis ; neurological depression ; heart failure ; benign prostate hypertrophy ; diabetes ; muscle spasm ; myocardial infarction ; stroke ; Alzheimer's disease ; anorexia ; cachexia ; multiple sclerosis ; hyperprolactinemia ; psychotropism ; mydriasis in ocular examination and surgery ; deficitary and productive schizophrenia, psychasthenia and non- endogenous depression ; kidney disease ; vasodilation ; chronic gastritis ; glaucoma ; depression ; rhinitis, including allergic rhinitis ; pain, including cancer pain, musculoskeletal pain, post-operative pain ; eye disease ; dyspepsia ; cough ; ulcer, including gastrointestinal, gastric and esophageal ulcers ; helicobacter pylori prophylaxis infection ; oesophagitis ; allergies, including non-asthma allergies ; cold ; asthma ; conjuctivitis ; urticaria ; diarrhea ; Creutzfeldt-Jakob disease ; dysmenorrhoea ; drug addiction and drug overdose ; septic shock treatment ; cerebral ischaemia ; drug posoning ; head trauma ; inflammation ; pruritus ; tardive dyskinesia ; emesis ; anxiety ; motility dysfunction ; cluster headaches ; hypertension ; cancer ; irritable bowel syndrome ; hemotherapy-induced nausea and vomiting ; thrombosis ; dementia ; opiate-induced nausea and vomiting ; bipolar depression ; migraine ; sleep disorders ; traumatic shock ; gastritis ; gastro-oesophageal reflux ; psychosis ; Parkinson disease ; Dependence treatment ; Pre- eclampsia ; Raynaud's disease ; Vasospasm ; haemostasis ; nausea and vomiting ; spasms ; post-operative nausea and vomiting ; alcoholism, alcohol addiction ; bulimia ; nicotine addiction ; obsessive-compulsive disorder ; panic disorder ; post-traumatic stress disorder ; premenstrual syndrome ; and dermatitis, including allergic dermatitis.

[0016] The present invention is also directed to methods of inhibiting the binding of MCH to MCH receptors comprising contacting a compound of Formula I with cells expressing MCH receptors, wherein the compound is present at a concentration sufficient to inhibit MCH binding to MCH receptors in vitro.

This method includes inhibiting the binding of MCH to MCH receptors in vivo, e. g., in a subject given an amount of a compound of Formula I that would be sufficient to inhibit the binding of MCH to the MCH receptors in vitro. The amount of a compound of Formula I that would be sufficient to inhibit the binding of MCH to the MCH receptor in vitro may be readily determined via a MCH receptor binding assay, such as the assay described hereinbelow in Example 24.

[0017] The present invention is also directed to methods for altering the signal-transducing activity of MCH receptors, particularly the MCH receptor-mediated release of intracellular calcium, said method comprising exposing cells expressing such receptors to an effective amount of a compound of the invention.

This method includes altering the signal-transducing activity of MCH receptors in vivo, e. g., in a subject given an amount of a compound of Formula I that would be sufficient to alter the signal-transducing activity of MCH receptors in vitro. The amount of a compound that would be sufficient to alter the signal-transducing activity of MCH receptors may be determined via a MCH receptor signal transduction assay, such as the calcium mobilization assay described hereinbelow in Example 23.

[0018] The present invention is also directed to methods of using compounds of Formula I and appropriately labeled derivatives thereof as standards and reagents in determining the ability of a potential pharmaceutical to bind to MCH receptor.

[0019] The present invention is also directed to methods of treating, preventing, or otherwise ameliorating melanin concentrating hormone-mediated disorders in a subject, the method comprising administering a compound of Formula I or a pharmaceutical composition comprising a compound of Formula I and a pharmaceutically-acceptable carrier, adjuvant, or diluent to said subject.

[0020] The present invention is also directed to methods of treating or preventing obesity in a subject, the method comprising administering a compound of Formula I or a pharmaceutical composition comprising a compound of Formula I and a pharmaceutically-acceptable carrier, adjuvant, or diluent to said subject.

[0021] The present invention is also directed to methods of treating or preventing conditions such as feeding disorders, including obesity, bulimia and bulimia nervosa ; sexual or reproductive disorders ; depression and anxiety ; epileptic seizure ; hypertension ; cerebral hemorrhage ; congestive heart failure ; sleep disturbances ; or any condition in which antagonism of an MCH receptor is beneficial.

[0022] The present invention is also directed to methods of treating eating disorders, particularly obesity and bulimia nervosa, comprising administering to a subject in need of such treatment a compound of Formula I in combination with leptin, a leptin receptor agonist, or a melanocortin receptor 4 (MC4) agonist.

[0023] The present invention is also directed to methods of using compounds of Formula I as positive controls in assays for activity of GPCRs, particularly MCH.

[0024] The present invention is also directed to methods of using appropriately labeled compounds of Formula I as probes for the localization of GPCRs, particularly MCH, in tissue sections.

[0025] Other objects and features will be in part apparent and in part pointed out hereinafter.

Abbreviations and Definitions [0026] The term"alkyl", where used alone or within other terms such as"haloalkyl","alkylsulfonyl","alkoxyalkyl"and "hydroxyalkyl", is a linear or branched radical having one to about twenty carbon atoms or, preferably, one to about twelve carbon atoms. More preferred alkyl radicals are"lower alkyl" radicals having one to about ten carbon atoms. Most preferred are lower alkyl radicals having one to about six carbon atoms.

Examples of such radicals include methyl, ethyl, propyl (e. g., n-propyl and isopropyl), butyl (e. g., n-butyl, isobutyl, sec- butyl, and tert-butyl), pentyl (e. g., n-pentyl and iso-amyl), hexyl, and the like.

[0027] The term"cycloalkyl"is a saturated carbocyclic radical having three to twelve carbon atoms. The cycloalkyl radical may be mono-, bi-, or tricyclic. More preferred cycloalkyl radicals are"lower cycloalkyl"radicals having three to about eight carbon atoms. Examples of such radicals include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0028] The term"alkenyl"is a linear or branched radical having at least one carbon-carbon double bond and having two to about twenty carbon atoms or, preferably, two to about twelve carbon atoms. More preferred alkyl radicals are"lower alkenyl" radicals having two to about six carbon atoms. Examples of alkenyl radicals include ethenyl, propenyl, allyl, butenyl and 4-methylbutenyl. The terms"alkenyl"and"lower alkenyl"also are radicals having"cis"and"trans"orientations, or alternatively,"E"and"Z"orientations.

[0029] The term"cycloalkenyl"is a partially unsaturated carbocyclic radical having three to twelve carbon atoms. The cycloalkenyl radicals may be mono-, bi-, or tricyclic. More preferred cycloalkenyl radicals are"lower cycloalkenyl" radicals having four to about eight carbon atoms. Examples of such radicals include cyclobutenyl, cyclopentenyl, cyclopentadienyl, and cyclohexenyl.

[0030] The term"alkynyl"is a linear or branched radical having at least one carbon-carbon triple bond and having two to about twenty carbon atoms or, preferably, two to about twelve carbon atoms. More preferred alkynyl radicals are"lower alkynyl"radicals having two to about ten carbon atoms. Most preferred are lower alkynyl radicals having two to about six carbon atoms. Examples of such radicals include propargyl, butynyl, and the like.

[0031] The terms"carboxy"or"carboxyl", whether used alone or with other terms, such as"carboxyalkyl", is-C02H.

[0032] The term"carboxyalkyl"is an alkyl radical as defined above substituted with a carboxy radical. More preferred are"lower carboxyalkyl"radicals, which are lower alkyl radicals as defined above substituted with a carboxy radical, and may be additionally substituted on the alkyl radical with halo. Examples of such lower carboxyalkyl radicals include carboxymethyl, carboxyethyl and carboxypropyl.

[0033] The term"halo"is a halogen such as fluorine, chlorine, bromine or iodine.

[0034] The term"haloalkyl"is an alkyl radical as defined above wherein any one or more of the carbon atoms is substituted with halo as defined above. Specifically included are monohaloalkyl, dihaloalkyl and polyhaloalkyl radicals. A monohaloalkyl radical, for one example, may have either an iodo, bromo, chloro or fluoro atom within the radical. Dihalo and polyhaloalkyl radicals may have two or more of the same halo atoms or a combination of different halo radicals. More preferred haloalkyl radicals are"lower haloalkyl"having one to six carbon atoms. Examples of lower haloalkyl radicals include fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl.

[0035] The terms"alkoxy"and"alkyloxy"are linear or branched oxy-containing radicals each having alkyl portions of one to about ten carbon atoms. More preferred alkoxy radicals are"lower alkoxy"radicals having one to six carbon atoms.

Examples of such radicals include methoxy, ethoxy, propoxy, butoxy and tert-butoxy. The"alkoxy"radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide haloalkoxy radicals. More preferred haloalkoxy radicals are"lower haloalkoxy"radicals having one to six carbon atoms and one or more halo radicals. Examples of such radicals include fluoromethoxy, chloromethoxy, trifluoromethoxy, trifluoroethoxy, fluoroethoxy and fluoropropoxy.

[0036] The term"alkoxyalkyl"is an alkyl radical having one or more alkoxy radicals attached to the alkyl radical, that is, to form monoalkoxyalkyl and polyalkoxyalkyl radicals. More preferred alkoxyalkyl radicals are"lower alkoxyalkyl"radicals having two to twelve carbon atoms. Examples of such radicals include methoxymethyl, methoxyethyl, methoxypropyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, dimethoxymethyl, dimethoxyethyl, methoxy (ethoxy) ethyl, dimethoxypropyl, and methoxy (ethoxy) propyl.

[0037] The term"alkoxycarbonyl"is a radical containing an alkoxy radical, as defined above, attached via an oxygen atom to a carbonyl radical, i. e., an ester radical. More preferred are "lower alkoxycarbonyl"radicals with alkyl portions having one to six carbons. Examples of such lower alkoxycarbonyl radicals include substituted or unsubstituted methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl and hexyloxycarbonyl.

[0038] The term "hydroxyalkyl" is a linear or branched alkyl radical having one to about ten carbon atoms, any one of which may be substituted with one or more hydroxyl radicals.

More preferred hydroxyalkyl radicals are"lower hydroxyalkyl" radicals having one to six carbon atoms and one or more hydroxyl radicals. Examples of such radicals include hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl and hydroxyhexyl.

[0039] The term"alkylamino"is an amino group that has been substituted with one or two alkyl radicals. Preferred are "lower N-alkylamino"radicals having alkyl portions having one to six carbon atoms. Suitable lower alkylamino may be mono-or dialkylamino, such as N-methylamino, N-ethylamino, N, N- dimethylamino, N, N-diethylamino or the like.

[0040] The term"alkylaminoalkyl"is a radical having one or more alkyl radicals attached to the nitrogen atom of an aminoalkyl radical.

[0041] The term"alkylaminocarbonyl"is an aminocarbonyl group that has been substituted with one or two alkyl radicals on the amino nitrogen atom. Preferred are"N-alkylaminocarbonyl" "N, N-dialkylaminocarbonyl"radicals. More preferred are"lower N-alkylaminocarbonyl"and"lower N, N-dialkylaminocarbonyl" radicals with lower alkyl portions as defined above.

[0042] The term"alkylthio"is a radical containing an alkyl radical of one to about ten carbon atoms attached to a divalent sulfur atom. More preferred alkylthio radicals are "lower alkylthio"radicals having alkyl radicals of one to six carbon atoms. Examples of such lower alkylthio radicals are methylthio, ethylthio, propylthio, butylthio and hexylthio.

[0043] The term"alkylthioalkyl"is a radical containing an alkylthio radical attached through the divalent sulfur atom to an alkyl radical of one to about ten carbon atoms. More preferred alkylthioalkyl radicals are"lower alkylthioalkyl" radicals having alkyl radicals of one to six carbon atoms.

Examples of such lower alkylthioalkyl radicals include methylthiomethyl, methylthioethyl, ethylthioethyl, and ethylthiopropyl.

[0044] The term"alkylsulfinyl"is a radical containing a linear or branched alkyl radical, of one to ten carbon atoms, attached to a divalent-S (=O)- radical. More preferred alkylsulfinyl radicals are"lower alkylsulfinyl"radicals having alkyl radicals of one to six carbon atoms. Examples of such lower alkylsulfinyl radicals include methylsulfinyl, ethylsulfinyl, butylsulfinyl and hexylsulfinyl.

[0045] The term"aminoalkyl"is an alkyl radical substituted with one or more amino radicals. More preferred are "lower aminoalkyl"radicals of one to six carbon atoms. Examples of such radicals include aminomethyl, aminoethyl, and the like.

[0046] The term"aminocarbonyl"is an amide group of the formula-C (=O) NH2.

[0047] The term"carbonyl", whether used alone or with other terms, such as"alkoxycarbonyl", is- (C=O)-.

[0048] The term"aryl", alone or in combination, is a carbocyclic aromatic system containing one, two or three rings wherein such rings may be attached together in a pendent manner or may be fused, and wherein at least one of the rings is aromatic. The term"aryl"includes aromatic radicals such as phenyl, naphthyl, tetrahydronaphthyl, indane and biphenyl. Aryl moieties may also be substituted at a substitutable position with one or more substituents selected independently from alkyl, alkoxyalkyl, alkylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, alkoxy, aralkoxy, hydroxyl, amino, halo, nitro, alkylamino, acyl, cyano, carboxy, aminocarbonyl, alkoxycarbonyl and aralkoxycarbonyl.

[0049] The terms"heterocyclyl"and"heterocyclo"are saturated or partially unsaturated heteroatom-containing ring- shaped radicals having one, two, or three rings wherein such rings may be attached together in a pendent manner or may be fused, where the heteroatoms may be selected from nitrogen, sulfur and oxygen. Examples of saturated heterocyclyl and heterocyclo radicals include saturated 3-to 6-membered heteromonocylic radicals containing one to four nitrogen atoms (e. g., pyrrolidinyl, imidazolidinyl, piperidino, piperazinyl, etc.) ; saturated 3-to 6-membered heteromonocyclic group containing one to two oxygen atoms and one to three nitrogen atoms (e. g., morpholinyl, etc.) ; saturated 3-to 6-membered heteromonocyclic group containing one to two sulfur atoms and one to three nitrogen atoms (e. g., thiazolidinyl, etc.).

Examples of partially unsaturated heterocyclyl and heterocyclo radicals include dihydrothiophene, dihydropyran, dihydrofuran and dihydrothiazole.

[0050] The term"heteroaryl"is an aromatic heteroatom- containing ring-shaped radical having one, two, or three rings wherein at least one ring is aromatic. Examples of heteroaryl radicals include unsaturated 3-to 6-membered heteromonocyclic group containing one to four nitrogen atoms, e. g., pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl (e. g., 4H-1, 2, 4-triazolyl, 1H- 1, 2, 3-triazolyl, 2H-1, 2, 3-triazolyl, etc.) tetrazolyl (e. g. 1H- tetrazolyl, 2H-tetrazolyl, etc.), etc. ; unsaturated condensed heterocyclyl group containing one to five nitrogen atoms, e. g., indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl, indazolyl, benzotriazolyl, tetrazolopyridazinyl (e. g., tetrazolo [1, 5-b] pyridazinyl, etc.), etc. ; unsaturated 3- to 6-membered heteromonocyclic group containing an oxygen atom, e. g., pyranyl, furyl, etc. ; unsaturated 3-to 6-membered heteromonocyclic group containing a sulfur atom, e. g., thienyl, etc. ; unsaturated 3-to 6-membered heteromonocyclic group containing one to two oxygen atoms and one to three nitrogen atoms, e. g., oxazolyl, isoxazolyl, oxadiazolyl (e. g., 1, 2, 4- oxadiazolyl, 1, 3, 4-oxadiazolyl, 1, 2, 5-oxadiazolyl, etc.) etc. ; unsaturated condensed heterocyclyl group containing one to two oxygen atoms and one to three nitrogen atoms (e. g., benzoxazolyl, benzoxadiazolyl, etc.) ; unsaturated 3-to 6- membered heteromonocyclic group containing one to two sulfur atoms and one to three nitrogen atoms, e. g., thiazolyl, thiadiazolyl (e. g., 1, 2, 4-thiadiazolyl, 1, 3, 4-thiadiazolyl, 1, 2, 5-thiadiazolyl, etc.) etc. ; unsaturated condensed heterocyclyl group containing one to two sulfur atoms and one to three nitrogen atoms (e. g., benzothiazolyl, benzothiadiazolyl, etc.) and the like. The term"heteroaryl"also includes radicals where heteroaryl radicals are fused with aryl radicals. Examples of such fused bicyclic radicals include benzofuran, benzothiophene, and the like. Said heterocyclyl group may be substituted at a substitutable position with one or more substituents selected independently from alkyl, hydroxyl, halo, alkoxy, oxo, amino and alkylamino.

[0051] The terms"heterocyclylalkyl"and"heterocycloalkyl§ are saturated and partially unsaturated heterocyclyl-substituted alkyl radicals, such as pyrrolidinylmethyl, and heteroaryl- substituted alkyl radicals, such as pyridylmethyl, quinolylmethyl, thienylmethyl, furylethyl, and quinolylethyl.

The heteroaryl in said heteroaralkyl may be additionally substituted with halo, alkyl, alkoxy, halkoalkyl and haloalkoxy.

[0052] The term"acyl"is a radical provided by the residue after removal of hydroxyl from an organic acid. Examples of such acyl radicals include alkanoyl and aroyl radicals.

[0053] The term"alkanoyl"or"alkylcarbonyl"are alkyl radicals as defined herein attached to a carbonyl radical.

Examples of such alkanoyl radicals include formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, and trifluoroacetyl.

[0054] The terms"arylcarbonyl" (also called"aroyl") and "aralkylcarbonyl"include radicals having aryl or aralkyl radicals, as defined herein, attached to a carbonyl radical.

Examples of such radicals include substituted or unsubstituted phenylcarbonyl, naththoyl, and benzylcarbonyl. The aryl in said aroyl and aralkylcarbonyl radicals may be additionally substituted.

[0055] The term"aralkoxy"is an aralkyl radical as defined herein attached through an oxygen atom to other radicals.

[0056] The term"aralkoxyalkyl"is an aralkoxy radical as defined herein attached through an oxygen atom to an alkyl radical.

[0057] The terms"aralkyl"and"arylalkyl"are aryl- substituted alkyl radicals such as benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, and diphenylethyl. The aryl in said aralkyl may be additionally substituted with halo, alkyl, alkoxy, haloalkyl and haloalkoxy. The terms benzyl and phenylmethyl are interchangeable.

[0058] The term"aralkylamino"is an aralkyl radical as defined herein attached through an amino nitrogen atom to other radicals. The terms"N-arylaminoalkyl"and"N-aryl-N-alkyl- aminoalkyl"are amino groups which have been substituted with one aryl radical or one aryl and one alkyl radical, respectively, and having the amino group attached to an alkyl radical. Examples of such radicals include N-phenylaminomethyl and N-phenyl-N-methylaminomethyl.

[0059] The term"aralkylthio"is an aralkyl radical attached to a sulfur atom.

[0060] The term"aralkylthioalkyl"is an aralkylthio radical attached through a sulfur atom to an alkyl radical.

[0061] The term"arylamino"is an amino group that has been substituted with one or two aryl radicals. An example of such arylamino radicals is N-phenylamino. The"arylamino"radicals may be further substituted on the aryl ring portion of the radical.

[0062] The term"aryloxyalkyl"is a radical having an aryl radical attached to an alkyl radical through a divalent oxygen atom.

[0063] The term"arylthioalkyl"is a radical having an aryl radical attached to an alkyl radical through a divalent sulfur atom.

[0064] The term"sulfonyl", whether used alone or linked to other terms such as alkylsulfonyl, is a divalent-SO2-radical.

[0065] The term"alkylsulfonyl"is an alkyl radical attached to a sulfonyl radical, where alkyl is defined as above.

More preferred alkylsulfonyl radicals are"lower alkylsulfonyl" radicals having one to six carbon atoms. Examples of such lower alkylsulfonyl radicals include methylsulfonyl, ethylsulfonyl and propylsulfonyl. The"alkylsulfonyl"radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide haloalkylsulfonyl radicals.

[0066] The terms"sulfamyl","aminosulfonyl"and "sulfonamidyl"are-S02NH2.

[0067] The term"pharmaceutically acceptable"is used adjectivally herein to mean that the modified noun is appropriate for use in a pharmaceutical product ; that is the "pharmaceutically-acceptable"material is relatively safe and/or non-toxic, though not necessarily providing a separable therapeutic benefit by itself. Pharmaceutically-acceptable cations include. metallic ions and organic ions. More preferred metallic ions include, but are not limited to, appropriate alkali metal salts, alkaline earth metal salts and other physiologically-acceptable metal ions. Exemplary ions include aluminum, calcium, lithium, magnesium, potassium, sodium and zinc, in their usual valences. Preferred organic ions include protonated tertiary amines and quaternary ammonium cations, including in part, trimethylamine, diethylamine, N, N'- dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine (N-methylglucamine) and procaine. Exemplary pharmaceutically acceptable acids include without limitation hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, methanesulfonic acid, acetic acid, formic acid, tartaric acid, maleic acid, malic acid, citric acid, isocitric acid, succinic acid, lactic acid, gluconic acid, glucuronic acid, pyruvic acid, oxalacetic acid, fumaric acid, propionic acid, aspartic acid, glutamic acid, benzoic acid, and the like.

[0068] The term"prodrug"refers to a chemical compound that can be converted into a therapeutic compound by metabolic or simple chemical processes within the body of the subject.

[0069] The term"subject"for purposes of treatment or prevention includes any human or animal subject who is in need of treatment. The subject can be a domestic livestock species, a laboratory animal species, a zoo animal or a companion animal.

In one embodiment, the subject is a mammal. In another embodiment, the mammal is a human being.

[0070] The term"PBS"stands for phosphate buffered saline.

[0071] The term"HEPES"stands for N-2- hydroxyethylpiperazine-N'-2-ethanesulfonic acid.

[0072] The term"BSA"stands for bovine serum albumin.

[0073] The term"STI"stands for soybean trypsin inhibitor.

[0074] The term"Pefabloc"stands for (4- (2- aminoethyl) benzenesulfonylfluoride, HC1 salt.

[0075] The term"Phosphoramidon"stands for N-a-L- rhamnopyranosyloxy (hydroxyphosphinyl)-L-leucyl-L-tryptophan.

[0076] The term"FCC"stands for flash column chromatography.

[0077] The term"Ki"stands for inhibitory rate constant.

[0078] The term"FLIPR"stands for fluorometric imaging plate reader.

[0079] The term"HEK 293"stands for the human embryonic kidney 293 cell line.

[0080] The term"Boc"stands for tert-butoxycarbonyl.

[0081] The term"DIC"stands for diisopropylcarbodiimide.

[0082] The term"DCM"stands for dichloromethane.

[0083] The term"DBU"stands for 1, 8- diazabicyclo [5. 4. 0] undec-7-ene.

[0084] The term"phosgene"stands for COC12.

[0085] The term"DCE"stands for dichloroethane.

[0086] The term"DMF"stands for dimethylformamide.

[0087] The term"EtOAc"stands for ethyl acetate.

[00883 The term"HOBt"stands for 1-Hydroxybenzotriazole hydrate.

[0089] The term"MeOH"stands for methanol.

[0090] The term"TFA"stands for trifluoroacetic acid.

[0091] The MCH receptor antagonists employed in the present invention can exist in tautomeric, geometric or stereoisomeric forms. The present invention contemplates all such compounds, including cis-and trans-geometric isomers, E-and Z-geometric isomers, R-and S-enantiomers, diastereomers, d-and 1-isomers, the racemic mixtures thereof and other mixtures thereof.

Pharmaceutically acceptable salts of such tautomeric, geometric or stereoisomeric forms are also included within the invention.

The terms"cis"and"trans", as used herein, denote a form of geometric isomerism in which two carbon atoms connected by a double bond and each substituted by a hydrogen and another group, will each have a hydrogen atom on the same side of the double bond ("cis") or on opposite sides of the double bond ("trans"). Some of the compounds described herein contain alkenyl groups, and are meant to include both cis and trans or "E"and"Z"geometric forms. Furthermore, some of the compounds described herein contain one or more stereocenters and are meant to include R, S, and mixtures or R and S forms for each stereocenter present.

[0092] The MCH receptor antagonists utilized in the present invention may be in the form of free bases or pharmaceutically- acceptable acid addition salts thereof. The term "pharmaceutically-acceptable salts"are salts commonly used to form alkali metal salts and to form addition salts of free acids or free bases. The nature of the salt may vary, provided that it is pharmaceutically acceptable. Suitable pharmaceutically- acceptable acid addition salts of compounds for use in the present methods may be prepared from an inorganic acid or from an organic acid. Examples of such inorganic acids are hydrochloric, hydrobromic, hydroiodic, nitric, carbonic, sulfuric and phosphoric acid. Appropriate organic acids may be selected from aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic, carboxylic and sulfonic classes of organic acids, examples of which are formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucuronic, maleic, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic, mesylic, 4-hydroxybenzoic, phenylacetic, mandelic, embonic (pamoic), methanesulfonic, ethanesulfonic, benzenesulfonic, pantothenic, 2-hydroxyethanesulfonic, toluenesulfonic, sulfanilic, cyclohexylaminosulfonic, stearic, algenic, hydroxybutyric, salicylic, galactaric and galacturonic acid. Suitable pharmaceutically-acceptable base addition salts of compounds of use in the present methods include metallic salts made from aluminum, calcium, lithium, magnesium, potassium, sodium and zinc or organic salts made from N, N'- dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine (N-methylglucamine), and procaine. All of these salts may be prepared by conventional means from the corresponding compound by reacting, for example, the appropriate acid or base with the compound of any Formula set forth herein.

[0093] The MCH receptor antagonists useful in the practice of the present invention can be formulated into pharmaceutical compositions and administered by any means that will deliver a therapeutically effective dose. Such compositions can be administered orally, parenterally, by inhalation spray, rectally, intradermally, transdermally, or topically, in dosage unit formulations containing conventional nontoxic pharmaceutically-acceptable carriers, adjuvants, and vehicles as desired. Topical administration may also involve the use of transdermal administration such as transdermal patches or iontophoresis devices. The term parenteral as used herein includes subcutaneous, intravenous, intramuscular, or intrasternal injection, or infusion techniques. Formulation of drugs is discussed in, e. g., Hoover, Remington's Pharmaceutical Sciences, (1975), and Liberman & Lachman, Eds., Pharmaceutical Dosage Forms, (1980).

[0094] Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions, can be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a nontoxic parenterally-acceptable diluent or solvent. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose, any bland fixed oil may be employed, including synthetic mono-or diglycerides.

In addition, fatty acids such as oleic acid are useful in the preparation of injectables. Dimethyl acetamide, surfactants including ionic and non-ionic detergents, and polyethylene glycols can be used. Mixtures of solvents and wetting agents such as those discussed above are also useful.

[0095] Suppositories for rectal administration of the compounds discussed herein can be prepared by mixing the active agent with a suitable non-irritating excipient such as cocoa butter, synthetic mono-, di-, or triglycerides, fatty acids, or polyethylene glycols, which are solid at ordinary temperatures but liquid at the rectal temperature, and which will therefore melt in the rectum and release the drug.

[0096] Solid dosage forms for oral administration may include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the compounds are ordinarily combined with one or more adjuvants appropriate to the indicated route of administration. If administered per os, the compounds can be admixed with lactose, sucrose, starch powder, cellulose esters of alkanoic acids, cellulose alkyl esters, talc, stearic acid, magnesium stearate, magnesium oxide, sodium and calcium salts of phosphoric and sulfuric acids, gelatin, acacia gum, sodium alginate, polyvinylpyrrolidone, and/or polyvinyl alcohol, and then tableted or encapsulated for convenient administration.

Such capsules or tablets can contain a controlled-release formulation as can be provided in a dispersion of active compound in hydroxypropylmethyl cellulose. In the case of capsules, tablets, and pills, the dosage forms can also comprise buffering agents such as sodium citrate, or magnesium or calcium carbonate or bicarbonate. Tablets and pills can additionally be prepared with enteric coatings.

[0097] For therapeutic purposes, formulations for parenteral administration can be in the form of aqueous or non- aqueous isotonic sterile injection solutions or suspensions.

These solutions and suspensions can be prepared from sterile powders or granules having one or more of the carriers or diluents mentioned for use in the formulations for oral administration. The compounds can be dissolved in water, polyethylene glycol, propylene glycol, ethanol, corn oil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodium chloride, and/or various buffers. Other adjuvants and modes of administration are well and widely known in the pharmaceutical art.

[0098] Liquid dosage forms for oral administration can include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs containing inert diluents commonly used in the art, such as water. Such compositions can also comprise adjuvants, such as wetting agents, emulsifying and suspending agents, and sweetening, flavoring, and perfuming agents.

[0099] The amount of active ingredient that can be combined with the carrier materials to produce a single dosage of the MCH receptor antagonist will vary depending upon the patient and the particular mode of administration. In general, the pharmaceutical compositions may contain an MCH receptor antagonist in the range of about 1 to about 250 mg, more typically, in the range of about 10 to about 200 mg and still more typically, between about 25 to about 150 mg. A daily dose of about 0. 01 to about 80 mg/kg body weight, or more typically, between about 0. 5 to about 50 mg/kg body weight and even more typically, from about 1 to about 25 mg/kg body weight, may be appropriate. The daily dose can be administered in one to about four doses per day.

[0100] The MCH receptor antagonists are administered in such amount as will be therapeutically effective in the treatment or control of the disorder or condition being treated.

It will be appreciated that the amount of active ingredients contained in an individual dose of each dosage form need not in itself constitute an effective amount, as the necessary effective amount could be reached by administration of a number of individual doses. Those skilled in the art will appreciate that the quantity of active MCH receptor antagonist to be administered will vary depending upon the age, sex, and body weight of the subject to be treated, the type of disease, or syndrome to be treated, the particular method and scheduling of administration, and what other MCH receptor antagonist, if any, is co-administered. Dosage amounts for an individual patient may thus be above or below the typical dosage ranges. Generally speaking, the MCH receptor antagonist can be employed in any amount known to be effective at treating, preventing or controlling the disorder or condition being treated. The doses may be single doses or multiple doses per day, with the number of doses taken per day and the time allowed between doses varying depending on the individual needs of the patient.

Optimization of treatment, including dosage amount, method and time of administration, is thus best determined by a skilled practitioner through close monitoring of patients on an individual basis. Those skilled in the art will appreciate that dosages may also be determined with guidance from Goodman & Goldman, The Pharmacological Basis of Therapeutics, 9th Ed.

(1996), App. II, pp. 1707-1711 and from Goodman & Goldman, The Pharmacological Basis of Therapeutics, loth Ed. (2001), App. II, pp. 475-493.

Description of the Preferred Embodiments [0101] In one embodiment of the present invention, the MCH receptor antagonist is a compound of Formula I, or a pharmaceutically-acceptable salt, tautomer or prodrug thereof, having the following structure : [0102] wherein : [0103] W is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano ; [0104] X is selected from the group consisting of-OR', -NR1R10, and -SR1; [0105] Y is selected from the group consisting of hydrogen, -N (R7) C (O) NR2R8,-N (R') C (O) OR2, -N (R') C (O) R2,-N (R7) SO2R2, and -NR2R7; [0106] Z is selected from the group consisting of-CH=CH-, -CH2N(R9)-, -C(O)-, -CH2N(R9)-, and-N (R12) C (O) N (R9)- ; [0107] R1 is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, and heteroarylalkyl, wherein Ru ils optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo ; [0108] R2 is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, cycloalkylalkyl, aralkenyl, arylcycloalkyl, and heteroarylalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo ; [01091 R3 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano ; [0110] R4 is selected from the group consisting of a bond, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, aralkyl, cycloalkylalkyl, aralkenyl, and heteroarylalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, alkoxycarbonyl, and halo ; [0111] R5 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0112] R6 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0113] R7 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano ; [0114] R5 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano, or R8 together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system ; [0115] R9 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0116] Rl° is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano ; [0117] R11 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano ; and [0118] R12 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano.

[0119] In another embodiment, the MCH receptor antagonist consists of compounds of Formula I, or a pharmaceutically- acceptable salt, tautomer or prodrug thereof, wherein : [0120] W is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano ; [0121] X is selected from the group consisting of -OR1, -NR1R10, and -SR1; [0122] Y is selected from the group consisting of hydrogen, - N (R') C (0) NR2R8,-N (R') C (0) OR2, -N(R7) C (0) R',-N (R7)SO2R2, and - NR ; [0123] Z is selected from the group consisting of-CH=CH-, -CH2N (R9)-,-C (O)-,-C (O) N (R9)-, and-N (Rl2) C (O) N (R9)- ; [0124] Ru ils selected from the group consisting of lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, aryl, lower aralkyl, heteroaryl, and lower heteroarylalkyl, wherein Ru ils optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo ; [0125] R2 is selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, heteroaryl, lower aralkyl, lower cycloalkylalkyl, lower aralkenyl, lower arylcycloalkyl, and lower heteroarylalkyl, or R2 together with Ra and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo ; [0126] R3 is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano ; [0127] R4 is selected from the group consisting of a bond, lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, heteroaryl, lower aralkyl, lower cycloalkylalkyl, lower aralkenyl, and lower heteroarylalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, lower alkoxycarbonyl, and halo ; [0128] R5 is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0129] R6 is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0130] R7 is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano ; [0131] R8 is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano, or R8 together with R and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system ; [0132] R9 is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0133] R1° is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano ; [0134] R' : L is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano ; and [0135] Rl2 is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano.

[0136] In another embodiment, the MCH receptor antagonist consists of compounds of Formula I, or a pharmaceutically- acceptable salt, tautomer or prodrug thereof, wherein : [0137] W is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano ; [0138] X is selected from the group consisting of-OR1, -NRlRlOs and-sRl ; [0139] Y is selected from the group consisting of hydrogen, -N(R7) C (O) NR2R8,-N (R') C (O) OR2, -N (R7) C (0) R2,-N (R7)SO2R2, and - NRzR ; [0140] Z is selected from the group consisting of-CH=CH-, -CH2N (R9)-,-C (O)-,-C (O) M (R9)-, and-N (R12) C (0) N (R9)- ; [0141] R is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro ; [0142] R is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, phenylcyclopropyl, phenylcyclobutyl, phenylcyclopentyl, phenylcyclohexyl, biphenylcyclopropyl, biphenylcyclobutyl, biphenylcyclopentyl, biphenylcyclohexyl, naphthylcyclopropyl, naphthylcyclobutyl, naphthylcyclopentyl, naphthylcyclohexyl, or R2 together with RB and the nitrogen to which they are attached may form a ring selected from the group consisting of hexahydroisoindolyl, tetrahydroisoindolyl, dihydroisoindolyl, isoindolinyl, hexahydroindolyl, tetrahydroindolyl, dihydroindolyl, indolinyl, octahydroquinolinyl, hexahydroquinolinyl, tetrahydroquinolinyl, dihydroquinolinyl, and quinolinyl, wherein R2 or the ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro ; [0143] R3 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano ; [0144] R4 is selected from the group consisting of a bond, methyl, ethyl, propyl, butyl, pentyl, hexyl, ethenyl, propenyl, allyl, butenyl, pentenyl, acetylenyl, propynyl, butynyl, pentynyl, hexynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, or R4 together with R9 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, chloro, bromo, and fluoro ; [0145] R5 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano, or R5 together with R6 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring ; [0146] R6 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano, or R6 together with R5 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring ; [0147] R7 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano ; [0148] R8 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano, or R8 together with R2 and the nitrogen to which they are attached may form an isoindolinyl ring ; [0149] R9 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano, or R9 together with R4 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring ; [0150] Rl° is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano ; [0151] Rll is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano ; and [0152] R12 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano.

[0153] In another embodiment, the MCH receptor antagonist consists of compounds of Formula I, or a pharmaceutically- acceptable salt, tautomer or prodrug thereof, wherein : [0154] W is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano ; [0155] X is-ORl ; [0156] Y is selected from the group consisting of hydrogen, - N (R') C (O) NR2R8,-N (R7) C (O) OR2, -N (R7) C (O) R 2,--N (R 7) S02R2, and NR2R7 [0157] Z is selected from the group consisting of-CH=CH-, -CH2N(R9)-, -C(O)-, -C(O) N (R9)-, and-N (R12) C (O) N (R9)- ; [0158] Ru ils selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, and heteroarylalkyl, wherein Ru ils optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo ; [0159] R2 is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, cycloalkylalkyl, aralkenyl, arylcycloalkyl, and heteroarylalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo ; [0160] R3 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano ; [0161] R4 is selected from the group consisting of a bond, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, aralkyl, cycloalkylalkyl, aralkenyl, and heteroarylalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, alkoxycarbonyl, and halo ; [0162] R5 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano, or R together with R6 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0163] R6 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0164] R7 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano ; [0165] R8 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano, or R8 together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system ; [0166] R9 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0167] Rl° is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano ; [0168] Rll is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano ; and [0169] Rl2 is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, halo, alkoxy, hydroxyalkyl, alkoxyalkyl, aryloxy, carboxyl, carboxyalkyl, and cyano.

[0170] In another embodiment, the MCH receptor antagonist consists of compounds of Formula I, or a pharmaceutically- acceptable salt, tautomer or prodrug thereof, wherein : [0171] W is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano ; [0172] X is -OR1 ; [0173] Y is selected from the group consisting of hydrogen, - N (R') C (O) NR2R8,-N (R7) C (O) oR2,-N (R7) C (O) R2,-N (R7)SO2R2, and -NR2R7; [0174] Z is selected from the group consisting of-CH=CH-, -CH2N(R9)-, -C(O)-, -C(O) N (R9)-, and-N (R12) C (0) N (R9)-; [0175] R : L is selected from the group consisting of lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, aryl, lower aralkyl, heteroaryl, and lower heteroarylalkyl, wherein Ru ils optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo ; [0176] R2 is selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, heteroaryl, lower aralkyl, lower cycloalkylalkyl, lower aralkenyl, lower arylcycloalkyl, and lower heteroarylalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with Ra is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo ; [0177] R3 is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano ; [0178] R4 is selected from the group consisting of a bond, lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, heteroaryl, lower aralkyl, lower cycloalkylalkyl, lower aralkenyl, and lower heteroarylalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5- or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, lower alkoxycarbonyl, and halo ; [0179] R5 is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0180] R6 is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano, or R6 together with R and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0181] R7 is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano ; [0182] R8 is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano, or R8 together with R and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system ; [0183] R9 is selected from the group consisting of hydrogen, hydroxy, lower, alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0184] Rl° is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano ; [0185] Rll is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano ; and [0186] Rl2 is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, halo, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, aryloxy, carboxyl, lower carboxyalkyl, and cyano.

[0187] In another embodiment, the MCH receptor antagonist consists of compounds of Formula I, or a pharmaceutically- acceptable salt, tautomer or prodrug thereof, wherein : [0188] W is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano ; [0189] X is-OR' ; [0190] Y is selected from the group consisting of hydrogen, -N(R7) C (O) NR2R8,-N (R7) C (O) oR2,-N (R7) C (O) R2,-N (R') SO2R2, and - NRR ; [0191] Z is selected from the group consisting of-CH=CH-, -CH2N (R9)-,-C (O)-,-C (O) N (R9)-, and-N (Rl2) C (0) N (R9)- ; [0192] Ru ils selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, wherein Ru ils optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro ; [0193] R2 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, phenylcyclopropyl, phenylcyclobutyl, phenylcyclopentyl, phenylcyclohexyl, biphenylcyclopropyl, biphenylcyclobutyl, biphenylcyclopentyl, biphenylcyclohexyl, naphthylcyclopropyl, naphthylcyclobutyl, naphthylcyclopentyl, naphthylcyclohexyl, or R2 together with R8 and the nitrogen to which they are attached may form a ring selected from the group consisting of hexahydroisoindolyl, tetrahydroisoindolyl, dihydroisoindolyl, isoindolinyl, hexahydroindolyl, tetrahydroindolyl, dihydroindolyl, indolinyl, octahydroquinolinyl, hexahydroquinolinyl, tetrahydroquinolinyl, dihydroquinolinyl, and quinolinyl, wherein R2 or the ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro ; [0194] R3 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano ; [0195] R4 is selected from the group consisting of a bond, methyl, ethyl, propyl, butyl, pentyl, hexyl, ethenyl, propenyl, allyl, butenyl, pentenyl, acetylenyl, propynyl, butynyl, pentynyl, hexynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, or R4 together with R9 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, chloro, bromo, and fluoro ; [0196] R5 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano, or R5 together with R6 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring ; [0197] R6 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano, or R6 together with Rs and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring ; [0198] R7 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano ; [0199] Ra is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano, or R8 together with R2 and the nitrogen to which they are attached may form an isoindolinyl ring ; [0200] R9 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano, or R9 together with R4 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring ; [0201] R10 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano ; [0202] R : Ll is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano ; and [0203] R12 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano.

[0204] In another embodiment, the MCH receptor antagonist is selected from a subclass of compounds of Formula I represented by Formula II : [0205] wherein : [0206] W is selected from the group consisting of hydrogen, hydroxy, alkyl, and alkoxy ; [0207] X is selected from the group consisting of -OR1, -NR1R10, and -SR1; [0208] Y is selected from the group consisting of hydrogen, -N(R7) C (O) NR2R8,-N (R7) C (O) oR2,-N (R7) C (O) R2,-N (R') S02R2, and -NR2R7 [0209] Z is selected from the group consisting of-CH=CH-, -CH2N(R9)-, -C(O)-, -C(O) N (R9)-, and-N (R12) C (0) N (R9)- ; [0210] R1 is selected from the group consisting of alkyl, cycloalkyl, aryl, and heteroaryl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo ; [0211] R2 is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, cycloalkylalkyl, aralkenyl, and arylcycloalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo ; [0212] R4 is selected from the group consisting of a bond, alkyl, alkenyl, and cycloalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, and halo ; [0213] R-9 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, and alkoxyalkyl, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0214] R6 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, and alkoxyalkyl, or R6 together with Rs and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0215] R7 is selected from the group consisting of hydrogen, alkyl, and aryl ; [0216] R8 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl, or R8 together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system ; [0217] R9 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0218] R10 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl ; and [0219] R12 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl ; [0220] or a pharmaceutically-acceptable salt, tautomer or prodrug thereof.

[0221] In another embodiment, the MCH receptor antagonist consists of compounds of Formula II, or a pharmaceutically- acceptable salt, tautomer or prodrug thereof, wherein : [0222] W is selected from the group consisting of hydrogen, hydroxy, lower alkyl, and lower alkoxy ; [0223] X is selected from the group consisting of-OR1, -NR1Rl0, and-SR1 ; [0224] Y is selected from the group consisting of hydrogen, - N (R') C (0) NR2R8,-N (R7) C (0) OR2, -N(R7) C (O) R2, -N(R7)SO2R2, and NR2R7 [0225] Z is selected from the group consisting of-CH=CH-, -CH2N (R9)-,-C (O)-,-C (O) N (R9)-, and-N (R12) C (O) N (R9)- ; [0226] R1 is selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, and heteroaryl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo ; [0227] R2 is selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, heteroaryl, lower aralkyl, lower cycloalkylalkyl, lower aralkenyl, and lower arylcycloalkyl, or R2 together with Ra and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo ; [0228] R4 is selected from the group consisting of a bond, lower alkyl, lower alkenyl, and lower cycloalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, and halo ; [0229] R5 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, and lower alkoxyalkyl, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0230] R6 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, and lower alkoxyalkyl, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0231] R7 is selected from the group consisting of hydrogen, lower alkyl, and aryl ; [0232] R8 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl, or R8 together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system ; [0233] R9 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0234] R1° is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl ; and [0235] R12 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl.

[0236] In another embodiment, the MCH receptor antagonist consists of compounds of Formula II, or a pharmaceutically- acceptable salt, tautomer or prodrug thereof, wherein : [0237] W is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, butoxy, pentyloxy, and hexyloxy ; [0238] X is selected from the group consisting of-OR1, -NRlRl0 and-sR1 ; [0239] Y is selected from the group consisting of hydrogen, -N(R7)C(O)NR2R8, -N(R7)C(O)OR2, -N(R7) C (O) R2,-N (R') S02R2, and -NR2R7; [0240] Z is selected from the group consisting of-CH=CH-, -CH2N(R9)-, -C(O)-, -C(O) N (R9)-, and-N (R12) C (O) N (R9)- ; [0241] R1 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, and benzodioxolyl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro ; [0242] R2 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, phenylcyclopropyl, phenylcyclobutyl, phenylcyclopentyl, phenylcyclohexyl, biphenylcyclopropyl, biphenylcyclobutyl, biphenylcyclopentyl, biphenylcyclohexyl, naphthylcyclopropyl, naphthylcyclobutyl, naphthylcyclopentyl, naphthylcyclohexyl, or R2 together with R8 and the nitrogen to which they are attached may form a ring selected from the group consisting of hexahydroisoindolyl, tetrahydroisoindolyl, dihydroisoindolyl, isoindolinyl, hexahydroindolyl, tetrahydroindolyl, dihydroindolyl, indolinyl, octahydroquinolinyl, hexahydroquinolinyl, tetrahydroquinolinyl, dihydroquinolinyl, and quinolinyl, wherein R2 or the ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro ; [0243] R3 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano ; [0244] R4 is selected from the group consisting of a bond, methyl, ethyl, propyl, butyl, pentyl, hexyl, ethenyl, propenyl, allyl, butenyl, pentenyl, acetylenyl, propynyl, butynyl, pentynyl, hexynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, or R4 together with R9 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, chloro, bromo, and fluoro ; [0245] R5 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, and pentoxypentyl, or R5 together with R6 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring ; [0246] R6 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, and pentoxypentyl, or R6 together with Rs and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring ; [0247] R7 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, phenyl, naphthyl, tetrahydronaphthyl, and biphenyl ; [0248] R8 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl, or R8 together with R2 and the nitrogen to which they are attached may form an isoindolinyl ring ; [0249] R9 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl, or R9 together with R4 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring ; [0250] R10 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl ; and [0251] R12 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl.

[0252] In another embodiment, the MCH receptor antagonist is selected from a subclass of compounds of Formula I represented by Formula III : [0253] wherein : [0254] X is selected from the group consisting of-OR1 and -SR1; [0255] Y is selected from the group consisting of hydrogen, -N(R7) C (O) NR2R8,-N (R') C (O) OR2,-N (R') C (0) R2,-N (R7) SO2R2, and -NR2R7; [0256] Z is selected from the group consisting of-CH=CH-, -CH2N(R9)-, -C(O) N (R9)-, and-NHC (O) NR9-; [0257] R1 is selected from the group consisting of alkyl, cycloalkyl, aryl, and heteroaryl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo ; [0258] R2 is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, cycloalkylalkyl, aralkenyl, and arylcycloalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo ; [0259] R4 is selected from the group consisting of a bond, alkyl, alkenyl, and cycloalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, and halo ; [0260] R5 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, and alkoxyalkyl, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0261] R6 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, and alkoxyalkyl, or R5 together with R5 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0262] R7 iS selected from the group consisting of hydrogen, alkyl, and aryl ; [0263] R8 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl, or R together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system ; [0264] R9 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0265] R10 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl ; and [0266] R12 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl ; [0267] or a pharmaceutically-acceptable salt, tautomer or prodrug thereof.

[0268] In another embodiment, the MCH receptor antagonist consists of compounds of Formula III, or a pharmaceutically- acceptable salt, tautomer or prodrug thereof, wherein : [0269] X is selected from the group consisting of-OR1 and -SR1; [0270] Y is selected from the group consisting of hydrogen, - N (R') C (O) NR2R8,-N (R7) C (0) OR2, -N(R7) C (O) R2,-N (R7) SO2R2, and -NR2R7; [0271] Z is selected from the group consisting of-CH=CH-, -CH2N (R9)-,-C (O) N (R9)-, and-NHC (O) NR9- ; [0272] R1 is selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, and heteroaryl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo ; [0273] R2 is selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, heteroaryl, lower aralkyl, lower cycloalkylalkyl, lower aralkenyl, and lower arylcycloalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo ; [0274] R4 is selected from the group consisting of a bond, lower alkyl, lower alkenyl, and lower cycloalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring, wherein R4 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, and halo ; [0275] Rs is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, and lower alkoxyalkyl, or Rs together with R6 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0276] R6 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, and lower alkoxyalkyl, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0277] R7 is selected from the group consisting of hydrogen, lower alkyl, and aryl ; [0278] R8 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl, or R8 together with R and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system ; [0279] R9 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0280] R10 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl ; and [0281] R12 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl.

[0282] In another embodiment, the MCH receptor antagonist consists of compounds of Formula III, or a pharmaceutically- acceptable salt, tautomer or prodrug thereof, wherein : [0283] X is selected from the group consisting of-OR'and -SR1 ; [0284] Y is selected from the group consisting of hydrogen, -N(R7) C (O) NR2R8,-N (R7) C (O) OR2,-N (R') C (O) R2,-N (R7)SO2R2, and NR2R7 [0285] Z is selected from the group consisting of-CH=CH-, -CH2N (R9)-,-C (O) N (R9)-, and-NHC (O) NR9- ; [0286] R1 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, and benzodioxolyl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro ; [0287] R2 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, phenylcyclopropyl, phenylcyclobutyl, phenylcyclopentyl, phenylcyclohexyl, biphenylcyclopropyl, biphenylcyclobutyl, biphenylcyclopentyl, biphenylcyclohexyl, naphthylcyclopropyl, naphthylcyclobutyl, naphthylcyclopentyl, naphthylcyclohexyl, or R2 together with R8 and the nitrogen to which they are attached may form a ring selected from the group consisting of hexahydroisoindolyl, tetrahydroisoindolyl, dihydroisoindolyl, isoindolinyl, hexahydroindolyl, tetrahydroindolyl, dihydroindolyl, indolinyl, octahydroquinolinyl, hexahydroquinolinyl, tetrahydroquinolinyl, dihydroquinolinyl, and quinolinyl, wherein R2 or the ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro ; [0288] R3 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano ; [0289] R4 is selected from the group consisting of a bond, methyl, ethyl, propyl, butyl, pentyl, hexyl, ethenyl, propenyl, allyl, butenyl, pentenyl, acetylenyl, propynyl, butynyl, pentynyl, hexynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, or R4 together with R9 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, chloro, bromo, and fluoro ; [0290] R5 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, and pentoxypentyl, wherein R5 together with R6 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring ; [0291] R6 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, and pentoxypentyl, or R6 together with R5 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring ; [0292] R7 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, phenyl, naphthyl, tetrahydronaphthyl, and biphenyl ; [0293] R8 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl, or R8 together with R2 and the nitrogen to which they are attached may form an isoindolinyl ring ; [0294] R9 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl, or R9 together with R4 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring ; [0295] R10 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl ; and [0296] R12 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl.

[0297] In another embodiment, the MCH receptor antagonist is selected from a subclass of compounds of Formula I represented by Formula IV : [0298] wherein : [0299] X is selected from the group consisting of-OR1 and -SR1 ; [0300] Z is selected from the group consisting of-CH=CH-, -CH2N (R9)-,-C (O) N (R9)-, and-NHC (O) NR9- ; [0301] R1 is selected from the group consisting of alkyl, cycloalkyl, aryl, and heteroaryl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo ; [0302] R2 is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, cycloalkylalkyl, aralkenyl, and arylcycloalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo ; [0303] R4 is selected from the group consisting of a bond, alkyl, alkenyl, and cycloalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, and halo ; [0304] R5 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, and alkoxyalkyl, or Rs together with R6 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0305] R6 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, and alkoxyalkyl, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0306] R7 is selected from the group consisting of hydrogen, alkyl, and aryl ; [0307] R8 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl, or R8 together with R and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system ; [0308] R9 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0309] R10 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl ; and [0310] R12 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl ; [0311'or a pharmaceutically-acceptable salt, tautomer or prodrug thereof.

[0312] In another embodiment, the MCH receptor antagonist consists of compounds of Formula IV, or a pharmaceutically- acceptable salt, tautomer or prodrug thereof, wherein : [0313] X is selected from the group consisting of-OR1 and -SR1; [0314] Z is selected from the group consisting of-CH=CH-, -CH2N (R9)-,-C (O) N (R9)-, and-NHC (O) NR9-; [0315] R1 is selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, and heteroaryl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo ; [0316] R2 is selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, heteroaryl, lower aralkyl, lower cycloalkylalkyl, lower aralkenyl, and lower arylcycloalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo ; [0317] R4 is selected from the group consisting of a bond, lower alkyl, lower alkenyl, and lower cycloalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, and halo ; [0318] R5 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, and lower alkoxyalkyl, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0319] R6 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, and lower alkoxyalkyl, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0320] R7 is selected from the group consisting of hydrogen, lower alkyl, and aryl ; [0321] R is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl, or R8 together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system ; [0322] R9 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0323] R10 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl ; and [0324] R12 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl.

[0325] In another embodiment, the MCH receptor antagonist consists of compounds of Formula IV, or a pharmaceutically- acceptable salt, tautomer or prodrug thereof, wherein : [0326] X is selected from the group consisting of-OR1 and _SR1 ; [0327] Z is selected from the group consisting of-CH=CH-, -CH2N (R9)-,-C (O) N (R9)-, and-NHC (O) NR9-; [0328] R1 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, and benzodioxolyl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro ; [0329] R2 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, phenylcyclopropyl, phenylcyclobutyl, phenylcyclopentyl, phenylcyclohexyl, biphenylcyclopropyl, biphenylcyclobutyl, biphenylcyclopentyl, biphenylcyclohexyl, naphthylcyclopropyl, naphthylcyclobutyl, naphthylcyclopentyl, naphthylcyclohexyl, or R together with R8 and the nitrogen to which they are attached may form a ring selected from the group consisting of hexahydroisoindolyl, tetrahydroisoindolyl, dihydroisoindolyl, isoindolinyl, hexahydroindolyl, tetrahydroindolyl, dihydroindolyl, indolinyl, octahydroquinolinyl, hexahydroquinolinyl, tetrahydroquinolinyl, dihydroquinolinyl, and quinolinyl, wherein R2 or ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro ; [0330] R3 is selected from the group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, chloro, bromo, fluoro, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, carboxyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, carboxyhexyl, and cyano ; [0331] R4 is selected from the group consisting of a bond, methyl, ethyl, propyl, butyl, pentyl, hexyl, ethenyl, propenyl, allyl, butenyl, pentenyl, acetylenyl, propynyl, butynyl, pentynyl, hexynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, or R4 together with R9 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, chloro, bromo, and fluoro ; [0332] R5 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, and pentoxypentyl, or R5 together with R6 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring ; [0333] R6 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, and pentoxypentyl, or R6 together with R5 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring ; [0334] R7 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, phenyl, naphthyl, tetrahydronaphthyl, and biphenyl ; [0335] R8 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl, or R8 together with R and the nitrogen to which they are attached may form an isoindolinyl ring ; [0336] R9 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl, or R9 together with R4 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring ; [0337] Rl° is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl ; and [0338] R12 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl.

[0339] In another embodiment, the MCH receptor antagonist is selected from a subclass of compounds of Formula I represented by Formula V : [0340] wherein : [0341] X is selected from the group consisting of-OR1 and _SR1 ; [0342] Z is selected from the group consisting of-CH=CH-, -CH2N (R9)-,-C (O) N (R9)-, and-NHC (O) NR9- ; [0343] Ru ils selected from the group consisting of alkyl, cycloalkyl, aryl, and heteroaryl, wherein Ru ils optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo ; [0344] R2 is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, cycloalkylalkyl, aralkenyl, and arylcycloalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with Ra is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo ; [0345] R4 is selected from the group consisting of a bond, alkyl, alkenyl, and cycloalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, and halo ; [0346] R5 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, and alkoxyalkyl, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0347] R6 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, and alkoxyalkyl, or R5 together with Rs and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0348] R7 is selected from the group consisting of hydrogen, alkyl, and aryl ; [0349] R8 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl, or R8 together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system ; and [0350] R9 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0351] or a pharmaceutically-acceptable salt, tautomer or prodrug thereof.

[0352] In another embodiment, the MCH receptor antagonist consists of compounds of Formula V, or a pharmaceutically- acceptable salt, tautomer or prodrug thereof, wherein : [0353] X is selected from the group consisting of-OR1 and _SR1 ; [0354] Z is selected from the group consisting of-CH=CH-, -CH2N (R9)-,-C (O) N (R9)-, and-NHC (O) NR9- ; [0355] Ru ils selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, and heteroaryl, wherein Ru ils optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo ; [0356] R2 is selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, heteroaryl, lower aralkyl, lower cycloalkylalkyl, lower aralkenyl, and lower arylcycloalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo ; [0357] R4 is selected from the group consisting of a bond, lower alkyl, lower alkenyl, and lower cycloalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, and halo ; [0358] R is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, and lower alkoxyalkyl, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0359] R6 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, and lower alkoxyalkyl, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0360] R7 is selected from the group consisting of hydrogen, lower alkyl, and aryl ; [0361] R8 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl, or R8 together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system ; and [0362] R9 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring.

[0363] In another embodiment, the MCH receptor antagonist consists of compounds of Formula V, or a pharmaceutically- acceptable salt, tautomer or prodrug thereof, wherein : [0364] X is selected from the group consisting of-OR1 and - SR. 1 ; [0365] Z is selected from the group consisting of-CH=CH-, -CH2N (R9)-,-C (O) N (R9)-, and-NHC (O) NR9- ; [0366] R1 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, and benzodioxolyl, wherein Ru ils optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro ; [0367] R2 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, phenylcyclopropyl, phenylcyclobutyl, phenylcyclopentyl, phenylcyclohexyl, biphenylcyclopropyl, biphenylcyclobutyl, biphenylcyclopentyl, biphenylcyclohexyl, naphthylcyclopropyl, naphthylcyclobutyl, naphthylcyclopentyl, naphthylcyclohexyl, or R2 together with R8 and the nitrogen to which they are attached may form a ring selected from the group consisting of hexahydroisoindolyl, tetrahydroisoindolyl, dihydroisoindolyl, isoindolinyl, hexahydroindolyl, tetrahydroindolyl, dihydroindolyl, indolinyl, octahydroquinolinyl, hexahydroquinolinyl, tetrahydroquinolinyl, dihydroquinolinyl, and quinolinyl, wherein R2 or the ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro ; [0368] R4 is selected from the group consisting of a bond, methyl, ethyl, propyl, butyl, pentyl, hexyl, ethenyl, propenyl, allyl, butenyl, pentenyl, acetylenyl, propynyl, butynyl, pentynyl, hexynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, or R4 together with R9 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, chloro, bromo, and fluoro ; [0369] R5 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, and pentoxypentyl, or R5 together with R6 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring ; [0370] R6 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, and pentoxypentyl, or R6 together with R5 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring ; [0371] R7 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, phenyl, naphthyl, tetrahydronaphthyl, and biphenyl ; [0372] R8 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl, or R8 together with R2 and the nitrogen to which they are attached may form an isoindolinyl ring ; and [0373] R9 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl, or R9 together with R4 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring.

[0374] In another embodiment, the MCH receptor antagonist is selected from a subclass of compounds of Formula I represented by Formula VI : [0375] wherein : [0376] X is selected from the group consisting of-OR1 and -SR1 ; [0377] Z is selected from the group consisting of-CH=CH-, -CH2N (R9)-,-C (O) N (R9)-, and-NHC (O) NR9- ; [0378] R1 is selected from the group consisting of alkyl, cycloalkyl, aryl, and heteroaryl, wherein Ru ils optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo ; [0379] R2 is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, cycloalkylalkyl, aralkenyl, and arylcycloalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, carboxyl, aryloxy, oxo, and halo ; [0380] R4 is selected from the group consisting of a bond, alkyl, alkenyl, and cycloalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, and halo ; [0381] R5 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, and alkoxyalkyl, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0382] R6 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, and alkoxyalkyl, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0383] R7 is selected from the group consisting of hydrogen, alkyl, and aryl ; and [0384] R9 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, and carboxyalkyl, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0385] or a pharmaceutically-acceptable salt, tautomer or prodrug thereof.

[0386] In another embodiment, the MCH receptor antagonist consists of compounds of Formula VI, or a pharmaceutically- acceptable salt, tautomer or prodrug thereof, wherein : [0387] X is selected from the group consisting of-OR1 and _SR1 ; [0388] Z is selected from the group consisting of-CH=CH-, -CH2N (R9)-,-C (O) N (R9)-, and-NHC (O) NR9- ; [0389] R1 is selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, and heteroaryl, wherein Ru ils optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo ; [0390] R2 is selected from the group consisting of lower alkyl, lower cycloalkyl, aryl, heteroaryl, lower aralkyl, lower cycloalkylalkyl, lower aralkenyl, and lower arylcycloalkyl, or R2 together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, carboxyl, aryloxy, oxo, and halo ; [0391] R4 is selected from the group consisting of a bond, lower alkyl, lower alkenyl, and lower cycloalkyl, or R4 together with R9 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, and halo ; [0392] R5 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, and lower alkoxyalkyl, or R5 together with R6 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0393] R6 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, and lower alkoxyalkyl, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0394] R7 is selected from the group consisting of hydrogen, lower alkyl, and aryl ; [0395] R8 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl, or R8 together with R and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system ; and [0396] R9 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, aryl, lower aralkyl, lower hydroxyalkyl, lower alkoxyalkyl, and lower carboxyalkyl, or R9 together with R4 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring.

[0397] In another embodiment, the MCH receptor antagonist consists of compounds of Formula VI, or a pharmaceutically- acceptable salt, tautomer or prodrug thereof, wherein : [0398] X is selected from the group consisting of-OR1 and _SR1 ; [0399] Z is selected from the group consisting of-CH=CH-, -CH2N (R9)-,-C (O) N (R9)-, and-NHC (O) NR9- ; [0400] R1 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, and benzodioxolyl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro ; [0401] R2 is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, phenylcyclopropyl, phenylcyclobutyl, phenylcyclopentyl, phenylcyclohexyl, biphenylcyclopropyl, biphenylcyclobutyl, biphenylcyclopentyl, biphenylcyclohexyl, naphthylcyclopropyl, naphthylcyclobutyl, naphthylcyclopentyl, naphthylcyclohexyl, or R2 together with R8 and the nitrogen to which they are attached may form a ring selected from the group consisting of hexahydroisoindolyl, tetrahydroisoindolyl, dihydroisoindolyl, isoindolinyl, hexahydroindolyl, tetrahydroindolyl, dihydroindolyl, indolinyl, octahydroquinolinyl, hexahydroquinolinyl, tetrahydroquinolinyl, dihydroquinolinyl, and quinolinyl, wherein R2 or the ring formed with R8is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, chloro, bromo, and fluoro ; [0402] R4 is selected from the group consisting of a bond, methyl, ethyl, propyl, butyl, pentyl, hexyl, ethenyl, propenyl, allyl, butenyl, pentenyl, acetylenyl, propynyl, butynyl, pentynyl, hexynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, indolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazole, tetrazolyl, benzodioxolyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclobutylbutyl, cyclobutylpenyyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, phenylethenyl, phenylpropenyl, phenylallyl, phenylbutenyl, phenylpentenyl, or R4 together with R9 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring, wherein R4 or the ring formed with R9 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, carboxyl, phenoxy, naphthyloxy, tetrahydronaphthyloxy, biphenylyloxy, oxo, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, chloro, bromo, and fluoro ; [0403] R5 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, and pentoxypentyl, or R5 together with R6 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring ; [0404] R6 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, and pentoxypentyl, or R6 together with R5 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring ; [0405] R7 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, phenyl, naphthyl, tetrahydronaphthyl, and biphenyl ; [0406] R8 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl, or R8 together with R2 and the nitrogen to which they are attached may form an isoindolinyl ring ; and [0407] R9 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, diphenylethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, propoxymethyl, propoxyethyl, propoxypropyl, propoxybutyl, propoxypentyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, pentoxymethyl, pentoxyethyl, pentoxypropyl, pentoxybutyl, pentoxypentyl, carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl, carboxypentyl, and carboxyhexyl, or R9 together with R4 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring.

[0408] In another embodiment, the MCH receptor antagonist is selected from a subclass of compounds of Formula I represented by Formula VII : [0409] wherein : [0410] R1 is selected from the group consisting of cycloalkyl and aryl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, and halo ; [0411] R2 is selected from the group consisting of alkyl, aryl, aralkyl, cycloalkylalkyl, aralkenyl, and arylcycloalkyl, or R2 together with Ra and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of alkyl, hydroxy, alkoxy, aryloxy, and halo ; [0412] R5 is selected from the group consisting of hydrogen and alkyl, or R5 together with RG and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0413] R6 is selected from the group consisting of hydrogen and alkyl, or R6 together with Rs and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; and [0414] R8 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, and aryl, or R8 together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system ; [0415] or a pharmaceutically-acceptable salt, tautomer or prodrug thereof.

[0416] In another embodiment, the MCH receptor antagonist consists of compounds of Formula VII, or a pharmaceutically- acceptable salt, tautomer or prodrug thereof, wherein : [0417] R1 is selected from the group consisting of lower cycloalkyl and aryl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, and halo ; [0418] R is selected from the group consisting of lower alkyl, aryl, lower aralkyl, lower cycloalkylalkyl, lower aralkenyl, and lower arylcycloalkyl, or R together with R8 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system, wherein R2 or the unsaturated fused heterocyclic ring formed with R is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, aryloxy, and halo ; [0419] R5 is selected from the group consisting of hydrogen and lower alkyl, or Rs together with R6 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; [0420] R6 is selected from the group consisting of hydrogen and lower alkyl, or R6 together with R5 and the nitrogen to which they are attached may form a saturated 5-or 6-membered heterocyclic ring ; and [0421] R8 is selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, and aryl, or R8 together with R2 and the nitrogen to which they are attached may form an unsaturated fused heterocyclic ring system.

[0422] In another embodiment, the MCH receptor antagonist consists of compounds of Formula VII, or a pharmaceutically- acceptable salt, tautomer or prodrug thereof, wherein : [0423] R1 is selected from the group consisting of cyclopentyl, cyclohexyl, phenyl, naphthyl, and biphenyl, wherein Ru ils optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, hydroxy, methoxy, ethoxy, propoxy, chloro, bromo, and fluoro ; [0424] R2 is selected from the group consisting of methyl, ethyl, propyl, butyl, phenyl, naphthyl, tetrahydronaphthyl, biphenyl, benzyl, phenylethyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, phenylethenyl, phenylpropenyl, phenylcyclopropyl, biphenylcyclopropyl, and naphthylcyclopropyl, or R2 together with R8 and the nitrogen to which they are attached may form a ring selected from the group consisting of dihydroisoindolyl, dihydroindolyl, tetrahydroisoquinolinyl, and tetrahydroquinolinyl, wherein R2 or the ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, butyl, hydroxy, methoxy, ethoxy, propoxy, phenoxy, naphthyloxy, biphenylyloxy, chloro, bromo, and fluoro ; [0425] R5 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, and hexyl, or R5 together with R6 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring ; [0426] R6 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, and hexyl, or R6 together with R5 and the nitrogen to which they are attached may form a pyrrolidinyl or a piperidinyl ring ; and [0427] R8 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, and biphenyl, or R8 together with R2 and the nitrogen to which they are attached may form a ring selected from the group consisting of dihydroisoindolyl, dihydroindolyl, tetrahydroisoquinolinyl, and tetrahydroquinolinyl.

[0428] In another embodiment, the MCH receptor antagonist consists of compounds of Formula VII, or a pharmaceutically- acceptable salt, tautomer or prodrug thereof, wherein : [0429] R1 is selected from the group consisting of phenyl, and naphthyl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of methyl, chloro, and fluoro ; [0430] R is selected from the group consisting of methyl, ethyl, phenyl, naphthyl, biphenyl, benzyl, phenylethyl, cyclopentylethyl, phenylethenyl, phenylcyclopropyl, or R2 together with R8 and the nitrogen to which they are attached may form a dihydroisoindolyl ring, wherein R2 or the ring formed with R8 is optionally substituted with one or more substituents selected from the group consisting of methyl, propyl, methoxy, phenoxy, chloro, bromo, and fluoro ; [0431] Rus ils hydrogen or R5 together with R6 and the nitrogen to which they are attached form a pyrrolidinyl ring ; [0432] R6 is hydrogen or R6 together with R5 and the nitrogen to which they are attached form a pyrrolidinyl ring ; and [0433] R8 is selected from the group consisting of hydrogen, methyl, and phenyl, or R8 together with R2 and the nitrogen to which they are attached may form a dihydroisoindolyl ring.

[0434] In another embodiment, the compound of Formula I is selected from the group of compounds listed in Table 1.

TABLE 1 Compound No. Structure No. N H O NCO NH I/ 4- [ (3, 4-dimethylphenyl) oxy]-3- {[(phenylamino) carbonyl] amino}-N-(2-( pyrrolidinyl) ethyl) benzamide MS m/z 473 (M+H) ; MW 472 5 O X non H ) ao H HN O 1 4- [ (3, 4-dimethylphenyl) oxy]-3- [ (3- phenylpropanoyl) amino]-N- (2- (1- pyrrolidinyl) ethyl) benzamide MS m/z 486 (M+H) ; MW 485 6 0 N"-N H Hay0 NH zNH 4- [ (3, 4-dimethylphenyl) oxy]-3- ({[(phenylmethyl) amino] carbonyl} amino)-N-(2-(1- pyrrolidinyl) ethyl) benzamide MS m/z 487 (M+H) ; MW 486 Compound No. Structure No. 8 ? C N---"-N oje H 4- (phenyloxy)-N- (2- (l- pyrrolidinyl) ethyl) benzamide MS m/z 311. 4 (M+H) ; MW 310. 4 10 0 rD non ) ao H 0 1- HN f O I 3-acetylamino-4- (3, 4-dimethylphenoxy)-N- (2- pyrrolidin-1-yl-ethyl) benzamide MS m/z 396 (M+H) ; MW 395 11 0 ) ao H H 0 1- HN O 4- (3, 4-dimethylphenoxy)-3-propionylamino-N- (2- pyrrolidin-1-yl-ethyl) benzamide MS m/z 400 (M+H) ; MW 409 S 0 12 e N H o HN O 3- (3-cyclopentylpropionylamino)-4- (3, 4- dimethylphenoxy)-N-(2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 478 (M+H) ; MW 477 Compound No. Structure No. zu H O i HN O 4- (3, 4-dimethylphenoxy)-3-phenylacetylamino-N- (2-pyrrolidin-1-yl-ethyl) benzamide MS m/z 472 (M+H) ; MW 471 15 0 rD Non NCO Han 0 ho O 4- (3, 4-dimethylphenoxy)-3- (3-phenyl- acryloylamino)-N-(2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 484 (M+H) ; MW 483 16 0 ru N--- N NCO O HNO 4- (3, 4-dimethylphenoxy)-3- [ (2-phenyl- cyclopropanecarbonyl) amino]-N- (2-pyrrolidin-l- yl-ethyl) benzamide MS m/z 498 (M+H) ; MW 497 Compound . Structure No. 17 ) ao H H O HN O naphthalene-2-carboxylic acid [2- (3, 4- dimethylphenoxy)-5-(2-pyrrolidin-1-yl- ethylcarbamoyl) phenyl] amide MS m/z 508 (M+H) ; MW 507 18 HN, o N NCO HN y0 HN\/O NH 4- (3, 4-dimethylphenoxy)-3- (3-ethylureido)-N- (2- pyrrolidin-1-yl-ethyl) benzamide MS m/z 425 (M+H) ; MW 424 20 0 /W H : au HN se0 HNO N- (2-aminoethyl)-4- (3, 4-dimethylphenoxy)-3- (3- phenylpropionylamino) benzamide MS m/z 432 (M+H) ; MW 431 Compound No. Structure No. 22 t t XN~ HNseo H N 0 1 HN O l 4-methoxy-3- (3-phenylpropionylamino)-N- (2- pyrrolidin-1-yl-ethyl) benzamide MS m/z 508 (M+H) ; MW 507 ) HNO Han 0 1 i HN O 4- (naphthalen-2-yl-oxy)-3- (3- phenylpropionylamino)-N- (2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 502 (M+H) ; MW 501 ? 0 >, NH NCO NH HN\/O NH e O 4- (3, 4-dimethylphenoxy)-3- [3- (2- methoxyphenyl) ureido]-N-(2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 503 (M+H) ; MW 502 Compound No. Structure No. 31 ? XH H O N ) ao H HN Nu 3- [3- (2, 4-dichlorophenyl) ureido]-4- (3, 4- dimethylphenoxy)-N- (2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 542 (M+H) ; MW 541 zu 32 N H O HNO NH / O 4- (3, 4-dimethylphenoxy)-3- [3- (4- phenoxyphenyl) ureido]-N-(2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 565 (M+H) ; MW 564 33 0 rD N ao H HNy 0 HN\/O NH I 3- (3-biphenyl-4-yl-ureido)-4- (3, 4- dimethylphenoxy)-N-(2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 549 (M+H) ; MW 548 Compound Structure No. N Fizz 0 1- HN\/O NH 4- (3, 4-dimethylphenoxy)-3- [3- (4- isopropylphenyl) ureido]-N-(2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 515 (M+H) ; MW 514 35 0 rD N jq-ll erz HAN han 4- (3, 4-dimethylphenoxy)-3- [3- (2, 6- dimethylphenyl) ureido]-N-(2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 501 (M+H) ; MW 500 36 0 Dan H H 0 1- HN NH 4- (3, 4-dimethylphenoxy)-3- (3-naphthalen-1-yl- ureido)-N- (2-pyrrolidin-1-yl-ethyl) benzamide MS m/z 523 (M+H) ; MW 522 Compound No. Structure No. "r H N NCO I NH w 3- [3- (2, 6-diisopropylphenyl) ureido]-4- (3, 4- dimethylphenoxy)-N- (2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 557 (M+H) ; MW 556 38 0 rD N'-- N \ I I H" o HNO NH Ber 3- [3- (4-bromophenyl) ureido]-4- (3, 4- dimethylphenoxy)-N- (2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 553 (M+H) ; MW 552 39 p 39 su DJIH H H HN F NH 4- (3, 4-dimethylphenoxy)-3- [3- (3- fluorophenyl) ureido]-N-(2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 491 (M+H) ; MW 490 Compound Structure No. N :) ao H je HN-f'0 NH lez 4- (3, 4-dimethylphenoxy)-3- [3- (3- methoxyphenyl) ureidol-N- (2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 503 (M+H) ; MW 502 g r) 41 0 rD H O HAN NH ci 3- [3- (2-chlorophenyl) ureido]-4- (3, 4- dimethylphenoxy)-N- (2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 507 (M+H) ; MW 506 ? ) 42 o rD H O HAN I\ N I\ 4- (3, 4-dimethylphenoxy)-3- (3, 3-diphenylureido)- N- (2-pyrrolidin-1-yl-ethyl) benzamide MS m/z 549 (M+H) ; MW 548 Compound No. Structure No. e J Han 0 HNO No. \ N HN or*O 4- (3, 4-dimethylphenoxy)-3- (3-methyl-3- phenylureido)-N- (2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 487 (M+H) ; MW 486 50 0 rD HNO H :) ao H N-f0 N 1, 3-dihydroisoindole-2-carboxylic acid [2- (3, 4- dimethylphenoxy)-5- (2-pyrrolidin-1-yl- ethylcarbamoyl) phenyl] amide MS m/z 499 (M+H) ; MW 498 51 0 rD F/ N. / H HN, ao HNO F, ¢, NH I/ 4- (4-fluoro-3-methylphenoxy)-3- [3- (3- fluorophenyl) ureido]-N-(2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 495 (M+H) ; MW 494 Compound No. Structure No. 52 ? H H CI O HAN Foc, NH 4- (3, 4-dichlorophenoxy)-3- [3- (3- fluorophenyl) ureido]-N-(2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 531 (M+H) ; MW 530 53 0 rD F N N FRO HNy 0 F NH 4- (3, 4-difluorophenoxy)-3- [3- (3- fluorophenyl) ureido]-N- (2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 499 (M+H) ; MW 498 zu 54 0 rD F N ao H HNy 0 F nu I F NH 4- (4-fluorophenoxy)-3- [3- (3- fluorophenyl) ureido]-N-(2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 481 (M+H) ; MW 480 Compound No. Structure 55 o X N---'-N H F O HAN F NH / 4- (3-fluorophenoxy)-3- [3- (3- fluorophenyl) ureido]-N-(2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 481 (M+H) ; MW 480 56 p F, NH H H HNy 0 F NH F NH s 3- [3- (3-fluorophenyl) ureido]-N- (2-pyrrolidin-l- yl-ethyl)-4-p-tolyloxybenzamide MS m/z 477 (M+H) ; MW 476 57 0 N"-'No HN otfi, O ,, Iao HNy 0 HN\/O F NH s 3- [3- (3-fluorophenyl) ureido]-N- (2-pyrrolidin-l- yl-ethyl)-4-m-tolyloxybenzamide MS m/z 477 (M+H) ; MW 476 Compound No. Structure No. N ) ao H O AJJU" No. 5 8 > O ç> Fs4gNH F F 3- [3- (3, 5-difluorophenyl) ureido]-4- (3, 4- dimethylphenoxy)-N- (2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 509 (M+H) ; MW 508 59 0 ru N NCO any0 HN\/O CNs, N H Ci 3- [3- (3, 5-dichlorophenyl) ureido]-4- (3, 4- dimethylphenoxy)-N-(2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 541 (M+H) ; MW 540 61 p / H HAN HN\/O F, ¢, N H / FNH 3- [3- (3-fluorophenyl) ureido]-4-phenoxy-N- (2- pyrrolidin-1-yl-ethyl) benzamide MS m/z 463 (M+H) ; MW 462 Compound Structure No. "ruz O 1J ( jp NH HNO NON 1- [2- (3, 4-dimethylphenoxy)-5- (2-pyrrolidin-l- yl-methylpyrrolidine-1-carbonyl) phenyl-3- phenylurea MS m/z 513 (M+H) ; MW 512 64 NCO / NCO O HN\/O F NH I/ 1-{2-(3, 4-dimethylphenoxy)-5-[(2-pyrrolidin-1- yl-ethylamino)-methyl] phenyl}-3- (3- fluorophenyl) urea MS m/z 477 (M+H) ; MW 476 65/ND 0 N N :) ao 0 1- HN otpO NH 1- [2- (3, 4-dimethylphenoxy)-5- (2-pyrrolidin-l- yl-methylpyrrolidine-1-carbonyl) phenyl-3- phenylurea MS m/z 513 (M+H) ; MW 512 Compound No. Structure 66 0 ci N Non HN nO O HNO HN\/O For NH F F 4- (3, 4-dichlorophenoxy)-3- [3- (3, 5- difluorophenyl) ureido]-N-(2-pyrrolidin-1-yl- ethyl) benzamide MS m/z 549 (M+H) ; MW 548 [0435] In another embodiment, the compound of Formula I is selected from the group of compounds of Formula V having the structure : [0436] wherein R2a, R2b, R2c, R2d, and R2e are as defined in Table 2.

Table 2 t'ompound R2a R2b R2c R2d R2e No. 2 0 0 H CH3 CH3 H H 201 2 01 H CH3 CH3 CH3 l H 202 202 H CH3 CH3 OCH3 H 2 0 3 H CH3 CH3 C 1 g 2 04 g CH3 CH3 Br H 205 H CH3 CH3 F H 206 H CH3 CH3 H CH3 2 0 7 H CH3 CH3 CH3 CH3 Compound R2a 2b 2e 2d 2e No. 208 H CH3 CH3 H OCH3 209 H CH3 CH3 CH3 OCH 210 H CH3 CH3 OCH3 OCH3 211 H CH3 CH3 Cl OCH3 212 H CH3 CH3 Br OCH3 213 H CH3 CH3 F OCH3 214 H CH3 CH3 H Ci 215 H CH3 CH3 CH3 ci 216 H CH3 CH3 OCH3 Ci 217 H CH3 CH3 ci Ci 218 H CH3 CH3 Br Cl 219 H CH3 CH3 F Cl 2 2 0 H CH3 CH3 H Br 2 21 H CH3 CH3 CH3 Br 222 H CH3 CH3 OCH3 Br 223 H CH3 CH3 Cl ber 224 H CH3 CH3 Br Br 225 H CH3 CH3 F Br 226 H CH3 CH3 H F 2 2 7 H CH3 CH3 CH3 F 228 H CH3 CH3 OCH3 F 2 2 9 H CH3 CH3 ci F 230 H CH3 CH3 Br F 231 H CH3 CH3 F F 232 H CH3 OCH3 H H 233 H CH3 OCH3 CH3 H 234 H CH3 OCH3 OCH3 H 235 H CH3 OCH3 ci H 236 H CH3 OCH3 Br H 237 H CH3 OCH3 F H 238 H CH3 OCH3 H CH3 239 H CH3 OCH3 CH3 CH3 240 H CH3 OCH3 OCH3 CH3 241 H CH3 OCH3 Cl CH3 242 H CH3 OCH3 Br CH3 243 H CH3 OCH3 F CH3 244 H CH3 OCH3 H OCH3 245 H CH3 OCH3 OCH3 OCH3 246 H CH3 OCH3 H ci 247 H CH3 OCH3 CH3 ci Compoun R2a R2b R2c R2d R2e No. 248 248 H CH3 OCH3 OCH3 ci OCH3 Cl C1 2 5 0 H CH3 OCH3 ci ci 2 51 H CH3 OCH3 F ci --5 2-H CH3 OCH3 H Br 253 H CH3 OCH3 CH3 Br 254 254 H CH3 OCH3 OCH3 Br 255 H CH3 OCH3 Cl 256 ber Hs OCH3 gp gr. 257 256 H CH3 OCH3 Br Br 258 H CH3 OCH3 F Br 259 2 5 8 H CH3 OCH3 F 259 260 H CH3 OCH3 CH3 F H n CH3 OCH3 Cl F 2 6 2 g CH3 OCH3 cl F 262 H 263 CH3 OCH3 Br F 264 H CH3 Cl H H 2 65 H CH3 ci 2 6 6 H CH3 Cl OCH3 H 267 H CH3 ci Ci H 268 H CH3 ci Br H 269 CH3 C 1 F H 2 7 0 H CH3 Ci H CH3 2 71 CH3 Cl CH3 CH3 2 7 2 H CH3 C l OCH3 CH3 273 7 CH3 Cl ci CH3 274 H CH3 Cl Br CH3 2 7 5 H CH3 C 1 g CH3 276 H CH3 C1 H OCH3 277 H CH3 Cl CH3 OCH3 oc3 OCH3 OCH3 279 H CH3 Cl Cl OCH3 2 8 0 g g3 Cl Br OCH3 2 81 H CH3 C1 F OCH 2 82 CH3 Cl Cl 2 8 3 H CH3 Cl Cl Cl 284 H CH3 Ci H Br 2 8 5 H CH3 ci CH3 Br 2 8 6 g H3 Cl OCH3 Br 287 H CH3 Cl Cl Br Compound R2a R2b Rzc Rza R2e No. 288 H CH3 Ci Br Br 289 H CH3 ci F Br 290 H CH3 Ci H F 291 H CH3 ci CH3 F 292 H CH3 Cl OCH3 F 293 H CH3 Ci ci F 294 H CH3 ci F F 295 H CH3 Br H H 296 H CH3 Br CH3 H 297 H CH3 Br OCH3 H 298 H CH3 Br ci H 299 H CH3 Br Br H 300 H CH3 Br F H 301 H CH3 Br H CH3 302 H CH3 Br CH3 CH3 303 H CH3 Br OCH3 CH3 304 H CH3 Br ci CH3 305 H CH3 Br Br CH3 306 H CH3 Br F CH3 307 H CH3 Br H OCH3 308 H CH3 Br CH3 OCH3 309 H CH3 Br OCH3 OCH3 310 H CH3 Br ci OCH3 311 H CH3 Br Br OCH3 312 H CH3 Br F OCH3 313 H CH3 Br H ci 314 H CH3 Br CH3 ci 315 H CH3 Br OCH3 ci 316 H CH3 Br Ci Ci 317 H CH3 Br Br Ci 318 H CH3 Br F Cl 319 H CH3 Br H Br 320 H CH3 Br Br Br 321 H CH3 Br H F 322 H CH3 Br CH3 F 323 H CH3 Br OCH3 F 324 H CH3 Br Ci F 325 H CH3 Br Br F 326 H CH3 Br F F 327 H CH3 F H H Compound R2a Rzb R2c R2d R2e No. 328 H CH3 F CH3 H 329 H CH3 F OCH3 H 330 H CH3 F Cl H 331 H CH3 F Br H 332 H CH3 F F H 333 H CH3 F H CH3 334 H CH3 F CH3 CH3 335 H CH3 F OCH3 CH3 336 H CH3 F Ci CH3 337 H CH3 F Br CH3 338 H CH3 F F CH3 339 H CH3 F H OCH3 340 H CH3 F CH3 OCH3 341 H CH3 F OCH3 OCH3 342 H CH3 F ci OCH3 343 H CH3 F Br OCH3 344 H CH3 F F OCH3 345 H CH3 F H ci 346 H CH3 F CH3 ci 347 H CH3 F OCH3 Cl 348 H CH3 F Cl Cl 349 H CH3 F Br Cl 350 H CH3 F F Cl 351 H CH3 F H Br 352 H CH3 F CH3 Br 353 H CH3 F OCH3 Br 354 H CH3 F ci Br 355 H CH3 F Br Br 356 H CH3 F F Br 357 H CH3 F H F 358 H CH3 F F F 359 H OCH3 CH3 H H 360 H OCH3 CH3 H CH3 361 H OCH3 CH3 H OCH3 362 H OCH3 CH3 H ci 363 H OCH3 CH3 H Br 364 H OCH3 CH3 H F 365 H OCH3 CH3 CH3 H 366 H OCH3 CH3 CH3 CH3 367 H OCH3 CH3 CH3 OCH3 Compound R2a R2b | R2c R2d R2e No. 368 H OCH3 CH3 CH3 ci 369 H OCH3 CH3 CH3 Br 370 H OCH3 CH3 CH3 F 371 H OCH3 CH3 OCH3 H 372 H OCH3 CH3 OCH3 OCH3 373 H OCH3 CH3 OCH3 Ci 374 H OCH3 CH3 OCH3 Br 375 H OCH3 CH3 OCH3 F 376 H OCH3 CH3 ci H 377 H OCH3 CH3 ci OCH3 378 H OCH3 CH3 ci Ci 379 H OCH3 CH3 Cl Br 380 H OCH3 CH3 ci F 381 H OCH3 CH3 Br H 382 H OCH3 CH3 Br OCH3 383 H OCH3 CH3 Br ci 384 H OCH3 CH3 Br Br 385 H OCH3 CH3 Br F 386 H OCH3 CH3 F H 387 H OCH3 CH3 F OCH3 388 H OCH3 CH3 F ci 389 H OCH3 CH3 F Br 390 H OCH3 CH3 F F 391 H OCH3 OCH3 H H 392 H OCH3 OCH3 H CH3 393 H OCH3 OCH3 H OCH3 394 H OCH3 OCH3 H ci 395 H OCH3 OCH3 H Br 396 H OCH3 OCH3 H F 397 H OCH3 OCH3 CH3 H 398 H OCH3 OCH3 CH3 CH3 399 H OCH3 OCH3 CH3 Ci 400 H OCH3 OCH3 CH3 Br 401 H OCH3 OCH3 CH3 F 402 H OCH3 OCH3 OCH3 H 403 H OCH3 OCH3 OCH3 CH3 404 H OCH3 OCH3 OCH3 OCH3 405 H OCH3 OCH3 OCH3 Ci 406 H OCH3 OCH3 OCH3 Br OCH3 OCH3 F Compound Co. R2a R2b R2c R2d 2e No. 408 H OCH3 OCH3 Ci H 409 H OCH3 OCH3 Ci CH3 3 410 H OCH3 OCH3 Ci ci 411 H OCH3 OCH3 Cl Br 412 H OCH3 OCH3 Ci F 413 H OCH3 OCH3 Br H 414 H OCH3 OCH3 Br H 415 H OCH3 OCH3 Br Cl 416 H OCH3 OCH3 Br Br 417 H OCH3 OCH3 Br F 418 H OCH3 OCH3 F H 419 H OCH3 OCH3 F CH3 420 H OCH3 OCH3 F Ci 421 H OCH3 OCH3 F Br 422 H OCH3 OCH3 F F 423 H OCH3 ci H H 424 H OCH3 ci H CH3 425 H OCH3 Ci H OCH3 3 426 H OCH3 ci H Ci H OCH3 ci H Br 428 H OCH3 Cl H F 429 H OCH3 ci CH3 H 430 H OCH3 Cl CH3 3 431 H OCH3 ci CH3 OCH3 432 H OCH3 ci CH3 Br 433 H OCH3 Cl CH3 F 3 434 H OCH3 ci OCH3 H 435 H OCH3 ci OCH3 CH3 436 H OCH3 Ci OCH3 OCHs 437 H OCH3 Ci OCH3 Br 438 H OCH3 ci OCH3 F 439 H OCH3 ci ci H 440 H OCH3 ci ci CH3 441 H OCH3 Ci Ci OCH3 442 H OCH3 Cl Cl Cl 443 H OCH3 ci ci Br 444 H OCH3 Cl Ci F 445 H OCH3 ci Br H 446 H OCH3 ci Br CH3 3 447 H OCH3 C1 Br OCH3 compound _ Compound 2a 2b 2c 2d p No. R R R R 2e 448 H OCH3 Ci Br Br 449 H OCH3 Cl F 450 H OCH3 Cl F cHH3 451 H OCH3 ci F OCH3 452 H OCH3 Cl F Br 453 H OCH3 l F F 454 H OCH3 Br H H 455 H OCH3 Br H CH3 3 456 H OCH3 Br H OCH3 457 H OCH3 Br H Cl 458 H OCH3 Br H Br 459 H OCH3 Br H F 460 H OCH3 Br CH3 H 461 H OCH3 Br CH3 CH3 462 H OCH3 Br CH3 OCH3 463 H OCH3 Br CH3 Cl 464 H OCH3 Br CH3 F 465 H OCH3 Br OCH3 H 466 H OCH3 Br OCH3 CH3 467 H OCH3 Br OCH3 OCH3 oc3 469 H OCH3 Br OCH3 F 470 H OCH3 Br ci H 471 H OCH3 Br ci CH3 472 H OCH3 Br Cl OCH 473 H OCH3 Br Cl Cl 474 H OCH3 Br ci F 475 H OCH3 Br Br H 476 H OCH3 Br Br CH3 H OCH3 Br Br OCH3 478 H OCH3 Br Br ci 479 H OCH3 Br Br Br 480 OCH3 Br Br F 481 H OCH3 Br F H 482 H OCH3 Br F CH3 3 483 H OCH3 Br F OCH F 484 H OCH3 Br F Cl 485 H OCH3 Br F F 486 H OCH3 F H H 487. OCH3 F H CH3 3 Compound No. No. 4 8 8 H OCH3 F H OCH3 489 H OCH3 F H Cl H OCH3 F H C1 490 H OCH3 F H Br 491 H OCH3 F H F 492 H OCH3 CH3 H 493 H OCH3 F CH3 CH3 494 H OCH3 F CH3 OCH3 495 H OCH3 F ci 496 H OCH3 F CH3 Br 497 H OCH3 F OCH3 H 498 H OCH3 F OCH3 CH3 499 H OCH3 F OCH3 OCH3 500 H OCH3 F OCH3 Cl 501 H OCH3 F OCH3 Br 502 H OCH3 F Cl H 503 H OCH3 F ci CH3 504 H OCH3 F ci OCH3 505 H OCH3 F Ci Cl 506 H OCH3 F C1 Br 507 H OCH3 F Br H 508 H OCH3 F Br CH3 510 H OCH3 F Br OCH 510 H OCH3 F Br Cl 511 H OCH3 F Br Br 512 H OCH3 F F H 513 H OCH3 F F CH3 514 H OCH3 F F OCH3 H OCH3 F Cl 516 H OCH3 F F Br 517 H OCH3 F F F 518 H Ci 519 H ci CH3 H CH3 3 520 H Cl CH3 H OCH3 521 H Cl CH3 H Cl 522 H C1 CH3 H Br 523 H C1 CH3 F 524 H Cl CH3 CH3 H 5 2 5 H C 1 CH3 CH3 CH3 527 H C1 CH3 CH3 OCH3 527 H Cl CH3 CH3 Cl Compound R2a R 2b R 2c R 2d R2e No. 528 H Cl CH3 CH3 Br 529 n Cl CH3 CH3 F 530 H Cl CH3 OCH3 H 531 H Cl CH3 OCH3 OCH3 532 H Cl CH3 OCH3 Cl 533 H Cl CH3 OCH3 Br 534 H C1 CH3 OCH3 F 535 H Ci CH3 ci H 536 H Cl CH3 ci OCH 537 H C1 CH3 ci C1 538 H Ci CH3 ci Br 539 H Cl CH3 Cl F 540 H Cl CH3 Br H 541 H ci CH3 Br OCH 542 H ci CH3 Br C1 543 H Cl CH3 Br Br 544 H Cl CH3 Br F 545 g Cl 546 H Cl CH3 F OCH3 547 H Cl CH3 F ci 548 H ci CH3 F Br 549 H ci CH3 F F 550 H Cl OCH3 H H 551 H C1 OCH3 H CH3 552 H Ci OCH3 H OCH3 553 H Cl OCH3 H Ci 554 H ci OCH3 H Br 555 H C1 OCH3 H F 556 H Cl OCH3 CH3 H 557 H C1 OCH3 CH3 CH3 Cl OCH3 559 H C1 OCH3 CH3 Br 560 H Cl OCH3 CH3 F 561 H Cl OCH3 OCH3 H 562 H Ci OCH3 OCH3 CH3 563 H Ci OCH3 OCH3 OCH3 564 H ci OCH3 OCH3 Cl 565 H ci OCH3 OCH3 Br 566 H Ci OCH3 OCH3 F 567 H Cl OCH3 Ci H Compound R2a 2b R2d R2e No. 568 H 569 H Cl OCH3 Cl Cl 570 C1 OCH3 C1 Br 571 C1 OCH3 C1 F 572 H Cl OCH3 Br H 573 g Cl 573 H Cl OCH3 Br CH3 OCH3 Br Cl 575 H Cl OCH3 Br Br 576 H ci OCH3 Br F 577 H Cl OCH3 g H C1 578 H C1 OCH3 F CH3 579 H C1 OCH3 F ci 580 g Cl OCH3 F Br 581 H Cl OCH3 g F 582 g C1 Cl H H 583 C1 C1 CH3 584 H Cl Cl H OCH3 585 H Ci Ci H C1 586 H ci ci H Br 587 H Cl Cl g F 588 H Cl Cl CH3 H 589 H Ci C1 CH3 CH3 590 H Cl CH3 CH3 Cul 591 91 CH3 OCH3 CZ CHs Br 592 H ci ci c3 F 593 H Ci Cl OCH3 H 594 H ci Cl OCH3 CH3 - CH3 OCH3 OCH3 596 H C1 Ci OCH3 Br 597 H ci ci OCH3 F 598 598 H ci Ci Cl 599 H C1 C1 C1 CH3 600 H Cl Ci Ci OCH3 601 H Cl ci Ci Ci 602 H Ci Ci ci Br 603 H Cl C1 C1 F 604 H Cl C1 Br H 605 Cl C1 Br CH3 606 H C1 C1 Br OCH 607 H Cl Ci Br Br Compound R2a R2b R2c R2d R2e No. 608 H Cl Cl F H 609 H ci ci F CH3 610 H Cl Ci F OCH3 611 H Ci ci F Br 612 H Ci Ci F F 613 H C1 Br H H 614 H Cl Br H CH3 615 H Ci Br H OCH3 616 H ci Br H ci 617 H Cl Br H Br 618 H Ci Br H F 619 H ci Br CH3 H 620 H C1 Br CH3 CH3 621 H ci Br CH3 OCH3 622 H Ci Br CH3 ci 623 H ci Br CH3 F 624 H ci Br OCH3 H 625 H C1 Br OCH3 CH3 626 H ci Br OCH3 OCH3 627 H Cl Br OCH3 ci 628 H Cl Br OCH3 F 629 H ci Br Ci H 630 H Ci Br ci CH3 631 H ci Br Ci OCH3 632 H Cl Br Ci Ci 633 H Cl Br Ci F 634 H Ci Br Br H 635 H Ci Br Br CH3 636 H ci Br Br OCH3 637 H ci Br Br Ci 638 H Ci Br Br Br 639 H C1 Br Br F 640 H Cl Br F H 641 H ci Br F CH3 642 H Ci Br F OCH3 643 g C1 Br F Ci 644 H Ci Br F F 645 H ci F H H 646 H Ci F H CH3 647 H Ci F H OCH3 Compound Rza R2b R2c R a No. 648 H Ci F H Ci 649 H ci F H Br 650 H C1 F H F 651 H Cl F CH3 H 652 H Cl F CH3 CH3 653 H Ci F CH3 OCH3 654 H Ci F CH3 Ci 655 H ci F CH3 Br 656 H ci F OCH3 H 657 H Cl F OCH3 CH3 658 H ci F OCH3 OCH3 659 H ci F OCH3 ci 660 H C1 F OCH3 Br 661 H Ci F ci H 662 H Ci F Ci CH3 663 H Ci F Ci OCH3 664 H Ci F ci ci 665 H Ci F Cl Br 666 H Ci F Br H 667 H Cl F Br CH3 668 H Ci F Br OCH3 669 H ci F Br ci 670 H ci F Br Br 671 H Ci F F H 672 H Ci F F CH3 673 H Ci F F OCH3 674 H ci F F Ci 675 H ci F F Br 676 H Ci F F F 677 H Br CH3 H H 678 H Br CH3 H CH3 679 H Br CH3 H OCH3 680 H Br CH3 H ci 681 H Br CH3 H Br 682 H Br CH3 H F 683 H Br CH3 CH3 H 684 H Br CH3 CH3 CH3 685 H Br CH3 CH3 OCH3 686 H Br CH3 CH3 Cl 687 H Br CH3 CH3 Br Compound R2a R2b R2c R2d 'R2e No. R R R 688 H Br CH3 CH3 F 689 H Br CH3 OCH3 H 690 H Br CH3 OCH3 OCH3 691 H Br CH3 OCH3 ci 692 H Br CH3 OCH3 Br 693 H Br CH3 OCH3 F 694 H Br CH3 Ci H 695 H B r CH3 cCl ocH 696 H Br CH3 Cl ci 697 H Br CH3 ci Br 698 H Br CH3 ci F 699 H Br CH3 Br H 700 H Br CH3 Br OCH 701 H Br CH3 Br Cl 702 H Br CH3 Br Br 703 H Br CH3 Br F 704 H Br CH3 F H 705 H Br CH3 F OCH3 706 H Br CH3 F C1 707 H Br CH3 F Br 708 H Br CH3 F F 709 H Br. OCH3 H H 710 Br OCH3 H CH3 711 H Br OCH3 H OCH3 H Br OCH3 H ci 713 H Br OCH3 H Br 714 H Br OCH3 H F 715 H Br OCH3 CH3 H 716 H Br OCH3 CH3 CH3 717 H Br OCH3 CH3 ci 718 H Br OCH3 CH3 Br 719 H Br OCH3 CH3 F 720 H Br OCH3 OCH3 H 721 H Br OCH3 OCH3 CH3 722 H Br OCH3 OCH3 OCH3 723 H Br OCH3 OCH3 ci 724 H Br OCH3 OCH3 Br 725 H Br OCH3 OCH3 F 726 H Br OCH3 ci H 727 H Br OCH3 ci CH, Compound Rza R2b R2d R2a No. 728 H Br OCH3 ci Ci 729 H Br OCH3 ci Br 730 H Br OCH3 Cl F 731 H Br l OCH3 Br H 732 H Br OCH3 Br CH3 733 OCH3 Br Ci 734 H Br OCH3 Br Br 735 H Br OCH3 Br F 73 6 g Br OCH3 g H Ber OCH3 F CH3 H3 OCH3 F Cl 739 H Bu OCH3 F Br r OCH3 g F 741 H Br Cl H H Br Cl H CH3 743 H Br OCH3 744 H Br Gl H Cl C1 H Cl 745 H Br Cl H Br 746 H Br Cl H F 747 g Br 747 H Br C1 CH3 H 748 H Br Cl CH3 CH3 749 H Br ci CH3 OCH3 750 H Br ci CH3 Br 751 H Br Ci CH3 F 752 H Br Cl OCH3 H 753 H Br ci OCH3 H 754 H Br Cl OCH3 OCH3 755 H Er Ci OCH3 Br 756 H Br Cl OCH3 F 756 758 H Br Cl C1 H 758 H Br Cl C1 CH3 759 H Br Cl Cl OCH3 760 H Br C1 C1 Cl 761 H Br Ci Ci Br 762 H Br Cl Cl F 763 763 H Br ci Br H 765 765 H Br ci Br OCH3 H Br Ci Br Br 767 H Br Cl F H 767 H Br C1 R F ß H Compound R2a Rzb R2c R2d R2e No. 768 H Br ci F CH3 769 H Br ci F OCH 770 H Br Ci F Br 771 H Br ci F F 772 H Br Br H H 773 H Br Br H CH3 774 H Br Br H OCH 775 H Br Br H ci 776 H Br Br H Br 777 H Br Br H F 778 H Br Br CH3 H 779 H Br Br CH3 CH3 780 H Br Br CH3 OCH3 781 H Br Br CH3 ci 782 H Br Br CH3 F 783 H Br Br OCH3 H 784 H Br Br OCH3 CH3 785 H Br Br OCH3 OCH3 786 H Br Br OCH3 ci 787 H Br Br OCH3 F 788 H Br Br ci H 789 H Br Br ci CH3 790 H Br Br Ci OCH3 791 H Br Br C1 Cl 792 H Br Br Ci F 793 H Br Br Br H 794 H Br Br Br CH3 795 H Br Br Br OCH3 796 H Br Br Br Ci 797 H Br Br Br Br 798 H Br Br Br F 799 H Br Br F H 800 H Br Br F CH3 801 H Br Br F OCH3 802 H Br Br F Ci 803 H Br Br F F 804 H Br F H H 805 H Br F H CH3 806 H Br F H OCH3 807 H Br F H Cl Compound R2a R2b R2c R2d R2e No. 808 H Br F H Br 809 H Br F H F 810 H Br F CH3 H 811 H Br F CH3 CH3 812 H Br F CH3 OCH3 813 H Br F CH : 3 Cl 814 H Br F CH3 Br 815 H Br F OCH3 H 816 H Br F OCH3 CH3 817 H Br F OCH3 OCH3 818 H Br F OCH3 Cl 819 H Br F OCH3 Br 820 H Br F Ci H 821 H Br F ci CH3 822 H Br F Ci OCH3 823 H Br F ci ci 824 H Br F ci Br 825 H Br F Br H 826 H Br F Br CH3 827 H Br F Br OCH 828 H Br F Br ci 829 H Br F Br Br 830 H Br F F H 831 H Br F F CH3 832 H Br F F OCH3 833 H Br F C1 834 H Br F F Br 835 H Br F F F 836 H F CH3 H H 837 H F CH3 H CH3 838 H F CH3 H OCH3 839 H F CH3 H ci 840 H F CH3 H Br 841 H F CH3 H F 842 H F CH3 CH3 H 843 H F CH3 CH3 CH3 844 H F CH3 CH3 OCH3 845 H F CH3 CH3 ci 846 H F CH3 CH3 Br 847 H F CH3 CH3 F Compound R2a Rzyb R2c R2d R2e No. 848 H F CH3 OCH3 H 849 H F CH3 OCH3 OCH3 850 H F CH3 OCH3 ci 851 H F CH3 OCH3 Br 852 H F CH3 OCH3 F 853 H F CH3 ci H 854 H F CH3 ci OCH3 855 H CH3 C1 C1 856 H F CH3 ci Br 857 H F CH3 ci F 858 H F CH3 Br H 859 H F CH3 Br OCH3 860 H F CH3 Br ci 861 H F CH3 Br Br 862 H F CH3 Br F 863 H F CH3 F H 864 H F CH3 F OCH3 865 H F CH3 F ci 866 H F CH3 F Br 867 H F CH3 F F 868 H F OCH3 H H 869 H F OCH3 H CH3 870 H F OCH3 H OCH3 871 H F OCH3 H ci 872 H F OCH3 H Br 873 H F OCH3 H F l 874 H F OCH3 CH3 H 875 H F OCH3 CH3 CH3 876 H F OCH3 CH3 ci 877 H F OCH3 CH3 Br 878 OCH3 CH3 F 879 H F OCH3 OCH3 H 880 H F OCH3 OCH3 CH3 881 H F OCH3 OCH3 OCH3 882 H F OCH3 OCH3 Ci 883 H F OCH3 OCH3 Br 884 H F OCH3 OCH3 F 885 H F OCH3 ci H 886 H F OCH3 Ci CH3 887 H F OCH3 Cl Cl Compound R2a R2b R2c R2d R2e No. 888 H F OCH3 ci Br 889 H F OCH3 Cl F 890 H F OCH3 Br H 891 H F OCH3 Br CH3 892 H F OCH3 Br Ci 893 H F OCH3 Br Br 894 H F OCH3 Br F 895 H F OCH3 F H 896 H F OCH3 F CH3 897 H F OCH3 F Ci 898 H F OCH3 F Br 899 H F OCH3 F F 900 H F ci H H 901 H F Cl H CH3 902 H F ci H OCH3 903 H F ci H C1 904 H F Cl H Br 905 H F Cl H F 906 H F Cl CH3 H 907 H F Cl CH3 CH3 908 H F Cl CH3 OCH3 909 H F ci CH3 Br 910 H F Cl CH3 F 911 H F Cl OCH3 H 912 H F Ci OCH3 CH3 913 H F Cl OCH3 OCH3 914 H F ci OCH3 Br 915 H F ci OCH3 F 916 H F ci Ci H 917 H F Cl C1 CH3 918 H F C1 Cl OCH3 919 H F Ci Ci Ci 920 H F ci ci Br 921 ? all F 922 H F Ci Br H 923 H F Ci Br CH3 924 H F ci Br OCH3 925 H F Cl Br Br 926 H F Ci F H 927 H F Cl F CH3 Compound za Compound R2a R2b R2c R2d R2e No. 928 H F ci F OCH3 929 H F ci F Br 930 H F C1 F F 931 H F Br H H 932 H F Br H CH3 933 H F Br H OCH3 934 H F Br H Cl 935 H F Br H Br 936 H F Br H F 937 H F Br CH3 H 938 H F Br CH3 CH3 939 939 H F Br CH3 OCH3 940 H F Br CH3 Ci 941 H F Br CH3 F 942 H F Br OCH3 H 943 H F Br OCH3 CH3 944 H F Br OCH3 OCH3 945 H F Er OCH3 Ci 946 H F Br OCH3 F 947 947 H F Br ci H 948 H F Br C1 CH3 949 H F Br ci OCH3 950 H F Br Cl Cl 951 H F Br Cl F 952 H F Br Br H 953 H F Br Br CH3 954 H F Br Br OCH3 955 H F Br Br C1 956 H F Br Br Br 957 F Br Br F 958 H F Br F H 959 H F Br F CH3 960 H F Br F OCH3 961 H F Br F Cl 962 H F Br F F 963 H F F H H H 964 F F H CH3 CH3 965 H F F OCH3 966 H F F ci Cl 967 H F F H Br Br Compound R2a R2b R2c R2d R2e No. 968 H F F H F 969 H F F CH3 H 970 H F F CH3 CH3 971 H F F CH3 OCH3 972 H F F CH3 C1 973 H F F CH3 Br 974 H F F OCH3 H 975 H F F OCH3 CH3 976 H F F OCH3 OCH3 977 H F F OCH3 Ci 978 H F F OCH3 Br 979 H F F Ci H 980 H F F ci CH3 981 H F F Ci OCH3 982 H F F Cl C1 983 H F F ci Br 984 H F F Br H 985 H F F Br CH3 986 H F F Br OCH3 987 H F F Br ci 988 H F F Br Br 989 H F F F H 990 H F F F CH3 991 H F F F OCH3 H F F F C1 993 H F F F Br 994 H F F F F 995 CH3 CH3 CH3 H H 996 CH3 CH3 CH3 CH3 H 997 CH3 CH3 CH3 OCH3 H 998 CH3 CH3 CH3 ci H 999 CH3 CH3 CH3 Br H 1000 CH3 CH3 CH3 F H 1001 CH3 CH3 CH3 H CH3 1002 CH3 CH3 CH3 CH3 CH3 1003 CH3 CH3 CH3 H OCH3 1004 CH3 CH3 CH3 CH3 OCH3 1005 CH3 CH3 CH3 OCH3 OCH3 1006 CH3 CH3 CH3 Ci OCH3 1007 CH3 CH3 CH3 Br OCH3 Compound R2a R2b R2c R2d R2e No. 1008 cl, CH3 CH3 F OCH 1009 CH3 CH3 CH3 H Ci 1010 CH3 CH3 CH3 CH3 Cl 1011 CH3 CH3 CH3 OCH3 ci 1012 CH3 CH3 CH3 C1 C1 1013 CH3 CH3 CH3 Br Ci 1014 CH3 CH3 CH3 F ci 1015 CH3 CH3 CH3 H Br 1016 CH3 CH3 CH3 CH3 Br 1017 CH3 CH3 CH3 OCH3 Br 1018 CH3 CH3 CH3 Ci Br 1019 CH3 CH3 CH3 Br Br 1020 CH3 CH3 CH3 F Br 1021 CH3 CH3 CH3 H F 1022 CH3 CH3 CH3 CH3 F 1023 CH3 CH3 CH3 OCH3 F 1024 CH3 CH3 CH3 Cl F 1025 CH3 CH3 CH3 B r F 1026 CH3 CH3 CH3 F F 1027 CH3 CH3 OCH3 H H 1028 CH3 CH3 OCH3 CH3 H 1029 CH3 CH3 OCH3 OCH3 H 1030 CH3 CH3 OCH3 ci H 1031 CH3 CH3 OCH3 Br H l 1032 CH3 CH3 OCH3 F H 1033 CH3 CH3 OCH3 H CH3 1034 CH3 CH3 OCH3 CH3 CH3 1035 CH3 CH3 OCH3 OCH3 CH3 1036 CH3 CH3 OCH3 Cl CH3 1037 CH3 CH3 OCH3 Br CH3 1038 CH3 CH3 OCH3 F CH3 1039 CH3 CH3 OCH3 H OCH3 1040 CH3 CH3 OCH3 OCH3 OCH3 1041 CH3 CH3 OCH3 H Cl 1042 CH3 CH3 OCH3 CH3 ci 1043 CH3 CH3 OCH3 OCH3 ci 1044 CH3 CH3 OCH3 Cl Ci 1045 CH3 CH3 OCH3 Br Ci 1046 CH3 CH3 OCH3 F ci 1047 CH3 CH3 OCH3 H Br Compound za zb zc R2d R2e No. 1048 CH3 CH3 OCH3 CH3 Br 1049 CH3 CH3 OCH3 OCH3 Br 1050 CH3 CH3 OCH3 Cl Br 1051 CH3 CH3 OCH3 Br Br 1052 CH3 CH3 OCH3 F Br 1053 CH3 CH3 OCH3 H F 1054 CH3 CH3 OCH3 CH3 F 1055 CH3 CH3 OCH3 OCH3 F 1056 CH3 CH3 OCH3 Ci F 1057 CH3 CH3 OCH3 Br F 1058 CH3 CH3 OCH3 F F 1059 CH3 CH3 ci H H 1060 CH3 CH3 Ci CH3 H 1061 CH3 CH3 Cl OCH3 H 1062 CH3 CH3 Cl Cl H 1063 CH3 CH3 Cl Br H 1064 CH3 CH3 ci F H 1065 CH3 CH3 Cl H CH3 1066 CH3 CH3 Cl CH3 CH3 1067 CH3 CH3 ci OCH3 CH3 1068 CH3 CH3 ci ci CH3 1069 CH3 CH3 C1 Br CH3 1070 CH3 CH3 Cl F CH3 10 71 Cg3 CH3 Cl H OCH3 1072 CH3 CH3 Cl CH3 OCH3 1073 CH3 CH3 ci OCH3 OCH3 1074 CH3 CH3 Ci ci OCH3 1075 CH3 CH3 C1 Br OCH3 1076 CH3 CH3 ci F OCH3 1077 CH3 CH3 C1 C1 1078 CH3 CH3 Cl Cl Cl 1079 CH3 CH3 Cl H Br 1080 CH3 CH3 ci CH3 Br 1081 CH3 CH3 Ci OCH3 Br 1082 CH3 CH3 Cl Cl Br 1083 CH3 CH3 ci Br Br 1084 CH3 CH3 Cl F Br 1085 CH3 CH3 Cl H F 1086 CH3 CH3 Cl CH3 F 1087 CH3 CH3 C1 OCH3 F Compound R2a R2b R2c R2d R2e No. 1088 CH3 CH3 Ci ci F 1089 CH3 CH3 Ci F F 1090 CH3 CH3 Br H H 1091 CH3 CH3 Br CH3 H 1092 CH3 CH3 Br OCH3 H 1093 CH3 CH3 Br C1 H 1094 CH3 CH3 Br Br H 1095 CH3 CH3 Br F H 1096 CH3 CH3 Br H CH3 1097 CH3 CH3 Br CH3 CH3 1098 CH3 CH3 Br OCH3 CH3 1099 CH3 CH3 Br ci CH3 1100 CH3 CH3 Br Br CH3 1101 CH3 CH3 Br F CH3 1102 CH3 CH3 Br H OCH3 1103 CH3 CH3 Br CH3 OCH3 1104 CH3 CH3 Br OCH3 OCH3 1105 CH3 CH3 Br ci OCH3 1106 CH3 CH3 Br Br OCH3 1107 CH3 CH3 Br F OCH3 1108 CH3 CH3 Br H Ci 1109 CH3 CH3 Br CH3 Ci 1110 CH3 CH3 Br OCH3 Cl 1111 CH3 CH3 Br C1 C1 1112 CH3 CH3 Br Br Ci 1113 CH3 CH3 Br F ci 1114 CH3 CH3 Br H Br 1115 CH3 CH3 Br Br Br 1116 CH3 CH3 Br H F 1117 CH3 CH3 Br CH3 F 1118 CH3 CH3 Br OCH3 F 1119 CH3 CH3 Br ci F 1120 CH3 CH3 Br Br F 1121 CH3 CH3 Br F F 1122 CH3 CH3 F H H 1123 CH3 CH3 F CH3 H 1124 CH3 CH3 F OCH3 H 1125 CH3 CH3 F Cl H 1126 CH3 CH3 F Br H 1127 CH3 CH3 F F H Compound R2a R2b R2c R2d R2e No. 1128 CH3 CH3 F H CH3 1129 CH3 CH3 F CH3 CH3 1130 CH3 CH3 F OCH3 CH3 1131 CH3 CH3 F Cl CH3 1132 CH3 CH3 F Br CH3 1133 CH3 CH3 F F CH3 1134 CH3 CH3 F H OCH3 1135 CH3 CH3 F CH3 OCH3 1136 CH3 CH3 F OCH3 OCH3 1137 CH3 CH3 F Cl OCH3 1138 CH3 CH3 F Br OCH3 1139 CH3 CH3 F F OCH3 1140 CH3 CH3 C1 1141 g3 Cg3 F CH3 ci CH3 CH3 F OCH3 Cl 1143 CH3 CH3 F Cl cul 1144 CH3 C F Br Cl 1145 CH3 CH3 C1 1146 CH3 CH3 F H Br 1147 CH3 CH3 F CH3 Br 1148 CH3 CH3 F OCH3 Br 1149 CH3 CH3 F Cl Br 1150 CH3 CH3 F Br Br 1151 CH3 CH3 F F Br 1152 CH3 CH3 F H F 1153 CH3 CH3 F F F 1154 CH3 OCH3 CH3 H H 1155 CH3 OCH3 CH3 H CH3 1156 CH3 OCH3 CH3 H OCH3 1157 CH3 OCH3 CH3 H C1 1158 CH3 OCH3 CH3 H Br 1159 CH3 OCH3 CH3 H F 1160 CH3 OCH3 CH3 CH3 H 1161 CH3 OCH3 CH3 CH3 CH3 1162 CH3 OCH3 CH3 CH3 OCH3 1163 CH3 OCH3 CH3 CH3 Cl 1164 CH3 OCH3 CH3 CH3 Br 1165 CH3 OCH3 CH3 CH3 F 1166 CH3 OCH3 CH3 OCH3 H 1167 CH3 OCH3 OCH3 OCH3 Compound R2a R2b R2c R2d R2e No. 1168 CH3 OCH3 CH3 OCH3 Ci 1169 CH3 OCH3 CH3 OCH3 Br 1170 CH3 OCH3 CH3 OCH3 F 1171 CH3 OCH3 CH3 C1 H 1172 CH3 OCH3 CH3 Ci OCH3 1173 CH3 OCH3 CH3 ci ci 1174 CH3 OCH3 CH3 ci Br 1175 CH3 OCH3 CH3 ci F 1176 CH3 OCH3 CH3 Br H 1177 CH3 OCH3 CH3 Br OCH3 1178 CH3 OCH3 CH3 Br ci 1179 CH3 OCH3 CH3 Br Br 1180 CH3 OCH3 CH3 Br F 1181 CH3 OCH3 CH3 F H 1182 CH3 OCH3 CH3 F OCH3 1183 CH3 OCH3 CH3 F Ci 1184 CH3 OCH3 CH3 F Br 1185 CH3 OCH3 CH3 F F 1186 CH3 OCH3 OCH3 H H 1187 CH3 OCH3 OCH3 H CH3 1188 CH3 OCH3 OCH3 H OCH3 1189 CH3 OCH3 OCH3 H ci 1190 CH3 OCH3 OCH3 H Br 1191 CH3 OCH3 OCH3 H F 1192 CH3 OCH3 OCH3 CH3 H 1193 CH3 OCH3 OCH3 CH3 CH3 1194 CH3 OCH3 OCH3 CH3 ci 1195 CH3 OCH3 OCH3 CH3 Br 1196 CH3 OCH3 OCH3 CH3 F 1197 CH3 OCH3 OCH3 OCH3 H 1198 CH3 OCH3 OCH3 OCH3 CH3 1199 CH3 OCH3 OCH3 OCH3 OCH3 1200 CH3 OCH3 OCH3 OCH3 Cl 1201 CH3 OCH3 OCH3 OCH3 Br 1202 CH3 OCH3 OCH3 OCH3 F 1203 CH3 OCH3 OCH3 Ci H 1204 CH3 OCH3 OCH3 ci CH3 1205 CH3 OCH3 OCH3 ci Ci 1206 CH3 OCH3 OCH3 Ci Br 1207 CH3 OCH3 OCH3 ci F Compound Rza Rzb Rzc R2d R2e No. 1208 CH3 OCH3 OCH3 Br H 1209 CH3 OCH3 OCH3 Br CH3 1210 CH3 OCH3 OCH3 Br Cl 1211 CH3 OCH3 OCH3 Br Br 1212 CH3 OCH3 OCH3 Br F 1213 CH3 OCH3 OCH3 F H 1214 CH3 OCH3 OCH3 F CH3 1215 CH3 OCH3 OCH3 F Cl 1216 CH3 OCH3 OCH3 F Br 1217 CH3 OCH3 OCH3 F F 1218 CH3 OCH3 ci H H 1219 CH3 OCH3 ci H CH3 1220 CH3 OCH3 ci H OCH3 1221 CH3 OCH3 Cl H ci 1222 CH3 OCH3 ci H Br 1223 CH3 OCH3 Cl H F 1224 CH3 OCH3 ci CH3 H 1225 CH3 OCH3 ci CH3 CH3 1226 CH3 OCH3 ci CH3 OCH3 1227 CH3 C 1 CH3 B r CH3 OCH3 Cl CH3 F 1229 CH3 OCH3 ci OCH3 H 1230 CH3 OCH3 Cl OCH3 CH3 1231 CH3 OCH3 ci OCH3 OCH3 1232 CH3 OCH3 Ci OCH3 Br 1233 CH3 OCH3 ci OCH3 F 1234 CH3 OCH3 Ci Ci H 1235 CH3 OCH3 C1 C1 CH3 1236 CH3 OCH3 Ci ci OCH3 1237 CH3 OCH3 Ci ci Cl 1238 CH3 OCH3 Ci ci Br 1239 CH3 OCH3 C1 Cl F 1240 CH3 OCH3 Ci Br H 1241 CH3 OCH3 ci Br CH3 1242 CH3 OCH3 ci Br OCH3 1243 CH3 OCH3 Ci Br Br 1244 CH3 OCH3 Ci F H 1245 CH3 OCH3 Ci F CH3 1246 CH3 OCH3 Ci F OCH3 1247 CH3 OCH3 Cl F Br Compound R2a R2b R2c R2d R2e No. 1248 CH3 OCH3 Cl F F 1249 CH3 OCH3 Br H H 1250 CH3 OCH3 Br H CH3 1251 CH3 OCH3 Br H OCH3 1252 CH3 OCH3 Br H Cl 1253 CH3 OCH3 Br H Br 1254 CH3 OCH3 Br H F 1255 CH3 OCH3 Br CH3 H 1256 CH3 OCH3 Br CH3 CH3 1257 CH3 OCH3 Br CH3 OCH3 1258 CH3 OCH3 Br CH3 C1 1259 CH3 OCH3 Br CH3 F 1260 CH3 OCH3 Br OCH3 H 1261 CH3 OCH3 Br OCH3 CH3 1262 CH3 OCH3 Br OCH3 OCH3 1263 CH3 OCH3 Br OCH3 ci 1264 CH3 OCH3 Br OCH3 F 1265 CH3 OCH3 Br ci H 1266 CH3 OCH3 Br ci CH3 1267 CH3 OCH3 Br Ci OCH3 1268 CH3 OCH3 Br ci ci 1269 CH3 OCH3 Br ci F 1270 CH3 OCH3 Br Br H 1271 CH3 OCH3 Br Br CH3 1272 CH3 OCH3 Br Br OCH3 1273 CH3 OCH3 Br Br Cl 1274 CH3 OCH3 Br Br Br 1275 CH3 OCH3 Br Br F 1276 CH3 OCH3 Br F H 1277 CH3 OCH3 Br F CH3 1278 CH3 OCH3 Br F OCH3 1279 CH3 OCH3 Br F Ci 1280 CH3 OCH3 Br F F 1281 CH3 OCH3 F H H 1282 CH3 OCH3 F H CH3 1283 CH3 OCH3 F H OCH3 1284 CH3 OCH3 F H Ci 1285 CH3 OCH3 F H Br 1286 CH3 OCH3 F H F 1287 CH3 OCH3 F CH3 H Compound R2a R2b R2c R2d R2e No. 1288 CH3 OCH3 F CH3 CH3 1289 CH3 OCH3 F CH3 OCH3 1290 CH3 OCH3 F CH3 ci 1291 CH3 OCH3 F CH3 Br 1292 CH3 OCH3 F OCH3 H 1293 CH3 OCH3 F OCH3 CH3 1294 CH3 OCH3 F OCH3 OCH3 1295 CH3 OCH3 F OCH3 Ci 1296 CH3 OCH3 F OCH3 Br 1297 CH3 OCH3 F Cl H 1298 CH3 OCH3 F Ci CH3 1299 CH3 OCH3 F ci OCH3 1300 CH3 OCH3 F ci Ci 1301 CH3 OCH3 F Ci Br 1302 CH3 OCH3 F Br H 1303 CH3 OCH3 F Br CH3 1304 CH3 OCH3 F Br OCH3 1305 CH3 OCH3 F Br ci 1306 CH3 OCH3 F Br Br 1307 CH3 OCH3 F F H 1308 CH3 OCH3 F F CH3 1309 CH3 OCH3 F F OCH3 1310 CH3 OCH3 F F ci 1311 CH3 OCH3 F F Br 1312 CH3 OCH3 F F F 1313 CH3 ci CH3 H H 1314 CH3 ci CH3 H CH3 1315 CH3 Ci CH3 H OCH3 1316 CH3 C1 CH3 H C1 1317 CH3 ci CH3 H Br 1318 CH3 ci CH3 H F 1319 CH3 ci CH3 CH3 H 1320 CH3 Cl CH3 CH3 CH3 1321 CH3 Cl CH3 CH3 OCH3 1322 CH3 Cl CH3 CH3 Cl 1323 CH3 C1 CH3 CH3 Br 1324 CH3 C 1 CH3 CH3 F 1325 CH3 Cl CH3 OCH3 H 1326 CH3 ci CH3 OCH3 OCH3 1327 CH3 Cl CH3 OCH3 Cl Compound R2a R2b R2c R2d R2e No. 1328 CH3 Cl CH3 OCH3 Br 1329 CH3 C 1 CH3 OCH3 F 1330 CH3 C1 CH3 C1 H 1331 CH3 Cl CH3 ci OCH3 1332 CH3 C1 CH3 Cl Cl 1333 CH3 C1 CH3 ci Br 1334 CH3 Cl CH3 Cl F 1335 CH3 C 1 CH3 B r H 1336 CH3 Cl CH3 Br OCH3 1337 CH3 C1 CH3 Br C1 1338 CH3 Cl CH3 Br Br 1339 CH3 Cl CH3 Br F 1340 CH3 Cl CH3 F H 1341 CH3 C1 CH3 F OCH3 1342 CH3 Cl CH3 F ci 1343 CH3 C1 CH3 F Br 1344 CH3 ci CH3 F F 1345 CH3 C1 OCH3 H H 1346 CH3 Cl OCH3 H CH3 1347 CH3 Cl OCH3 H OCH3 1348 CH3 Cl OCH3 H Ci 1349 CH3 C1 OCH3 H Br 1350 CH3 Cl OCH3 H F 1351 CH3 C1 OCH3 CH3 H 1352 CH3 C1 OCH3 CH3 CH3 1353 CH3 Cl OCH3 CH3 ci 1354 CH3 ci OCH3 CH3 Br 1355 CH3 C1 OCH3 CH3 F 1356 CH3 ci OCH3 OCH3 H 1357 CH3 ci OCH3 OCH3 CH3 1358 CH3 C1 OCH3 OCH3 OCH3 1359 CH3 Cl OCH3 OCH3 Cl 1360 CH3 ci OCH3 OCH3 Br 1361 CH3 Cl OCH3 OCH3 F 1362 CH3 Cl OCH3 ci H 1363 CH3 C1 OCH3 ci CH3 1364 CH3 Cl OCH3 ci Cl 1365 CH3 Cl OCH3 Ci Br 1366 CH3 C1 OCH3 Ci F 1367 CH3 Cl OCH3 Br H Compound R2a R2b Rz2c R2d R2e No. 1368 CH3 C1 OCH3 Br CH3 1369 CH3 C1 OCH3 Br ci 1370 CH3 C1 OCH3 Br Br 1371 CH3 Ci OCH3 Br F 1372 CH3 C1 OCH3 F H 1373 CH3 ci OCH3 F CH3 1374 CH3 C1 OCH3 F Cl 1375 CH3 C1 OCH3 F Br 1376 CH3 C1 OCH3 F F 1377 CH3 ci Ci H H 1378 CH3 C1 C1 H CH3 1379 CH3 Cl Cl H OCH3 1380 CH3 ci ci H Ci 1381 CH3 Cl Ci H Br 1382 CH3 Cl Ci H F 1383 CH3 Cl Cl CH3 H 1384 CH3 C1 C1 CH3 CH3 1385 CH3 C1 C1 CH3 OCH3 1386 CH3 C1 C1 CH3 Br 1387 CH3 C1 C1 CH3 F 1388 CH3 Cl Cl OCH3 H 1389 CH3 Cl Cl OCH3 CH3 1390 CH3 ci Ci OCH3 OCH3 1391 CH3 Cl Cl.. OCH3 Br 1392 CH3 Cl Cl OCH3 F 1393 CH3 Ci Ci Ci H 1394 CH3 C1 C1 C1 CH3 1395 CH3 Cl Cl Cl OCH3 1396 CH3 ci Ci ci Cl 1397 CH3 Cl Ci ci Br 1398 CH3 ci Ci ci F 1399 CH3 Ci ci Br H 1400 CH3 C1 Cl Br CH3 1401 CH3 Ci Ci Br OCH3 1402 CH3 Ci C1 Br Br 1403 CH3 ci Ci F H 1404 CH3 ci Ci F CH3 1405 CH3 C1 C1 F OCH3 1406 CH3 ci ci F Br 1407 CH3 C1 C1 F F Compound R2a R2b R2c R2d R2e No. 14 0 8 Cg3 C 1 B r H H 1409 CH3 C1 Br H CH3 1410 CH3 C1 Br H OCH3 1411 CH3 ci Br H ci 1412 CH3 ci Br H Br 1413 CH3 ci Br H F 1414 CH3 ci Br CH3 H 1415 CH3 ci Br CH3 CH3 1416 CH3 Ci Br CH3 OCH3 1417 CH3 ci Br CH3 Ci 1418 CH3 Cl Br CH3 F 1419 CH3 ci Br OCH3 H 1420 CH3 Cl Br OCH3 CH3 1421 CH3 Cl Br OCH3 OCH3 1422 CH3 C1 Br OCH3 ci 1423 CH3 ci Br OCH3 F 1424 CH3 ci Br ci H 1425 CH3 Cl Br ci CH3 1426 CH3 Cl Br ci OCH3 1427 CH3 ci Br ci Ci 1428 CH3 ci Br ci F 1429 CH3 Ci Br Br H 1430 CH3 Cl Br Br CH3 1431 CH3 Cl Br Br OCH3 1432 CH3 Cl Br Br ci 1433 CH3 Cl Br Br Br 1434 CH3 C1 Br Br F 1435 CH3 Ci Br F H 1436 CH3 C1 Br F CH3 1437 CH3 Cl Br F OCH3 1438 CH3 ci Br F Cl 1439 CH3 C1 Br F F 1440 CH3 C1 F H H 1441 CH3 ci F H CH3 1442 CH3 Ci F H OCH3 1443 CH3 ci F H Cl 1444 CH3 Ci F H Br 1445 CH3 C1 F H F 1446 CH3 Ci F CH3 H 1447 CH3 C1 F CH3 CH3 Compound R R2b R2c R2d R2e No. 1448 CH3 Cl F CH3 OCH3 1449 CH3 Ci F CH3 ci 1450 CH3 C1 F CH3 Br 1451 CH3 C1 F OCH3 H 1452 CH3 Cl F OCH3 CH3 1453 CH3 ci F. OCH3 OCH3 1454 CH3 ci F OCH3 ci 14 5 5 Cg3 C1 F OCH3 Br 1456 CH3 ci F ci H 1457 CH3 Cl F Cl CH3 1458 CH3 C1 F ci OCH3 1459 CH3 Cl F ci ci 1460 CH3 ci F Ci Br 1461 CH3 Cl F Br H 1462 CH3 C1 F Br CH3 1463 CH3 ci F 13r OCH3 1464 CH3 ci F Br Cl 1465 CH3 Cl F Br Br 1466 CH3 Cl F F H 1467 CH3 C 1 F F CH3 1468 CH3 ci F F OCH 1469 CH3 ci F F Cl 1470 CH3 Cl F F Br 1471 CH3 Cl F F F 1472 CH3 Br CH3 H H 1473 CH3 Br CH3 H CH3 1474 CH3 Br CH3 H OCH3 1475 CH3 Br CH3 H Cl 1476 CH3 Br CH3 H Br 1477 CH3 Br CH3 H F 1478 CH3 Br CH3 CH3 H 1479 CH3 Br CH3 CH3 CH3 1480 CH3 Br CH3 CH3 OCH3 1481 CH3 Br CH3 CH3 Ci 1482 CH3 Br CH3 CH3 Br 1483 CH3 Br CH3 CH3 F 1484 CH3 Br CH3 OCH3 H 1485 CH3 Br CH3 OCH3 OCH3 1486 CH3 Br CH3 OCH3 ci 1487 CH3 Br CH3 OCH3 Br Compound Rz8 Rzb Rac Raa No. 1488 CH3 Br CH3 OCH3 F 1489 CH3 | Br CH3 C1 H 1490 CH3 Br CH3 ci OCH3 1491 CH3 Br CH3 Cl C1 1492 CH3 Br CH3 Cl Br 1493 CH3 Br CH3 C1 F 1494 CH3 Br CH3 Br H 1495 CH3 Br CH3 Br OCH3 1496 CH3 Br CH3 Br Ci 1497 CH3 Br CH3 Br Br 1498 CH3 Br CH3 Br F 1499 CH3 Br CH3 F H 1500 CH3 Br CH3 F OCH3 3 1501 CH3 Br CH3 F Ci 1502 CH3 Br CH3 F Br 1503 CH3 Br CH3 F F 1504 CH3 Br OCH3 H H 1505 CH3 Br OCH3 H CH3 1506 CH3 Br OCH3 H OCH3 1507 CH3 Br OCH3 H ci 1508 CH3 Br OCH3 H Br 1509 CH3 Br OCH3 H F 1510 CH3 Br OCH3 CH3 H 1511 CH3 Br OCH3 CH3 CH3 1512 CH3 Br OCH3 CH3 ci 1513 CH3 Br OCH3 CH3 Br 1514 CH3 Br OCH3 CH3 F 1515 CH3 Br OCH3 OCH3 H 1516 CH3 Br OCH3 OCH3 CH3 1517 CH3 Br OCH3 OCH3 OCH3 1518 CH3 Br OCH3 OCH3 ci 1519 CH3 Br OCH3 OCH3 Br 1520 CH3 Br OCH3 OCH3 F 1521 CH3 Br OCH3 Ci H 1522 CH3 Br OCH3 Cl CH3 1523 CH3 Br OCH3 Cl Cl 1524 CH3 Br OCH3 Cl Br 1525 CH3 Br OCH3 Cl F 1526 CH3 Br OCH3 Br H 1527 CH3 Br OCH3 Br CH3 Compound RZa R2b R2c R2d R2e No. 1528 CH3 Br OCH3 Br Ci 1529 CH3 Br OCH3 Br Br 1530 CH3 Br OCH3 Br F 1531 CH3 Br OCH3 F H 1532 CH3 Br OCH3 F CH3 1533 CH3 Br OCH3 F Cl 1534 CH3 Br OCH3 F Br 1535 CH3 Br OCH3 F F 1536 CH3 Br ci H H 1537 CH3 Br ci H CH3 1538 CH3 Br Cl H OCH3 1539 CH3 Br Ci H Ci 1540 CH3 Br Ci H Br 1541 CH3 Br ci H F 1542 CH3 Br C1 CH3 H 1543 CH3 Br Cl CH3 CH3 1544 CH3 Br ci CH3 OCH3 1545 CH3 Br Ci CH3 Br 1546 CH3 Br Ci CH3 F 1547 CH3 Br C1 OCH3 1548 CH3 Br ci OCH3 CH3 1549 CH3 Br ci OCH3 OCH3 1550 CH3 Br ci OCH3 Br 1551 CH3 Br C1 OCH3 F 1552 CH3 Br Ci Ci H 1553 CH3 Br Ci ci CH3 1554 CH3 Br ci ci OCH3 1555 CH3 Br Ci Ci Ci 1556 CH3 Br Ci Ci Br 1557 CH3 Br Ci Ci F 1558 CH3 Br Ci Br H 1559 CH3 Br C1 Br CH3 1560 CH3 Br Cl Br OCHs 1561 CH3 Br ci Br Br 1562 CH3 Br Ci F H 1563 CH3 Br C1 F CH3 1564 CH3 Br Ci F OCH3 1565 CH3 Br ci F Br 1566 CH3 Br C1 F F 1567 CH3 Br Br H H Compound R 2a R 2b R2c R2d R2e No. 1568 CH3 Br Br H CH3 1569 CH3 Br Br H OCH3 1570 CH3 Br Br H Ci 1571 CH3 Br Br H Br 1572 CH3 Br Br H F 1573 CH3 Br Br CH3 H 1574 CH3 Br Br CH3 CH3 1575 CH3 Br Br CH3 OCH3 1576 CH3 Br Br CH3 ci 1577 CH3 Br Br CH3 F 1578 CH3 Br Br OCH3 H 1579 CH3 Br Br OCH3 CH3 1580 CH3 Br Br OCH3 OCH3 1581 CH3 Br Br OCH3 ci 1582 CH3 Br Br OCH3 F 1583 CH3 Br Br Ci H 1584 CH3 Br Br ci CH3 1585 CH3 Br Br ci OCH3 1586 CH3 Br Br Ci Ci 1587 CH3 Br Br ci F 1588 CH3 Br Br Br H 1589 CH3 Br Br Br CH3 1590 CH3 Br Br Br OCH3 1591 CH3 Br Br Br C1 1592 CH3 Br Br Br Br 1593 CH3 Br Br Br F 1594 CH3 Br Br F H 1595 CH3 Br Br F CH3 1596 CH3 Br Br F OCH3 1597 CH3 Br Br F Ci 1598 CH3 Br Br F F 1599 CH3 Br F H H 1600 CH3 Br F H CH3 1601 CH3 Br F H OCH3 1602 CH3 Br F H ci 1603 CH3 Br F H Br 1604 CH3 Br F H F 1605 CH3 Br F CH3 H 1606 CH3 Br F CH3 CH3 1607 CH3 Br F CH3 OCH3 Compound Rza R2b R2c R2d R2e No. 1608 CH3 Br F CH3 Ci 1609 CH3 Br F CH3 Br 1610 CH3 Br F OCH3 H 1611 CH3 Br F OCH3 CH3 1612 CH3 Br F OCH3 OCH3 1613 CH3 Br F OCH3 ci 1614 CH3 Br F OCH3 Br 1615 CH3 Br F ci H 1616 CH3 Br F ci CH3 1617 CH3 Br F Ci OCH3 1618 CH3 Br F Cl Ci 1619 CH3 Br F Ci Br 1620 CH3 Br F Br H 1621 CH3 Br F Br CH3 1622 CH3 Br F Br OCH3 1623 CH3 Br F Br Ci 1624 CH3 Br F Br Br 1625 CH3 Br F F H 1626 CH3 Br F F CH3 1627 CH3 Br F F OCH3 1628 CH3 Br F F C1 1629 CH3 Br F F Br 1630 CH3 Br F F F 1631 CH3 F CH3 H H 1632 CH3 F CH3 H CH3 1633 CH3 F CH3 H OCH3 1634 CH3 F CH3 H Cl 1635 CH3 F CH3 H Br 1636 CH3 F CH3 H F 1637 CH3 F CH3 CH3 H 1638 CH3 F CH3 CH3 CH3 1639 CH3 F CH3 CH3 OCH3 1640 CH3 F CH3 CH : 3 Cl 1641 CH3 F CH3 CH3 Br 1642 CH3 F CH3 CH3 F 1643 CH3 F CH3 OCH3 H 1644 CH3 F CH3 OCH3 OCH3 1645 CH3 F CH3 OCH3 Cl 1646 CH3 F CH3 OCH3 Br 1647 CH3 F CH3 OCH3 F Compound R2a R2b Rac R2d R2e No. 1648 CH3 F CH3 ci H 1649 CH3 F CH3 C1 OCH 1650 CH3 CH3 C 1 C 1 1651 CH3 F CH3 C 1 Br 1652 CH3 F CH3 Cl F 1653 CH3 F CH3 Br H 1654 CH3 F CH, 13r OCH3 1655 CH3 CH3 Br ci 1656 CH3 F CH3 Br Br 1657 CH3 F CH3 Br F 1658 CH3 F CH3 F H 1659 CH3 F CH3 F OCH3 1660 CH3 F CH3 F Cl 1661 CH3 F CH3 F Br 1662 CH3 F CH3 F F 1663 CH3 F OCH3 H H 1664 CH3 F OCH3 H CH3 1665 CH3 F OCH3 H OCH3 l 1666 CH3 F OCH3 H Cl 1667 CH3 F OCH3 H Br 1668 CH3 F OCH3 H F 1669 CH3 F OCH3 CH3 H 1670 CH3 F OCH3 CH3 CH3 1671 CH3 F OCH3 CH3 Cl 1672 CH3 F OCH3 CH3 Br 1673 CH3 F OCH3 CH3 F 1674 CH3 F OCH3 OCH3 H 1675 CH3 F OCH3 OCH3 CH3 1676 CH3 F OCH3 OCH3 OCH3 1677 CH3 F OCH3 OCH3 Cl 1678 CH3 F OCH3 OCH3 Br 1679 CH3 F OCH3 OCH3 F 1680 CH3 F OCH3 ci H 1681 CH3 F OCH3 Ci CH3 1682 CH3 F OCH3 Cl C1 1683 CH3 F OCH3 ci Br 1684 CH3 F OCH3 ci F 1685 CH3 F OCH3 Br H 1686 CH3 F OCH3 Br CH3 1687 CH3 F _ OCH3 Br C1 Compound R2a R2b R2c R2d R2e No. 1688 CH3 F OCH3 Br Br 1689 CH3 F OCH3 Br F 1690 CH3 F OCH3 F H 1691 CH3 F OCH3 F CH3 1692 CH3 F OCH3 F Cl 1693 CH3 F OCH3 F Br 1694 CH3 F OCH3 F F 1695 CH3 F Cl H H 1696 CH3 F ci H CH3 1697 CH3 F Cl H OCH3 1698 CH3 F ci H ci 1699 CH3 F ci H Br 1700 CH3 F Cl H F 1701 CH3 F Ci CH3 H 1702 CH3 F Cl CH3 CH3 1703 CH3 F Cl CH3 OCH3 1704 CH3 F Ci CH3 Br 1705 CH3 F Cl CH3 F 1706 CH3 F Cl OCH3 H 1707 CH3 F Cl OCH3 CH3 1708 CH3 F Ci OCH3 OCH3 1709 CH3 F Ci OCH3 Br 1710 CH3 F Cl OCH3 F 1711 CH3 F Cl Cl H 1712 CH3 F Cl Cl CH3 1713 CH3 F ci ci OCH3 1714 CH3 F Ci Ci ci 1715 CH3 F ci ci Br 1716 CH3 F Cl Cl F 1717 CH3 F Cl Br H 1718 CH3 F Cl Br CH3 1719 CH3 F ci Br OCH3 1720 CH3 F C1 Br Br 1721 CH3 F ci F H 1722 CH3 F ci F CH3 1723 CH3 F Cl F OCH3 1724 CH3 F Cl F Br 1725 CH3 F Cl F F 1726 CH3 F Br H H 1727 CH3 F Br H CH3 Compound R2a R2b R2 R2d R2e No. 1728 CH3 F Br H OCH3 1729 CH3 F Br H Ci 1730 CH3 F Br H Br 1731 CH3 F Br H F 1732 CH3 F Br CH3 H 1733 CH3 F Br CH3 CH3 1734 CH3 F Br CH3 OCH3 1735 CH3 F Br CH3 Ci 1736 CH3 F Br CH3 F 1737 CH3 F Br OCH3 H 1738 CH3 F Br OCH3 CH3 1739 CH3 F Br OCH3 OCH3 1740 CH3 F Br OCH3 Ci 1741 CH3 F Br OCH3 F 1742 CH3 F Br Ci H 1743 CH3 F Br Cl CH3 1744 CH3 F Br ci OCH3 1745 CH3 F Br ci ci 1746 CH3 F Br Ci F 1747 CH3 F Br Br H 1748 CH3 F Br Br CH3 1749 CH3 F Br Br OCH3 1750 CH3 F Br Br Ci 1751 CH3 F Br Br Br 1752 CH3 F Br Br F 1753 CH3 F Br F H 1754 CH3 F Br F CH3 1755 CH3 F Br F OCH3 1756 CH3 F Br F Cl 1757 CH3 F Br F F 1758 CH3 F F H H 1759 CH3 F F H CH3 1760 CH3 F F H OCH3 1761 CH3 F F H C1 1762 CH3 F F H Br 1763 CH3 F F H F 1764 CH3 F F CH3 H 1765 CH3 F F CH3 CH3 1766 CH3 F F CH3 OCH3 1767 CH3 F F ci Compound R2a R2b R2c R2d R2e No. 1768 CH3 F F CH3 Br 1769 CH3 F F OCH3 H 1770 CH3 F F OCH3 CH3 1771 CH3 F F OCH3 OCH3 1772 CH3 F F OCH3 Cl 1773 CH3 F F OCH3 Br 1774 CH3 F F Ci H 1775 CH3 F F ci CH3 1776 CH3 F F ci OCH3 1777 CH3 F F C1 Cl 1778 CH3 F F ci Br 1779 CH3 F F Br H 1780 CH3 F F Br CH3 1781 CH3 F F Br OCH3 1782 CH3 F F Br Ci 1783 CH3 F F Br Br 1784 CH3 F F F H 1785 CH3 F F F CH3 1786 CH3 F F F OCH3 1787 CH3 F F F ci 1788 CH3 F F F Br 1789 CH3 F F F F 1790 OCH3 CH3 CH3 H H 1791 OCH3 CH3 CH3 CH3 H 1792 OCH3 CH3 CH3 OCH3 H 1793 OCH3 CH3 CH3 Cl H 1794 OCH3 CH3 CH3 Br H 1795 OCH3 CH3 CH3 F H 1796 OCH3 CH3 CH3 H CH3 1797 OCH3 CH3 CH3 CH3 CH3 1798 OCH3 CH3 CH3 H OCH3 1799 OCH3 CH3 CH3 CH3 OCH3 1800 OCH3 CH3 CH3 OCH3 OCH3 1801 OCH3 CH3 CH3 ci OCH3 1802 OCH3 CH3 CH3 Br OCH3 1803 OCH3 CH3 CH3 F OCH3 1804 OCH3 CH3 CH3 H C1 1805 OCH3 CH3 CH3 CH3 Ci 1806 OCH3 CH3 CH3 OCH3 ci 1807 OCH3 CH3 CH3 ci Cl Compound R2a R2b R2o R2d R2e No. 1808 OCH3 CH3 CH3 Br Ci 1809 OCH3 CH3 CH3 F Ci 1810 OCH3 CH3 CH3 H Br 1811 OCH3 CH3 CH3 CH3 Br 1812 OCH3 CH3 CH3 OCH3 Br 1813 OCH3 CH3 CH3 ci Br 1814 OCH3 CH3 CH3 Br Br 1815 OCH3 CH3 CH3 F Br 1816 OCH3 CH3 CH3 H F 1817 OCH3 CH3 CH3 CH3 F 1818 OCH3 CH3 CH3 OCH3 F 1819 OCH3 CH3 CH3 Cl F 1820 OCH3 CH3 CH3 Br F 1821 OCH3 CH3 CH3 F F 1822 OCH3 CH3 OCH3 H H 1823 OCH3 CH3 OCH3 CH3 H 1824 OCH3 CH3 OCH3 OCH3 H 1825 OCH3 CH3 OCH3 Ci H 1826 OCH3 CH3 OCH3 Br H 1827 OCH3 CH3 OCH3 H 1828 OCH3 CH3 OCH3 H CH3 1829 OCH3 CH3 OCH3 CH3 CH3 1830 OCH3 CH3 OCH3 OCH3 CH3 1831 OCH3 CH3 OCH3 Ci CH3 1832 OCH3 CH3 OCH3 Br CH3 1833 OCH3 CH3 OCH3 F CH3 1834 OCH3 CH3 OCH3 H OCH3 1835 OCH3 CH3 OCH3 OCH3 OCH3 1836 OCH3 CH3 OCH3 H Cl 1837 OCH3 CH3 OCH3 CH3 Cl 1838 OCH3 CH3 OCH3 OCH3 Cl 1839 OCH3 CH3 OCH3 Ci ci 1840 OCH3 CH3 OCH3 Br C1 1841 OCH3 CH3 OCH3 F ci 1842 OCH3 CH3 OCH3 H Br 1843 OCH3 CH3 OCH3 CH3 Br 1844 OCH3 CH3 OCH3 OCH3 Br 1845 OCH3 CH3 OCH3 ci Br 1846 OCH3 CH3 OCH3 Br Br 1847 OCH3 CH3 OCH3 F Br Compound R2a R2b R2c R2d R2e No. 1848 OCH3 CH3 OCH3 H F 1849 OCH3 CH3 OCH3 CH3 F I 1850 OCH3 CH3 OCH3 OCH3 F 1851 OCH3 CH3 OCH3 ci F 1852 OCH3 CH3 OCH3 Br F 1853 OCH3 CH3 OCH3 F F 1854 OCH3 CH3 ci H H 1855 OCH3 CH3 Ci CH3 H 1856 OCH3 CH3 Cl OCH3 H 1857 OCH3 CH3 Ci Ci H 1858 OCH3 CH3 ci Br H 1859 OCH3 CH3 ci F H 1860 OCH3 CH3 ci H CH3 1861 OCH3 CH3 ci CH3 CH3 1862 OCH3 CH3 ci OCH3 CH3 1863 OCH3 CH3 ci ci CH3 1864 OCH3 CH3 Cl Br CH3 1865 OCH3 CH3 ci F CH3 1866 OCH3 CH3 Ci H OCH3 1867 OCH3 CH3 ci CH3 OCH 1868 OCH3 CH3 ci OCH3 OCH3 1869 OCH3 CH3 Cl C1 OCH3 1870 OCH3 CH3 ci Br OCH3 1871 OCH3 CH3 Ci F OCH3 OCH3 CH3 Cl H ci 1873 OCH3 CH3 Ci Cl Cl 1874 OCH3 CH3 ci H Br 1875 OCH3 CH3 ci CH3 Br 1876 OCH3 CH3 ci OCH3 Br 1877 OCH3 CH3 ci Cl Br 1878 OCH3 CH3 Ci Br Br 1879 OCH3 CH3 Ci F Br 1880 OCH3 CH3 ci H F 1881 OCH3 CH3 ci CH3 F 1882 OCH3 CH3 Cl OCH3 F 1883 OCH3 CH3 Ci Ci F 1884 OCH3 CH3 ci F F 1885 OCH3 CH3 Br H H 1886 OCH3 CH3 Br CH3 H 1887 OCH3 CH3 Br OCH3 H Compound Rza R2b R2c R2d R2e No. 1888 OCH3 CH3 Br ci H 1889 OCH3 CH3 Br Br H 1890 OCH3 CH3 Br F H 1891 OCH3 CH3 Br H CH3 1892 OCH3 CH3 Br CH3 CH3 1893 OCH3 CH3 Br OCH3 CH3 1894 OCH3 CH3 Br ci CH3 1895 OCH3 CH3 Br Br CH3 1896 OCH3 CH3 Br F CH3 1897 OCH3 CH3 Br H OCH3 1898 OCH3 CH3 Br CH3 OCH3 1899 OCH3 CH3 Br OCH3 OCH3 1900 OCH3 CH3 Br Ci OCH3 1901 OCH3 CH3 Br Br OCH3 1902 OCH3 CH3 Br F OCH3 1903 OCH3 CH3 Br H ci 1904 OCH3 CH3 Br CH3 ci 1905 OCH3 CH3 Br OCH3 ci 1906 OCH3 CH3 Br Ci ci 1907 OCH3 CH3 Br Br ci 1908 OCH3 CH3 Br F ci 1909 OCH3 CH3 Br H Br 1910 OCH3 CH3 Br Br Br 1911 OCH3 CH3 Br H F 1912 OCH3 CH3 Br CH3 F 1913 OCH3 CH3 Br OCH3 F 1914 OCH3 CH3 Br C1 F 1915 OCH3 CH3 Br Br F 1916 OCH3 CH3 Br F F 1917 OCH3 CH3 F H H 1918 OCH3 CH3 F CH3 H 1919 OCH3 CH3 F OCH3 H 1920 OCH3 CH3 F ci H 1921 OCH3 CH3 F Br H 1922 OCH3 CH3 F F H 1923 OCH3 CH3 F H CH3 1924 OCH3 CH3 F CH3 CH3 1925 OCH3 CH3 F OCH3 CH3 1926 OCH3 CH3 F ci CH3 1927 OCH3 CH3 F Br CH3 Compound Rza Rab R2c R2d R2e No. 1928 OCH3 CH3 F F CH3 1929 OCH3 CH3 F H OCH3 1930 OCH3 CH3 F CH3 OCH3 1931 OCH3 CH3 F OCH3 OCH3 1932 OCH3 CH3 F Ci OCH3 1933 OCH3 CH3 F Br OCH3 1934 OCH3 CH3 F F OCH3 1935 OCH3 CH3 F H Ci 1936 OCH3 CH3 F CH3 Ci 1937 OCH3 CH3 F OCH3 Ci 1938 OCH3 CH3 F Cl Cl 1939 OCH3 CH3 F Br Ci 1940 OCH3 CH3 F F Ci 1941 OCH3 CH3 F H Br 1942 OCH3 CH3 F CH3 Br 1943 OCH3 CH3 F OCH3 Br 1944 OCH3 CH3 F Ci Br 1945 OCH3 CH3 F Br Br 1946 OCH3 CH3 F F Br 1947 OCH3 CH3 F H F 1948 OCH3 CH3 F F F 1949 OCH3 OCH3 CH3 H H 1950 OCH3 OCH3 CH3 H CH3 1951 OCH3 OCH3 CH3 H OCH3 1952 OCH3 OCH3 CH3 H ci 1953 OCH3 OCH3 CH3 H Br 1954 OCH3 OCH3 CH3 H F 1955 OCH3 OCH3 CH3 CH3 H 1956 OCH3 OCH3 CH3 CH3 CH3 1957 OCH3 OCH3 CH3 CH3 OCH 1958 OCH3 OCH3 CH3 CH3 ci 1959 OCH3 OCH3 CH3 CH3 Br 1960 OCH3 OCH3 CH3 CH3 F 1961 OCH3 OCH3 CH3 OCH3 H 1962 OCH3 OCH3 CH3 OCH3 OCH3 1963 OCH3 OCH3 CH3 OCH3 Ci 1964 OCH3 OCH3 CH3 OCH3 Br 1965 OCH3 OCH3 CH3 OCH3 F 1966 OCH3 OCH3 CH3 Cl H 1967 OCH3 OCH3 CH3 C1 OCH3 Compound R2a R2b R2c R2d R2e No. 1968 OCH3 OCH3 CH3 Ci Ci 1969 OCH3 OCH3 CH3 Ci Br 1970 OCH3 OCH3 CH3 ci F 1971 OCH3 OCH3 CH3 Br H 1972 OCH3 OCH3 CH3 Br OCH3 1973 OCH3 OCH3 CH3 Br Ci 1974 OCH3 OCH3 CH3 Br Br 1975 OCH3 OCH3 CH3 Br F 1976 OCH3 OCH3 CH3 F H 1977 OCH3 OCH3 CH3 F OCH3 1978 OCH3 OCH3 CH3 F ci 1979 OCH3 OCH3 CH3 F Br 1980 OCH3 OCH3 CH3 F F 1981 OCH3 OCH3 OCH3 H H 1982 OCH3 OCH3 OCH3 H CH3 1983 OCH3 OCH3 OCH3 H OCH3 1984 OCH3 OCH3 OCH3 H Cl 1985 OCH3 OCH3 OCH3 H Br 1986 OCH3 OCH3 OCH3 H F i 987 OCH3 OCH3 OCH3 CH3 H 1988 OCH3 OCH3 OCH3 CH3 CH3 1989 OCH3 OCH3 OCH3 CH3 ci 1990 OCH3 OCH3 OCH3 CH3 Br 1991 OCH3 OCH3 OCH3 CH3 F 1992 OCH3 OCH3 OCH3 OCH3 H 1993 OCH3 OCH3 OCH3 OCH3 CH3 1994 OCH3 OCH3 OCH3 OCH3 OCH3 1995 OCH3 OCH3 OCH3 OCH3 Ci 1996 OCH3 OCH3 OCH3 OCH3 Br 1997 OCH3 OCH3 OCH3 OCH3 F 1998 OCH3 OCH3 OCH3 ci H 1999 OCH3 OCH3 OCH3 Ci CH3 2000 OCH3 OCH3 OCH3 Ci Cl 2001 OCH3 OCH3 OCH3 ci Br 2002 OCH3 OCH3 OCH3 ci F 2003 OCH3 OCH3 OCH3 Br H 2004 OCH3 OCH3 OCH3 Br CH3 2005 OCH3 OCH3 OCH3 Br Ci 2006 OCH3 OCH3 OCH3 Br Br 2007 OCH3 OCH3 OCH3 Br F Compound Rza Rzb Rzc Rzd R2e No. 2008 OCH3 OCH3 OCH3 F H 2009 OCH3 OCH3 OCH3 F CH3 2010 OCH3 OCH3 OCH3 F Cl 2011 OCH3 OCH3 OCH3 F Br 2012 OCH3 OCH3 OCH3 F F 2013 OCH3 OCH3 Cl H H 2014 OCH3 OCH3 ci H CH3 2015 OCH3 OCH3 ci H OCH3 2016 OCH3 OCH3 ci H ci 2017 OCH3 OCH3 ci H Br 2018 OCH3 OCH3 ci H F 2019 OCH3 OCH3 ci CH3 H 2020 OCH3 OCH3 ci CH3 CH3 2021 OCH3 OCH3 Ci CH3 OCH3 2022 OCH3 OCH3 ci CH3 Br 2023 OCH3 OCH3 Cl CH3 F 2024 OCH3 OCH3 ci OCH3 H 2025 OCH3 OCH3 ci OCH3 CH3 2026 OCH3 OCH3 ci OCH3 OCH3 2027 OCH3 OCH3 Ci OCH3 Br 2028 OCH3 OCH3 Ci OCH3 F 2029 OCH3 OCH3 Ci ci H 2030 OCH3 OCH3 C 1 C 1 CH3 2031 OCH3 OCH3 ci ci OCH3 2032 OCH3 OCH3 ci Cl Cl 2033 OCH3 OCH3 ci ci Br 2034 OCH3 OCH3 Cl Cl F 2035 OCH3 OCH3 ci Br H 2036 OCH3 OCH3 ci Br CH3 2037 OCH3 OCH3 Ci Br OCH3 2038 OCH3 OCH3 Cl Br Br 2039 OCH3 OCH3 ci F H 2040 OCH3 OCH3 Ci F CH3 2041 OCH3 OCH3 Cl F OCH3 2042 OCH3 OCH3 ci F Br 2043 OCH3 OCH3 ci F F 2044 OCH3 OCH3 Br H H 2045 OCH3 OCH3 Br H CH3 2046 OCH3 OCH3 Br H OCH3 2047 OCH3 OCH3 Br H C1 Compound R2a R2b R2c R2d R2e No. 2048 OCH3 OCH3 Br H Br 2049 OCH3 OCH3 Br H F 2050 OCH3 OCH3 Br CH3 H 2051 OCH3 OCH3 Br CH3 CH3 2052 OCH3 OCH3 Br CH3 OCH3 2053 OCH3 OCH3 Br CH3 Ci 2054 OCH3 OCH3 Br CH3 F 2055 OCH3 OCH3 Br OCH3 H 2056 OCH3 OCH3 Br OCH3 CH3 2057 OCH3 OCH3 Br OCH3 OCH3 2058 OCH3 OCH3 Br OCH3 ci 2059 OCH3 OCH3 Br OCH3 F 2060 OCH3 OCH3 Br Ci H 2061 OCH3 OCH3 Br ci CH3 2062 OCH3 OCH3 Br Ci OCH3 2063 OCH3 OCH3 Br Ci ci 2064 OCH3 OCH3 Br Ci F 2065 OCH3 OCH3 Br Br H 2066 OCH3 OCH3 Br Br CH3 2067 OCH3 OCH3 Br Br OCH3 2068 OCH3 OCH3 Br Br ci 2069 OCH3 OCH3 Br Br Br 2070 OCH3 OCH3 Br Br F 2071 OCH3 OCH3 Br F H 2072 OCH3 OCH3 Br F CH3 2073 OCH3 OCH3 Br F OCH3 2074 OCH3 OCH3 Br F ci 2075 OCH3 OCH3 Br F F 2076 OCH3 OCH3 F H H 2077 OCH3 OCH3 F H CH3 2078 OCH3 OCH3 F H OCH3 2079 OCH3 OCH3 F H ci 2080 OCH3 OCH3 F H Br 2081 OCH3 OCH3 F H F 2082 OCH3 OCH3 F CH3 H 2083 OCH3 OCH3 F CH3 CH3 2084 OCH3 OCH3 F CH3 OCH3 2085 OCH3 OCH3 F CH3 ci 2086 OCH3 OCH3 F CH3 Br 2087 OCH3 OCH3 Compound R2a R2b R2c R2d R2e No. 2088 OCH3 OCH3 F OCH3 CH3 2089 OCH3 OCH3 F OCH3 OCH3 2090 OCH3 OCH3 F OCH3 Cl 2091 OCH3 OCH3 F OCH3 Br 2092 OCH3 OCH3 F Ci H 2093 OCH3 OCH3 F ci CH3 2094 OCH3 OCH3 F ci OCH3 2095 OCH3 OCH3 F ci Cl 2096 OCH3 OCH3 F ci Br 2097 OCH3 OCH3 F Br H 2098 OCH3 OCH3 F Br CH3 2099 OCH3 OCH3 F Br OCH3 2100 OCH3 OCH3 F Br Ci 2101 OCH3 OCH3 F Br Br 2102 OCH3 OCH3 F F H 2103 OCH3 OCH3 F F CH3 2104 OCH3 OCH3 F F OCH3 2105 OCH3 OCH3 F F Ci 2106 OCH3 OCH3 F F Br 2107 OCH3 OCH3 F F F 2108 OCH3 Cl CH3 H H 2109 OCH3 Cl CH3 H CH3 2110 OCH3 Cl CH3 H OCH3 2111 OCH3 C1 CH3 H ci 2112 OCH3 ci CH3 H Br 2113 OCH3 ci CH3 H F 2114 OCH3 C 1 CH3 CH3 H 2115 OCH3 ci CH3 CH3 CH3 2116 OCH3 ci CH3 CH3 OCH3 2117 OCH3 ci CH3 CH3 Cl 2118 OCH3 C 1 CH3 CH3 Br 2119 OCH3 ci CH3 CH3 F 2120 OCH3 ci CH3 OCH3 H 2121 OCH3 Ci CH3 OCH3 OCH3 2122 OCH3 ci CH3 OCH3 Cl 2123 OCH3 ci CH3 OCH3 Br 2124 OCH3 ci CH3 OCH3 F 2125 OCH3 Ci CH3 Ci H 2126 OCH3 Ci CH3 ci OCH3 2127 OCH3 C1 CH3 C1 C1 Compound R2a | R2b R2c R2d R2e No. 2128 OCH3 C1 CH3 Ci Br 2129OCH3Cl CH3 ci F 2130 OCH3 C 1 CH3 Br H 2131 OCH3 Ci CH3 Br OCH3 2132 OCH3 ci CH3 Br Ci 2133 OCH3 Ci CH3 Br Br 2134 OCH3 C1 CH3 Br F 2135 OCH3 Cl CH3 F H 2136 OCH3 Ci CH3 F OCH3 2137 OCH3 Cl CH3 F Ci 2138 OCH3 C1 CH3 F Br 2139 OCH3 Cl CH3 F F 2140 OCH3 Ci OCH3 H H 2141 OCH3 Cl OCH3 H CH3 2142 OCH3 ci OCH3 H OCH3 2143 OCH3 ci OCH3 H Ci 2144 OCH3 ci OCH3 H Br 2145 OCH3 C 1 OCH3 H F 2146 OCH3 ci OCH3 CH3 H OCH3 C1 OCH3 CH3 CH3 2148 OCH3 Ci OCH3 CH3 Ci 2149 OCH3 ci OCH3 CH3 Br 2150 OCH3 Cl OCH3 CH3 F 2151 OCH3 ci OCH3 OCH3 H 2152 OCH3 ci OCH3 OCH3 CH3 2153 OCH3 ci OCH3 OCH3 OCH3 2154 OCH3 Ci OCH3 OCH3 ci 2155 OCH3 Cl OCH3 OCH3 Br 2156 OCH3 Cl OCH3 OCH3 F 2157 OCH3 Cl OCH3 Cl H 2158 OCH3 Cl OCH3 Cl CH3 2159 OCH3 ci OCH3 ci Ci 2160 OCH3 ci OCH3 Ci Br 2161 OCH3 ci OCH3 ci F 2162 OCH3 Ci OCH3 Br H 2163 OCH3 ci OCH3 Br CH3 2164 OCH3 ci OCH3 Br ci 2165 OCH3 ci OCH3 Br Br 2166 OCH3 Cl OCH3 Br F 2167 OCH3 C1 OCH3 F H Compound Rza Rzb R2c R2d R2e No. 2168 OCH3 Cl OCH3 F CH3 3 2169 OCH3 Cl OCH3 F Ci 2170 OCH3 Ci OCH3 F Br 2171 OCH3 ci OCH3 F F 2172 OCH3 ci ci H H 2173 OCH3 C1 C1 H CH3 2174 OCH3 ci ci H OCH3 2175 OCH3 Ci C1 H Cl 2176 OCH3 ci ci H Br 2177 OCH3 Ci ci H F 2178 OCH3 Cl Cl CH3 H 2179 OCH3 ci ci CH3 CH3 2180 OCH3 C1 C1 CH3 OCH3 2181 OCH3 ci Ci CH3 Br 2182 OCH3 Ci Ci CH3 F 2183 OCH3 Cl Cl OCH3 H 2184 OCH3 ci Cl OCH3 CH3 2185 OCH3 ci ci OCH3 OCH3 2186 OCH3 ci ci OCH3 Br 2187 OCH3 ci ci OCH3 F 2188 OCH3 C1 C1 C1. _ OCH3 C1 Cl C1 CH3 2190 OCH3 ci Ci ci OCH3 2191 OCH3 ci Ci ci Ci 2192 OCH3 Cl Cl C1 Br 2193 OCH3 C1 C1 Cl F 2194 OCH3 Ci Cl Br H 2195 OCH3 Ci ci Br CH3 2196 OCH3 ci ci Br OCH3 2197 OCH3 ci Ci Br Br 2198 OCH3 Ci Cl F H 2199 OCH3 Ci ci F CH3 2200 OCH3 ci ci F OCH3 2201 OCH3 Ci ci F Br 2202 OCH3 C1 C1 F F 2203 OCH3 Cl Br H H 2204 OCH3 Cl Br H CH3 2205 OCH3 Ci Br H OCH3 2206 OCH3 ci Br H Ci 2207 OCH3 C1 Br H Br Compound R2a R2b R2c R2d R2e No. 2208 OCH3 C1 Br F 2209 OCH3 Cl Br CH3 H 2210 OCH3 C1 Br CH3 CH3 2211 OCH3 Cl Br CH3 OCH3 2212 OCH3 ci Br CH3 ci 2213 OCH3 ci Br CH3 F 2214 OCH3 C1 Br OCH3 H 2215 OCH3 Cl Br OCH3 CH3 2216 OCH3 ci Br OCH3 OCH3 2217 OCH3 ci Br OCH3 ci 2218 OCH3 ci Br OCH3 F 2219 OCH3 ci Br Ci H 2220 OCH3 ci Br ci CH3 2221 OCH3 Cl Br Ci OCH3 2222 OCH3 ci Br Ci ci 2223 OCH3 Ci Br Ci F 2224 OCH3 Ci Br Br H 2225 OCH3 Cl Br Br CH3 2226 OCH3 Cl Br Br OCH3 2227 OCH3 Cl Br Br ci 2228 OCH3 Ci Br Br Br OCH3 C1 Br Br F 2230 OCH3 Ci Br F H 2231 OCH3 Ci Br F CH3 2232 OCH3 Ci Br F OCH3 2233 OCH3 Ci Br F Ci 2234 OCH3 Cl Br F F 2235 OCH3 ci F H H 2236 OCH3 C1 F H CH3 2237 OCH3 Cl F H OCH3 2238 OCH3 ci F H Cl OCH3 C1 F H Br 2240 OCH3 ci F H F 2241 OCH3 Ci F CH3 H 2242 OCH3 C1 F CH3 CH3 2243 OCH3 Ci F CH3 OCH3 2244 OCH3 ci F CH3 ci 2245 OCH3 ci F CH3 Br 2246 OCH3 ci F OCH3 H 2247 OCH3 ci OCH3 CH3 Compound Rza R2b R2c R2d R2e No. 2248 OCH3 Ci F OCH3 OCH3 2249 OCH3 ci F OCH3 C1 2250 OCH3 Ci F OCH3 Br 2251 OCH3 ci F Cl H 2252 OCH3 Cl F C 1 CH3 2253 OCH3 ci F ci OCH3 2254 OCH3 ci F Ci Ci 2255 OCH3 Ci F C1 Br 2256 OCH3 Cl F Br H 2257 OCH3 Ci F Br CH3 2258 OCH3 Ci F Br OCH3 2259 OCH3 Ci F Br ci 2260 OCH3 Ci F Br Br 2261 OCH3 ci F F H 2262 OCH3 Cl F F CH3 2263 OCH3 Cl F F OCH3 2264 OCH3 Cl F F Cl 2265 OCH3 Cl F F Br 2266 OCH3 Cl F F F 2267 OCH3 Br CH3 H H 2268 OCH3 Br CH3 H CH3 2269 OCH3 Br CH3 H OCH3 2270 OCH3 Br CH3 H Cl 2271 OCH3 Br CH3 H Br 2272 OCH3 Br CH3 H F 2273 OCH3 Br CH3 CH3 H 2274 OCH3 Br CH3 CH3 CH3 2275 OCH3 Br CH3 CH3 OCH3 2276 OCH3 Br CH3 CH3 Cl 2277 OCH3 Br CH3 CH3 Br 2278 OCH3 Br CH3 CH3 F 2279 OCH3 Br CH3 OCH3 H 2280 OCH3 Br CH3 OCH3 OCH3 2281 OCH3 Br CH3 OCH3 ci 2282 OCH3 Br CH3 OCH3 Br 2283 OCH3 Br CH3 OCH3 F 2284 OCH3 Br CH3 ci H 2285 OCH3 Br CH3 Cl OCH3 2286 OCH3 Br CH3 Cl ci 2287 OCH3 Br CH3 Cl Br Compound R2a R2b R2c Raa Rze No. 2288 OCH3 Br CH3 ci 2289 OCH3 Br CH3 Br H 2290 OCH3 Br CH3 Br OCH3 2291 OCH3 Br CH3 Br ci 2292 OCH3 Br CH3 Br Br 2293 OCH3 Br CH3 Br F 2294 OCH3 Br CH3 F H 2295 OCH3 Br CH3 F OCH3 2296 OCH3 Br CH3 F Ci 2297 OCH3 Br CH3 F Br 2298 OCH3 Br CH3 F F 2299 OCH3 Br OCH3 H H 2300 OCH3 Br OCH3 H CH3 2301 OCH3 Br OCH3 H OCH3 2302 OCH3 Br OCH3 H ci 2303 OCH3 Br OCH3 H Br 2304 OCH3 Br OCH3 H F 2305 OCH3 Br OCH3 CH3 H 2306 OCH3 Br OCH3 CH3 CH3 2307 OCH3 Br OCH3 CH3 Ci 2308 OCH3 Br OCH3 CH3 Br 2309 OCH3 Br OCH3 CH3 F 2310 OCH3 Br OCH3 OCH3 H 2311 OCH3 Br OCH3 OCH3 CH3 2312 OCH3 Br OCH3 OCH3 OCH3 2313 OCH3 Br OCH3 OCH3 Ci 2314 OCH3 Br OCH3 OCH3 Br 2315 OCH3 Br OCH3 OCH3 F 2316 OCH3 Br OCH3 Ci H 2317 OCH3 Br OCH3 Ci CH3 2318 OCH3 Br OCH3 Ci Ci 2319 OCH3 Br OCH3 ci Br 2320 OCH3 Br OCH3 ci F 2321 OCH3 Br OCH3 Br H 2322 OCH3 Br OCH3 Br CH3 2323 OCH3 Br OCH3 Br C1 2324 OCH3 Br OCH3 Br Br 2325 OCH3 Br OCH3 Br F 2326 OCH3 Br OCH3 F H 2327 OCH3 Br OCH3 F CH3 Compound R2a R2b R2c R2d R2e No. 2328 OCH3 Br OCH3 F Ci 2329 OCH3 Br OCH3 F Br 2330 OCH3 Br OCH3 F F 2331 OCH3 Br ci H H 2332 OCH3 Br ci H CH3 2333 OCH3 Br ci H OCH3 2334 OCH3 Br ci H Ci 2335 OCH3 Br ci H Br 2336 OCH3 Br Ci H F 2337 OCH3 Br Ci CH3 H 2338 OCH3 Br Cl CH3 CH3 2339 OCH3 Br Cl CH3 OCH3 2340 OCH3 Br ci CH3 Br 2341 OCH3 Br ci CH3 F 2342 OCH3 Br ci OCH3 H 2343 OCH3 Br Ci OCH3 CH3 2344 OCH3 Br Ci OCH3 OCH3 2345 OCH3 Br ci OCH3 Br 2346 OCH3 Br Ci OCH3 F 2347 OCH3 Br Ci ci H 2348 OCH3 Br ci ci CH3 2349 OCH3 Br ci Ci OCH3 2350 OCH3 Br ci ci Ci 2351 OCH3 Br ci ci Br 2352 OCH3 Br Ci ci F 2353 OCH3 Br Ci Br H 2354 OCH3 Br ci Br CH3 2355 OCH3 Br ci Br OCH3 2356 OCH3 Br Ci Br Br 2357 OCH3 Br ci F H 2358 OCH3 Br Ci F CH3 2359 OCH3 Br ci F OCH3 2360 OCH3 Br ci F Br 2361 OCH3 Br ci F F 2362 OCH3 Br Br H H 2363 OCH3 Br Br H CH3 2364 OCH3 Br Br H OCH3 2365 OCH3 Br Br H Ci 2366 OCH3 Br Br H Br 2367 OCH3 Br Br s H F Compound R2a Rzb R2c R2d R2e No. 2368 OCH3 Br Br CH3 H 2369 OCH3 Br Br CH3 CH3 2370 OCH3 Br Br CH3 OCH3 2371 OCH3 Br Br CH3 ci 2372 OCH3 Br Br CH3 F 2373 OCH3 Br Br OCH3 H 2374 OCH3 Br Br OCH3 CH3 2375 OCH3 Br Br OCH3 OCH3 2376 OCH3 Br Br OCH3 ci 2377 OCH3 Br Br OCH3 F 2378 OCH3 Br Br ci H 2379 OCH3 Br Br ci CH3 2380 OCH3 Br Br Ci OCH3 2381 OCH3 Br Br ci Ci 2382 OCH3 Br Br Ci F 2383 OCH3 Br Br Br H 2384 OCH3 Br Br Br CH3 2385 OCH3 Br Br Br OCH3 2386 OCH3 Br Br Br ci 2387 OCH3 Br Br Br Br 2388 OCH3 Br Br Br F 2389 OCH3 Br Br F H 2390 OCH3 Br Br F CH3 2391 OCH3 Br Br F OCH3 2392 OCH3 Br Br F Ci 2393 OCH3 Br Br F F 2394 OCH3 Br F H H 2395 OCH3 Br F H CH3 2396 OCH3 Br F H OCH3 2397 OCH3 Br F H ci 2398 OCH3 Br F H Br 2399 OCH3 Br F H F 2400 OCH3 Br F CH3 H 2401 OCH3 Br F CH3 CH3 2402 OCH3 Br F CH3 OCH3 2403 OCH3 Br F CH3 ci 2404 OCH3 Br F CH3 Br 2405 OCH3 Br F OCH3 H 2406 OCH3 Br F OCH3 CH3 2407 OCH3 Br F OCH3 OCH3 Compound Rza R2b R2c Rza No. 2408 OCH3 Br F OCH3 Cl 2409 OCH3 Br F OCH3 Br 2410 OCH3 Br F Cl H 2411 OCH3 Br F Ci CH3 2412 OCH3 Br F ci OCH3 2413 OCH3 Br F ci ci 2414 OCH3 Br F Ci Br l TY 2415 OCH3 Br F Br H 2416 OCH3 Br F Br CH3 2417 OCH3 Br F Br OCH3 2418 OCH3 Br F Br Ci 2419 OCH3 Br F Br Br 2420 OCH3 Br F F H 2421 OCH3 Br F F CH3 2422 OCH3 Br F F OCH 2423 OCH3 Br F F ci 2424 OCH3 Br F F Br 2425 OCH3 Br F F F 2426 OCH3 F CH3 H H 2427 OCH3 F CH3 H CH3 2428 OCH3 F CH3 H OCH3 2429 OCH3 F CH3 H Cl 2430 OCH3 F CH3 H Br 2431 OCH3 F CH3 H F 2432 OCH3 F CH3 CH3 H 2433 OCH3 F CH3 CH3 CH3 2434 OCH3 F CH3 CH3 OCH3 2435 OCH3 F CH3 CH3 Cl 2436 OCH3 F CH3 CH3 Br 2437 OCH3 F CH3 CH3 F 2438 OCH3 F CH3 OCH3 H 2439 OCH3 F CH3 OCH3 OCH3 2440 OCH3 F CH3 OCH3 ci 2441 OCH3 F CH3 OCH3 Br 2442 OCH3 F CH3 OCH3 F 2443 OCH3 F CH3 ci H 2444 OCH3 F CH3 ci OCH3 2445 OCH3 F CH3 C1 Cl 2446 OCH3 F CH3 Ci Br 2447 OCH3 F CH3 Cl F Compound R2a R2b R2c Rza R2e No. 2448 OCH3 F CH3 Br H 2449 OCH3 F CH3 Br OCH3 2450 OCH3 F CH3 Br C1 2451 OCH3 F CH3 Br Br 2452 OCH3 F CH3 Br F 2453 OCH3 F CH3 F H 2454 OCH3 F CH3 F OCH3 2455 OCH3 F CH3 F Ci 2456 OCH3 F CH3 F Br 2457 OCH3 F CH3 F F 2458 OCH3 F OCH3 H H 2459 OCH3 F OCH3 H CH3 2460 OCH3 F OCH3 H OCH3 2461 OCH3 F OCH3 H ci 2462 OCH3 F OCH3 H Br 2463 OCH3 F OCH3 H F 2464 OCH3 F OCH3 CH3 H 2465 OCH3 F OCH3 CH3 CH3 2466 OCH3 F OCH3 CH3 ci 2467 OCH3 F OCH3 CH3 Br 2468 OCH3 F OCH3 CH3 F 2469 OCH3 F OCH3 OCH3 H 2470 OCH3 F OCH3 OCH3 CH3 2471 OCH3 F OCH3 OCH3 OCH 2472 OCH3 F OCH3 OCH3 Ci 2473 OCH3 F OCH3 OCH3 Br 2474 OCH3 F OCH3 OCH3 F 2475 OCH3 F OCH3 ci H 2476 OCH3 F OCH3 Cl CH3 2477 OCH3 F OCH3 ci Ci 2478 OCH3 F OCH3 ci Br 2479 OCH3 F OCH3 ci F 2480 OCH3 F OCH3 Br H 2481 OCH3 F OCH3 Br CH3 2482 OCH3 F OCH3 Br Ci 2483 OCH3 F OCH3 Br Br 2484 OCH3 F OCH3 Br F 2485 OCH3 F OCH3 F H 2486 OCH3 F OCH3 F CH3 2487 OCH3 F OCH3 F OCH3 F Compound R2a R2b R2c R2d R2e No. 2488 OCH3 F OCH3 F Br 2489 OCH3 F OCH3 F F 2490 OCH3 F Cl H H 2491 OCH3 F Ci H CH3 2492 OCH3 F Ci H OCH3 2493 OCH3 F Ci H ci 2494 OCH3 F C1 H Br 2495 OCH3 F ci H F 2496 OCH3 F Ci CH3 H 2497 OCH3 F C1 CH3 CH3 2498 OCH3 F Ci CH3 OCH3 2499 OCH3 F ci CH3 Br 2500. OCH3 F ci CH3 F 2501 OCH3 F ci OCH3 H 2502 OCH3 F C1 OCH3 CH3 2503 OCH3 F ci OCH3 OCH3 2504 OCH3 F Cl-OCH3 Br 2505 OCH3 F C 1 OCH3 F 2506 OCH3 F ci ci H 2507 OCH3 F ci Ci CH3 2, 508 OCH3 F C1 C1 OCH 2509 OCH3 F Ci Cl-Cl 2510 OCH3 F Cl Ci Br 2511 OCH3 F Ci Ci F 2512 OCH3 F ci Br H 2513 OCH3 F ci Br CH3 2514 OCH3 F ci Br OCH3 2515 OCH3 F ci Br Br 2516 OCH3 F Ci F H 2517 OCH3 F ci F CH3 2518 OCH3 F ci F OCH3 2519 OCH3 F Ci F Br 2520 OCH3 F Ci F F 2521 OCH3 F Br H H 2522 OCH3 F Br H CH3 2523 OCH3 F Br H OCH3 2524 OCH3 F Br H Ci 2525 OCH3 F Br H. Br 2526 OCH3 F Br H F 2527 OCH3 F Br CH3 H Compound R2a R2b R2c R2d R2e No. 2528 OCH3 F Br CH3 CH3 2529 OCH3 F Br CH3 OCH3 2530 OCH3 F Br CH3 Ci 2531 OCH3 F Br CH3 F 2532 OCH3 F Br OCH3 H 2533 OCH3 F Br OCH3 CH3 2534 OCH3 F Br OCH3 OCH3 2535 OCH3 F Br OCH3 ci 2536 OCH3 F Br OCH3 F 2537 OCH3 F Br ci H 2538 OCH3 F Br ci CH3 2539 OCH3 F Br C1 OCH 2540 OCH3 F Br ci Ci 2541 OCH3 F Br ci F 2542 OCH3 F Br Br H 2543 OCH3 F Br Br CH3 2544 OCH3 F Br Br OCH3 2545 OCH3 F Br Br Ci 2546 OCH3 F Br Br Br 2547 OCH3 F Br Br F 2548 OCH3 F Br F H 2549 OCH3 F Br F CH3 2550 OCH3 F Br F OCH3 2551 OCH3 F Br F ci 2552 OCH3 F Br F F 2553 OCH3 F F H H 2554 OCH3 F F H CH3 2555 OCH3 F F H OCH3 2556 OCH3 F F H Ci 2557 OCH3 F F H Br 2558 OCH3 F F H F 2559 OCH3 F F CH3 H 2560 OCH3 F F CH3 CH3s 2561 OCH3 F F CH3 OCH3 2562 OCH3 F F CH3 Ci 2563 OCH3 F F CH3 Br 2564 OCH3 F F OCH3 H 2565 OCH3 F F OCH3 CH3 2566 OCH3 F F OCH3 OCH3 2567 OCH3 F F OCH3 Cl Compound R2a R2b R2c R2d R2e No. 2568 OCH3 F F OCH3 Br 2569 OCH3 F F Cl H 2570 OCH3 F F ci CH3 2571 OCH3 F F ci OCH3 2572 OCH3 F F Ci ci 2573 OCH3 F F ci Br 2574 OCH3 F F Br H 2575 OCH3 F F Br CH3 2576 OCH3 F F Br OCH3 2577 OCH3 F F Br Cl 2578 OCH3 F F Br Br 2579 OCH3 F F F H 2580 OCH3 F F F CH3 2581 OCH3 F F F OCH3 2582 OCH3 F F F Cl 2583 OCH3 F F F Br 2584 OCH3 F F F F 2585 ci CH3 CH3 H H 2586 C1 CH3 CH3 CH3 H Cl CH3 CH3 OCH3 H 2588 C1 CH3 CH3 C1 H 2589 cri CH3 CH3 Br H 2590 cri CH3 CH3 F H 2591 Cl CH CH3 H CH3 2592 C 1 CH3 CH3 CH3 CH3 2593 cri CH3 CH3 H OCH3 2594 C1 CH3 CH3 CH3 OCH3 2595 C1 CH3 CH3 OCH3 OCH3 2596 C 1 CH3 CH3 Cl OCH3 2597 ci CH3 CH3 Br OCH3 2598 ci CH3 CH3 F OCH3 2599 C1 CH3 CH3 C1 2600 Cl CH3 CH3 CH3 ci 2601 ci CH3 CH3 OCH3 ci 2602 C1 CH3 CH3 Cl Cl 2603 Cl CH3 CH3 Br ci 2604 C1 CH3 CH3 C1 2605 C1 CH3 CH3 H Br 2606 C1 CH3 CH3 CH3 Br 2607 ci CH3 CH3 OCH3 Br Compound R2a R2b Rac R2d R2e No. 2608 d CH3 CH3 ci Br 2 6 0 9 C1 CH3 CH3 Br Br 2610 C1 CH3 CH3 F Br 2611 C 1 CH3 CH3 H F 2612 ci CH3 CH3 CH3 F 2613 ci CH3 CH3 OCH3 F 2614 C1 CH3 CH3 ci F 2615 ci CH3 CH3 Br F 2616 ci CH3 CH3 F F 2617 C1 CH3 OCH3 H H 2618 ci CH3 OCH3 CH3 H 2619 ci CH3 OCH3 OCH3 H 2620 ci CH3 OCH3 ci H 2621 C1 CH3 OCH3 Br H 2622 C1 CH3 OCH3 F H 2623 ci CH3 OCH3 H CH3 2624 C1 CH3 OCH3 CH3 CH3 2625 ci CH3 OCH3 OCH3 CH3 2626 ci CH3 OCH3 ci CH3 2627 C 1 CH3 OCH3 Br CH3 2628 ci CH3 OCH3 F CH3 2629 ci CH3 OCH3 H OCH3 2630 ci CH3 OCH3 OCH3 OCH3 2631 ci CH3 OCH3 H Ci 2632 C1 CH3 OCH3 CH3 C1 2633 ci CH3 OCH3 OCH3 ci 2634 ci CH3 OCH3 Cl Ci 2635 ci CH3 OCH3 Br ci 2636 C 1 CH3 OCH3 F ci 2637 cri CH3 OCH3 H Br 2638 C1 CH3 OCH3 CH3 Br 2639 C1 CH3 OCH3 OCH3 Br 2640 ci CH3 OCH3 Ci Br 2641 ci CH3 OCH3 Br Br 2642 C1 CH3 OCH3 F Br 2643 ci CH3 OCH3 H F 2644 C1 CH3 OCH3 CH3 F 2645 ci CH3 OCH3 OCH3 F 2646 C1 CH3 OCH3 Ci F 2647 ci CH3 OCH3 Br F Compound R2a RZb R2c R2d R2e No. 2648 ci CH3 OCH3 F F 2649 ci CH3 ci H H 2650 C1 CH3 C1 CH3 H 2651 C1 CH3 ci OCH3 H 2652 ci CH3 Ci Cl H 2653 ci CH3 Cl Br H 2654 ci CH3 ci F H 2655 ci CHs Cl H CH3 2656 C 1 CH3 ci CH3 CH3 2 6 5 7 Cl CH3 Ci OCH3 CH3 2658 ci CH3 ci ci CH3 2 65 9 CI CH3 ci Br CH3 2660 ci CH3 ci F CH3 2661 Cl CH3 ci H OCH3 2662 C1 CH3 ci CH3 OCH3 2663 ci CH3 ci OCH3 OCH3 2664 ci CH3 Ci ci OCH3 2665 ci CH3 ci Br OCH3 2666 d CH3 ci F OCH3 2667l CH3 Cl H ci 2668 ci CH3 Ci ci ci 2669 ci CH3 Ci H Br 2670 Ci CH3 Cl CH3 Br 2671 ci CH3 ci OCH3 Br 2672 C1 CH3 C1 C1 Br 2673 ci CH3 Ci Br Br 2674 ci CH3 ci F Br 2675 ci CH3 ci H F 2676 ci CH3 C1 CH3 F 2677 C1 CH3 C1 OCH3 F 2678 C1 CH3 C1 C1 F 2679 ci CH3 ci F F 2680 ci CH3 Br H H 2681 ci CH3 Br CH3 H 2682 ci CH3 Br OCH3 H 2683 ci CH3 Br Ci H 2684 ci CH3 Br Br H 2685 ci CH3 Br F H 2686 C1 CH3 Br H CH3 2687 C1 CH3 Br CH3 CH3 Compound Raa R2b R2c R2d R2e No. 2688 ci CH3 Br OCH3 CH3 2689 ci CH3 Br Cl CH3 2690 C1 CH3 Br Br CH3 2691 ci CH3 Br F CH3 2692 ci CH3 Br H OCH3 2693 Cl CH3 Br CH3 OCH3 2694 ci CH3 Br OCH3 OCH3 2695 C1 CH3 Br ci OCH3 2696 d CH3 Br Br OCH3 2697 C 1 CH3 | Br F OCH3 2698 ci CH3 Br H Ci 2699 C1 CH3 Br CH3 Cl 2700 C1 CH3 Br OCH3 Ci 2701 ci CH3 Br ci Ci 2702 ci CH3 Br Br ci 2703 C1 CH3 Br F Cl 2704 ci CH3 Br H Br 2705 ci CH3 Br Br Br 2706 ci CH3 Br H F 2707 cri CH3 Br CH3 F 2708 d cHg Br OCH3 F 2709 C1 CH3 Br Ci F 2710 ci CH3 Br Br F 2711 ci CH3 Br F F 2712 ci CH3 F H H 2713 ci CH3 F CH3 H 2714 Cl CH3 F OCH3 H 2715 ci CH3 F Cl H 2716 ci CH3 F Br H 2717 ci CH3 F F H 2718 ci CH3 F H CH3 2719 ci CH3 F CH3 CH3 2720 C1 CH3 F OCH3 CH3 2721 ci CH3 F ci CH3 2722 ci CH3 F Br CH3 2723 C 1 CH3 F F CH3 2724 Cl CH3 F H OCH3 2725 ci CH3 F CH3 OCH3 2726 ci CH3 F OCH3 OCH3 2727 ci CH3 F C1 OCH Compound 23 zb p2c zd 2e No. 2728 C1 CH3 F Br OCH3 2729 C 1 CH3 F F OCH3 2730 Cl CH3 F H CI 2731 ci CH3 F CH3 Cl 2732 C1 CH3 F OCH3 Cl 2733 ci CH3 F Cl ci 2734 ci CH3 F Br ci 2735 ci CH3 F F Cl 2736 C1 CH3 F H Br 2 7 3 7 C 1 CH3 F CH3 Br 2738 ci CH3 F OCH3 Br 2739 ci CH3 F ci Br 2740 ci CH3 F Br Br 2741 ci CH3 F F Br 2742 ci CH3 F H F 2743 ci CH3 F F F 2744 ci OCH3 CH3 H H 2745 ci OCH3 CH3 H CH3 2746 ci OCH3 CH3 H OCH3 2747 ci OCH3 CH3 H ci 2748 ci OCH3 CH3 H Br 2749 ci OCH3 CH3 H F 2750 Cl OCH3 CH3 CH3 H 2751 ci OCH3 CH3 CH3 CH3 2752 ci OCH3 CH3 CH3 OCH3 2753 C1 OCH3 CH3 CH3 ci 2754 C1 OCH3 CH3 CH3 Br 2755 C1 OCH3 CH3 CH3 F 2756 ci OCH3 CH3 OCH3 H 2757 ci OCH3 CH3 OCH3 OCH3 2758 ci OCH3 CH3 OCH3 Cl 2759 ci OCH3 CH3 OCH3 Br 2760 ci OCH3 CH3 OCH3 F 2761 ci OCH3 CH3 ci H 2762 ci OCH3 CH3 Cl OCH3 2763 ci OCH3 CH3 Cl Cl 2764 ci OCH3 CH3 ci Br 2765 ci OCH3 CH3 CI F 2766 C1 OCH3 CH3 Br H 2767 C1 OCH3 CH3 Br OCH Compound Rza R2b R2 R2d R2e No. 2768 cl OCH3 CH3 Br ci 2769 ci OCH3 CH3 Br Br 2770 C1 OCH3 CH3 Br F 2771 ci OCH3 CH3 F H 2772 ci OCH3 CH3 F OCH3 2773 ci OCH3 CH3 F ci 2774 C 1 OCH3 CH3 F Br 2775 Cl OCH3 CH3 F F 2776 ci OCH3 OCH3 H H 2777 ci OCH3 OCH3 H CH3 2778 ci OCH3 OCH3 H OCH3 2779 ci OCH3 OCH3 H Cl 2780 cl OCH3 OCH3 H Br 2781 ci OCH3 OCH3 H F 2782 ci OCH3 OCH3 CH3 H 2783 ci OCH3 OCH3 CH3 CH3 2784 ci OCH3 OCH3 CH3 Ci 2785 ci OCH3 OCH3 CH3 Br 2786 ci OCH3 OCH3 CH3 F 2787 ci OCH3 OCH3 OCH3 H 2788 ci OCH3 OCH3 OCH3 CH3 2789 ci OCH3 OCH3 OCH3 OCH3 C1 OCH3 OCH3 OCH3 Cl 2791 cl OCH3 OCH3 OCH3 Br 2792 C1 OCH3 OCH3 OCH3 F 2793 ci OCH3 OCH3 Cl H 2794 ci OCH3 OCH3 ci CH3 2795 ci OCH3 OCH3 Cl Cl 2796 ci OCH3 OCH3 ci Br 2797 ci OCH3 OCH3 ci F 2798 ci OCH3 OCH3 Br H 2799 ci OCH3 OCH3 Br CH3 2800 ci OCH3 OCH3 Br Ci 2801 ci OCH3 OCH3 Br Br 2802 ci OCH3 OCH3 Br F 2803 ci OCH3 OCH3 F H 2804 ci OCH3 OCH3 F CH3 2805 ci OCH3 OCH3 F Cl 2806 ci OCH3 OCH3 F Br 2807 ci OCH3 OCH3 F F N °-R 2 a R 2 b R 2 c R 2 d R 2 e Compound R 2a R2b R 2c R2d R2e No. C1 OCH3 Cl H H 2809 ci OCH3 ci H CH3 2810 ci OCH3 Cl H OCH3 2811 ci OCH3 ci H ci 2812 ci OCH3 ci H Br 2813 ci OCH3 Ci H F 2814 ci OCH3 ci CH3 H 2815 ci OCH3 ci CH3 CH3 2816 ci OCH3 ci CH3 OCH3 2817 ci OCH3 Ci CH3 Br Cl OCH3 Cl CH3 F 2819 ci OCH3 ci OCH3 H 2820 ci OCH3 Ci OCH3 CH3 2821 ci OCH3 ci OCH3 OCH3 2822 C1 OCH3 C1 OCH3 Br 2823 C1 OCH3 C1 OCH3 F 2824 ci OCH3 ci ci H 2825 C1 OCH3 Cl Ci CH3 2826 ci OCH3 Cl Ci OCH3 2827 ci OCH3 Ci Ci C1 2828 ci OCH3 ci ci Br 2829 ci OCH3 Cl Cl F 2830 ci OCH3 Cl Br H 2831 ci OCH3 Cl Br CH3 2832 ci OCH3 Cl Br OCH3 2833 ci OCH3 ci Br Br 2834 ci OCH3 Ci F H 2835 ci OCH3 ci F CH3 2836 Cl OCH3 Cl F OCH3 2837 ci OCH3 Cl F Br 2838 ci OCH3 ci F F 2839 ci OCH3 Br H H 2840 C1 OCH3 Br H CH3 2841 ci OCH3 Br H OCH3 2842 ci OCH3 Br H Ci 2843 ci OCH3 Br H Br 2844 ci OCH3 Br H F 2845 C1 OCH3 Br CH3 H 2846 C1 OCH3 Br CH3 CH3 2847 ci OCH3 Br CH3 OCH3 Compound Rza R2b R2c R2d R2e No. 2848 C1 OCH3 Br CH3 Ci 2849 cl OCH3 Br CH3 F 2850 C1 OCH3 Br OCH3 H 2851 cl OCH3 Br OCH3 CH3 2852 cl OCH3 Br OCH3 OCH3 2853 C1 OCH3 Br OCH3 ci 2854 C1 OCH3 Br OCH3 F 2855 ci OCH3 Br Ci H 2856 C1 OCH3 Br Ci CH3 Cl OCH3 Br Ci OCH3 2858 C1 OCH3 Br ci ci 2859 cl OCH3 Br Cl F 2860 ci OCH3 Br Br H 2861 cl OCH3 Br Br CH3 2862 C1 OCH3 Br Br OCH3 2863 cl OCH3 Br Br Ci 2864 cl OCH3 Br Br Br 2865 cl OCH3 Br Br F 2866 cl OCH3 Br F H 2867 C1 OCH3 Br F CH3 2868 cl OCH3 Br F OCH3 2869 cl OCH3 Br F ci 2870 cl OCH3 Br F F 2871 cl OCH3 F H H 2872 C1 OCH3 F H CH3 2873 C1 OCH3 | F H OCH3 2874 ci OCH3 F H Cl 2875 Cl OCH3 F H Br 2876 C1 OCH3 F H F 2877 Cl OCH3 F CH3 H 2878 cl. OCH3 F CH3 CH3 2879 C1 OCH3 F CH3 OCH3 2880 C1 OCH3 F CH3 Ci 2881 cl OCH3 F CH3 Br 2882 C1 OCH3 F OCH3 H 2883 cl OCH3 F OCH3 CH3 2884 ci OCH3 F OCH3 OCH3 2885 cl OCH3 F OCH3 Ci 2886 cl OCH3 F OCH3 Br 2887 C1 OCH3 F ci H Compound Rza R2b R2c R2d R2e No. 2888 C1 OCH3 F ci CH3 2889 ci OCH3 F Ci OCH3 2890 ci OCH3 F Cl ci 2891 ci OCH3 F ci Br 2892 ci OCH3 F Br H 2893 ci OCH3 F Br CH3 2894 ci OCH3 F Br OCH3 2895 ci OCH3 F Br Ci 2896 ci OCH3 F Br Br 2897 Cl OCH3 F F H 2898 ci OCH3 F F CH3 2899 ci OCH3 F F OCH3 2900 ci OCH3 F F ci 2901 ci OCH3 F F Br 2902 ci OCH3 F F F 2903 ci ci CH3 H H 2904 ci Cl CH3 H CH3 2905 ci Cl CH3 H OCH3 2906 C1 C1 CH3 H Ci 2907 ci Ci CH3 H Br 2908 Cl ci CH3 H F 2909 C1 C1 CH3 CH3 H 2910 ci ci CH3 CH3 CH3 2911 ci Cl CH3 CH3 OCH3 2912 ci Cl CH3 CH3 Cl 2913 Ci Cl CH3 CH3 Br 2914 C1 Cl CH3 CH3 F 2915 ci Cl CH3 OCH3 H 2916 ci Ci CH3 OCH3 OCH3 2917 C1 C1 CH3 OCH3 Cl 2918 ci Cl CH3 OCH3 Br 2919 ci Cl CH3 OCH3 F 2920 Cl Cl CH3 ci H 2921 ci Cl CH3 Cl OCH3 2922 ci ci CH3 ci Cl 2923 Ci Ci CH3 ci Br 2924 Ci ci CH3 Cl F 2925 ci ci CH3 Br H 2926 ci ci CH3 Br OCH3 2927 ci C1 CH3 Br Cl Compound No. 2928 ClCH3Br Br 2929 Cl Cl CH3 Br F 2930 ci ci CH3 F H 293 Cl Cl CHB F OC0 2932 ci C1 CH3 F C1 2933 ci Ci CH3 F Br 2934 ci Ci CH3 F F 2935 ci cl OCH3 H H 2936 ci Cl OCH3 H CH3 2937 ci Ci OCH3 H OCH3 2938 ci Ci OCH3 H C1 2939 ci ci OCH3 H Br 2940 ci Ci OCH3 H F 2941 ci Cl OCH3 CH3 H 2942 C1 Cl OCH3 CH3 CH3 2943 ci Cl OCH3 CH3 ci 2944 ci Ci OCH3 CH3 Br 2945 ci ci OCH3 CH3 F 2946 ci ci OCH3 OCH3 H 2947 C1 C1 OCH3 OCH3 CH3 2948 C1 ci OCH3 OCH3 OCH3 2949 ci Cl OCH3 OCH3 Cl 2950 ci Cl OCH3 OCH3 Br 2951 ci Cl OCH3 OCH3 F 2952 ci Cl OCH3 Cl H 2953 C l C l OCH3 Cl CH3 2954 ci Cl OCH3 Cl ci 2955 ci Cl OCH3 ci Br 2956 ci Cl OCH3 Cl F 2957 ci Cl OCH3 Br H 2958 ci Cl OCH3 Br CH3 2959 ci ci OCH3 Br Ci 2960 Cl Ci OCH3 Br Br 2961 ci ci OCH3 Br F 2962 C1 C1 OCH3 F H 2963 ci Cl OCH3 F CH3 2964 ci Cl OCHs F Cl 2965 ci Ci OCH3 F Br 2966 ci Ci OCH3 F F 2967 ci C1 Cl H H Compound Rza R2b Rzc 2d R2e No. 2968 ci Cl ci H CH3 2969 ci Ci Ci H OCH3 2970 ci ci ci H ci 2971 ci ci Ci H Br 2972 C1 Cl Cl H F 2973 ci Ci ci CH3 H 2974 ci ci C1 CH3 CH3 2975 ci ci Ci CH3 OCH3 2976 ci ci ci CH3 Br 2977 ci ci Ci CH3 F 2978 | C1 C1 C1 OCH3 H 2979 C1 C1 C1 OCH3 CH3 2980 ci ci ci OCH3 OCH3 2981 ci Ci Ci OCH3 Br 2982 C1 C1 C1 OCH3 F 2983 C1 Cl Cl Cl H 2984 C1 C1 C1 C1 CH3 2985 ci Ci ci ci OCH3 2986 ci Ci Ci ci ci 2987 ci Cl C1 C1 Br 2988 ci Cl Cl Cl F 2989 ci ci ci Br H 2990 ci ci ci Br CH3 2991 ci ci ci Br OCH3 2992 ci Cl Cl Br Br 2993 Cl Cl C1 F 2994 ci Ci Ci F CH3 2995 ci Ci ci F OCH3 2996 ci Ci Ci F Br 2997 ci ci ci F F 2998 ci ci Br H H 2999 ci ci Br H CH3 3000 ci Ci Br H OCH3 3001 ci Ci Br H Cl 3002 ci ci Br H Br 3003 ci ci Br H F 3004 ci ci Br CH3 H 3005 ci Cl Br CH3 CH3 3006 ci Cl Br CH3 OCH3 3007 ci Cl Br CH3 Cl Compound Rza R2b R2c R2d R2e No. 3008 ci ci Br CH3 F 3009 ci Ci Br OCH3 H 3010 C1 C1 Br OCH3 CH3 3011 ci Cl Br OCH3 OCH3 3012 Cl Cl Br OCH3 C1 3. 013 ci ci Br OCH3 F 3014 ci Ci Br Ci H 3015 ci Ci Br ci CH3 3016 ci ci Br Ci OCH3 3017 ci ci Br Ci ci 3018 ci Ci Br ci F 3019 ci ci Br Br H 3020 ci ci Br Br CH3 3021 ci Ci Br Br OCH3 3022 ci Ci Br Br ci 3023 ci ci Br Br Br 3024 ci ci Br Br F 3025Cl Cl Br F H 3026 ci Cl Br F CH3 3027 ci Cl Br F OCH3 3028 Cl Cl Br F ci 3029 ci Ci Br F F 3030 ci ci F H H 3031 ci ci F H CH3 3032Cl Cl F H OCH3 3033 Cl C1 F H Cl 3034 ci Cl F H Br 3035 ci Cl F H F 3036 ci Cl F CH3 H 3037 Cl Cl F CH3 CH3 3038 C1 C1 F CH3 OCH 3039 ci ci F CH3 Ci 3040 ci ci F CH3 Br 3041 ci Ci F OCH3 H 3042 ci Cl F OCH3 CH3 3043 ci Ci F OCH3 OCH3 3044 ci Ci F OCH3 Ci 3045 ci ci F OCH3 Br 3046 ci ci F Ci H 3047 ci Ci F Ci CH3 N O o R 2 a R 2 b R 2 c R 2 d R 2 e Compound RZa Rzb Rz Rza Rze No. 3048 cl cl F Cl OCH3 3049 ci Ci F Cl C1 3050 Cl C1 F Cl Br 3051 ci Ci F Br H 3052 ci ci F Br CH3 3053 cl Ci F Br OCH3 3054 C1 C1 F Br Cl 3055 ci cl F Br Br 3056 C1 cl F F H 3057 cl Cl F'F CH3 3058 cl Ci F F OCH3 3059 ci Cl F F Cl 3060 ci ci F F Br 3061 ci C1 F F F 3062 ci Br CH3 H H 3063 cl Br CH3 CH3 3064 cl Br CH : 3 H OCH3 3065 ci Br CH3 H Ci 3066 cl Br CH3 H Br 3067 cl Br CH3 H F 3068 cl Br CH3 CH3 H 3069 C1 Br CH3 CH3 CH3 3070 cl Br CH3 CH3 OCH3 3071 cl Br CH3 CH3 Cl 3072 cl Br CH3 CH3 Br 3073 Cl Br CH3 CH3 F 3074 cl Br CH3 OCH3 H 3075 cl Br CH3 OCH3 OCH3 3076 cl Br CH3 OCH3 Ci 3077 cl Br CH3 OCH3 Br 3078 cl Br CH3 OCH3 F 3079 cl Br CH3 Ci H 3080 cl Br CH3 Cl OCH3 3081 cl Br CH3 Ci Ci 3082 cl Br CH3 ci Br 3083 ci Br CH3 Ci F 3084 cl Br CH3 Br H 3085 cl Br CH3 Br OCH3 3086 ci Br CH3 Br Ci 3087 cl Br CH3 Br Br Compound Rza R2b R2c R2d R2e No. 3088 ci Br CH3 Br F 3089 Cl Br CH3 F H 3090 Cl Br CH3 F OCH3 3091 ci Br CH3 F C1 3092 ci Br CH3 F Br 3093 cl Br CH3 F F 3094 ci Br OCH3 H H 3095 ci Br OCH3 H CH3 3096 ci Br OCH3 H OCH3 3097 cl Br OCH3 H Ci 3098 ci Br OCH3 H Br 3099 ci Br OCH3 H F 3100 ci Br OCH3 CH3 H 3101 ci Br OCH3 CH3 CH3 3102 ci Br OCH3 CH3 ci 3103 ci Br OCH3 CH3 Br 3104 ci Br OCH3 CH3 F 3105 ci Br OCH3 OCH3 H 3106 ci Br OCH3 OCH3 CH3 3107 ci Br OCH3 OCH3 OCH3 3108 ci Br OCH3 OCH3 ci 3109 ci Br OCH3 OCH3 Br 3110 ci Br OCH3 OCH3 F 3111 ci Br OCH3 ci H 3112 ci Br OCH3 ci CH3 3113 cl Br OCH3 Ci Ci 3114 cl Br OCH3 Ci Br 3115 ci Br OCH3 Ci F 3116 ci Br OCH3 Br H 3117 ci Br OCH3 Br CH3 3118 ci Br OCH3 Br Ci 3119 cl Br OCH3 Br Br 3120 cl Br OCH3 Br F 3121 ci Br OCH3 F H 3122 ci Br OCH3 CH3 3123 ci Br OCH3 F ci 3124 ci Br OCH3 F Br 3125 ci Br OCH3 F F 3126 ci Br ci H H 3127 ci Br ci H CH3 Compound RZa R2b R2c R2d R2e No. 3128 ci Br Cl H OCH 3129 ci Br Cl H Ci 3130 ci Br ci H Br 3131 ci Br ci H F 3132 ci Br Ci CH3 H 3133 Cl Br Cl CH3 CH3 3134 ci Br Cl CH3 OCH3 3135 ci Br Cl CH3 Br 3136 ci Br Cl CH3 F 3137 ci Br ci OCH3 H 3138 ci Br Cl OCH3 CH3 3139 ci Br Ci OCH3 OCH3 3140 ci Br Ci OCH3 Br 3141 ci Br Ci OCH3 F 3142 C1 Br C1 C1 H 3143 ci Br ci ci CH3 3144 ci Br Ci ci OCH3 3145 ci Br ci ci Ci 3146 ci Br Ci ci Br 3147 ci Br ci Ci F 3148 ci Br ci Br H 3149 ci Br Cl Br CH3 3150 ci Br Ci Br OCH3 3151 ci Br ci Br Br 3152 ci Br ci F H 3153 ci Br ci F CH3 3154 ci Br ci F OCH 3155 ci Br Ci F Br 3156 ci Br ci F F 3157 ci Br Br H H 3158 ci Br Br H CH3 3159 ci Br Br H OCH3 3160 ci Br Br H Ci 3161 ci Br Br H Br 3162 ci Br Br H F 3163 ci Br Br CH3 H 3164 ci Br Br CH3 CH3 3165 ci Br Br CH3 OCH3 3166 ci Br Br CH3 ci 3167 ci Br Br CH3 F Compound R 2a R 2b R2a R2d R2e No. 3168 ci Br Br OCH3 H 3169 ci Br Br OCH3 CH3 3170 ci Br Br OCH3 OCH3 3171 ci Br Br OCH3 Ci 3172 ci Br Br OCH3 F 3173 ci Br Br ci H 3174 ci Br Br ci CH3 3175 ci Br Br Ci OCH3 3176 ci Br Br Ci Ci 3177 ci Br Br ci F 3178 ci Br Br Br H 3179 ci Br Br Br CH3 3180 ci Br Br Br OCH3 3181 ci Br Br Br Ci 3182 ci Br Br Br Br 3183 ci Br Br Br F 3184 ci Br Br F H 3185 ci Br Br F CH3 3186 ci Br Br F OCH3 3187 ci Br Br F Ci 3188 ci Br Br F F 3189 ci Br F H H 3190 ci Br F H CH3 3191 ci Br F H OCH3 3192 Cl Br F H Cl 3193 ci Br F H Br 3194 ci Br F H F 3195 ci Br F CH3 H 3196 ci Br F CH3 CH3 3197 ci Br F CH3 OCH3 3198 Cl Br F CH3 Cl 3199 Cl Br F CH3 Br 3200 ci Br F OCH3 H 3201 Cl Br F OCH3 CH3 3202 Cl Br F OCH3 OCH3 3203 Cl Br F OCH3 Ci 3204 ci Br F OCH3 Br 3205 C1 Br F Cl H 3206 ci Br F ci CH3 3207 ci Br F C1 OCH3 Compound R2a R2b R2c R2d R2e No. 3208 ci Br F Cl Ci 3209 Cl Br F ci Br 3210 Ci Br F Br H 3211 Ci Br F Br CH3 3212 Cl Br F Br OCH3 3213 Cl Br F Br Ci 3214 ci Br F Br Br 3215 ci Br F F H 3216 C1 Br F F CH3 3217 C1 Br F F OCH3 3218 ci Br F F ci 3219 Ci Br F F Br 3220 Cl Br F F F 3221 ci F CH3 H H 3222 C1 F CH3 H CH3 3223 Cl F CH3 H OCH3 3224 ci F CH3 H ci 3225 ci F CH3 H Br 3226 ci F CH3 H F 3227 C1 F CH3 CH3 H 3228 Cl F CH3 CH3 CH3 3229 Cl F CH3 CH3 OCH3 3230 Cl F CH3 CH3 Cl 3231 Cl F CH3 CH3 Br 3232 Cl F CH3 CH3 F 3233 Cl F CH3 OCH3 H 3234 Cl F CH3 OCH3 OCH3 3235 Cl F CH3 OCH3 Cl 3236 Cl F CH3 OCH3 Br 3237 Cl F CH3 OCH3 F 3238 Cl F CH3 Cl H 3239 Cl F CH3 ci OCH3 3240 ci F CH3 Ci Ci 3241 Ci F CH3 Cl Br 3242 Ci F CH3 ci F 3243 Ci F CH3 Br H 3244 Cl F CH3 Br OCH3 3245 Ci F CH3 Br Cl 3246 Ci F CH3 Br Br 3247 ci F CH3 Br F Compound Ra R2b R2c R2d R2e No. 3248 ci F CH3 F H 3249 ci F CH3 F OCH3 3250 ci F CH3 F ci 3251 ci F CH3 F Br 3252 ci F CH3 F F 3253 ci F OCH3 H H 3254 ci F OCH3 H CH3 3255 ci F OCH3 H OCH3 3256 ci F OCH3 H ci 3257 ci F OCH3 H Br 3258 ci F OCH3 H F 3259 ci F OCH3 CH3 H 3260 ci F OCH3 CH3 CH3 3261 ci F OCH3 CH3 Ci 3262 ci F OCH3 CH3 Br 3263 ci F OCH3 CH3 F 3264 ci F OCH3 OCH3 H 3265 ci F OCH3 OCH3 CH3 3266 ci F OCH3 OCH3 OCH3 3267 ci F OCH3 OCH3 Cl 3268 ci F OCH3 OCH3 Br 3269 ci F OCH3 OCH3 F 3270 ci F OCH3 ci H 3271 ci F OCH3 C1 CH3 3272 C1 F OCH3 ci ci 3273 ci F OCH3 ci Br 3274 ci F OCH3 Ci F 3275 ci F OCH3 Br H Cl F OCH3 Br CH3 3277 ci F OCH3 Br Ci 3278 ci F OCH3 Br Br 3279 ci F OCH3 Br F 3280 ci F OCH3 F H 3281 ci F OCH3 F CH3 3282 ci F OCH3 F Ci 3283 ci F OCH3 F Br 3284 ci F OCH3 F F 3285 ci F Ci H H 3286 ci F Ci H CH3 3287 ci F ci H OCH3 Compound R2a R2b R2c R2d R2e No. 3288l F Cl H Ci 3289 ci F Cl H Br 3290 C1 F C1 H F 3291 ci F Cl CH3 H 3292 ci F ci CH3 CH3 3293 ci F ci CH3 OCH3 3294 C1 F Ci CH3 Br 3295 C1 F ci CH3 F 3296 ci F ci OCH3 H 3297 ci F C1. OCH3 CH3 3298 ci F ci OCH : 3 OCH3 3299 ci F Ci OCH3 Br 3300 ci F ci OCH3 F 3301 ci F ci ci H 3302 ci F Ci ci CH3 3303 ci F ci ci OCH3 3304 ci F ci ci ci 3305 ci F Cl Cl Br 3306 ci F Ci Ci F 3307 ci F ci Br H 3308 Cl F ci Br CH3 3309 ci F Ci Br OCH3 3310 ci F Ci Br Br 3311 ci F ci F H 3312 ci F ci F CH3 3313 ci F Cl F OCH3 3314 ci F Cl F Br 3315 ci F Cl F F 3316 ci F Br H H 3317 ci F Br H CH3 3318 ci F Br H OCH3 3319 ci F Br H Ci 3320 ci F Br H Br 3321 ci F Br H F 3322 ci F Br CH3 H 3323 ci F Br CH3 CH3 3324 ci F Br CH3 OCH3 3325 ci F Br CH3 Cl 3326 ci F Br CH3 F 3327 ci F Br OCH3 H Compound R2a R2b R2c R2d R2e No. 3328 ci F Br OCH3 CH3 3329 ci F Br OCH3 OCH3 3330 ci F Br OCH3 Cl 3331 ci F Br OCH3 F 3332 ci F Br Cl H 3333 ci F Br Cl CH3 3334 ci F Br Cl OCH3 3335 ci F Br Cl ci 3336 ci F Br Cl F 3337 ci F Br Br H 3338 ci F Br Br CH3 3339 ci F Br Br OCH3 3340 ci F Br Br ci 3341 ci F Br Br Br 3342 ci F Br Br F 3343 ci F Br F H 3344 ci F Br F CH3 3345 ci F Br F OCH3 3346 ci Br C1 3347 ci F Br F F 3348 ci F F H H 3349 ci F F H CH3 3350 ci F F H OCH3 3351 ci F F H Ci 3352 ci F F H Br 3353 ci F F H F 3354 ci F F CH3 H 3355 ci F F CH3 CH3 3356 ci F F CH3 OCH3 3357 ci F F CH3 ci 3358 C1 CH3 Br 3359 ci F F OCH3 H 3360 ci F F OCH3 CH3 3361 ci F F OCH3 OCH3 3362 ci F F OCH3 Cl 3363 ci F F OCH3 Br 3364 ci F F Ci H 3365 Cl F F Cl CH3 3366 ci F F ci OCH3 3367 ci F F Cl Cl Compound Rza R2b R2c R2d R2e No. 3368 ci F F Ci Br 3369 ci F F Br H 3370 ci F F Br CH3 3371 ci F F Br OCH3 3372 ci F F Br Cl 3373 ci F F Br Br 3374 ci F F F H 3375 cl F F F CH3 3376 ci F F F OCH3 3377 Cl F F F ci 3378 ci F F F Br 3379 ci F F F F 3380 Br CH3 CH3 H H 3381 Br CH3 CH3 CH3 H 3382 Br CH3 CH3 OCH3 H 3383 Br CH3 CH3 C1 3384 Br CH3 CH3 Br H 3385 Br CH3 CH3 F H 3386 Br CH3 CH3 H CH3 3387 Br CH3 CH3 CH3 CH3 3388 Br CH3 CH3 H OCH3 3389 Br CH3 CH3 CH3 OCH3 3390 Br CH3 CH3 OCH3 OCH3 3391 Br CH3 CH3 Ci OCH3 3392 Br CH3 CH3 Br OCH3 3393 Br CH3 CH3 F OCH3 3394 Br CH3 CH3 H Cl 3395 Br CH3 CH3 CH3 Cl 3396 Br CH3 CH3 OCH3 ci 3397 Br CH3 CH3 C1 Cl 3398 Br CH3 CH3 Br Cl 3399 Br CH3 CH3 F Cl 3400 Br CH3 CH3 H Br 3401 Br CH3 CH3 CH3 Br 3402 Br CH3 CH3 OCH3 Br 3403 Br CH3 CH3 Cl Br 3404 Br CH3 CH3 Br Br 3405 Br CH3 CH3 F Br 3406 Br CH3 CH3 H F 3407 Br CH3 CH3 CH3 F Compound R2a R2b R2c R2d R2e No. 3408 Br CH3 CH3 OCH3 F 3409 Br CH3 CH3 Cl F 3410 Br CH3 CH3 Br F 3411 Br CH3 CH3 F F 3412 Br CH3 OCH3 H H 3413 Br CH3 OCH3 CH3 H 3414 Br CH3 OCH3 OCH3 H 3415 Br CH3 OCH3 ci H 3416 Br CH3 OCH3 Br H 3417 Br CH3 OCH3 F H 3418 Br CH3 OCH3 CH3 3419 Br CH3 OCH3 CH3 CH3 3420 Br CH3 OCH3 OCH3 CH3 3421 Br CH3 OCH3 Ci CH3 3422 Br CH3 OCH3 Br CH3 3423 Br CH3 OCH3 F CH3 3424 Br CH3 OCH3 OCH 3425 Br CH3 OCH3 OCH3 OCH3 3426 Br CH3 OCH3 H Cl 3427 Br CH3 OCH3 CH3 Ci 3428 Br CH3 OCH3 OCH3 ci 3429 Br CH3 OCH3 ci ci 3430 Br CH3 OCH3 Br Ci 3431 Br CH3 OCH3 F ci 3432 Br CH3 OCH3 H Br 3433 Br CH3 OCH3 CH3 Br 3434 Br CH3 OCH3 OCH3 Br 3435 Br CH3 OCH3 ci Br 3436 Br CH3 OCH3 Br Br 3437 Br CH3 OCH3 F Br 3438 Br CH3 OCH3 H F 3439 Br CH3 OCH3 CH3 F 3440 Br CH3 OCH3 OCH3 F 3441 Br CH3 OCH3 ci F 3442 Br CH3 OCH3 Br F 3443 Br CH3 OCH3 F F 3444 Br CH3 ci H H 3445 Br CH3 ci CH3 H 3446 Br CH3 ci OCH3 H 3447 Br CH3 Cl ci H Compound Rza Rzb R2c R2d R2e No. 3448 Br CH3 Ci Br H 3449 Br CH3 Ci F H 3450 Br CH3 Ci H CH3 3451 Br CH3 ci CH3 CH3 3452 Br CH3 Ci OCH3 CH3 3453 Br CH3 Ci ci CH3 3454 Br CH3 Cl Br CH3 3455 Br CH3 Cl F CH3 3456 Br CH3 Ci H OCH3 3457 Br CH3 Cl CH3 OCH3 3458 Br CH3 Cl OCH3 OCH3 3459 Br CH3 ci Cl OCH3 3460 Br CH3 C1 Br OCH3 3461 Br CH3 ci F OCH3 3462 Br CH3 ci H Cl 3463 Br CH3 Cl Cl Cl 3464 Br CH3 Ci H Br 3465 Br CH3 ci CH3 Br 3466 Br CH3 ci OCH3 Br 3467 Br CH3 Ci ci Br 3468 Br CH3 ci Br Br 3469 Br CH3 ci F Br 3470 Br CH : 3 Cl H F 3471 Br CH3 Ci CH3 F 3472 Br CH3 ci OCH3 F 3473 Br CH3 ci ci F 3474 Br CH3 ci F F 3475 Br CH3 Br H H 3476 Br CH3 Br CH3 H 3477 Br CH3 Br OCH3 H 3478 Br CH3 Br ci H 3479 Br CH3 Br Br H 3480 Br CH3 Br F H 3481 Br CH3 Br H CH3 3482 Br CH3 Br CH3 CH3 3483 Br CH3 Br OCH3 CH3 3484 Br CH3 Br ci CH3 3485 Br CH3 Br Br CH3 3486 Br CH3 Br F CH3 3487 Br CH3 Br H OCH3 Compound R2a R2b R2c R2d R2e No. 3488 Br CH3 Br CH3 OCH3 3489 Br CH3 Br OCH3 OCH3 3490 Br CH3 Br Ci OCH3 3491 Br CH3 Br Br OCH3 3492 Br CH3 Br F OCH3 3493 Br CH3 Br H Ci 3494 Br CH3 Br CH3 Cl 3495 Br CH3 Br OCH3 Cl 3496 Br CH3 Br ci Ci 3497 Br CH3 Br Br ci 3498 Br CH3 Br F ci 3499 Br CH3 Br H Br 3500 Br CH3 Br Br Br 3501 Br CH3 Br H F 3502 Br CH3 Br CH3 F 3503 Br CH3 Br OCH3 F 3504 Br CH3 Br Ci F 3505 Br CH3 Br Br F 3506 Br CH3 Br F F 3507 Br CH3 F H H 3508 Br CH3 F CH3 H 3509 Br CH3 F OCH3 H 3510 Br CH3 F Cl H 3511 Br CH3 F Br H 3512 Br CH3 F F H 3513 Br CH3 F CH3 3514 Br CH3 F CH3 CH3 3515 Br CH3 F OCH3 CH3 3516 Br CH3 F Ci CH3 3517 Br CH3 F Br CH3 3518 Br CH3 F F CH3 3519 Br CH3 F H OCH3 3520 Br CH3 F CH3 OCH3 3521 Br CH3 F OCH3 OCH3 3522 Br CH3 F Ci OCH3 3523 Br CH3 F Br OCH3 3524 Br CH3 F F OCH3 3525 Br CH3 F H Ci 3526 Br CH3 F CH3 Ci 3527 Br N3 F OCHs Cl Compound R2a R2b R2c R2d R2e No. 3528 Br CH3 F ci Ci 3529 Br CH3 F Br Ci 3530 Br CH3 F F Ci 3531 Br CH3 F H Br 3532 Br CH3 F CH3 Br 3533 Br CH3 F OCH3 Br 3534 Br CH3 F ci Br 3535 Br CH3 F Br Br 3536 Br CH3 F F Br 3537 Br CH3 F H F 3538 Br CH3 F F F 3539 Br OCH3 CH3 H H 3540 Br OCH3 CH3 H CH3 3541 Br OCH3 CH3 H OCH3 3542 Br OCH3 CH3 H ci 3543 Br OCH3 CH3 H Br 3544 Br OCH3 CH3 H F 3545 Br OCH3 CH3 CH3 H 3546 Br OCH3 CH3 CH3 CH3 3547 Br OCH3 CH3 CH3 OCH3 3548 Br OCH3 CH3 CH3 C1 3549 Br OCH3 CH3 CH3 Br 3550 Br OCH3 CH3 CH3 F 3551 Br OCH3 CH3 OCH3 H 3552 Br OCH3 CH3 OCH3 OCH3 3553 Br OCH3 CH3 OCH3 Cl 3554 Br OCH3 CH3 OCH3 Br 3555 Br OCH3 CH3 OCH3 F 3556 Br OCH3 CH3 C1 H 3557 Br OCH3 CH3 ci OCH3 3558 Br OCH3 CH3 Ci ci 3559 Br OCH3 CH3 ci Br 3560 Br OCH3 CH3 Cl F 3561 Br OCH3 CH3 Br H 3562 Br OCH3 CH3 Br OCH3 3563 Br OCH3 CH3 Br Cl 3564 Br OCH3 CH3 Br Br 3565 Br OCH3 CH3 Br F 3566 Br OCH3 CH3 F H 3567 Br OCH3 CH3 F OCH3 Compound Rza R2b R2c R2d R2e No. 3S68 Br OCH3 CH3 F ci 3569 Br OCH3 CH3 F Br 3570 Br OCH3 CH3 F F 3571 Br OCH3 OCH3 H H 3572 Br OCH3 OCH3 H CH3 3573 Br OCH3 OCH3 H OCH3 3574 Br OCH3 OCH3 H 3575 Br OCH3 OCH3 H Br 3576 Br OCH3 OCH3 H F 3577 Br OCH3 OCH3 CH3 H 3578 Br OCH3 OCH3 CH3 CH3 3579 Br OCH3 OCH3 CH3 ci 3580 Br OCH3 OCH3 CH3 Br 3581 Br OCH3 OCH3 CH3 F 3582 Br OCH3 OCH3 OCH3 H 3583 Br OCH3 OCH3 OCH3 CH3 3584 Br OCH3 OCH3 OCH3 OCH3 3585 Br OCH3 OCH3 OCH3 ci 3586 Br OCH3 OCH3 OCH3 Br 3587 Br OCH3 OCH3 OCH3 F 3588 Br OCH3 OCH3 ci H 3589 Br OCH3 OCH3 ci CH3 3590 Br OCH3 OCH3 Cl ci 3591 Br OCH3 OCH3 Cl Br 3592 Br OCH3 OCH3 Cl F 3593 Br OCH3 OCH3 Br H 3594 Br OCH3 OCH3 Br CH3 3595 Br OCH3 OCH3 Br ci 3596 Br OCH3 OCH3 Br Br 3597 Br OCH3 OCH3 Br F 3598 Br OCH3 OCH3 F H 3599 Br OCH3 OCH3 F CH3 3600 Br OCH3 OCH3 F Ci 3601 Br OCH3 OCH3 F Br 3602 Br OCH3 OCH3 F F 3603 Br OCH3 ci H H 3604 Br OCH3 Cl CH3 3605 Br OCH3 C1 H OCH3 3606 Br OCH3 ci H Ci 3607 Br OCH3 ci H Br Compound R2a R2b R2c R2d R2e No. 3608 Br OCH3 ci H F 3609 Br OCH3 C1 CH3 H 3610 Br OCH3 ci CH3 CH3 3611 Br OCH3 ci CH3 OCH3 3612 Br OCH3 Ci CH3 Br 3613 Br OCH3 Ci CH3 F 3614 Br OCH3 Cl OCH3 H 3615 Br OCH3 ci OCH3 CH3 3616 Br OCH3 Cl OCH3 OCH3 3617 Br OCH3 ci OCH3 Br 3618 Br OCH3 Ci OCHs F 3619 Br OCH3 Ci ci H 3620 Br OCH3 ci ci CH3 3621 Br OCH3 ci Ci OCH3 3622 Br OCH3 Ci ci ci 3623 Br OCH3 Ci Ci Br 3624 Br OCH3 Cl ci F 3625 Br OCH3 ci Br H 3626 Br OCH3 ci Br CH3 3627 Br OCH3 ci Br OCH3 3628 Br OCH3 ci Br Br 3629 Br OCH3 Ci F H 3630 Br OCH3 Cl F CH3 3631 Br OCH3 Ci F OCH3 3632 Br OCH3 Ci F Br 3633 Br OCH3 ci F F 3634 Br OCH3 Br H H 3635 Br OCH3 Br H CH3 3636 Br OCH3 Br H OCH3 3637 Br OCH3 Br Cl 3638 Br OCH3 Br H Br 3639 Br OCH3 Br H F 3640 Br OCH3 Br CH3 H 3641 Br OCH3 Br CH3 CH3 3642 Br OCH3 Br CH3 OCH3 l 3643 Br OCH3 Br CH3 Cl 3644 Br OCH3 Br CH3 F 3645 Br OCH3 Br OCH3 H 3646 Br OCH3 Br OCH3 CH3 3647 Br OCH3 Br OCH3 OCH3 Compound R2a R2b R2c R2d R2e No. 3648 Br OCH3 Br OCH3 Ci 3649 Br OCH3 Br OCH3 F 3650 Br OCH3 Br Ci H 3651 Br OCH3 Br Ci CH3 3652 Br OCH3 Br ci OCH3 3653 Br OCH3 Br ci Ci 3654 Br OCH3 Br ci F 3655 Br OCH3 Br Br H 3656 Br OCH3 Br Br CH3 3657 Br OCH3 Br Br OCH3 3658 Br OCH3 Br Br ci 3659 Br OCH3 Br Br Br 3660 Br OCH3 Br Br F 3661 Br OCH3 Br F H 3662 Br OCH3 Br CH3 3663 Br OCH3 Br F OCH3 3664 Br OCH3 Br F ci 3665 Br OCH3 Br F F 3666 Br OCH3 F H H 3667 Br OCH3 F H CH3 3668 Br OCH3 F H OCH3 3669 Br OCH3 F H ci 3670 Br OCH3 F H Br 3671 Br OCH3 F H F 3672 Br OCH3 F CH3 H 3673 Br OCH3 F CH3 CH3 3674 Br OCH3 F CH3 OCH3 3675 Br OCH3 F CH3 ci 3676 Br OCH3 F CH3 Br 3677 Br OCH3 F OCH3 H 3678 Br OCH3 F OCH3 CH3 3679 Br OCH3 F OCH3 OCH3 3680 Br OCH3 F OCH3 C 1 3681 Br OCH3 F OCH3 Br 3682 Br OCH3 F ci H 3683 Br OCH3 F Ci CH3 3684 Br OCH3 F Ci OCH3 3685 Br OCH3 F ci Ci 3686 Br OCH3 F Ci Br 3687 Br OCH3 F Br H Compound R2a R2b R2c R2d R2e No. 3688 Br OCH3 F Br CH3 3689 Br OCH3 F Br OCH3 3690 Br OCH3 F Br Ci 3691 Br OCH3 F Br Br 3692 Br OCH3 F F H 3693 Br OCH3 F F CH3 3694 Br OCH3 F F OCH3 3695 Br OCH3 F F Ci 3696 Br OCH3 F F Br 3697 Br OCH3 F F F 3698 Br ci CH3 H H 3699 Br Cl CHg H CH3 3700 Br Ci CH3 H OCH3 3701 Br Ci CH3 H Ci 3702 Br C1 CH3 H Br 3703 Br Cl CH3 H F 3704 Br Ci CH3 CH3 H 3705 Br Ci CH3 CH3 CH3 3706 Br ci CH3 CH3 OCH3 3707 Br C1 CH3 CH3 C1 3708 Br ci CH3 CH3 Br 3709 Br C1 CH3 CH3 F 3710 Br ci CH3 OCH3 H 3711 Br ci CH3 OCH3 OCH3 3712 Br ci CH3 OCH3 C1 3713 Br Cl CH3 OCH3 Br 3714 Br Cl CH3 OCH3 F 3715 Br ci CH3 Ci H 3716 Br Ci CH3 ci OCH3 3717 Br ci CH3 C1 C1 3718 Br Ci CH3 ci Br 3719 Br ci CH3 ci F 3720 Br Ci CH3 Br H 3721 Br C1 CH3 Br OCH 3722 Br Ci CH3 Br Cl 3723 Br Ci CH3 Br Br 3724 Br Ci CH3 Br F 3725 Br C1 CH3 H 3726 Br ci CH3 F OCH3 3727 Br Cl CH3 F Cl Compound R2a R2b R2c R2d R2e No. 3728 Br Cl 0 F Br 3729 Br Cl CH3 F F 3730 Br ci OCH3 H H 3731 Br C1 OCH3 H CH3 3732 Br Ci OCH3 H OCH3 3733 Br Ci OCH3 H Ci 3734 Br ci OCH3 H Br 3735 Br ci OCH3 H F 3736 Br C1 OCH3 CH3 H 3737 Br C1 OCH3 CH3 CH3 3738 Br ci OCH3 CH3 ci 3739 Br C1 OCH3 CH3 Br 3740 Br ci OCH3 CH3 F 3741 Br Ci OCH3 OCH3 H 3742 Br C1 OCH3 OCH3 CH3 3743 Br ci OCH3 OCH3 OCH3 3744 Br Cl OCH3 OCH3 Cl 3745 Br Cl OCH3, OCH3 Br 3746 Br Cl OCH3 OCH3 F 3747 Br ci OCH3 Ci H 3748 Br Ci OCH3 ci CH3 3749 Br ci OCH3 ci Ci 3750 Br ci OCH3 Ci Br 3751 Br ci OCH3 Cl F 3752 Br ci OCH3 Br H 3753 Br ci OCH3 Br CH3 3754 Br ci OCH3 Br ci 3755 Br ci OCH3 Br Br 3756 Br Ci OCH3 Br F 3757 Br Cl OCH3 F H 3758 Br Ci OCH3 F CH3 3759 Br ci OCH3 F Ci 3760 Br Ci OCH3 F Br 3761 Br ci OCH3 F F 3762 Br Cl C1 H H 3763 Br Ci Ci H CH3 3764 Br Ci ci H OCH3 3765 Br Cl C1 H Ci 3766 Br ci Ci H Br 3767 Br ci ci H F Compound Rza Rzb R2c 2d R2e No. 3768 Br Ci Ci CH3 H 3769 Br ci ci CH3 CH3 3770 Br Ci ci CH3 OCH3 3771 Br Ci Ci CH3 Br Br C1 C1 CH3 F 3773 Br ci ci OCH3 H 3774 Br C1 C1 OCH3 CH3 3775 Br Ci Ci OCH3 OCH3 Br C1 Cl OCH3 Br 3777 Br ci ci OCH3 F 3778 Br Cl C1 Cl H 3779 Br ci ci ci CH3 3780 Br C1 C1 C1 OCH 3781 Br C1 C1 Cl C1 3782 Br Cl C1 Cl Br 3783 Br ci Ci ci F 3784 Br Ci ci Br H 3785 Br ci Ci Br CH3 Br Cl Cl Br OCH3 3787 Br ci ci Br Br 3788 Br C1 C1 F H 3789 Br ci ci F CH3 3790 Br ci ci F OCH3 3791 Br ci ci F Br 3792 Br ci ci F F 3793 Br C1 Br H H 3794 Br C1 Br H CH3 3795 Br ci Br H OCH3 3796 Br ci Br H C1 3797 Br C1 Br H Br 3798 Br C1 Br H F 3799 Br Cl Br CH3 H 3800 Br Cl Br CH3 CH3 3801 Br C1 Br CH3 OCH3 3802 Br Ci Br CH3 Ci 3803 Br ci Br CH3 F 3804 Br ci Br OCH3 H 3805 Br C1 Br OCH3 CH3 3806 Br C1 Br OCH3 OCH3 3807 Br C1 Br OCH3 C1 Compound R2a R2b Roc R2d R2e No. 3808 Br C1 Br OCH3 F 3809 Br ci Br ci H 3810 Br Ci Br Cl CH3 3811 Br Ci Br Ci OCH3 3812 Br Cl Br ci ci 3813 Br Ci Br Ci F 3814 Br Ci Br Br H 3815 Br ci Br Br CH3 3816 Br ci Br Br OCH3 3817 Br Ci Br Br ci 3818 Br ci Br Br Br 3819 Br Ci Br Br F 3820 Br ci Br F H 3821 Br ci Br F CH3 3822 Br Ci Br F OCH3 3823 Br Cl Br F Ci 3824 Br Ci Br F F 3825 Br ci F H H 3826 Br ci F H CH3 3827 Br Cl F H OCH3 3828 Br C1 F H ci 3829 Br ci F H Br 3830 Br Cl F H F 3831 Br ci F CH3 H 3832 Br ci F CH3 CH3 3833 Br C1 F CH3 OCHs 3834 Br ci F CH3 ci 3835 Br Ci F CH3 Br 3836 Br ci F OCH3 H 3837 Br Ci F OCH3 CH3 3838 Br ci F OCH3 OCH3 3839 Br C1 F OCH3 Ci 3840 Br Ci F OCH3 Br 3841 Br Ci F Cl H 3842 Br Ci F ci CH3 3843 Br ci F ci OCH3 3844 Br ci F ci Ci 3845 Br Ci F Cl Br 3846 Br ci F Br H 3847 Br Cl F Br CH3 Compound R 2a R 2b R 2c R2d R2e No. 3848 Br C1 F Br OCH3 3849 Br C1 F Br ci 3850 Br Ci F Br Br 3851 BY-Cl F F H 3852 Br Ci F F CH3 3853 Br Ci F F OCH3 3854 Br Ci F F Cl 3855 Br Cl F F Br 3856 Br Cl F F F 3857 Br Br CH3 H H 3858 Br Br CH3 H CH3 3859 Br Br CH3 H OCH3 3860 Br Br CH3 H Ci 3861 Br Br CH3 H Br 3862 Br Br CH3 H F 3863 Br Br CH3 CH3 H 3864 Br Br CH3 CH3 CH3 3865 Br Br CH3 CH3 OCH3 3866 Br Br CH3 CH3 C1 3867 Br Br CH3 CH3 Br 3868 Br Br CH3 CH3 F 3869 Br Br CH3 OCH3 H 3870 Br Br CH3 OCH3 OCH3 3871 Br Br CH3 OCH3 Ci 3872 Br Br CH3 OCH3 Br 3873 Br Br CH3 OCH3 F 3874 Br Br CH3 ci H 3875 Br Br CH3 Ci OCH3 3876 Br Br CH3 Cl C1 3877 Br Br CH3 ci Br 3878 Br Br CH3 ci F 3879 Br Br CH3 Br H 3880 Br Br CH3 Br OCH3 3881 Br Br CH3 Br Ci 3882 Br Br CH3 Br Br 3883 Br Br CH3 Br F 3884 Br Br CH3 F H 3885 Br Br CH3 F OCH3 3886 Br Br CH3 F Ci 3887 Br Br CH3 F Br Compound R R2b R2c R2d R2e No. 3888 Br Br CH3 F F 3889 Br Br OCH3 H H 3890 Br Br OCH3 H CH3 3891 Br Br OCH3 H OCH3 3892 Br Br OCH3 H Ci 3893 Br Br OCH3 H Br 3894 Br Br OCH3 H F 3895 Br Br OCH3 CH3 H 3896 Br Br OCH3 CH3 CH3 3897 Br Br OCH3 CH3 C1 3898 Br Br OCH3 CH3 Br 3899 Br Br OCH3 CH3 F 3900 Br Br OCH3 OCH3 H 3901 Br Br OCH3 OCH3 CH3 3902 Br Br OCH3 OCH3 OCH3 3903 Br Br OCH3 OCH3 ci 3904 Br Br OCH3 OCH3 Br 3905 Br Br OCH3 OCH3 F 3906 Br Br OCH3 ci H 3907 Br Br OCH3 Ci CH3 3908 Br Br OCH3 ci ci 3909 Br Br OCH3 Ci Br 3910 Br Br OCH3 ci F 3911 Br Br OCH3 Br H 3912 Br Br OCH3 Br CH3 3913 Br Br OCH3 Br ci 3914 Br Br OCH3 Br Br 3915 Br Br OCH3 Br F 3916 Br Br OCH3 F H 3917 Br Br OCH3 F CH3 3918 Br Br OCH3 F ci 3919 Br Br OCH3 F Br 3920 Br Br OCH3 F F 3921 Br Br Ci H H 3922 Br Br Ci H CH3 3923 Br Br ci H OCH3 3924 Br Br ci H C1 3925 Br Br ci H Br 3926 Br Br Ci H F 3927 Br Br Cl CH3 H Compound Rza Rzb Rzc Rzd R2e No. 3928 Br Br l C1 CH3 CH3 3929 Br Br ci CH3 OCH3 3930 Br Br ci CH3 Br 3931 Br Br Cl CH3 F 3932 Br Br ci OCH3 H 3933 Br Br Ci OCH3 CH3 3934 Br Br ci OCH3 OCH3 3935 Br Br ci OCH3 Br 3936 Br Br Ci OCH3 F 3937 Br Br ci Ci H 3938 Br Br Ci ci CH3 3939 Br Br Ci Ci OCH3 3940 Br Br Ci Ci Ci 3941 Br Br Ci ci Br 3942 Br Br ci Ci F 3943 Br Br C1 Br H 3944 Br Br ci Br CH3 3945 Br Br ci Br OCH3 3946 Br Br Ci Br Br 3947 Br Br ci F H 3948 Br Br Ci F CH3 3949 Br Br Ci F OCH3 3950 Br Br Ci F Br 3951 Br Br Ci F F 3952 Br Br Br H H 3953 Br Br Br H CH3 3954 Br Br Br H OCH3 3955 Br Br Br H ci 3956 Br Br Br H Br 3957 Br Br Br H F 3958 Br Br Br CH3 H 3959 Br Br Br CH3 CH3 3960 Br Br Br CH3 OCH3 3961 Br Br Br CH : 3 Cl 3962 Br Br Br CH3 F 3963 Br Br Br OCH3 H 3964 Br Br Br OCH3 CH3 3965 Br Br Br OCH3 OCH3 3966 Br Br Br OCH3 Ci 3967 Br Br Br OCH3 F _ _ r : : ; R R p2e Nô. No. 3968'ber Br Br H 3969 Br Br Br Cl CH3 3970 Br Br Br Ci OCH3 3971 Br Br Br Ci C1 3972 Br Br Br Cl F 3973 Br Br Br Br H 3974 Br Br Br Br CH3 3975 Br Br Br Br OCH3 3976 Br Br Br Br Ci 3977 Br Br Br Br Br 3978 Br Br Br Br F 3979 Br Br Br F H 3980 Br Br Br F CH3 3981 Br Br Br F OCH3 3982 82 Br Br F Ci 3983 Br Br Br F F 3984 Br Br F H H 3985 Br Br F H CH3 3986 Br Br F H OCH3 3987 Br Br F H Ci 3988 Br Br F H Br Br Br F H F 3990 Br Br F CH3 H 3991 Br Br F CH3 CH3 3992 Br Br F CH3 OCH3 3993 Br Br F CH3 Cl 3994 Br Br F CH3 Br 3995 Br Br F OCH3 H 3996 Br Br F OCH3 CH3 3997 Br Br F OCH3 OCH3 3998 Br Br F OCH3 ci 3999 Br Br F OCH3 Br 4000 Br Br F ci H 4001 Br Br F ci CH3 4002 Br Br F Ci OCH3 4003 Br Br F Ci ci 4004 Br Br F ci Br 4005 Br Br F Br H 4006 Br Br F Br CH3 4007 Br Br F Br OCH Compound R2a R2b R2c R2d R2e No. 4008 Br Br F Br ci 4009 Br Br F Br Br 4010 Br Br F F H 4011 Br Br F F CH3 4012 Br Br F F OCH3 4013 Br Br F F Ci 4014 Br Br F F Br 4015 Br Br F F F 4016 Br F CH3 H H 4017 Br F CH3. H CH3 4018 Br F CH3 H OCH3 4019 Br F CH3 H ci 4020 Br F CH3 H Br 4021 Br F CH3 H F 4022 Br F CH3 CH3 H 4023 Br F CH3 CH3 CH3 4024 Br F CH3 CH3 OCH3 4025 Br F CH3 CH3 Ci 4026 Br F CH3 CH3 Br 4027 Br F CH3 CH3 F 4028 Br F CH3 OCH3 H 4029 Br F CH3 OCH3 OCH3 4030 Br F CH3 OCH3 ci 4031 Br F CH3 OCH3 Br 4032 Br F CH3 OCH3 F 4033 Br F CH3 ci H 4034 Br F CH3 ci OCH3 4035 Br F CH3 Ci Ci 4036 Br F CH3 Cl Br 4037 Br F CH3 Ci F 4038 Br F CH3 Br H 4039 Br F CH3 Br OCH3 4040 Br F CH3 Br Cl 4041 Br F CH3 Br Br 4042 Br F CH3 Br F 4043 Br F CH3 F H 4044 Br F CH3 F OCH3 4045 Br F CH3 F Cl 4046 Br F CH3 F Br 4047 Br F CH3 F F Compound Rza R2b R2c R2d R2e No. 4048 Br F OCH3 H H 4049 Br F OCH3 H CH3 4050 Br F OCH3 H OCH3 4051 Br F OCH3 H Cl 4052 Br F OCH3 H Br 4053 Br F OCH3 H F 4054 Br F OCH3 CH3 H 4055 Br F OCH3 CH3 CH3 4056 Br F OCH3 CH3 Cl 4057 Br F OCH3 CH3 Br 4058 Br F OCH3 CH3 F 4059 Br F OCH3 OCH3 H 4060 Br F OCH3 OCH3 CH3 4061 Br F OCH3 OCH3 OCH3 4062 Br F OCH3 OCH3 Ci 4063 Br F OCH3 OCH3 Br 4064 Br F OCH3 OCH3 F 4065 Br F OCH3 Ci H 4066 Br F OCH3 ci CH3 4067 Br F OCH3 ci Ci 4068 Br F OCH3 ci Br 4069 Br F OCH3 ci F 4070 Br F OCH3 Br H 4071 Br F OCH3 Br CH3 4072 Br F OCH3 Br ci 4073 Br F OCH3 Br Br 4074 Br F OCH3 Br F 4075 Br F OCH3 F H 4076 Br F OCH3 F CH3 4077 Br F OCH3 F ci 4078 Br F OCH3 F Br 4079 Br F OCH3 F F 4080 Br F Ci H H 4081 Br F ci H CH3 4082 Br F Cl H OCH3 4083 Br F C1 H C1 4084 Br F ci H Br 4085 Br F Ci H F 4086 Br F C1 CH3 H 4087 Br F C1 CH3 CH3 Compound Rza R2b R2c R2d R2e No. 4088 Br F C1 CH3 OCH 4089 Br F Ci CH3 Br 4090 Br F ci CH3 F 4091 Br F C1 OCH3 H 4092 Br F C1 OCH3 CH3 4093 Br F Ci OCH3 OCH3 4094 Br F ci OCH3 Br 4095 Br F Ci OCH3 F 4096 Br F ci Ci H 4097 Br F ci Ci CH3 4098 Br F ci Ci OCH3 4099 Br F ci ci ci 4100 Br F Ci ci Br 4101 Br F Cl Cl F 4102 Br F Ci Br H 4103 Br F Cl Br CH3 4104 Br F ci Br OCH3 4105 Br F Ci Br Br 4106 ber F Cl F H 4107 Br F ci F CH3 4108 Br F Ci F OCH3 4109 Br F Cl F Br 4110 Br F C1 F F 4111 Br F Br H H 4112 Br F Br H CH3 4113 Br F Br H OCH3 4114 Br Br C1 4115 Br F Br H Br 4116 Br F Br H F 4117 Br F Br CH3 H 4118 Br F Br CH3 CH3 4119 Br F Br CH3 OCH3 4120 Br F Br CH3 Ci 4121 Br F Br CH3 F 4122 Br F Br OCH3 H 4123 Br F Br OCH3 CH3 4124 Br F Br OCH3 OCH3 4125 Br F Br OCH3 Cl 4126 Br F Br OCH3 F 4127 Br F Br C1 H Compound R2a R2b R2c R2d R2e No. 4128 Br F Br Cl CH3 4129 Br F Br Ci OCH3 4130 Br F Br Ci Ci 4131 Br F Br ci F 4132 Br F Br Br H 4133 Br F Br Br CH3 4134 Br F Br Br OCH 4135 Br F Br Br Ci 4136 Br F Br Br Br 4137 Br F Br Br F 4138 Br F Br F H 4139 Br F Br F CH3 4140 Br F Br F OCH3 4141 Br F Br F ci 4142 Br F Br F F 4143 Br F F H H 4144 Br F F H CH3 4145 Br F F H OCH3 4146 Br F F H ci 4147 Br F F H Br 4148 Br F F H F 4149 Br F F CH3 H 4150 Br F F CH3 CH3 4151 Br F F CH3 OCH3 4152 Br F F CH3 Cl 4153 Br F F CH3 Br 4154 Br F F OCH3 H 4155 Br F F OCH3 CH3 4156 Br F F OCH3 OCH3 4157 Br F F OCH3 Cl 4158 Br F F OCH3 Br 4159 Br F F ci H 4160 Br F F ci CH3 4161 Br F F ci OCH3 4162 Br F F Ci ci 4163 Br F F ci Br 4164 Br F F Br H 4165 Br F F Br CH3 4166 Br F F Br OCH3 4167 Br F F Br Cl Compound R2a R2b R2c R2d R2e No. 4168 Br F F Br Br 4169 Br F F F H 4170 Br F F F CH3 4171 Br F F F OCH3 4172 Br F F F ci 4173 Br F F F Br 4174 Br F F F F 4175 F CH3 CH3 H H 4176 F CH3 CH3 CH3 H 4177 F CH3 CH3 OCH3 H 4178 F CH3 CH3 ci H 4179 F CH3 CH3 Br H 4180 F CH3 CH3 F H 4181 F CH3 CH3 H CH3 4182 F CH3 CH3 CH3 CH3 4183 F CH3 CH3 H OCH3 4184 F CH3 CH3 CH3 OCH3 4185 F CH3 CH3 OCH3 OCH3 4186 F CH3 CH3 C1 OCH3 4187 F CH3 CH3 Br OCH3 4188 F CH3 CH3 F OCH3 4189 F CH3 CH3 H Ci 4190 F CH3 CH3 CH3 C 1 4191 F CH3 CH3 OCH3 ci 4192 F CH3 CH3 Cl Cl 4193 F CH3 CH3 Br ci 4194 F CH3 CH3 F ci 4195 CH3 CH3 H Br 4196 F CH3 CH3 CH3 Br 4197 CH3 CH3 OCH3 Br 4198 F CH3 CH3 ci Br 4199 F CH3 CH3 Br Br 4200 F CH3 CH3 F Br 4201 F CH3 CH3 H F 4202 F CH3 CH3 CH3 F 4203 F CH3 CH3 OCH3 F 4204 F CH3 CH3 Cl F 4205 F CH3 CH3 Br F 4206 F CH3 CH3 F F 4207 F CH3 OCH3 H H Compound Rza R2b R2c R2d R2e No. 4208 F CH3 OCH3 CH3 H 4209 F CH3 OCH3 OCH3 H 4210 F CH3 OCH3 C 1 H 4211 F CH3 OCH3 Br H 4212 F CH3 OCH3 F H 4213 F CH3 OCH3 H CH3 4214 F CH3 OCH3 CH3 CH3 4215 F CH3 OCH3 OCH3 CH3 4216 F CH3 OCH3 C1 CH3 4217 F CH3 OCH3 Br CH3 4218 F CH3 OCH3 F CH3 4219 F CH3 OCH3 H OCH3 4220 F CH3 OCH3 OCH3 OCH3 4221 F CH3 OCH3 H ci 4222 F CH3 OCH3 CH3 Cl 4223 F CH3 OCH3 OCH3 Ci 4224 F CH3 OCH3 Ci ci 4225 CH3 OCH3 Br Ci 4226 F CH3 OCH3 F C 1 4227 F CH3 OCH3 H Br 4228 F CH3 OCH3 CH3 Br 4229 F CH3 OCH3 OCH3 Br 4230 F CH3 OCH3 ci Br 4231 F CH3 OCH3 Br Br 4232 F CH3 OCH3 F Br 4233 F CH3 OCH3 H F 4234 F CH3 OCH3 CH3 F 4235 F CH3 OCH3 OCH3 F 4236 F CH3 OCH3 Cl F 4237 F CH3 OCH3 Br F 4238 F CH3 OCH3 F F 4239 F CH3 Cl H H 4240 F CH3 Cl CH3 H 4241 F CH3 Cl OCH3 H 4242 F CH3 ci ci H 4243 F CH3 ci Br H 4244 F CH3 Ci F H 4245 F CH3 Cl H CH3 4246 F CH3 Cl N3 CH3 4247 F CH3 Cl OCH3 CH3 Compound R2a R2b Rzc R2d R2e No. 4248 F CH3 Cl C1 CH3 4249 F CH3 Cl Br CH3 4250 F CH3 ci F CH3 4251 F CH3 Ci H OCH3 4252 F CH3 ci CH3 OCH3 4253 F CH3 Cl OCH3 OCH3 4254 F CH3 C 1 Cl OCH3 4255 F CH3 ci Br OCH3 4256 F CH3 Ci F OCH3 4257 F CH3 Ci H ci 4258 F CH3 ci ci Ci 4259 F CH3 ci H Br 4260 F CH3 Cl CH3 Br 4261 F CH3 ci OCH3 Br 4262 F CH3 ci ci Br 4263 F CH3 Ci Br Br 4264 F CH3 ci F Br 4265 F CH3 ci H F 4266 F CH3 ci CH3 F 4267 F CH3 Ci OCH3 F 4268 F CH3 ci Ci F 4269 F CH3 ci F F 4270 F CH3 Br H H 4271 F CH3 Br CH3 H 4272 F CH3 Br OCH3 H 4273 F CH3 Br ci H 4274 F CH3 Br Br H 4275 F CH3 Br F H 4276 F CH3 Br H CH3 4277 F CH3 Br CH3 CH3 4278 F CH3 Br OCH3 CH3 4279 F CH3 Br C1 CH3 l 4280 F CH3 Br Br CH3 4281 F CH3 Br F CH3 4282 F CH3 Br H OCH3 4283 F CH3 Br CH3 OCH3 4284 F CH3 Br OCH3 OCH3 4285 F CH3 Br C1 OCH3 4286 F CH3 Br Br OCH3 4287 F CH3 Br F OCH3 Compound R2a Rzb R2c R2d R2e No. 4288 F CH3 Br H Ci 4289 F CH3 Br CH3 C1 4290 F CH3 Br OCH3 Ci 4291 F CH3 Br ci Ci 4292 F CH3 Br Br Cl 4293 F CH3 Br F Cl 4294 F CH3 Br H Br 4295 F CH3 Br Br Br 4296 F CH3 Br H F 4297 F CH3 Br CH3 F 4298 F CH3 Br OCH3 F 4299 F CH3 Br ci F 4300 F CH3 Br Br F 4301 F CH3 Br F F 4302 F CH3 F H H 4303 F CH3 F CH3 H 4304 F CH3 F OCH3 H 4305 F CH3 F Ci H 4306 F CH3 F Br H 4307 F CH3 F F H 4308 F CH3 F H CH3 4309 F CH3 F CH3 CH3 4310 F CH3 F OCH3 CH3 4311 F CH3 F Cl CH3 4312 F CH3 F Br CH3 4313 F CH3 F CH3 4314 F CH3 F H OCH3 4315 F CH3 F CH3 OCH3 4316 F CH3 F OCH3 OCH3 4317 F CH3 F Ci OCH3 4318 F CH3 F Br OCH3 4319 F CH3 F F OCH3 4320 F CH3 F H ci 4321 F CH3 F CH3 Cl 4322 F CH3 F OCH3 C1 4323 F CH3 F Ci Cl 4324 F CH3 F Br Cl 4325 F CH3 F F Cl 4326 F CH3 F H Br 4327 F CH3 F CH3 Br Compound R2a Rztb R2c R2d R2e No. 4328 F CH3 F OCH3 Br 4329 F CH3 F Cl Br 4330 F CH3 F Br Br 4331 F CH3 F F Br 4332 F CH3 F H F 4333 F CH3 F F F 4334 F OCH3 CH3 H H 4335 F OCH3 CH3 H CH3 4336 F OCH3 CH3 H OCH3 4337 F OCH3 CH3 H ci 4338 F OCH3 CH3 H Br 4339 F OCH3 CH3 H F 4340 F OCH3 CH3 CH3 H 4341 F OCH3 CH3 CH3 CH3 4342 F OCH3 CH3 CH3 OCH3 4343 F OCH3 CH3 CH3 Cl 4344 F OCH3 CH3 CH3 Br 4345 F OCH3 CH3 CH3 F 4346 F OCH3 CH3 OCH3 H 4347 F OCH3 CH3 OCH3 OCH3 4348 F OCH3 CH3 OCH3 Cl 4349 F OCH3 CH3 OCH3 < Br 4350 F OCH3 CH3 OCH3 F 4351 F OCH3 CH3 Cl H 4352 F OCH3 CH3 ci OCH3 4353 F OCH3 CH3 ci Cl 4354 F OCH3 CH3 Cl Br 4355 F OCH3 CH3 Cl F 4356 F OCH3 CH3 Br H 4357 F OCH3 CH3 Br OCH3 4358 F OCH3 CH3 Br Cl 4359 F OCH3 CH3 Br Br 4360 F OCH3 CH3 Br F 4361 F OCH3 CH3 F H 4362 F OCH3 CH3 F OCH3 4363 F OCH3 CH3 F Cl 4364 F OCH3 CH3 F Br 4365 F OCH3 CH3 F F 4366 F OCH3 OCH3 H H 4367 F OCH3 OCH3 H CH3 Compound R2a Rzb R2c R2d R2e No. 4368 F OCH3 OCH3 H OCH3 4369 F OCH3 OCH3 H Cl 4370 F OCH3 OCH3 H Br 4371 F OCH3 OCH3 H F 4372 F OCH3 OCH3 CH3 H 4373 F OCH3 OCH3 CH3 CH3 4374 F OCH3 OCH3 CH3 ci 4375 F OCH3 OCH3 CH3 Br 4376 F OCH3 OCH3 CH3 F 4377 F OCH3 OCH3 OCH3 H 4378 F OCH3 OCH3 OCH3 CH3 4379 F OCH3 OCH3 OCH3 OCH3 4380 F OCH3 OCH3 OCH3 Ci 4381 F OCH3 OCH3 OCH3 Br 4382 F OCH3 OCH3 OCH3 F 4383 F OCH3 OCH3 ci H 4384 F OCH3 OCH3 Ci CH3 4385 F OCH3 OCH3 Ci ci 4386 F OCH3 OCH3 ci Br 4387 F OCH3 OCH3 Ci F 4388 F OCH3 OCH3 Br H 4389 F OCH3 OCH3 Br CH3 4390 F OCH3 OCH3 Br ci 4391 F OCH3 OCH3 Br Br 4392 F OCH3 OCH3 Br F 4393 F OCH3 OCH3 F H 4394 F OCH3 OCH3 CH3 4395 F OCH3 OCH3 F ci 4396 F OCH3 OCH3 F Br 4397 F OCH3 OCH3 F F 4398 F OCH3 ci H H 4399 F OCH3 ci H CH3 4400 F OCH3 ci H OCH3 4401 F OCH3 ci H Cl 4402 F OCH3 Ci H Br 4403 F OCH3 ci H F 4404 F OCH3 C1 CH3 H 4405 F OCH3 C1 CH3 CH3 4406 F OCH3 ci CH3 OCH3 4407 F OCH3 ci CH3 Br Compound za R2b R2c R2d R2e No. 4408 F OCH3 C1 CH3 F 4409 F OCH3 Ci OCH3 H 4410 F OCH3 ci OCH3 CH3 4411 F OCH3 C1 OCH3 OCH3 4412 F OCH3 Ci OCH3 Br 4413 F OCH3 ci OCH3 F 4414 F OCH3 Ci Cl H 4415 F OCH3 Ci Ci CH3 4416 F OCH3 ci Ci OCH3 4417 F OCH3 Ci ci ci 4418 F OCH3 Ci ci Br 4419 F OCH3 ci ci F 4420 F OCH3 ci Br H 4421 F OCH3 Ci Br CH3 4422 F OCH3 Cl Br OCH3 4423 F OCH3 ci Br Br 4424 F OCH3 Ci F H 4425 F OCH3 Ci F CH3 4426 F OCH3 Cl F OCH3 4427 F OCH3 Ci F Br 4428 F OCH3 C 1 F F 4429 F OCH3 Br H H 4430 F OCH3 Br H CH3 4431 F OCH3 Br H OCH3 4432 F OCH3 Br H Ci 4433 F OCH3 Br H Br 4434 F OCH3 Br H F 4435 F OCH3 Br CH3 H 4436 F OCH3 Br CH3 CH3 4437 F OCH3 Br CH3 OCH3 4438 F OCH3 Br CH3 ci 4439 F OCH3 Br CH3 F 4440 F OCH3 Br OCH3 H 4441 F OCH3 Br OCH3 CH3 4442 F OCH3 Br OCH3 OCH3 4443 F OCH3 Br OCH3 Cl 4444 F OCH3 Br OCH3 F 4445 F OCH3 Br C1 4446 F OCH3 Br ci CH3 4447 F OCH3 Br OCH3 Compound R2b R2c R2d R2e No. 4448 F OCH3 Br Ci ci 4449 F OCH3 Br C1 F 4450 F OCH3 Br Br H 4451 F OCH3 Br Br CH3 4452 F OCH3 Br Br OCH3 4453 F OCH3 Br Br Ci 4454 F OCH3 Br Br Br 4455 F OCH3 Br Br F 4456 F OCH3 Br F H 4457 F OCH3 Br F CH3 4458 F OCH3 Br F OCH3 4459 F OCH3 Br F ci 4460 F OCH3 Br F F 4461 F OCH3 F H H 4462 F OCH3 F H CH3 4463 F OCH3 F H OCH3 4464 F OCH3 F H ci 4465 F OCH3 F H Br 4466 F OCH3 F H F 4467 F OCH3 F CH3 H 4468 F OCH3 F CH3 CH3 4469 F OCH3 F CH3 OCH3 4470 F OCH3 F CH3 Cl 4471 F OCH3 F CH3 Br 4472 F OCH3 F OCH3 H 4473 F OCH3 F OCH3 CH3 4474 F OCH3 F OCH3 OCH3 4475 F OCH3 F OCH3 Cl 4476 F OCH3 F OCH3 Br 4477 F OCH3 F Cl H 4478 F OCH3 F Cl CH3 4479 F OCH3 F ci OCH3 4480 F OCH3 F Ci Cl 4481 F OCH3 F Ci Br 4482 F OCH3 F Br H 4483 F OCH3 F Br CH3 4484 F OCH3 F Br OCH3 4485 F OCH3 F Br Cl 4486 F OCH3 F Br Br 4487 F OCH3 F F H Compound R2a R2b R2c R2d R2e No. 4488 F OCH3 F F CH3 4489 F OCH3 F F OCH3 4490 F OCH3 F F Cl 4491 F OCH3 F F Br 4492 F OCH3 F F F 4493 F Ci CH3 H H 4494 F C1 CH3 H CH3 4495 F ci CH3 H OCH3 4496 F ci CH3 H ci 4497 F ci CH3 H Br 4498 F ci CH3 H F 4499 F C1 CH3 CH3 H 4500 F C1 CH3 CH3 CH3 4501 F C1 CH3 CH3 OCH3 4502 F Cl CH3 CH3 Ci 4503 F Cl CH : 3 CH3 Br 4504 F Cl CH3 CH3 F 4505 F Cl CH3 OCH3 H 4506 F Ci CH3 OCH3 OCH3 4507 F C1 CH3 OCH3 ci 4508 p Cl CH3 OCH3 Br 4509 F Cl CH3 OCH3 F 4510 F Ci CH3 ci H 4511 F Cl CH3 ci OCH3 4512 F ci CH3 ci ci 4513 F ci CH3 ci Br 4514 F ci CH3 Ci F 4515 F Ci CH3 Br H 4516 F Ci CH3 Br OCH3 4517 F Ci CH3 Br Ci 4518 F ci CH3 Br Br 4519 F Ci CH3 Br F 4520 F ci CH3 F H 4521 F ci CH3 F OCH3 4522 F C1 CH3 F C1 4523 F ci CH3 F Br 4524 F ci CH3 F F 4525 F Ci OCH3 H H 4526 F Cl OCH3 H CH3 4527 F ci OCH3 H OCH Compound R2a Rzb Rac R2d R2e No. 4528 F cl OCH3 H Ci 4529 F Ci OCH3 H Br 4530 F C 1 OCH3 H F 4531 F C 1 OCH3 CH3 H 4532 F C1 OCH3 CH3 CH3 4533 F Cl OCH3 CH3 ci 4534 F C1 OCH3 CH3 Br 4535 F C 1 OCH3 CH3 F 4536 F Cl OCH3 OCH3 H 4537 F Ci OCH3 OCH3 CH3 4538 F Cl OCH3 OCH3 OCH3 4539 F ci OCH3 OCH3 ci 4540 F Ci OCH3 OCH3 Br 4541 F ci OCH3 OCH3 F 4542 F ci OCH3 ci H 4543 F ci OCH3 Ci CH3 4544 F Ci OCH3 Ci Ci 4545 F Ci OCH3 Ci Br 4546 F Ci OCH3 ci F 4547 F C1 OCH3 Br H 4548 p Cl OCH3 Br CH3 4549 F Cl OCH3 Br Cl 4550 F Cl OCH3 Br Br 4551 F Cl OCH3 Br F 4552 F Cl OCH3 F H 4553 p Cl OCH3 F CH3 4554 F Ci OCH3 F Ci 4555 F Ci OCH3 F Br 4556 F Ci OCH3 F F 4557 F C1 Cl H H 4558 F ci ci H CH3 4559 F ci Ci H OCH3 4560 F Ci ci H Cl 4561 F Ci ci H Br 4562 F Ci ci H F 4563 F ci ci CH3 H 4564 F Cl C1 CH3 CH3 4565 p Cl Cl CH3 OCH3 4566 F ci ci CH3 Br 4567 F ci ci CH3 F Compound R2a R2b R2c R2d R2e No. 4568 F ci ci OCH3 H 4569 F ci ci OCH3 CH3 4570 F Ci Ci OCH3 OCH3 4571 F Ci Cl OCH3 Br 4572 F ci ci OCH3 F 4573 F Ci ci Ci H 4574 F ci Ci ci CH3 4575 F Ci ci Cl OCH3 4576 F ci Ci ci Ci 4577 F ci Ci Cl Br F Cl Cl Cl F F Cl Cl Br H 4580 F Ci Ci Br CH3 4581 F ci C1 Br OCH3 4582 F ci ci Br Br 4583 F ci Ci F H 4584 F Ci ci F CH3 4585 F Ci ci F OCH3 4586 F ci ci F Br 4587 F C1 C1 F F 4588 F ci Br H H 4589 F Ci Br H CH3 4590 F Cl Br H OCH3 4591 F ci Br H Ci 4592 F Cl Br H Br 4593 F ci Br H F 4594 F ci Br CH3 H 4595 F Ci Br CH3 CH3 4596 F Cl Br CH3 OCH3 4597 F ci Br CH3 Ci 4598 F Ci Br CH3 F 4599 F ci Br OCH3 H 4600 F Ci Br OCH3 CH3 4601 F ci Br OCH3 OCH3 4602 F Ci Br OCH3 Ci 4603 F Cl Br OCH3 F 4604 F Cl Br Cl H 4605 F Ci Br Cl CH3 4606 F Ci Br Ci OCH3 4607 F Cl Br Cl Cl N °-R 2 a R 2 b R 2 c R 2 d R 2 e Compound F Rzb R2 Rza Rze No. 4608 F cil Br Cl F 4609 F ci Br Br H 4610 F ci Br Br CH3 4611 F ci Br Br OCH3 4612 F cl Br Br Cl 4613 F ci Br Br Br 4614 F Cl Br Br F 4615 F C1 Br F H 4616 F Cl Br F CH3 4617 F Ci Br OCH3 4618 F ci Br F Cl 4619 F ci Br F F 4620 F C1 F H H 4621 F ci F H CH3 4622 F ci F H OCH3 4623 F ci F H C1 4624 F Ci F H Br 4625 F Cl F H F 4626 F ci F CH3 H 4627 F ci F CH3 CH3 4628 p Cl F CH3 OCH3 4629 F ci F CH3 Cl 4630 F ci CH3 Br 4631 F Ci F OCH3 H 4632 F C1 F OCH3 CH3 4633 g Cl F OCH3 OCH3 4634 F ci F OCH3 C1 4635 F ci F OCH3 Br 4636 g C1 g 4637 F ci F Cl CH3 4638 F ci F Cl OCH3 4639 F Ci F Cl Cl 4640 Cl F ci Br 4641 F Ci F Br H 4642 F Ci F Br CH3 4643 F ci F Br OCH3 4644 F Ci Br C1 4645 F Ci F Br Br 4646 P cl F F H 4647 F Ci F F CH3 Compound R2a R2b R2c R2d R2e No. 4648 F ci F F OCH3 4649 F Ci F F Ci 4650 F ci F F Br 4651 F Ci F F F 4652 F Br CH3 H H 4653 F Br CH3 H CH3 4654 F Br CH3 H OCH3 4655 F Br CH3 H ci 4656 F Br CH3 H Br 4657 F Br CH3 H F 4658 F Br CH3 CH3 H 4659 F Br CH3 CH3 CH3 4660 F Br CH3 CH3 OCH3 4661 F Br CH3 CH3 ci 4662 F Br CH3 CH3 Br 4663 F Br CH3 CH3 F 4664 F Br CH3 OCH3 H 4665 F Br CH3 OCH3 OCH3 4666 F Br CH3 OCH3 Cl 4667 F Br CH3 OCH3 Br 4668 F Br CH3 OCH3 F 4669 F Br CH3 ci H 4670 F Br CH3 ci OCH3 4671 F Br CH3 Ci Ci 4672 F Br CH3 Ci Br 4673 F Br CH3 ci F 4674 F Br CH3 Br H 4675 F Br CH3 Br OCH3 4676 F Br CH3 Br Ci 4677 F Br CH3 Br Br 4678 F Br CH3 Br F 4679 F Br CH3 F H 4680 F Br CH3 F OCH3 4681 F Br CH3 F Ci 4682 F Br CH3 F Br 4683 F Br CH3 F F 4684 F Br OCH3 H H 4685 F Br OCH3 H CH3 4686 F Br OCH3 H OCH3 4687 F Br OCH3 H C1 Compound R2a R2b R2c R2d R2e No. 4688 F Br OCH3 H Br 4689 F Br OCH3 H F 4690 F Br OCH3 CH3 H 4691 F Br OCH3 CH3 CH3 4692 F Br OCH3 CH3 ci 4693 p Br OCH3 CH3 Br 4694 p Br OCH3 CH3 F 4695 F Br OCH3 OCH3 H 4696 F Br OCH3 OCH3 CH3 4697 F Br OCH3 OCH3 OCH3 4698 F Br OCH3 OCH3 ci 4699 F Br OCH3 OCH3 Br 4700 F Br OCH3 OCH3 F 4701 F Br OCH3 ci H 4702 F Br OCH3 Ci CH3 4703 F Br OCH3 Ci Ci 4704 F Br OCH3 ci Br 4705 F Br OCH3 Cl F 4706 F Br OCH3 Br H 4707 F Br OCH3 Br CH3 4708 F Br OCH3 Br Ci 4709 F Br OCH3 Br Br 4710 F Br OCH3 Br F 4711 F Br OCH3 F H 4712 F Br OCH3 F CH3 4713 F Br OCH3 F ci 4714 F Br OCH3 F Br 4715 F Br OCH3 F F 4716 F Br ci H H 4717 F Br Cl H CH3 4718 F Br ci H OCH3 4719 F Br ci H ci 4720 F Br ci H Br 4721 F Br ci H F 4722 F Br ci CH3 H 4723 F Br C1 CH3 CH3 4724 F Br C1 CH3 OCH3 4725 F Br Ci CH3 Br 4726 F Br ci CH3 F 4727 F Br C1 OCH3 H Compound R2a R2b Rzc R2d R2e No. 4728 F Br Ci OCH3 CH3 4729 F Br ci OCH3 OCH3 4730 F Br ci OCH3 Br 4731 F Br ci OCH3 F 4732 F Br ci Ci H 4733 F Br ci ci CH3 4734 F Br ci ci OCH3 4735 F Br Ci Ci Ci 4736 F Br Cl Gl Br 4737 F Br ci ci F 4738 F Br Cl Br H 4739 F Br ci Br CH3 4740 F Br Ci Br OCH3 4741 F Br Ci Br Br 4742 F Br Ci F H 4743 F Br Ci F CH3 4744 F Br Ci F OCH3 4745 F Br Ci F Br 4746 F Br ci F F 4747 F Br Br H H 4748 F Br Br H CH3 4749 F Br Br H OCH3 4750 F Br Br H Ci 4751 F Br Br H Br 4752 F Br Br H F 4753 F Br Br CH3 H 4754 F Br Br CH3 CH3 4755 F Br Br CH3 OCH3 4756 F Br Br CH3 Ci 4757 F Br Br CH3 F 4758 F Br Br OCH3 H 4759 F Br Br OCH3 CH3 4760 F Br Br OCH3 OCH3 4761 F Br Br OCH3 Cl 4762 F Br Br OCH3 F 4763 F Br Br Cl H 4764 F Br Br Cl CH3 4765 F Br Br ci OCH3 4766 F Br Br ci Cl 4767 F Br Br Cl F Compound R2a R2b R2c R2d R2e No. 4768 F Br Br Br H 4769 F Br Br Br CH3 4770 F Br Br Br OCH3 4771 F Br Br Br Ci 4772 F Br Br Br Br 4773 F Br Br Br F 4774 F Br Br F H 4775 F Br Br F CH3 4776 F Br Br F OCH3 4777 F Br Br F ci 4778 F Br Br F F 4779 F Br F H H 4780 F Br F H CH3 4781 F Br F H OCH3 4782 F Br F H C1 4783 F Br F H Br 4784 F Br F H F 4785 F Br F CH3 H 4786 F Br F CH3 CH3 4787 F Br F CH3 OCH3 4788 F Br F CH3 Ci 4789 F Br F CH3 Br 4790 F Br F OCH3 H 4791 F Br F OCH3 CH3 4792 F Br F OCH3 OCH3 4793 F Br F OCH3 Ci 4794 F Br F OCH3 Br 4795 F Br F ci H 4796 F Br F ci CH3 4797 F Br F C1 OCH3 4798 F Br F Cl C1 4799 F Br F Ci Br 4800 F Br F Br H 4801 F Br F Br CH3 4802 F Br F Br OCH3 4803 F Br F Br ci 4804 F Br F Br Br 4805 F Br F F H 4806 F Br F F CH3 4807 F Br F F OCH3 Compound R2a R2b R2c R2d R2e No. 4808 F Br F F Ci 4809 F Br F F Br 4810 F Br F F F 4811 F F CH3 H H 4812 F F CH3 H CH3 4813 F F CH3 H OCH3 4814 F F CH3 H Cl 4815 F F CH3 H Br 4816 F F CH3 H F 4817 F F CH3 CH3 H 4818 F F CH3 CH3 CH3 4819 F F CH3 CH3 OCH3 4820 F F CH3 CH3 Cl 4821 F F CH3 CH3 Br 4822 F F CH3 CH3 F 4823 F F CH3 OCH3 H 4824 F F CH3 OCH3 OCH3 4825 F F CH3 OCH3 ci 4826 F F CH3 OCH3 Br 4827 F F CH3 OCH3 F 4828 F F CH3 Ci H 4829 F F CH3 Ci OCH3 4830 F CH3 ci ci 4831 F F CH3 Ci Br 4832 F F CH3 Ci F 4833 F F CH3 Br H 4834 F F CH3 Br OCH3 4835 F F CH3 Br ci 4836 F F CH3 Br Br 4837 F F CH3 Br F 4838 F F CH3 F H 4839 F F CH3 F OCH3 4840 F F CH3 F Cl 4841 F F CH3 F Br 4842 F F CH3 F F 4843 F F OCH3 H H 4844 F F OCH3 H CH3 4845 F F OCH3 H OCH3 4846 F F OCH3 H Cl 4847 F F OCH3 H Br Compound R2a R2b R2c R2d R2e No. 4848 F F OCH3 H F 4849 F F OCH3 CH3 H 4850 F F OCH3 CH3 CH3 4851 F F OCH3 CH3 Ci 4852 F F OCH3 CH3 Br 4853 F F OCH3 CH3 F 4854 F F OCH3 OCH3 H 4855 F F OCH3 OCH3 CH3 4856 F F OCH3 OCH3 OCH3 4857 F F OCH3 OCH3 ci 4858 F F OCH3 OCH3 Br 4859 F F OCH3 OCH3 F 4860 F F OCH3 Ci H 4861 F F OCH3 ci CH3 4862 F F OCH3 Ci Ci 4863 F F OCH3 ci Br 4864 F F OCH3 ci F 4865 F F OCH3 Br H 4866 F F OCH3 Br CH3 4867 F F OCH3 Br Ci 4868 F F OCH3 Br Br 4869 F F OCH3 Br F 4870 F F OCH3 F H 4871 F F OCH3 F CH3 4872 F F OCH3 F Cl 4873 F F OCH3 F Br 4874 F F OCH3 F F 4875 F F Cl H H 4876 F F Cl H CH3 4877 F F ci H OCH3 4878 F F C1 H Cl 4879 Cl Br 4880 F F Cl H F 4881 F F Cl CH3 H 4882 F F Cl CH3 CH3 4883 F F C1 CH3 OCH3 4884 F F ci CH3 Br 4885 F F Cl CH3 F 4886 F F ci OCH3 H 4887 F C1 OCH3 CH3 Compound R2a R2b Rzc R2d R2e No. 4888 F F Ci OCH3 OCH3 4889 F F ci OCH3 Br 4890 F F ci OCH3 F 4891 F F ci ci H 4892 F F Ci Ci CH3 4893 F F Ci ci OCH3 4894 F C1 C1 C1 4895 F F ci Ci Br 4896 F F ci Ci F 4897 F F Ci Br H 4898 F F C1 Br CH3 4899 F F ci Br OCH3 4900 F F ci Br Br 4901 F F Ci F H 4902 F F Cl F CH3 4903 F C1 F OCH3 4904 F F Cl F Br 4905 p F Cl F F 4906 F F Br H H 4907 F F Br H CH3 4908 F F Br H OCH3 4909 F F Br H Cl 4910 F F Br H Br 4911 F F Br H F 4912 F F Br CH3 H 4913 F F Br CH3 CH3 4914 p F Br CH3 OCH3 4915 p F Br CH3 Ci 4916 F F Br CH3 F 4917 F F Br OCH3 H 4918 F F Br OCH3 CH3 4919 F F Br OCH3 OCH3 4920 F F Br OCH3 ci 4921 F F Br OCH3 F 4922 F F Br ci H 4923 F F Br Ci CH3 4924 F F Br Ci OCH3 4925 F F Br ci C1 4926 F F Br Ci F 4927 F F Br Br H Compound 2a R2b 2a R2d R2e No. 4928 F F Br Br CH3 4929 F F Br Br OCH 4930 F F Br Br ci 4931 F F Br Br Br 4932 F F Br Br F 4933 F F Br F H 4934 F F Br-F CH3 4935 F F Br F OCH3 4936 F F Br F ci 4937 F F Br F F 4938 F F F H H 4939 F F F H CH3 4940 g F F H OCH3 4941 F F F H Ci 4942 F F F H Br 4943 F F F H F 4944 F F F CH3 H 4945 F F F CH3 CH3 4946 F F F CH3 OCH3 4947 F F F CH3 ci 4948 F F F CH3 Br 4949 F F F OCH3 H 4950 F F F OCH3 CH3 4951 F F F OCH3 OCH3 4952 F F F OCH3 Ci 4953 F F F OCH3 Br 4954 F F F Ci H 4955 F F F ci CH3 4956 F F F Ci OCH3 4957 F F F Ci Ci 4958 F F F Cl Br 4959 F F F Br H 4960 F F F Br CH3 4961 F F F Br OCH 4962 F F F Br ci 4963 F F F Br Br 4964 F F F F H 4965 F F F F CH3 4966 F F F F OCH3 4967 g g I F F F F C1 Compound R2a R2b R2c R2d R2e No. 4968 F F F F Br 4969 F F F F F [0437] In another embodiment, the compound of Formula I is selected from the group of compounds of Formula V having the structure : [0438] wherein R2a R2b, R2c, R2d, and R2e are as defined in Table 2.

[0439] In another embodiment, the compound of Formula I is selected from the group of compounds of Formula V having the structure : [0440] wherein R, R, R, R, and R2e are as defined in Table 2.

[0441] In another embodiment, the compound of Formula I is selected from the group of compounds of Formula V having the structure : [0442] wherein R2a, R2b, R2c, R2d, and R2e are as defined in Table 2.

[0443] In another embodiment, the compound of Formula I is selected from the group of compounds of Formula V having the structure : [0444] wherein R, R, R, R, and R2e are as defined in Table 2.

[0445] In another embodiment, the compound of Formula I is selected from the group of compounds of Formula V having the structure : [0446] wherein R2a, R2b, R2c, R2d, and R2e are as defined in Table 2.

[0447] In another embodiment, the compound of Formula I is selected from the group of compounds of Formula V having the structure : [0448] wherein R2a, R I R, R, and R2e are as defined in Table 2.

[0449] In another embodiment, the compound of Formula I is selected from the group of compounds of Formula V having the structure : [0450] wherein R2a, R R2c, R2d, and R are as defined in Table 2.

[0451] In another embodiment, the compound of Formula I is selected from the group of compounds of Formula V having the structure : [0452] wherein R2a, R, R, R, and R2e are as defined in Table 2.

[0453] In another embodiment, the compound of Formula I is selected from the group of compounds of Formula V having the structure : [0454] wherein R2a, R2bh, R2c, R2d, and R2e are as defined in Table 2.

[0455] In another embodiment, the compound of Formula I is selected from the group of compounds of Formula V having the structure : [0456] wherein R2a, R2b, R2c, R2d, and R2e are as defined in Table 2.

[0457] In another embodiment, the compound of Formula I is selected from the group of compounds of Formula V having the structure : [0458] wherein R2a, R2b R2C R2d, and R2e are as defined in Table 2.

[0459] In another embodiment, the compound of Formula I is selected from the group of compounds of Formula V having the structure : [0460] wherein R2a, R, R, R2d, and R2e are as defined in Table 2.

[0461] In another embodiment, the compound of Formula I is selected from the group of compounds of Formula V having the structure : [0462] wherein R2a, R2b, R2c, R2d, and R2e are as defined in Table 2.

[0463] In another embodiment, the compound of Formula I is selected from the group of compounds of Formula V having the structure : [0464] wherein R2a, R2b, R2-, R2d, and R2e are as defined in Table 2.

[0465] In another embodiment, the compound of Formula I is selected from the group of compounds of Formula V having the structure : [0466] wherein R, R"R, R, and R are as defined in Table 2.

[0467] The compounds of Formula I are MCH receptor antagonists, as demonstrated by the ligand binding assays described hereinbelow. MCH receptor antagonist activity has been correlated with pharmaceutical activity for the treatment of eating disorders such as obesity and hyperphagia, and diabetes.

Compounds of Formula I exhibit good activity in standard in vitro MCH calcium mobilization assays and/or receptor binding assays, specifically in the assays described hereinbelow, see Examples 23 and 24. Generally, compounds of Formula I have an Ki of about 10 uM or less, preferably about 1 uM or less, more preferably about 100 nM or less, or even more preferably about 10 nM or less, as determined by a standard in vitro MCH receptor mediated calcium mobilization assay as exemplified by Example 23, hereinbelow. Generally compounds of Formula I are MCH receptor antagonists and exhibit IC50 values of about 10 uM or less, preferably about 1 uM or less, more preferably about 100 nM or less, or even more preferably about 10 nM or less, as determined by a standard in vitro MCH receptor binding assay such as is described hereinbelow in Example 24.

[0468] Preferably, the MCH receptor antagonists of Formula I bind specifically, and still more preferably with high affinity, to MCH receptors.

[0469] The following examples illustrate the invention.

Example 1 OCH3 OH OCH3 OCH3 F R'-NH, (10 eq) N-RI CHO DCE, Na (OAc) 3BH HN-R HOBT, DIC overnight, r. t. overnight, r. t. -NOz Step#1 1 step#2 #2 Step #2 OH OH OH Step #3 1-11 DBU, DMF overnight, r. t. OCH3 OCH3 Tin (II) CI, DMF \/O N-R 0 0 overnight, r. t. NH NOZ Step #4 O O i R R2 2 4 3 Step 1 OCH3 OCH3 R'-N H2 (10 eq) CHO DCE, Na (OAc) 3BH w H\NR overnight, r. t. 1 [0470] To a 2 L glass bottle was added 4-formyl-3- methoxyphenoxy-polystyrene resin (100-180 mesh, 1. 1 mmol/g loading, 20 g, 22 mmol), amine (5 eq, 110 mmol), and anhydrous DCE (500 mL). The resulting mixture was shaken for one hour at room temperature. Then, Na (OAc) 3BH (5 eq, 110 mmol) was added and the mixture was shaken overnight at room temperature. The mixture was degassed every half-hour for the first three hours.

The resin was filtered and washed with MeOH (2x) and DCM (2x) to afford 1.

Step 2 0 OCH3 D)-) 1 J L) L. H3 OCH3 F OCH3 - NOa /HN-R HOBT, DIC overnight, r. t. 1 2 NO2 F F [0471] To a 2 L glass bottle was added 1, 4-fluoro-3- nitrobenzoic acid (24. 4 mmol, 132 mmol), HOBt (18 g, 132 mmol), DIC (42 mL, 264 mmol), and DMF (500 mL). The resulting mixture was shaken overnight at room temperature. The resin was filtered and washed with DMF (2x), MeOH (2x), and DCM (2x) to afford 2.

Step 3 OCHs OCHs OCH3 OH OCH3 ° < NR1 ¢3R2 » \NR = R2 \/N-R 0) 1 0 DBU, DMF NO2 overnight, r. t. WNO2 F F O R2 [0472] To a 2 L glass bottle was added 2, phenol (27 g, 220 mmol), DBU (20 mL, 132 mmol), and DMF (400 mL). The resulting mixture was shaken overnight at room temperature. Then, the resin was filtered and washed with DMF (2x) and DCM (2x) to afford 3.

Step 4 OCHs OCHs OCH3 LOCH3 I N-R Tin (II) CI, DMF \/N-R O O overnight, r. t. O/ 0 0 O O X R2 (SR2 2 [0473] To a 2 L glass bottle was added 3, Tin (II) Cl-2H20 (49. 5 g, 220 mmol) and DMF (400 mL). The resulting mixture was then shaken overnight at room temperature. The resin was filtered and washed with DMF (2x) and DCM (2x) to afford 4.

Example 2 Method 1 [0474] Starting material (10 mg, 0. 021 mmol) was combined with 1, 2-dibromoethane (2. 3 AL, 0. 025 mmol) and NaH (1 mg, 0. 042 mmol) in 0. 5 mL DMF at room temperature. The mixture was then heated to 80°C for 1 hour. The reaction mixture was worked up with water and EtOAc.

Method 2 [0475] Starting material (20 mg, 0. 04 mmol) was combined with 1, 2-diiodoethane (14. 3 mg, 0. 05 mmol) and NaH (2 mg, 0. 08 mmol) in 0. 5 mL DMF, then reacted as described above.

Example 3 , l zozo NCO/ NN N N _,, N- dozy I I I o 30% TFA in DCM HN\/O O NH2 Pyridine : DCM 45 min., r. t. wNH overnight, r. t. /\ O 30 [0476] To a peptide vessel was added resin (1. 1 mmol/g loading, 100 mg, 0. 11 mmol), 2-methoxyphenylisocyanate (1. 1 mmol), and pyridine : DCM (5 mL, 1 : 1 ratio). The resulting mixture was shaken overnight at room temperature. The resin was washed with DCM (2x). Then, 30% TFA in DCM (10 mL) was added and the resulting mixture was shaken for 45 min. at room temperature. The resin was filtered and washed with DCM (2x).

The filtrate was concentrated to afford 30.

[0477] Examples 4-16 were prepared according to the procedure shown in Example 3.

Example 4 Q / Nco CI/ I I H 0 CI 30% TFA in DCM HNO Pyridine : DCM 45 min., r. t. NH O NHa overnight, r. t. CI \ CI 31 Example 5 0 NCO n N ¢0sSCI > XH Han 0 ci 30% TFA in DCM Pyridine : DCM 45 min r t NH O NH, overnight, r. t. ci cri 32 Example 6 NCO O N- CI O / NN H O/O HN\/O 30% TFA in DCM NU 0 NH2 Pyridine : DCM 45 min., r. t. overnight, r. t. 0 33 Example 7 0 O. N NCO to t N~ Han 0 O HN O 30% TFA in DCM NU 0 NH2 Pyridine : DCM 45 min., r. t. overnight, r. t. 34 Example 8 o N-- o N NCO N / NCO I/H 30% TFA in DCM HN\/O P ridine : DCM, NH O NH Pyridine : DCM 45 min., r. t. XNH overnight, r. t. 35 Example 9 0 N NCO I/H \ \ O 30% TFA in DCM HN y 0 H N H Pyridine : DCM 45 min., r. t. O NH2 Y 45 min., r. t. 0 NH ? Pyr ! dine : DCM 45m ! n., r. t. fT" overnight, r. t. 36 Example 10 Q zu NCO \ I I/H H 1 30% TFA in DCM HN P ridine : DCM HN /-\ ho)- 0 NH2 Pyrid ! ne : DCM 45min., r. t. \ 9 overnight, r. t. 37 Example 11 0 0 O N NCO s I o, o HN\/O cri 30% TFA in DCM b nu O NH Pyridine : DCM 45 min., r. t. overnight, r. t. Cl+) CI Example 12 oxo T--i NCO N- N J ? l hune HN. /O Br 30% TFA in DCM '/NH O NH2 Pyridine : DCM 45 min., r. t. overnight, r. t. zu \ 38 Example 13 rus N'-N \/, N'/ NCO I I/H N O I O HN\/O 4 F 30% TFA in DCM jp-ll _/ $ Pyridine : DCM 45 min., r. t. overnight, r. t. F \ 39 Example 14 /0 0 ru 0 non NCO neo ao I H O HN\/O $ O 30% TFA in DCM _/ O NH Pyridine : DCM 45 min., r. t. \ overnight, r. tu m O\ 0""40 Example 15 /0 zu NCO / I \ H CI //\ O ci I NCO 30% TFA in DCM , N Pyridine : DCM 45 min., r. t. overnight, r. t. \ 41 41 Example 16 o Q NCO I I HN, N H 0 'CN o HN O 30/o TFA in DCM O<NH2 Pyridine : DCM 45 min., r. t. NH overnight, r. t. CN Example 17 Q o C p N- N N N Ich JAZZ HN O 0 COC12 I N 30% TFA HN -----/ N H ß COC12 WJ NH toluene N 0 NH2 N 44 [0478] To a round bottom flask was added resin (500 mg, 0. 55 mmol) and DCM (15 mL). The resulting mixture was cooled to - 78°C. Then, 20% phosgene in toluene (540 mg) was added dropwise. The resulting mixture was warmed to room temperature and shaken for 3 hours. The resin was filtered and washed with DCM (2x). The resin was transferred to a peptide vessel and excess (10-15 eq) of aminopyridine along with 15 mL of DCM were added. The resulting mixture was shaken overnight at room temperature. The resin was washed with DCM (2x). Then, 30% TFA in DCM (50 mL) was added and the resulting mixture was shaken for 45 min. at room temperature. The resin was filtered and washed with DCM (2x). The filtrate was concentrated to afford 44.

Example 18 [0479] To a peptide vessel was added resin (1. 1 mmol/g, 200 mg, 0. 22 mmol), phenylchloroformate (143 AL, 1. 1 mmol), and DCM : pyridine (7 mL, 1 : 1 ratio). The resulting mixture was shaken overnight at room temperature. The resin was washed with DCM (2x). Then, 30% TFA in DCM (50 mL) was added and the resulting mixture was shaken for 45 min. at room temperature. The resin was filtered and washed with DCM (2x). The filtrate was concentrated to afford 45.

Example 19 0/nô zozo N NCO 0 0 0 Dao H p O N 0 N-H O 2 0 30% TFA ci ci v > s s DMF : DCM in DCM DCM : pyridine Na (OAc) 3BH 45 min., r. t. overnight, r. t. 62 [0480] To a peptide vessel was added resin (1. 1 mmol/g, 1. 1 g, 1. 21 mmol), 1, 1-dimethylethyl 2-oxoethyl (phenyl) carbamate (490 mg, 3. 63 mmol), and DCM : DMF (10 mL, 1 : 1 ratio). The mixture was shaken for 30 min. at room temperature. Then, Na (OAc) 3BH (1. 27 g, 6. 05 mmol) was added and the mixture was shaken overnight at room temperature. The mixture was degassed every half hour for the first 3 hours. The resin was washed with MeOH (2x) and DCM (2x). Then, 30% TFA in DCM (50 mL) was added and resulting mixture was shaken for 45 min. at room temperature.

The resin was filtered and washed with DCM (2x). The filtrate was concentrated and dried. Then, phosgene (27. 1 ßL, 0. 274 mmol) and DCM : pyridine (5 mL, 1 : 1 ratio) were added to the crude mixture. The resulting mixture was stirred at room temperature for 45 min. The mixture was concentrated and purified by column chromatography to afford 62.

Example 20 o Q-o j (Y tO N) ° X H NCO O N N O /$ AH ¢ 30% TFA 0 Ht 0 0 30% TFA rN,, f*,, O DMF : DCM DCM in DCM O NH2 Na (OAc) 3BH overnight, r. t. 49 [0481] To a peptide vessel was added resin (1. 1 mmol/g, 500 mg, 0. 55 mmol), acetaldehyde (93 ßL, 1. 65 mmol), and DCM : DMF (8 mL, 1 : 1 ratio). The mixture was shaken for 30 min. at room temperature. Then, Na (OAc) 3BH (580 mg, 2. 75 mmol) was added and the mixture was shaken overnight at room temperature. The mixture was degassed every half hour for the first three hours.

The resin was washed with MeOH (2x) and DCM (2x). Then, isocyanatobenzene (327 SL, 2. 75 mmol) and DCM (10 mL) were added to the resin in the peptide vessel. The resulting mixture was shaken overnight at room temperature. The resin was washed with DCM (2x). Then, 30% TFA in DCM (50 mL) was added and resulting mixture was shaken for 45 min. at room temperature. The resin was filtered and washed with DCM (2x). The filtrate was concentrated to afford 49.

Example 21 0 //\ I I H H / N N HN O O COCI2 30% TFA N gt COCI2 30% TFA Ng toluene DCM in DCM O NH2-78 Cto r-t. 2h, r. t. 46 [0482] To a round bottom flask was added resin (1. 1 mmol/g, 400 mg, 0. 44 mmol) and DCM (7 mL). The resulting mixture was stirred at-78°C and phosgene (217 mg, 2. 2 mmol) was added dropwise. The mixture was warmed up to room temperature and shaken for 3 hours. The resin was washed with DCM (2x) and transferred to a peptide vessel. Then, 1, 2, 3, 4- tetrahydroquinoline (585 UL, 4. 4 mmol) was added to the vessel.

The resulting mixture was shaken for 2 hours. The resin was washed with DCM (2x). Then, 30% TFA in DCM (30 mL) was added and resulting mixture was shaken for 45 min. at room temperature.

The resin was filtered and washed with DCM (2x). The filtrate was concentrated to afford 46.

Example 22 NEZ oh p N NCO r w W 0 I o w Na2S204 I i HN/O N02 DBU, DMF EtOH : HzO pM NH rt, overnight reflux 63 [0483] To a 20 ml vial was added 1- ( (4-fluoro-3- nitrophenyl) carbonyl)-2- (l-pyrrolidinylmethyl) pyrrolidine (520 mg, 1. 62 mmol), 3, 4-dimethylphenol (237 mg, 1. 94 mmol), DBU (271 AL, 1. 78 mmol), and DMF (10 mL). The resulting mixture was stirred overnight at room temperature. The mixture was extracted with H20 and EtOAc. The organic layers were combined, dried with MgS04, and concentrated to give a crude intermediate. The intermediate was purified by column chromatography to give a pure intermediate. Then, EtOH : H2O (3 : 1) and Na2S204 (10 eq) were. added to the intermediate. The resulting mixture was refluxed overnight. Then, the mixture was cooled to room temperature and extracted with H2O and EtOAc. The organic layers were combined, dried with MgS04, and concentrated to give a crude intermediate.

The crude intermediate was purified by column chromatography to give a pure intermediate. The purified intermediate was placed in a round bottom flask and DCM and phenylisocyanate (1 eq) were added. The resulting mixture was stirred at room temperature for 1 hour. The solvent was removed and the crude desired product was purified by column chromatography to afford 63.

Example 23 Functional Assay [0484] Human embryonic kidney cells (293 total) expressing either human, rat, or mouse MCH receptor were harvested from 150 mm culture dishes using PBS. Spinning at 1500 rpm for 2 minutes initially pelleted cells. The resulting pellet was then homogenized in 15 mL ice cold sucrose buffer (25 mM HEPES, 0. 3 M sucrose, pH 7. 4) with a motorized, glass fitted, Teflons homogenizer. The homogenate was centrifuged at 48, 000 X g at 4°C for 10 minutes, resuspended in 15 mL assay buffer (25 mM HEPES, 10 mM MgCl2, 0. 2% BSA, 0. 1 mg/mL STI, 0. 1 mg/mL Pefabloc, M Phosphoramidon, pH 7. 4) with a Tissue-Tearor (Biospec Products) and centrifuged again at 48, 000 X g for 10 minutes. The pellet was homogenized for a third time in 15 mL assay buffer using the Tissue-Tearor and again centrifuged at 48, 000 X g for 10 minutes. The resulting pellet was resuspended in assay buffer at a wet weight concentration of 10-20 mg/mL.

[0485] Pharmacological analyses were conducted using either a HT-PS100 device (Axiom Biotechnologies, San Diego, CA), which provides high-resolution dose-response fluorometric measurements of [Ca++] i mobilization, or using a FLIPS device (Molecular Devices, Sunnyvale, CA).

HT-PS100 Protocol : [0486] Materials : HEK 293 cells were stably transfected with the rat MCH 1 receptor and maintained under G418 antibiotic pressure. HT-PS100 assay buffer consisted of Physiological Saline Solution (145 mM NaCl, 5. 4 mM KCL, 1. 0 mM NaH2PO4, 1. 8 mM CaCl2, 0. 8 mM MgS04, 15. 0 mM HEPES, pH 7. 4, 11. 2 mM glucose) + 50 ßM Pluronic-F127. MCH peptide (Amgen, Inc.) was reconstituted in assay buffer and served as the positive agonist control for all experiments. Test compounds were prepared as 10 mM stocks in 100% DMSO and diluted to a top end working concentration of 100 AM in 96 well plates.

[0487] Methods : HEK 293 stably expressing MCH1R were maintained in Dulbeco's modified Eagle's medium (GIBCO/Life Technologies, Rockville, MD) supplemented with 2 mM glutamine and 10% dialyzed fetal bovine serum (HyClone, Logan, UT) at 37°C, 5% C02. Cells were harvested by 10'treatment with Versene (GIBCO/Life Technologies) followed by trituration, washing twice with cold (4°C) hybridoma medium (Serum/Protein free, with L- glutamine, sodium bicarbonate, MOPS buffer) (Sigma-Aldrich Corp, St. Louis, MO) and resuspended at 2 x 106 cells/mL in the same medium. The resuspended cells were loaded with the fluorescent calcium indicator Fura-2 by incubating with Fura-2AM (Molecular Probes, Eugene, OR) at 1. 6 AM for 60'at room temperature. The loaded cells were then washed twice with hybridoma medium, adjusted to 2 x 105 cells/mL and kept at ambient temperature in a spinner flask under gentle stirring for up to 6 hours during the experiment.

[0488] Receptor-stimulated intracellular calcium responses were detected in the flow-through detector cuvette of the HT- PS100 by monitoring increases in the ratio of Fura-2 fluorescence intensities R340/380 measured at alternating 340/380 nm excitation and 510 nm emission.

[0489] Preliminary static experiments, conducted to determine the kinetics of MCHlR's dose response to MCH peptide, indicated the optimum time point to capture the maximum Ca++ transients was 30 s. No interference with DMSO was seen up to 1%. Based on these observations, subsequent experiments were conducted on the HT-PS100 to generate high resolution dose response curves, characterize agonist/antagonist properties, and evaluate antagonist potencies via Schild experiments. During HT- PS100 validation, reproducible EC50s for MCH of 10 nM were generated within a broad range of cell passage and harvest density. HT-PS100 gradient generation was calibrated with a standardized stock of fluorescein.

[0490] Test compounds were screened for MCH1R activity in the HT-PS100 for both agonist and antagonist action. Agonist mode challenges were conducted at a maximum gradient concentration of 100 ßM. Antagonist activity was tested by 30 s pre-incubation of cells at a compound concentration of 100 ßM, with subsequent introduction of MCH at a concentration 5-fold of EC50 as determined in preliminary experiments. Compounds that showed inhibition of the MCH-induced Ca++ response were automatically tagged for re-interrogation, IC50 generation, and Schild analysis.

[0491] Schild experiments were conducted on the HT-PS100 for selected compounds by 30 s pre-incubation of cells with antagonist compounds prior to administering MCH peptide. Several fixed concentrations of antagonist compounds were prepared in 10-fold increments, and presented to the cells 30 s before introducing a gradient of increasing MCH concentration. Values for compound pA2 were calculated by linear regression of Log (DR - 1) MCH EC50 as a function of Log (antagonist concentration), where DR is the dose ratio of MCH ECso values determined in the presence and absence of antagonist.

[0492] The following compounds had Ki values of 100 uM or less in the HT-PS100 assay : Compound Nos.. Of these, Compound Nos. had Ki values of 100 nM or less in this assay.

FLIPR protocol : [0493] Materials : Pharmacological analysis was conducted using a FLIPR device (Molecular Devices, Sunnyvale, CA). CHOK1- Gqi cells were stably transfected with the rat MCH1 receptor and maintained under G418 antibiotic pressure. FLIPR (D assay buffer consisted of phenol red-free DMEM + 2. 5 mM probenecid. MCH peptide (Amgen, Inc.) was reconstituted in assay buffer and served as the positive agonist control for all experiments. Test compounds were prepared as 10 mM stocks in 100% DMSO and diluted to a top end working concentration of 10 ßM in 96 well black, flat bottom, collagen-I coated plates (Becton Dickinson, Bedford, MA).

[0494] Methods : CHOK1-Gqi cells stably expressing MCH1R were maintained in Dulbeco's modified Eagle's medium (GIBCO/Life Technologies, Rockville, MD) supplemented with 2 mM glutamine and 10% dialyzed fetal bovine serum (HyClone, Logan, UT) at 37°C, 5% C02. Cells were harvested by 10'treatment with Versene (GIBCO/Life Technologies) followed by trituration, washing twice with cold (4°C) hybridoma medium (Serum/Protein free, with L- glutamine, sodium bicarbonate, MOPS buffer) (Sigma-Aldrich Corp, St : Louis, MO) and replated onto 96 well black, flat bottom, collagen-I coated plates to a density of 10, 000 cells/well. The cells were then loaded with the fluorescent calcium indicator Fura-2 (Molecular Probes, Eugene, OR) at 1. 6 AM for 60'at room temperature. The loaded cells were then washed twice with 90 ßl/well of wash buffer (1XHBSS, 20 mM HEPES, 2. 5 mM probenecid).

[0495] Receptor-stimulated intracellular calcium responses were detected using FLIPR'by monitoring increases in the Fura-2 fluorescence response.

[0496] Test compounds were screened for MCH1R activity in the FLIPR for both agonist and antagonist action. Agonist mode challenges were conducted at a maximum gradient concentration of 1 uM. Antagonist activity was tested by 10 min pre-incubation of cells at a compound concentration of defined to be 300X the ECso of MCH (typically 1 uM), with subsequent introduction of MCH at a concentration 5-fold of EC50 as determined in preliminary experiments. Compounds that showed inhibition of MCH induced MCH1R dependant Ca++ responses were automatically tagged for re- interogation, ICso generation, and Schild analysis.

[0497] Schild experiments were conducted on the FLIPR for selected compounds by co-administering antagonist compounds together with MCH peptide. Several fixed concentrations of antagonist compounds were prepared in 10-fold increments, and presented to the cells in a gradient of increasing MCH concentration. Values for compound pA2 were calculated by linear regression of MCH EC50s as a function'of antagonist concentration.

[0498] The following compounds had Ki values of 100 AM or less in the rMCH FLIPR assay : Compound Nos. 1, 5, 6, 15, 22, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 51, 53, 54, 55, 56, 57, 58, 59, and 64. Of these, Compound Nos. 1, 6, 15, 31, 32, 38, 39, 40, and 41 had Ki values of 100 nM or less in this assay.

[0499] The following compounds had Ki values of 100 ßM or less in the hMCH FLIPRs assay : Compound Nos. 1, 5, 6, 34, 35, 36, 37, 38, 40, 41, 51, 52, 53, 54, 55, 56, 57, 58, 59, and 64.

Of these, Compound Nos. 1, 6, 34, 35, 38, 40, 41, 51, 56, and 57 had Ki values of 100 nM or less in this assay.

Example 24 Ligand Binding Assay [0500] Binding assays were determined as described below using mouse, rat or human MCH 1 receptors (mMCHIR, rMCHIR, and hMCHIR, respectively) expressed in HEK 293 ; IC50 values were calculated.

[0501] Binding assays were performed in 96-well U-bottom plates. Membranes (100 yg tissue) were incubated at 30°C for 90 minutes in assay buffer with various peptides in the presence of 0. 2 nM 1251 native-MCH (Perkin-Elmer Life Sciences, Boston, MA) in 100 AL total volume. Non-specific binding was assessed in the presence of 1 ßM cold native-MCH. The reaction was terminated by rapid filtration through Unfilter-96 GF/C glass fiber filter plates (FilterMate 196 Harvester, Packard Instrument Co., Meriden, CT) pre-soaked in PBS/0. 5% BSA, followed by three washes with 300 ßL ice-cold water. Bound radioactivity was determined using a TopCount microplate scintillation and luminescence counter (Packard Instrument Co., Meriden, CT).

Nonlinear regression analyses of drug concentration curves were performed using GraphPad Prism@ (GraphPad Software, Inc., San Diego, CA).

[0502] The following compounds had IC50 values of 100 yM or less in the rMCH assay : Compound Nos. 1, 10, 12, 13, 15, 16, 17, 18, 22, 27, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 51, 52, 53, 54, 55, 56, 57, 58, 59, 61, 63, 64, 65, and 66.

Of these, Compound Nos. 1, 31, 38, 39, 40, 41, 51, 52, 53, 54, 55, 56, 57, 58, 59, 61, and 66 had IC. 50 values of 100 nM or less in the rMCH assay.

[0503] The following compounds had IC, 50 values of 100 ßM or less in the hMCH assay : Compound Nos. 1, 5, 6, 8, 10, 12, 13, 15, 16, 17, 18, 20, 22, 27, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 58, 59, 64, 65, and 66. Of these, Compound Nos. 1, 6, 31, 32, 33, 34, 36, 37, 38, 39, 40, 41, 58, 59, and 66 had IC50 values of 100 nM or less in the hMCH assay.

[0504] In view of the above, it will be seen that the several objects of the invention are achieved.

[0505] The above description of the embodiments and examples are intended only to acquaint others skilled in the art with the invention, its principles, and its practical application, so that others skilled in the art may adapt and apply the invention in its numerous forms, as may be best suited to the requirements of a particular use. The present invention, therefore, is not limited to the above embodiments, and may be variously modified.

[0506] With reference to the use of the word (s)"comprise" or"comprises"or"comprising"or"including"or"having"in the above description and/or in the following claims, it should be noted that unless the context requires otherwise, those words are used on the basis and clear understanding that they are to be interpreted inclusively, rather than exclusively, and that each of those words is to be so interpreted in construing the above description and/or the following claims. When introducing elements of the present invention or the preferred embodiment (s) thereof, the articles"a,""an,""the,"and"said"are intended to mean that there are one or more of the elements.

[0507] In view of the above, it will be seen that the several objects of the invention are achieved and other advantageous results attained.

[0508] As various changes could be made in the above compounds and methods without departing from the scope of the invention, it is intended that all matter contained in the above description shall be interpreted as illustrative and not in a limiting sense.

[0509] The entire texts of all U. S. Patents and other references cited herein are hereby incorporated by reference into this patent.