CHANNELS

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Patent Application No. 61/759,300, filed January 31, 2013, the entire contents of which are incorporated herein by reference.

TECHNICAL FIELD OF THE INVENTION

[001] The invention relates to compounds useful as inhibitors of sodium channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders including pain.

BACKGROUND OF THE INVENTION

[002] Pain is a protective mechanism that allows healthy animals to avoid tissue damage and to prevent further damage to injured tissue. Nonetheless there are many conditions where pain persists beyond its usefulness, or where patients would benefit from inhibition of pain.

Neuropathic pain is a form of chronic pain caused by an injury to the sensory nerves (Dieleman, J.P., et al., Incidence rates and treatment of neuropathic pain conditions in the general population. Pain, 2008. 137(3): p. 681-8). Neuropathic pain can be divided into two categories, pain caused by generalized metabolic damage to the nerve and pain caused by a discrete nerve injury. The metabolic neuropathies include post herpetic neuropathy, diabetic neuropathy, and drug-induced neuropathy. Discrete nerve injuries indications include post amputation pain, post-surgical nerve injury pain, and nerve entrapment injuries like neuropathic back pain.

[003] Voltage-gated sodium channels (Na _v 's) play a critical role in pain signaling. Na _v 's are key biological mediators of electrical signaling as they are the primary mediators of the rapid upstroke of the action potential of many excitable cell types (e.g. neurons, skeletal myocytes, cardiac myocytes). The evidence for the role of these channels in normal physiology, the pathological states arising from mutations in sodium channel genes, preclinical work in animal models, and the clinical pharmacology of known sodium channel modulating agents all point to the central role of Na _v 's in pain sensation (Rush, A.M. and T.R. Cummins, Painful Research: Identification of a Small-Molecule Inhibitor that Selectively Targets ΝαγΙ-8 Sodium Channels. Mol Interv, 2007. 7(4): p. 192-5); England, S., Voltage -gated sodium channels: the search for subtype- selective analgesics. Expert Opin Inves tig Drugs 17 (12), p. 1849-64 (2008); Krafte, D. S. and Bannon, A. W., Sodium channels and nociception: recent concepts and therapeutic opportunities. Curr Opin Pharmacol 8 (1), p. 50-56 (2008)). Na _v 's are the primary mediators of the rapid upstroke of the action potential of many excitable cell types (e.g. neurons, skeletal myocytes, cardiac myocytes), and thus are critical for the initiation of signaling in those cells (Hille, Bertil, Ion Channels of Excitable Membranes, Third ed. (Sinauer Associates, Inc., Sunderland, MA, 2001)). Because of the role Na _v 's play in the initiation and propagation of neuronal signals, antagonists that reduce Na _v currents can prevent or reduce neural signaling and Na _v channels have long been considered likely targets to reduce pain in conditions where hyper-excitability is observed (Chahine, M., Chatelier, A., Babich, O., and Krupp, J. J., Voltage-gated sodium channels in neurological disorders. CNS Neurol Disord Drug Targets 7 (2), p. 144-58 (2008)). Several clinically useful analgesics have been identified as inhibitors of Na _v channels. The local anesthetic drugs such as lidocaine block pain by inhibiting Na _v channels, and other compounds, such as carbamazepine, lamotrigine, and tricyclic antidepressants that have proven effective at reducing pain have also been suggested to act by sodium channel inhibition (Soderpalm, B., Anticonvulsants: aspects of their mechanisms of action. Eur J Pain 6 Suppl A, p. 3-9 (2002); Wang, G. K., Mitchell, J., and Wang, S. Y., Block of persistent late Na ⁺ currents by antidepressant sertraline and paroxetine. JMembr Biol 222 (2), p. 79-90 (2008)).

[004] The Na _v 's form a subfamily of the voltage-gated ion channel super- family and comprises 9 isoforms, designated Navl .1 -Navl .9. The tissue localizations of the nine isoforms vary greatly. Navl .4 is the primary sodium channel of skeletal muscle, and Navl .5 is primary sodium channel of cardiac myocytes. Na _v 's 1.7, 1.8 and 1.9 are primarily localized to the peripheral nervous system, while Na _v 's 1.1, 1.2, 1.3, and 1.6 are neuronal channels found in both the central and peripheral nervous systems. The functional behaviors of the nine isoforms are similar but distinct in the specifics of their voltage-dependent and kinetic behavior (Catterall, W. A., Goldin, A. L., and Waxman, S. G., International Union of Pharmacology. XL VII.

Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol Rev 57 (4), p. 397 (2005)).

[005] Immediately upon their discovery, Na _v l .8 channels were identified as likely targets for analgesia (Akopian, A.N., L. Sivilotti, and J.N. Wood, A tetrodotoxin-resistant voltage- gated sodium channel expressed by sensory neurons. Nature, 1996. 379(6562): p. 257-62). Since then, Na _v l .8 has been shown to be the most significant carrier of the sodium current that maintains action potential firing in small DRG neurons (Blair, N.T. and B.P. Bean, Roles of tetrodotoxin (TTX)-sensitive Na+ current, TTX-resistant Na ⁺ current, and Ca ²⁺ current in the action potentials of nociceptive sensory neurons. JNeurosci., 2002. 22(23): p. 10277-90). Na _v 1.8 is essential for spontaneous firing in damaged neurons, like those that drive neuropathic pain (Roza, C, et al., The tetrodotoxin-resistant Na ⁺ channel Na _v 1.8 is essential for the expression of spontaneous activity in damaged sensory axons of mice. J. Physiol., 2003. 550(Pt 3): p. 921 -6; Jarvis, M.F., et al., A- 803467, a potent and selective Na _v 1.8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the rat. Proc Natl Acad Sci. U S A, 2007. 104(20): p. 8520-5; Joshi, S.K., et al., Involvement of the TTX-resistant sodium channel Navl .8 in inflammatory and neuropathic,but not post-operative, pain states. Pain, 2006. 123(1-2): pp. 75-82; Lai, J., et al., Inhibition of neuropathic pain by decreased expression of the tetrodotoxin-resistant sodium channel, Na _v 1.8. Pain, 2002. 95(1-2): p. 143-52; Dong, X.W., et al., Small interfering RNA-mediated selective knockdown of Na( _v )1.8 tetrodotoxin-resistant sodium channel reverses mechanical allodynia in neuropathic rats. Neuroscience, 2007. 146(2): p. 812-21 ; Huang, H.L., et al., Proteomic profiling of neuromas reveals alterations in protein composition and local protein synthesis in hyper- excitable nerves. Mol Pain, 2008. 4: p. 33; Black, J.A., et al., Multiple sodium channel isoforms and mitogen-activated protein kinases are present in painful human neuromas. Ann Neurol, 2008. 64(6): p. 644-53; Coward, K., et al., Immunolocalization of SNS/PN3 and NaN/SNS2 sodium channels in human pain states. Pain, 2000. 85(1-2): p. 41 -50; Yiangou, Y., et al., SNS/PN3 and SNS2/NaN sodium channel-like immunoreactivity in human adult and neonate injured sensory nerves. FEBS Lett, 2000. 467(2-3): p. 249-52; Ruangsri, S., et al., Relationship of axonal voltage- gated sodium channel 1.8 (Na _v l .8) mRNA accumulation to sciatic nerve injury-induced painful neuropathy in rats. J Biol Chem. 286(46): p. 39836-47). The small DRG neurons where Na _v 1.8 is expressed include the nociceptors critical for pain signaling. Na _v l .8 is the primary channel that mediates large amplitude action potentials in small neurons of the dorsal root ganglia (Blair, N.T. and B.P. Bean, Roles of tetrodotoxin (TTX)-sensitive Na ⁺ current, TTX-resistant Na ⁺ current, and Ca ²⁺ current in the action potentials of nociceptive sensory neurons. J Neurosci., 2002. 22(23): p. 10277-90). Na _v l .8 is necessary for rapid repetitive action potentials in nociceptors, and for spontaneous activity of damaged neurons. (Choi, J.S. and S.G. Waxman, Physiological interactions between Na _v 1.7 and Na _v 1.8 sodium channels: a computer simulation study. J Neurophysiol. 106(6): p. 3173-84; Renganathan, M., T.R. Cummins, and S.G. Waxman,

Contribution of Na( _v )1.8 sodium channels to action potential electrogenesis in DRG neurons. J Neurophysiol., 2001. 86(2): p. 629-40; Roza, C, et al., The tetrodotoxin-resistant Na ⁺ channel Na _v l .8 is essential for the expression of spontaneous activity in damaged sensory axons of mice. J Physiol., 2003. 550(Pt 3): p. 921 -6). In depolarized or damaged DRG neurons, Na _v 1.8 appears to be the primary driver of hyper-excitablility (Rush, A.M., et al., A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons. Proc Natl Acad Sci USA, 2006. 103(21): p. 8245-50). In some animal pain models, Na _v l .8 mRNA expression levels have been shown to increase in the DRG (Sun, W., et al., Reduced conduction failure of the main axon of polymodal nociceptive C-fibres contributes to painful diabetic neuropathy in rats. Brain. 135(Pt 2): p. 359-75; Strickland, I.T., et al., Changes in the expression of NaVl .7, Na _v 1.8 and Na _v 1.9 in a distinct population of dorsal root ganglia innervating the rat knee joint in a model of chronic inflammatory joint pain. Eur J Pain, 2008. 12(5): p. 564-72; Qiu, F., et al., Increased expression of tetrodotoxin-resistant sodium channels Na _v l .8 and Na _v l .9 within dorsal root ganglia in a rat model of bone cancer pain. Neurosci. Lett. 512(2): p. 61 -6). [006] The primary drawback to the known Na _v inhibitors is their poor therapeutic window, and this is likely a consequence of their lack of isoform selectivity. Since Na _v l .8 is primarily restricted to the neurons that sense pain, selective Na _v 1.8 blockers are unlikely to induce the adverse events common to non-selective Na _v blockers. Accordingly, there remains a need to develop additional Na _v channel antagonists preferably those that are more Navl .8 selective and more potent with increased metabolic stability and with fewer side effects.

SUMMARY OF THE INVENTION

[007] It has now been found that compounds of this invention, and pharmaceutically acceptable salts and compositions thereof, are useful as inhibitors of voltage-gated sodium channels.

[008] These compounds have the general formula I:

or a pharmaceutically acceptable salt thereof.

[009] These compounds and pharmaceutically acceptable salts and compositions are useful for treating or lessening the severity of a variety of diseases, disorders, or conditions, including, but not limited to, chronic pain, gut pain, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, idiopathic pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence or cardiac arrhythmia.

Detailed Description of the Invention

[0010] In one aspect, the invention provides compounds of formula I:

or a pharmaceutically acceptable salt thereof,

wherein, independently for each occurrence:

Y is C or N;

Ar ¹ is a 5-6 membered aromatic monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is optionally fused to a 5 -membered monocyclic aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein Ar ¹ has m substituents, each independently selected from - WR ^W ;

m is an integer from 0 to 5 inclusive;

W is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -O- -CO-,

R ^w is absent, H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , OCF ₃ , or a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfurR' is Ci-C ₆ alkyl;

R ¹ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen and wherein up to two non-adjacent CH ₂ units of said C ₁ -C6 alkyl may be replaced with -0-;

R ² is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ³ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁴ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁵ is H, halogen, CN, or -X-R ^x ;

R ⁵ is H, halogen, CN, or -X-R ^x ;

R ⁶ is H, halogen, CN, or -X-R ^x ;

R ⁶ is H, halogen, CN, or -X-R ^x ;

R ⁷ is H, halogen, CN, or -X-R ^x ;

X is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C ₁ -C6 alkyl may be replaced with -0-; and

R ^x is absent, H, or C ₃ -C ₈ cycloaliphatic, wherein up to two non-adjacent CH ₂ units of said C ₃ -C ₈ cycloaliphatic may be replaced with -O- and said C ₃ -C ₈ cycloaliphatic is substituted with 0-3 substituents selected from halogen and C ₁ -C4 alkyl. [0011] For purposes of this invention, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75 ^th Ed. Additionally, general principles of organic chemistry are described in "Organic Chemistry," Thomas Sorrell, University Science Books, Sausalito: 1999, and "March's Advanced Organic Chemistry," 5 ^th Ed., Ed.: Smith, M.B. and March, J., John Wiley & Sons, New York: 2001, the entire contents of which are hereby incorporated by reference.

[0012] As described herein, compounds of the invention can optionally be substituted with one or more substituents, such as are illustrated generally above, or as exemplified by particular classes, subclasses, and species of the invention. As described herein, the variables in formula I encompass specific groups, such as, for example, alkyl and cycloalkyl. As one of ordinary skill in the art will recognize, combinations of substituents envisioned by this invention are those combinations that result in the formation of stable or chemically feasible compounds. The term "stable," as used herein, refers to compounds that are not substantially altered when subjected to conditions to allow for their production, detection, and preferably their recovery, purification, and use for one or more of the purposes disclosed herein. In some embodiments, a stable compound or chemically feasible compound is one that is not substantially altered when kept at a temperature of 40°C or less, in the absence of moisture or other chemically reactive conditions, for at least a week.

[0013] The phrase "optionally substituted" may be used interchangeably with the phrase "substituted or unsubstituted." In general, the term "substituted," whether preceded by the term "optionally" or not, refers to the replacement of hydrogen radicals in a given structure with the radical of a specified substituent. Specific substituents are described above in the definitions and below in the description of compounds and examples thereof. Unless otherwise indicated, an optionally substituted group can have a substituent at each substitutable position of the group, and when more than one position in any given structure can be substituted with more than one substituent selected from a specified group, the substituent can be either the same or different at every position. A ring substituent, such as a heterocycloalkyl, can be bound to another ring, such as a cycloalkyl, to form a spiro-bicyclic ring system, e.g., both rings share one common atom. As one of ordinary skill in the art will recognize, combinations of substituents envisioned by this invention are those combinations that result in the formation of stable or chemically feasible compounds.

[0014] The phrase "up to," as used herein, refers to zero or any integer number that is equal or less than the number following the phrase. For example, "up to 4" means any one of 0, 1 , 2, 3, and 4.

[0015] The term "aliphatic," "aliphatic group" or "alkyl" as used herein, means a straight- chain (i.e., unbranched) or branched, substituted or unsubstituted hydrocarbon chain that is completely saturated or that contains one or more units of unsaturation. Unless otherwise specified, aliphatic groups contain 1 - 20 aliphatic carbon atoms. In some embodiments, aliphatic groups contain 1 - 10 aliphatic carbon atoms. In other embodiments, aliphatic groups contain 1 - 8 aliphatic carbon atoms. In still other embodiments, aliphatic groups contain 1 - 6 aliphatic carbon atoms, and in yet other embodi ments aliphatic groups contain 1 - 4 aliphatic carbon atoms. Suitable aliphatic groups include, but are not limited to, linear or branched, substituted or unsubstituted alkyl, alkenyl, alkynyl groups.

[0016] The terms "cycloaliphatic" or "cycloalkyl" mean a monocyclic hydrocarbon ring, or a polycyclic hydrocarbon ring system that is completely saturated or that contains one or more units of unsaturation, but which is not aromatic and has a single point of attachment to the rest of the molecule. The term "polycyclic ring system," as used herein, includes bicyclic and tricyclic 4- to 12- membered structures that form at least two rings, wherein the two rings have at least one atom in common (e.g., 2 atoms in common) including fused, bridged, or spirocyclic ring systems.

[0017] The term "halogen" or "halo" as used herein, means F, CI, Br or I. Unless otherwise specified, the term "heterocycle," "heterocyclyl," "heterocycloaliphatic,"

"heterocycloalkyl," or "heterocyclic" as used herein means non-aromatic, monocyclic, bicyclic, or tricyclic ring systems in which one or more ring atoms in one or more ring members is an independently selected heteroatom. Heterocyclic ring can be saturated or can contain one or more unsaturated bonds. In some embodiments, the "heterocycle," "heterocyclyl,"

"heterocycloaliphatic," "heterocycloalkyl," or "heterocyclic" group has three to fourteen ring members in which one or more ring members is a heteroatom independently selected from oxygen, sulfur, nitrogen, or phosphorus, and each ring in the ring system contains 3 to 7 ring members.

[0018] The term "heteroatom" means oxygen, sulfur, nitrogen, phosphorus, or silicon (including, any oxidized form of nitrogen, sulfur, phosphorus, or silicon; the quaternized form of any basic nitrogen or; a substitutable nitrogen of a heterocyclic ring, for example N (as in 3,4- dihydro-2 f-pyrrolyl), NH (as in pyrrolidinyl) or NR ⁺ (as in N-substituted pyrrolidinyl)).

[0019] The term "unsaturated," as used herein, means that a moiety has one or more units of unsaturation but is not aromatic.

[0020] The term "alkoxy," or "thioalkyl," as used herein, refers to an alkyl group, as previously defined, attached to the principal carbon chain through an oxygen ("alkoxy") or sulfur ("thioalkyl") atom.

[0021] The term "aryl" used alone or as part of a larger moiety as in "aralkyl,"

"aralkoxy," or "aryloxyalkyl," refers to monocyclic, bicyclic, and tricyclic ring systems having a total of five to fourteen ring carbon atoms, wherein at least one ring in the system is aromatic and wherein each ring in the system contains 3 to 7 ring carbon atoms. The term "aryl" may be used interchangeably with the term "aryl ring."

[0022] The term "heteroaryl," used alone or as part of a larger moiety as in "heteroaralkyl" or "heteroarylalkoxy," refers to monocyclic, bicyclic, and tricyclic ring systems having a total of five to fourteen ring members, wherein at least one ring in the system is aromatic, at least one ring in the system contains one or more heteroatoms, and wherein each ring in the system contains 3 to 7 ring members. The term "heteroaryl" may be used interchangeably with the term "heteroaryl ring" or the term "heteroaromatic."

[0023] Unless otherwise stated, structures depicted herein are also meant to include all isomeric (e.g., enantiomeric, diastereomeric, and geometric (or conformational)) forms of the structure; for example, the R and S configurations for each asymmetric center, (Z) and (E) double bond isomers, and (Z) and (E) conformational isomers. Therefore, single stereochemical isomers as well as enantiomeric, diastereomeric, and geometric (or conformational) mixtures of the present compounds are within the scope of the invention. Unless otherwise stated, all tautomeric forms of the compounds of the invention are within the scope of the invention. Thus, included within the scope of the invention are tautomers of compounds of formula I. The structures also include zwitterioinc forms of the compounds or salts of formula I where appropriate. Examples of tautomeric forms include those depicted below:

[0024] Additionally, unless otherwise stated, structures depicted herein are also meant to include compounds that differ only in the presence of one or more isotopically enriched or isotopically-labeled atoms. The isotopically-labeled compounds may have one or more atoms replaced by an atom having an atomic mass or mass number usually found in nature. Examples of isotopes present in compounds of formula I include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine and chlorine, such as, but not limited to, ² H, H, ¹ C, ¹⁴ C, ¹⁵ N, ^ls O, ¹⁷ 0, ⁵ S and ¹⁸ F. Certain isotopically-labeled compounds of formula I, in addition to being useful as as therapuetic agents, are also useful in drug and/or substrate tissue distribution assays, as analytical tools or as probes in other biological assays. In one aspect of the present invention, tritiated (e.g., H) and carbon-14 (e.g., ¹⁴ C) isotopes are useful given their ease of detectability. In another aspect of the present invention, replacement of one or more hydrogen atoms with heavier isotopes such as deuterium, (e.g., ² H) can afford certain therapeutic advantages.

[0025] In the formulas and drawings, a line transversing a ring and bonded to an R group such as in

means that the R group, i.e. the WR can be attached to any substitutable ring atom on either ring of the bicyclic ring system.

[0026] Within a definition of a term as, for example, X, R ^x , R ¹ , R ² , R ³ , R ⁴ , or W when a CH ₂ unit or, interchangeably, methylene unit may be replaced, for example, by -0-, it is meant to include any CH ₂ unit, including a CH ₂ within a terminal methyl group. For example,

CH2CH2CH2OH is within the definition of C1-C6 alkyl wherein up to two non-adjacent CH ₂ units may be replaced by -O- because the CH2 unit of the terminal methyl group has been replaced by - O-.

[0027] In one embodiment, the invention features a compound of formula I and the attendant definitions, wherein Y is C. In another embodiment, Y is N.

[0028] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein Ar ¹ is selected from:

wherein ring Ai is a 5-6 membered aromatic monocyclic ring having 0-4 heteroatoms

independently selected from nitrogen, oxygen, or sulfur; or

Ai and A ₂ , together, form an 8-9 membered aromatic, bicyclic ring, wherein each ring contains 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0029] In another embodiment, the invention features a compound of formula I and the Ai is a 6 membered aromatic ring having 0-4 heteroatoms, independently selected from nitrogen, oxygen, or sulfur. In another embodiment, Ai is phenyl. In another embodiment, Ai is a 6 membered aromatic ring having 1 or 2 heteroatoms, independently selected from nitrogen. In another embodiment, Ai is pyridyl, pyrimidinyl, pyrazinyl or triazinyl.

[0030] In another embodiment, the invention features a compound of formula I and the Ai is a 5-membered aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, Ai is a 5 -membered aromatic ring having 1 -4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, Ai is pyrrolyl, pyrazolyl, thiazolyl, thiadiazolyl, imidazolyl, oxazolyl, triazolyl, or tetrazolyl.

[0031] In another embodiment, the invention features a compound of formula I and the attendant defin ^ is phenyl, and A ₂ is a 5- membered aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, A ₂ is a 5 -membered aromatic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, A ₂ is pyrrolyl, pyrazolyl, thiazolyl, thiadiazolyl, imidazolyl, oxazolyl, or triazolyl.

[0032] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein m is zero. In another embodiment, m is an integer from 1 to 5. In another embodiment, m is 1. In another embodiment, m is 2. In another embodiment, m is 3. In another embodiment, m is 4. In another embodiment, m is 5.

[0033] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein W is a bond and R ^w is halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is a bond and R ^w is halogen. In another embodiment, W is a bond and R ^w is OH. In another embodiment, W is a bond and R ^w is NH ₂ . In another embodiment, W is a bond and R ^w is NHR'. In another embodiment, W is a bond and R ^w is CN. In another embodiment, W is a bond and R ^w is CF ₃ . In another embodiment, W is a bond and R ^w is OCF ₃ .

[0034] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is CH ₃ , CH ₂ CH ₃ ,

CH ₂ CH ₂ CH ₃ , or isopropyl. In another embodiment, W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or O-isopropyl. In another embodiment, W is OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ . In another embodiment, W is OCH ₂ CH ₂ OCH ₃ , CH ₂ OH, OC(CH ₃ ) ₃ , or CH ₂ CH ₂ OCH ₃ .

[0035] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO ₂ -, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl may be replaced with - 0-, -CO-, -S-, -SO-, or -SO ₂ -, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R is NH ₂ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NH ₂ . In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NHR'.

[0036] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein W is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -, and R ^w absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said C ₂ alkyl may be replaced with -0-, -CO-, -S-, -SO-, -S0 ₂ -, and R ^w is absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is absent.

[0037] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein W is a bond and R ^w is a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 1 -4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is pyrrolyl, pyrazolyl, thiazolyl, thiadiazolyl, imidazolyl, oxazolyl, triazolyl, or tetrazolyl.

[0038] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein R ¹ is H. In another embodiment, R ¹ is halogen. In another embodiment, R ¹ is CN. In another embodiment, R ¹ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ¹ is CF ₃ .

[0039] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein R ² is H. In another embodiment, R ² is halogen. In another embodiment, R ² is CI. In another embodiment, R ² is F. In another embodiment, R ² is CN. In another embodiment, R ² is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ² is CF ₃ . In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ² is OCF ₃ . In another embodiment, R ² is F, CI, CN, CF ₃ or OCF ₃ .

[0040] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein R ³ is H. In another embodiment, R ³ is halogen. In another embodiment, R ³ is CI. In another embodiment, R ³ is F. In another embodiment, R ³ is CN. In another embodiment, R ³ is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ³ is i-butyl. In another embodiment, R ³ is CF3. In another embodiment, R ³ is CF ₂ CF ₃ .

[0041] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein R ⁴ is H. In another embodiment, R ⁴ is halogen. In another embodiment, R ⁴ is CN. In another embodiment, R ⁴ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁴ is CF ₃ .

[0042] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein R ¹ , R ² , R ³ , and R ⁴ is H.

[0043] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein R ⁵ is H. In another embodiment, R ⁵ is halogen. In another embodiment, R ⁵ is CI. In another embodiment, R ⁵ is F. In another embodiment, R ⁵ is CN. In another embodiment, R ⁵ is -X-R ^x . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁵ is CH ₃ . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Q-C6 alkyl is replaced with -0-. In another embodiment, R ⁵ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or OCH(CH ₃ ) ₂ . In another embodiment, R ⁵ is OCH ₃ . In another embodiment, R ⁵ is CH ₂ OH. In another embodiment, R ⁵ is OCF ₃ . In another embodiment, R ⁵ is OCHF ₂ .

[0044] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein R ⁵ is H. In another embodiment, R ⁵ is halogen. In another embodiment, R ⁵ is CI. In another embodiment, R ⁵ is F. In another embodiment, R ⁵ is CN. In another embodiment, R ⁵ is -X-R ^x . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Q-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁵ is CH ₃ . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Q-C6 alkyl is replaced with -0-. In another embodiment, R ⁵ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or OCH(CH ₃ ) ₂ . In another embodiment, R ⁵ is OCH ₃ . In another embodiment, R ⁵ is CH ₂ OH. In another embodiment, R ⁵ is OCF ₃ . In another embodiment, R ⁵ is OCHF ₂ .

[0045] In another embodiment, the invention features a compound of formula I and the attendant definitions, R ⁶ is H. In another embodiment, R ⁶ is halogen. In another embodiment, R ⁶ is CI. In another embodiment, R ⁶ is F. In another embodiment, R ⁶ is CN. In another embodiment, R ⁶ is -X-R ^x . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen. In another embodiment, R ⁶ is CH ₃ . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Q-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said C1-C6 alkyl is replaced with -0-. In another embodiment, R ⁶ is OCH ₃ .

[0046] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein R ⁶ is H. In another embodiment, R ⁶ is halogen. In another embodiment, R ⁶ is CI. In another embodiment, R ⁶ is F. In another embodiment, R ⁶ is CN. In another embodiment, R ⁶ is -X-R ^x . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Q-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁶ is CH ₃ . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Q-C6 alkyl is replaced with -0-. In another embodiment, R ⁶ is OCH ₃ .

[0047] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein R ⁷ is H. In another embodiment, R ⁷ is halogen. In another embodiment, R ⁷ is CI. In another embodiment, R ⁷ is F. In another embodiment, R ⁷ is CN. In another embodiment, R is -X-R . In another embodiment, R is -X-R wherein R is absent. In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁷ is CH ₃ , CH ₂ CH ₃ , CH2CH ₂ CH ₃ or isopropyl. In another embodiment, R ⁷ is CF ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein two non-adjacent CH2 units of said C1-C6 alkyl are replaced with -0-. In another embodiment, R ⁷ is OCH2CH ₂ OCH ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁷ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , OC(CH ₃ ) ₃ , CH ₂ CH ₂ OCH ₃ . In another embodiment, R ⁷ is OCF ₃ , OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ .

[0048] In another embodiment, the invention features a compound of formula I wherein R ⁷ is -X-R ^x wherein X is a bond and R ^x is C ₃ -Cs cycloaliphatic and said C ₃ -Cs cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is a bond and R ^x is cyclopropyl.

[0049] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein R ⁷ is -X-R ^x wherein X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -O- and R ^x is C ₃ -C ₈ cycloaliphatic and said C ₃ -C ₈ cycloaliphatic is substituted with up 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is OCH ₂ and R ^x is cyclopropyl. [0050] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein ring A is selected from:

[0051] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein R ¹ is H or alkyl wherein said alkyl is substituted with 0- 6 halogen. In another embodiment, R ¹ is CF ₃ .

[0052] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein R ² is H, halogen, or C _\ -C alkyl wherein said C _\ -C alkyl is substituted with 0-6 halogen and wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ² is F, CI, CF3 or OCF3

[0053] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein R ³ is H, halogen or C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ³ is i-butyl, CI, CF ₃ or CF ₂ CF ₃ .

[0054] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein R ⁴ is H, halogen or C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁴ is CF ₃ .

[0055] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein R ¹ , R ² , R ³ and R ⁴ are H.

[0056] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein R ⁵ and R ⁷ are each independently halogen, or -X-R ^x and R ⁵ , R ⁶ , and R ⁶ are each hydrogen. In another embodiment, R ⁵ and R ⁷ are each independently F, CI, CH ₃ , OCF ₃ , or OCH ₃ .

[0057] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein ring A is selected from:

[0058] In another embodiment, ring A is selected from:

[0059] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein Ar ¹ is , Ai is a 6 membered aromatic ring having 0-4 heteroatoms, independently selected from nitrogen, oxygen, or sulfur, m is 1, W is a bond or C _\ -Ce alkyl wherein up to two non-adjacent CH ₂ units of said C _\ -Ce alkyl may be replaced with -CO-, or -S0 ₂ -, and R ^w is selected from H, OH, NH ₂ , or CN.

[0060] In another embodiment, Ai is phenyl or pyridyl, m is 1 and WR ^W is selected from H, S0 ₂ NH ₂ , C0 ₂ H, S0 ₂ CH ₃ , CONH ₂ or CN.

[0061] In another embodiment, the invention features a compound of formula I and the attendant definitions, wherein Ar ¹ is _? Ai is phenyl, A ₂ is a 5-membered aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, m is 1, W is a bond or Ci-C ₆ alkyl wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -CO-, or -S0 ₂ -, and R ^w is selected from H, OH, NH ₂ , or CN.

[0062] In another embodiment, Ai _is phenyl, A ₂ is pyrrolyl, pyrazolyl, thiazolyl, thiadiazolyl, imidazolyl, oxazolyl, or triazolyl, m is 1 and WR ^W is selected from H or C0 ₂ H.

[0063] In another aspect, the invention provides a compound of formula I-A:

I-A

or a pharmaceutically acceptable salt thereof,

wherein, independently for each occurrence:

Y is C or N;

Ai is a 5-6 membered aromatic ring having 0-4 heteroatoms, independently selected from nitrogen, oxygen, or sulfur;

m is an integer from 0 to 5 inclusive;

W is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-,

R ^w is absent, H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , OCF ₃ , or a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R' is C C ₆ alkyl;

R ¹ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen and wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ² is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ³ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁴ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁵ is H, halogen, CN, or -X-R ^x ;

R ⁵ is H, halogen, CN, or -X-R ^x ;

R ⁶ is H, halogen, CN, or -X-R ^x ;

R ⁶ is H, halogen, CN, or -X-R ^x ; R ⁷ is H, halogen, CN, or -X-R ^x ;

X is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-; and

R ^x is absent, H, or C3-C8 cycloaliphatic, wherein up to two non-adjacent CH ₂ units of said C3-C8 cycloaliphatic may be replaced with -O- and said C ₃ -C ₈ cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl.

[0064] In one embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein Y is C. In another embodiment, Y is N.

[0065] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein Ai is a 6 membered aromatic ring having 0-4 heteroatoms, independently selected from nitrogen, oxygen, or sulfur. In another embodiment, Ai is phenyl. In another embodiment, Ai is a 6 membered aromatic ring having 1 or 2 heteroatoms, independently selected from nitrogen. In another embodiment, Ai is pyridyl, pyrimidinyl, pyrazinyl or triazinyl.

[0066] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein Aj is a 5 -membered aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, Ai is a 5- membered aromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, Ai is pyrrolyl, pyrazolyl, thiazolyl, thiadiazolyl, imidazolyl, oxazolyl, triazolyl, or tetrazolyl.

[0067] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein ring Ai is selected from:

[0068] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein m is zero. In another embodiment, m is an integer from 1 to 5. In another embodiment, m is 1. In another embodiment, m is 2. In another embodiment, m is 3. In another embodiment, m is 4. In another embodiment, m is 5.

[0069] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein W is a bond and R ^w is halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is a bond and R is halogen. In another embodiment, W is a bond and R ^w is OH. In another embodiment, W is a bond and R ^w is NH ₂ . In another embodiment, W is a bond and R ^w is NHR'. In another embodiment, W is a bond and R ^w is CN. In another embodiment, W is a bond and R ^w is CF ₃ . In another embodiment, W is a bond and R ^w is OCF ₃ .

[0070] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein W is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO2-; and R ^w is absent. In another embodiment, W is CH ₃ , CH ₂ CH ₃ ,

CH2CH2CH3, or isopropyl. In another embodiment, W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-,-S-, -SO-, or -SO2-; and R ^w is absent. In another embodiment, W is OCH3, OCH2CH3, OCH2CH2CH3, or O-isopropyl. In another embodiment, W is OCH ₂ CF ₃ , OCH2CH2CH2CF3, or OCHF ₂ . In another embodiment, W is OCH ₂ CH ₂ OCH ₃ , CH ₂ OH, OC(CH ₃ ) ₃ , or CH ₂ CH ₂ OCH ₃ .

[0071] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl may be replaced with - 0-, -CO-, -S-, -SO-, -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -SO2-, and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, N¾, or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one C¾ unit of said Ci alkyl is replaced with -CO- and R ^w is N¾. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -SO2- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -SO2- and R ^w is H. In another embodiment, W is Ci alkyl wherein one C¾ unit of said Ci alkyl is replaced with -SO2- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NH ₂ . In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -SO2- and R ^w is NHR'. [0072] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -, and R ^w absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said C ₂ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -, and R ^w is absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is absent.

[0073] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein W is a bond and R ^w is a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5-membered aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5-membered aromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is pyrrolyl, pyrazolyl, thiazolyl, thiadiazolyl, imidazolyl, oxazolyl, triazolyl, or tetrazolyl.

[0074] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein ring Ai is selected from:

[0075] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein R ¹ is H. In another embodiment, R ¹ is halogen. In another embodiment, R ¹ is CN. In another embodiment, R ¹ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ¹ is CF ₃ .

[0076] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein R ² is H. In another embodiment, R ² is halogen. In another embodiment, R ² is CI. In another embodiment, R ² is F. In another embodiment, R ² is CN. In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ² is CF ₃ . In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ² is OCF ₃ . In another embodiment, R ² is F, CI, CN, CF ₃ or OCF ₃ .

[0077] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein R ³ is H. In another embodiment, R ³ is halogen. In another embodiment, R ³ is CI. In another embodiment, R ³ is F. In another embodiment, R ³ is CN. In another embodiment, R ³ is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen. In another embodiment, R ³ is i-butyl. In another embodiment, R ³ is CF ₃ . In another embodiment, R ³ is CF ₂ CF ₃ .

[0078] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein R ⁴ is H. In another embodiment, R ⁴ is halogen. In another embodiment, R ⁴ is CN. In another embodiment, R ⁴ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁴ is CF ₃ .

[0079] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein R ¹ , R ² , R ³ , and R ⁴ is H.

[0080] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein R ⁵ is H. In another embodiment, R ⁵ is halogen. In another embodiment, R ⁵ is CI. In another embodiment, R ⁵ is F. In another embodiment, R ⁵ is CN. In another embodiment, R ⁵ is -X-R ^x . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁵ is CH ₃ . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Q-C6 alkyl is replaced with -0-. In another embodiment, R ⁵ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or OCH(CH ₃ ) ₂ . In another embodiment, R ⁵ is OCH ₃ . In another embodiment, R ⁵ is CH ₂ OH. In another embodiment, R ⁵ is OCF ₃ . In another embodiment, R ⁵ is OCHF ₂ .

[0081] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein R ⁵ is H. In another embodiment, R ⁵ is halogen. In another embodiment, R ⁵ is CI. In another embodiment, R ⁵ is F. In another embodiment, R ⁵ is CN. In another embodiment, R ⁵ is -X-R ^x . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Q-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁵ is CH ₃ . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said C1-C6 alkyl is replaced with -0-. In another embodiment, R ⁵ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or OCH(CH ₃ ) ₂ . In another embodiment, R ⁵ is OCH ₃ . In another embodiment, R ⁵ is CH ₂ OH. In another embodiment, R ⁵ is OCF ₃ . In another embodiment, R ⁵ is OCHF ₂ .

[0082] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, R ⁶ is H. In another embodiment, R ⁶ is halogen. In another embodiment, R ⁶ is CI. In another embodiment, R ⁶ is F. In another embodiment, R ⁶ is CN. In another embodiment, R ⁶ is -X-R ^x . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen. In another embodiment, R ⁶ is CH ₃ . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said C1-C6 alkyl is replaced with -0-. In another embodiment, R ⁶ is OCH ₃ .

[0083] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein R ⁶ is H. In another embodiment, R ⁶ is halogen. In another embodiment, R ⁶ is CI. In another embodiment, R ⁶ is F. In another embodiment, R ⁶ is CN. In another embodiment, R ⁶ is -X-R ^x . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Q-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁶ is CH ₃ . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said C1-C6 alkyl is replaced with -0-. In another embodiment, R ⁶ is OCH ₃ .

[0084] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein R ⁷ is H. In another embodiment, R ⁷ is halogen. In another embodiment, R ⁷ is CI. In another embodiment, R ⁷ is F. In another embodiment, R ⁷ is CN. In another embodiment, R ⁷ is -X-R ^x . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁷ is CH ₃ , CH ₂ CH ₃ , CH ₂ CH ₂ CH ₃ or isopropyl. In another embodiment, R ⁷ is CF ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein two non-adjacent CH ₂ units of said C1-C6 alkyl are replaced with -0-. In another embodiment, R ⁷ is OCH ₂ CH ₂ OCH ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said C1-C6 alkyl is replaced with -0-. In another embodiment, R ⁷ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , OC(CH ₃ ) ₃ , CH ₂ CH ₂ OCH ₃ . In another embodiment, R ⁷ is OCF ₃ , OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ . [0085] In another embodiment, the invention features a compound of formula I-A wherein R ⁷ is -X-R ^x wherein X is a bond and R ^x is C3-C8 cycloaliphatic and said C3-C8 cycloaliphatic is substituted with 0-3 substituents selected from halogen and Q-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is a bond and R ^x is cyclopropyl.

[0086] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein R ⁷ is -X-R ^x wherein X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -O- and R ^x is C ₃ -C ₈ cycloaliphatic and said C ₃ -C ₈ cycloaliphatic is substituted with up 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is OCH ₂ and R ^x is cyclopropyl.

[0087] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein ring A is selected from:

[0088] In another embodiment ring A is selected from:

[0089] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein R ¹ , R ² , R ³ and R ⁴ are H.

[0090] In another embodiment, the invention features a compound of formula I-A and the attendant definitions, wherein R ⁵ and R ⁷ are each independently halogen, or -X-R ^x and R ⁵ , R ⁶ , and R ⁶ are each hydrogen. In another embodiment, R ⁵ and R ⁷ are each independently F, CI, CH ₃ , OCF ₃ , or OCH _3.

[0091] In another aspect, the invention provides a compound of formula I-B:

I-B

or a pharmaceutically acceptable salt thereof,

wherein, independently for each occurrence:

Y is C or N;

m is an integer from 0 to 5 inclusive;

W is a bond or C _\ -C(, alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C _\ -C _& alkyl may be replaced with -0-, -CO-,

R ^w is absent, H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , OCF ₃ , or a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R' is Ci-Ce alkyl;

R ¹ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen and wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ² is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ³ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁴ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁵ is H, halogen, CN, or -X-R ^x ;

R ⁵ is H, halogen, CN, or -X-R ^x ;

R ⁶ is H, halogen, CN, or -X-R ^x ;

R ⁶ is H, halogen, CN, or -X-R ^x ;

R ⁷ is H, halogen, CN, or -X-R ^x ; X is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-; and

R ^x is absent, H, or C ₃ -C ₈ cycloaliphatic, wherein up to two non-adjacent CH ₂ units of said C ₃ -C ₈ cycloaliphatic may be replaced with -O- and said C ₃ -C ₈ cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl.

[0092] In one embodiment, the invention features a compound of formula I-B and the attendant definitions, wherein Y is C. In another embodiment, Y is N.

[0093] In another embodiment, the invention features a compound of formula I-B and the attendant definitions, wherein m is zero. In another embodiment, m is an integer from 1 to 5. In another embodiment, m is 1. In another embodiment, m is 2. In another embodiment, m is 3. In another embodiment, m is 4. In another embodiment, m is 5.

[0094] In another embodiment, the invention features a compound of formula I-B and the attendant definitions, wherein W is a bond and R ^w is halogen, OH, NH ₂ , NHR', NO2, CN, CF ₃ , or OCF ₃ . In another embodiment, W is a bond and R ^w is halogen. In another embodiment, W is a bond and R ^w is OH. In another embodiment, W is a bond and R ^w is NH ₂ . In another embodiment, W is a bond and R ^w is NHR'. In another embodiment, W is a bond and R ^w is CN. In another embodiment, W is a bond and R ^w is CF ₃ . In another embodiment, W is a bond and R ^w is OCF ₃ .

[0095] In another embodiment, the invention features a compound of formula I-B and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is CH ₃ , CH ₂ CH ₃ ,

CH ₂ CH ₂ CH ₃ , or isopropyl. In another embodiment, W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or O-isopropyl. In another embodiment, W is OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ . In another embodiment, W is OCH ₂ CH ₂ OCH ₃ , CH ₂ OH, OC(CH ₃ ) ₃ , or CH ₂ CH ₂ OCH ₃ .

[0096] In another embodiment, the invention features a compound of formula I-B and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl may be replaced with - 0-, -CO-, -S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NH ₂ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NH ₂ . In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NHR'.

[0097] In another embodiment, the invention features a compound of formula I-B and the attendant definitions, wherein W is d-C ₆ alkyl wherein said d-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -, and R ^w absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said C ₂ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -, and R ^w is absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is absent.

[0098] In another embodiment, the invention features a compound of formula I-B and the attendant definitions, wherein W is a bond and R ^w is a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5-membered aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5-membered aromatic ring having 1 -4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is pyrrolyl, pyrazolyl, thiazolyl, thiadiazolyl, imidazolyl, oxazolyl, triazolyl, or tetrazolyl.

[0099] In another embodiment, the invention features a compound of formula I-B and the attendant definitions, wherein ring Aj is selected from:

[00100] In another embodiment, the invention features a compound of formula I-B and the attendant definitions, wherein R ¹ is H. In another embodiment, R ¹ is halogen. In another embodiment, R ¹ is CN. In another embodiment, R ¹ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ¹ is CF ₃ .

[00101] In another embodiment, the invention features a compound of formula I-B and the attendant definitions, wherein R ² is H. In another embodiment, R ² is halogen. In another embodiment, R ² is CI. In another embodiment, R ² is F. In another embodiment, R ² is CN. In another embodiment, R ² is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ² is CF ₃ . In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ² is OCF ₃ . In another embodiment, R ² is F, CI, CN, CF ₃ or OCF ₃ .

[00102] In another embodiment, the invention features a compound of formula I-B and the attendant definitions, wherein R ³ is H. In another embodiment, R ³ is halogen. In another embodiment, R ³ is CI. In another embodiment, R ³ is F. In another embodiment, R ³ is CN. In another embodiment, R ³ is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ³ is i-butyl. In another embodiment, R ³ is CF ₃ . In another embodiment, R ³ is CF ₂ CF ₃ .

[00103] In another embodiment, the invention features a compound of formula I-B and the attendant definitions, wherein R ⁴ is H. In another embodiment, R ⁴ is halogen. In another embodiment, R ⁴ is CN. In another embodiment, R ⁴ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁴ is CF ₃ .

[00104] In another embodiment, the invention features a compound of formula I-B and the attendant definitions, wherein R ¹ , R ² , R ³ , and R ⁴ is H.

[00105] In another embodiment, the invention features a compound of formula I-B and the attendant definitions, wherein R ⁵ is H. In another embodiment, R ⁵ is halogen. In another embodiment, R ⁵ is CI. In another embodiment, R ⁵ is F. In another embodiment, R ⁵ is CN. In another embodiment, R ⁵ is -X-R ^x . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁵ is CH ₃ . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Q-C6 alkyl is replaced with -0-. In another embodiment, R ⁵ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or OCH(CH ₃ ) ₂ . In another embodiment, R ⁵ is OCH ₃ . In another embodiment, R ⁵ is CH ₂ OH. In another embodiment, R ⁵ is OCF ₃ . In another embodiment, R ⁵ is OCHF ₂ .

[00106] In another embodiment, the invention features a compound of formula I-B and the attendant definitions, wherein R ⁵ is H. In another embodiment, R ⁵ is halogen. In another embodiment, R ⁵ is CI. In another embodiment, R ⁵ is F. In another embodiment, R ⁵ is CN. In another embodiment, R ⁵ is -X-R ^x . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Q-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁵ is CH ₃ . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Q-C6 alkyl is replaced with -0-. In another embodiment, R ⁵ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or OCH(CH ₃ ) ₂ . In another embodiment, R ⁵ is OCH ₃ . In another embodiment, R ⁵ is CH ₂ OH. In another embodiment, R ⁵ is OCF ₃ . In another embodiment, R ⁵ is OCHF ₂ .

[00107] In another embodiment, the invention features a compound of formula I-B and the attendant definitions, R ⁶ is H. In another embodiment, R ⁶ is halogen. In another embodiment, R ⁶ is CI. In another embodiment, R ⁶ is F. In another embodiment, R ⁶ is CN. In another embodiment, R ⁶ is -X-R ^x . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen. In another embodiment, R ⁶ is CH ₃ . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said C1-C6 alkyl is replaced with -0-. In another embodiment, R ⁶ is OCH ₃ .

[00108] In another embodiment, the invention features a compound of formula I-B and the attendant definitions, wherein R ⁶ is H. In another embodiment, R ⁶ is halogen. In another embodiment, R ⁶ is CI. In another embodiment, R ⁶ is F. In another embodiment, R ⁶ is CN. In another embodiment, R ⁶ is -X-R ^x . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Q-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁶ is CH ₃ . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Q-C6 alkyl is replaced with -0-. In another embodiment, R ⁶ is OCH ₃ .

[00109] In another embodiment, the invention features a compound of formula I-B and the attendant definitions, wherein R ⁷ is H. In another embodiment, R ⁷ is halogen. In another embodiment, R ⁷ is CI. In another embodiment, R ⁷ is F. In another embodiment, R ⁷ is CN. In another embodiment, R is -X-R . In another embodiment, R is -X-R wherein R is absent. In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁷ is CH ₃ , CH ₂ CH ₃ , CH ₂ CH ₂ CH ₃ or isopropyl. In another embodiment, R ⁷ is CF ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein two non-adjacent CH ₂ units of said C1-C6 alkyl are replaced with -0-. In another embodiment, R ⁷ is OCH ₂ CH ₂ OCH ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁷ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , OC(CH ₃ ) ₃ , CH ₂ CH ₂ OCH ₃ . In another embodiment, R ⁷ is OCF ₃ , OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ .

[00110] In another embodiment, the invention features a compound of formula I-B wherein R ⁷ is -X-R ^x wherein X is a bond and R ^x is C ₃ -Cs cycloaliphatic and said C ₃ -Cs cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is a bond and R ^x is cyclopropyl.

[00111] In another embodiment, the invention features a compound of formula I-B and the attendant definitions, wherein R ⁷ is -X-R ^x wherein X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -O- and R ^x is C ₃ -C ₈ cycloaliphatic and said C ₃ -C ₈ cycloaliphatic is substituted with up 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is OCH ₂ and R ^x is cyclopropyl.

[00112] In another embodiment, the invention features a compound of formula I-B and the attendant definitions, wherein ring A is selected from:

[00113] In another aspect, the invention provides a compound of formula I-B-l:

I-B-l

or a pharmaceutically acceptable salt thereof,

wherein, independently for each occurrence:

Y is C or N; m is an integer from 0 to 5 inclusive;

W is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -O- -CO-,

R ^w is absent, H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , OCF ₃ , or a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R' is Ci-C ₆ alkyl;

R ¹ is H, halogen, CN, or Ci-C ₆ alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen and wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ² is H, halogen, CN, or C C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non -adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-;

R ³ is H, halogen, CN, or C C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁴ is H, halogen, CN, or C C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁵ is halogen, CN, or -X-R ^x ;

X is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-; and

R ^x is absent, H, or C ₃ -C ₈ cycloaliphatic, wherein up to two non-adjacent CH ₂ units of said C ₃ -C ₈ cycloaliphatic may be replaced with -O- and said C ₃ -C ₈ cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl.

[00114] In one embodiment, the invention features a compound of formula I-B-l and the attendant definitions, wherein Y is C. In another embodiment, Y is N.

[00115] In another embodiment, the invention features a compound of formula I-B-l and the attendant definitions, wherein m is zero. In another embodiment, m is an integer from 1 to 5. In another embodiment, m is 1. In another embodiment, m is 2. In another embodiment, m is 3. In another embodiment, m is 4. In another embodiment, m is 5.

[00116] In another embodiment, the invention features a compound of formula I-B-l and the attendant definitions, wherein W is a bond and R ^w is halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is a bond and R ^w is halogen. In another embodiment, W is a bond and R ^w is OH. In another embodiment, W is a bond and R ^w is NH _2. In another embodiment, W is a bond and R ^w is NHR'. In another embodiment, W is a bond and R ^w is CN. In another embodiment, W is a bond and R ^w is CF ₃ . In another embodiment, W is a bond and R ^w is OCF ₃ . [00117] In another embodiment, the invention features a compound of formula I-B-l and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is CH ₃ , CH ₂ CH ₃ ,

CH ₂ CH ₂ CH ₃ , or isopropyl. In another embodiment, W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or O-isopropyl. In another embodiment, W is OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ . In another embodiment, W is OCH ₂ CH ₂ OCH ₃ , CH ₂ OH, OC(CH ₃ ) ₃ , or CH ₂ CH ₂ OCH ₃ .

[00118] In another embodiment, the invention features a compound of formula I-B-l and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO ₂ -, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl may be replaced with - 0-, -CO-, -S-, -SO-, or -SO ₂ -, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NH ₂ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NH ₂ . In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -SO ₂ - and R ^w is NHR'.

[00119] In another embodiment, the invention features a compound of formula I-B-l and the attendant definitions, wherein W is d-C ₆ alkyl wherein said d-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said d-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -, and R ^w absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said C ₂ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -, and R ^w is absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -SO2-, and R ^w is absent.

[00120] In another embodiment, the invention features a compound of formula I-B-l and the attendant definitions, wherein W is a bond and R ^w is a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 1 -4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is pyrrolyl, pyrazolyl, thiazolyl, thiadiazolyl, imidazolyl, oxazolyl, triazolyl, or tetrazolyl.

[00121] In another embodiment, the invention features a compound of formula I-B-l and the attendant definitions, wherein ring Ai is selected from:

[00122] In another embodiment, the invention features a compound of formula I-B-l and the attendant definitions, wherein R ¹ is H. In another embodiment, R ¹ is halogen. In another embodiment, R ¹ is CN. In another embodiment, R ¹ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ¹ is CF ₃ .

[00123] In another embodiment, the invention features a compound of formula I-B-l and the attendant definitions, wherein R ² is H. In another embodiment, R ² is halogen. In another embodiment, R ² is CI. In another embodiment, R ² is F. In another embodiment, R ² is CN. In another embodiment, R ² is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ² is CF ₃ . In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ² is OCF ₃ . In another embodiment, R ² is F, CI, CN, CF ₃ or OCF ₃ .

[00124] In another embodiment, the invention features a compound of formula I-B-l and the attendant definitions, wherein R ³ is H. In another embodiment, R ³ is halogen. In another embodiment, R ³ is CI. In another embodiment, R ³ is F. In another embodiment, R ³ is CN. In another embodiment, R ³ is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ³ is i-butyl. In another embodiment, R ³ is CF3. In another embodiment, R ³ is CF ₂ CF ₃ . [00125] In another embodiment, the invention features a compound of formula I-B-l and the attendant definitions, wherein R ⁴ is H. In another embodiment, R ⁴ is halogen. In another embodiment, R ⁴ is CN. In another embodiment, R ⁴ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁴ is CF ₃ .

[00126] In another embodiment, the invention features a compound of formula I-B-l and the attendant definitions, wherein R ¹ , R ² , R ³ , and R ⁴ is H.

[00127] In another embodiment, the invention features a compound of formula I-B-l and the attendant definitions, wherein R ⁵ is halogen. In another embodiment, R ⁵ is CI. In another embodiment, R ⁵ is F. In another embodiment, R ⁵ is CN. In another embodiment, R ⁵ is -X-R ^x . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen. In another embodiment, R ⁵ is CH ₃ . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁵ is OCH ₃ , OCH ₂ CH ₃ ,

OCH ₂ CH ₂ CFI ₃ , or OCH(CH ₃ ) ₂ . In another embodiment, R ⁵ is OCH ₃ . In another embodiment, R ⁵ is CH ₂ OH. In another embodiment, R ⁵ is OCF ₃ . In another embodiment, R ⁵ is OCHF ₂ .

[00128] In another embodiment, the invention features a compound of formula I-B-l and the attendant definitions, wherein ring A is selected from:

[00129] In another aspect, the invention provides a compound of formula I-B-2:

I-B-2

or a pharmaceutically acceptable salt thereof,

wherein, independently for each occurrence:

Y is C or N;

m is an integer from 0 to 5 inclusive; W is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -O- -CO-,

R ^w is absent, H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , OCF ₃ , or a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R' is Ci-C ₆ alkyl;

R ¹ is H, halogen, CN, or C C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen and wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ² is H, halogen, CN, or C C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ³ is H, halogen, CN, or Ci-C ₆ alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen, wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁴ is H, halogen, CN, or C C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁷ is halogen, CN, or -X-R ^x ;

X is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-; and

R ^x is absent, H, or C ₃ -C ₈ cycloaliphatic, wherein up to two non-adjacent CH ₂ units of said C ₃ -C ₈ cycloaliphatic may be replaced with -O- and said C ₃ -C ₈ cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl.

[00130] In one embodiment, the invention features a compound of formula I-B-2 and the attendant definitions, wherein Y is C. In another embodiment, Y is N.

[00131] In another embodiment, the invention features a compound of formula I-B-2 and the attendant definitions, wherein m is zero. In another embodiment, m is an integer from 1 to 5. In another embodiment, m is 1. In another embodiment, m is 2. In another embodiment, m is 3. In another embodiment, m is 4. In another embodiment, m is 5.

[00132] In another embodiment, the invention features a compound of formula I-B-2 and the attendant definitions, wherein W is a bond and R ^w is halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is a bond and R ^w is halogen. In another embodiment, W is a bond and R ^w is OH. In another embodiment, W is a bond and R ^w is NH _2. In another embodiment, W is a bond and R ^w is NHR'. In another embodiment, W is a bond and R ^w is CN. In another embodiment, W is a bond and R ^w is CF ₃ . In another embodiment, W is a bond and R ^w is OCF ₃ . [00133] In another embodiment, the invention features a compound of formula I-B-2 and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is CH ₃ , CH ₂ CH ₃ ,

CH ₂ CH ₂ CH ₃ , or isopropyl. In another embodiment, W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or O-isopropyl. In another embodiment, W is OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ . In another embodiment, W is OCH ₂ CH ₂ OCH ₃ , CH ₂ OH, OC(CH ₃ ) ₃ , or CH ₂ CH ₂ OCH ₃ .

[00134] In another embodiment, the invention features a compound of formula I-B-2 and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl may be replaced with - O- -CO-,-S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NH ₂ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NH ₂ . In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with

[00135] In another embodiment, the invention features a compound of formula I-B-2 and the attendant definitions, wherein W is d-C ₆ alkyl wherein said d-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -O- - CO-,-S-, -SO-, or -S0 ₂ -, and R ^w absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said C ₂ alkyl may be replaced with -O- -CO-,-S-, -SO-, or -S0 ₂ -, and R ^w is absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -SO2-, and R ^w is absent.

[00136] In another embodiment, the invention features a compound of formula I-B-2 and the attendant definitions, wherein W is a bond and R ^w is a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 1 -4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is pyrrolyl, pyrazolyl, thiazolyl, thiadiazolyl, imidazolyl, oxazolyl, triazolyl, or tetrazolyl.

[00137] In another embodiment, the invention features a compound of formula I-B-2 and the attendant definitions, wherein ring Ai is selected from:

[00138] In another embodiment, the invention features a compound of formula I-B-2 and the attendant definitions, wherein R ¹ is H. In another embodiment, R ¹ is halogen. In another embodiment, R ¹ is CN. In another embodiment, R ¹ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ¹ is CF ₃ .

[00139] In another embodiment, the invention features a compound of formula I-B-2 and the attendant definitions, wherein R ² is H. In another embodiment, R ² is halogen. In another embodiment, R ² is CI. In another embodiment, R ² is F. In another embodiment, R ² is CN. In another embodiment, R ² is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ² is CF ₃ . In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ² is OCF ₃ . In another embodiment, R ² is F, CI, CN, CF ₃ or OCF ₃ .

[00140] In another embodiment, the invention features a compound of formula I-B-2 and the attendant definitions, wherein R ³ is H. In another embodiment, R ³ is halogen. In another embodiment, R ³ is CI. In another embodiment, R ³ is F. In another embodiment, R ³ is CN. In another embodiment, R ³ is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ³ is i-butyl. In another embodiment, R ³ is CF3. In another embodiment, R ³ is CF ₂ CF ₃ . [00141] In another embodiment, the invention features a compound of formula I-B-2 and the attendant definitions, wherein R ⁴ is H. In another embodiment, R ⁴ is halogen. In another embodiment, R ⁴ is CN. In another embodiment, R ⁴ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁴ is CF ₃ .

[00142] In another embodiment, the invention features a compound of formula I-B-2 and the attendant definitions, wherein R ¹ , R ² , R ³ , and R ⁴ is H.

[00143] In another embodiment, the invention features a compound of formula I-B-2 and the attendant definitions, wherein R ⁷ is halogen. In another embodiment, R ⁷ is CI. In another embodiment, R ⁷ is F. In another embodiment, R ⁷ is CN. In another embodiment, R ⁷ is -X-R ^x . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen. In another embodiment, R ⁷ is CH ₃ , CH ₂ CH ₃ , CH2CH2CH3 or isopropyl. In another embodiment, R ⁷ is CF3. In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein two non-adjacent CH ₂ units of said Ci-C ₆ alkyl are replaced with -0-. In another embodiment, R ⁷ is OCH2CH2OCH3. In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁷ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , OC(CH ₃ ) ₃ , CH ₂ CH ₂ OCH ₃ . In another embodiment, R ⁷ is OCF ₃ , OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF3, or OCHF ₂ .

[00144] In another embodiment, the invention features a compound of formula I-B-2 wherein R ⁷ is -X-R ^x wherein X is a bond and R ^x is C3-C8 cycloaliphatic and said C3-C8 cycloaliphatic is substituted with 0-3 substituents selected from halogen and Q-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is a bond and R ^x is cyclopropyl.

[00145] In another embodiment, the invention features a compound of formula I-B-2 and the attendant definitions, wherein R ⁷ is -X-R ^x wherein X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -O- and R ^x is C ₃ -C ₈ cycloaliphatic and said C ₃ -C ₈ cycloaliphatic is substituted with up 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is OCH ₂ and R ^x is cyclopropyl.

[00146] In another embodiment, the invention features a compound of formula I-B-2 and the attendant definitions, wherein ring A is selected from:

I-B-3

or a pharmaceutically acceptable salt thereof,

wherein, independently for each occurrence:

Y is C or N;

m is an integer from 0 to 5 inclusive;

W is a bond or C -Ce alkyl wherein said C -Ce alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-,

R ^w is absent, H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , OCF ₃ , or a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R' is Ci-C ₆ alkyl;

R ¹ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen and wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-;

R ² is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ³ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁴ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-; R ⁶ is halogen, CN, or -X-R ^x ;

R ⁷ is halogen, CN, or -X-R ^x ;

X is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-; and

R ^x is absent, H, or C ₃ -C ₈ cycloaliphatic, wherein up to two non-adjacent CH ₂ units of said C ₃ -C ₈ cycloaliphatic may be replaced with -O- and said C ₃ -C ₈ cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl.

[00148] In one embodiment, the invention features a compound of formula I-B-3 and the attendant definitions, wherein Y is C. In another embodiment, Y is N.

[00149] In another embodiment, the invention features a compound of formula I-B-3 and the attendant definitions, wherein m is zero. In another embodiment, m is an integer from 1 to 5. In another embodiment, m is 1. In another embodiment, m is 2. In another embodiment, m is 3. In another embodiment, m is 4. In another embodiment, m is 5.

[00150] In another embodiment, the invention features a compound of formula I-B-3 and the attendant definitions, wherein W is a bond and R ^w is halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is a bond and R ^w is halogen. In another embodiment, W is a bond and R ^w is OH.. In another embodiment, W is a bond and R ^w is NH ₂ . In another embodiment, W is a bond and R ^w is NHR'. In another embodiment, W is a bond and R ^w is CN. In another embodiment, W is a bond and R ^w is CF ₃ . In another embodiment, W is a bond and R ^w is OCF ₃ .

[00151] In another embodiment, the invention features a compound of formula I-B-3 and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is CH ₃ , CH ₂ CH ₃ ,

CH ₂ CH ₂ CH ₃ , or isopropyl. In another embodiment, W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or O-isopropyl. In another embodiment, W is OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ . In another embodiment, W is OCH ₂ CH ₂ OCH ₃ , CH ₂ OH, OC(CH ₃ ) ₃ , or CH ₂ CH ₂ OCH ₃ .

[00152] In another embodiment, the invention features a compound of formula I-B-3 and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl may be replaced with - 0-, -CO-, -S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -SO ₂ -, and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NH ₂ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NH ₂ . In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -SO ₂ - and R ^w is NHR'.

[00153] In another embodiment, the invention features a compound of formula I-B-3 and the attendant definitions, wherein W is d-C ₆ alkyl wherein said d-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said d-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -, and R ^w absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said C ₂ alkyl may be replaced with -O- -CO-, -S-, -SO-, or -S0 ₂ -, and R ^w is absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is absent.

[00154] In another embodiment, the invention features a compound of formula I-B-3 and the attendant definitions, wherein W is a bond and R ^w is a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is pyrrolyl, pyrazolyl, thiazolyl, thiadiazolyl, imidazolyl, oxazolyl, triazolyl, or tetrazolyl.

[00155] In another embodiment, the invention features a compound of formula I-B-3 and the attendant definitions, wherein ring Ai is selected from:

[00156] In another embodiment, the invention features a compound of formula I-B-3 and the attendant definitions, wherein R ¹ is H. In another embodiment, R ¹ is halogen. In another embodiment, R ¹ is CN. In another embodiment, R ¹ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ¹ is CF ₃ .

[00157] In another embodiment, the invention features a compound of formula I-B-3 and the attendant definitions, wherein R ² is H. In another embodiment, R ² is halogen. In another embodiment, R ² is CI. In another embodiment, R ² is F. In another embodiment, R ² is CN. In another embodiment, R ² is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ² is CF ₃ . In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ² is OCF ₃ . In another embodiment, R ² is F, CI, CN, CF ₃ or OCF ₃ .

[00158] In another embodiment, the invention features a compound of formula I-B-3 and the attendant definitions, wherein R ³ is H. In another embodiment, R ³ is halogen. In another embodiment, R ³ is CI. In another embodiment, R ³ is F. In another embodiment, R ³ is CN. In another embodiment, R ³ is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ³ is i-butyl. In another embodiment, R ³ is CF ₃ . In another embodiment, R ³ is CF ₂ CF ₃ .

[00159] In another embodiment, the invention features a compound of formula I-B-3 and the attendant definitions, wherein R ⁴ is H. In another embodiment, R ⁴ is halogen. In another embodiment, R ⁴ is CN. In another embodiment, R ⁴ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁴ is CF ₃ .

[00160] In another embodiment, the invention features a compound of formula I-B-3 and the attendant definitions, wherein R ¹ , R ² , R ³ , and R ⁴ is H.

[00161] In another embodiment, the invention features a compound of formula I-B-3 and the attendant definitions, R ⁶ is halogen. In another embodiment, R ⁶ is CI. In another embodiment, R ⁶ is F. In another embodiment, R ⁶ is CN. In another embodiment, R ⁶ is -X-R ^x . In another embodiment, R is -X-R wherein R is absent. In another embodiment, R is -X-R wherein R is absent and X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁶ is CH ₃ . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Q-C6 alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁶ is OCH ₃ .

[00162] In another embodiment, the invention features a compound of formula I-B-3 and the attendant definitions, wherein R ⁷ is halogen. In another embodiment, R ⁷ is CI. In another embodiment, R ⁷ is F. In another embodiment, R ⁷ is CN. In another embodiment, R ⁷ is -X-R ^x . In another embodiment, R is -X-R wherein R is absent. In another embodiment, R is -X-R wherein R ^x is absent and X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁷ is CH ₃ , CH ₂ CH ₃ , CH2CH2CH3 or isopropyl. In another embodiment, R ⁷ is CF ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein two non-adjacent CH ₂ units of said Ci-C ₆ alkyl are replaced with -0-. In another embodiment, R ⁷ is OCH2CH2OCH3. In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁷ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , OC(CH ₃ ) ₃ , CH ₂ CH ₂ OCH ₃ . In another embodiment, R ⁷ is OCF ₃ , OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ .

[00163] In another embodiment, the invention features a compound of formula I-B-3 wherein R ⁷ is -X-R ^x wherein X is a bond and R ^x is C ₃ -Cs cycloaliphatic and said C ₃ -Cs cycloaliphatic is substituted with 0-3 substituents selected from halogen and Q-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is a bond and R ^x is cyclopropyl.

[00164] In another embodiment, the invention features a compound of formula I-B-3 and the attendant definitions, wherein R ⁷ is -X-R ^x wherein X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -O- and R ^x is C ₃ -C ₈ cycloaliphatic and said C ₃ -C ₈ cycloaliphatic is substituted with up 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is OCH ₂ and R ^x is cyclopropyl.

[00165] In another embodiment, the invention features a compound of formula I-B-3 and the attendant definitions, wherein ring A is selected from:

[00166] In another aspect, the invention provides a compound of formula I-B-4:

I-B-4

or a pharmaceutically acceptable salt thereof,

wherein, independently for each occurrence:

Y is C or N;

m is an integer from 0 to 5 inclusive;

W is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-,

R ^w is absent, H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , OCF ₃ , or a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R' is C C ₆ alkyl;

R ¹ is H, halogen, CN, or C C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen and wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ² is H, halogen, CN, or C C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ³ is H, halogen, CN, or C C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁴ is H, halogen, CN, or C C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁵ is halogen, CN, or -X-R ^x ;

R ⁷ is halogen, CN, or -X-R ^x ;

X is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-; and

R ^x is absent, H, or C ₃ -C ₈ cycloaliphatic, wherein up to two non-adjacent CH ₂ units of said C ₃ -C ₈ cycloaliphatic may be replaced with -O- and said C ₃ -C ₈ cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl.

[00167] In one embodiment, the invention features a compound of formula I-B-4 and the attendant definitions, wherein Y is C. In another embodiment, Y is N.

[00168] In another embodiment, the invention features a compound of formula I-B-4 and the attendant definitions, wherein m is zero. In another embodiment, m is an integer from 1 to 5. In another embodiment, m is 1. In another embodiment, m is 2. In another embodiment, m is 3. In another embodiment, m is 4. In another embodiment, m is 5. [00169] In another embodiment, the invention features a compound of formula I-B-4 and the attendant definitions, wherein W is a bond and R ^w is halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is a bond and R ^w is halogen. In another embodiment, W is a bond and R ^w is OH.. In another embodiment, W is a bond and R ^w is NH ₂ . In another embodiment, W is a bond and R ^w is NHR'. In another embodiment, W is a bond and R ^w is CN. In another embodiment, W is a bond and R ^w is CF ₃ . In another embodiment, W is a bond and R ^w is OCF ₃ .

[00170] In another embodiment, the invention features a compound of formula I-B-4 and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is CH ₃ , CH ₂ CH ₃ ,

CH ₂ CH ₂ CH ₃ , or isopropyl. In another embodiment, W is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or O-isopropyl. In another embodiment, W is OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ . In another embodiment, W is OCH ₂ CH ₂ OCH ₃ , CH ₂ OH, OC(CH ₃ ) ₃ , or CH ₂ CH ₂ OCH ₃ .

[00171] In another embodiment, the invention features a compound of formula I-B-4 and the attendant definitions, wherein W is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl may be replaced with - 0-, -CO-, -S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NH ₂ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NH ₂ . In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with

[00172] In another embodiment, the invention features a compound of formula I-B-4 and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO2-, and R ^w absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said C ₂ alkyl may be replaced with -O- -CO-,-S-, -SO-, or -S0 ₂ -, and R ^w is absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is absent.

[00173] In another embodiment, the invention features a compound of formula I-B-4 and the attendant definitions, wherein W is a bond and R ^w is a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 1 -4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is pyrrolyl, pyrazolyl, thiazolyl, thiadiazolyl, imidazolyl, oxazolyl, triazolyl, or tetrazolyl.

[00174] In another embodiment, the invention features a compound of formula I-B-4 and the attendant definitions, wherein ring Ai is selected from:

[00175] In another embodiment, the invention features a compound of formula I-B-4 and the attendant definitions, wherein R ¹ is H. In another embodiment, R ¹ is halogen. In another embodiment, R ¹ is CN. In another embodiment, R ¹ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ¹ is CF ₃ .

[00176] In another embodiment, the invention features a compound of formula I-B-4 and the attendant definitions, wherein R ² is H. In another embodiment, R ² is halogen. In another embodiment, R ² is CI. In another embodiment, R ² is F. In another embodiment, R ² is CN. In another embodiment, R ² is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ² is CF3. In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ² is OCF ₃ . In another embodiment, R ² is F, CI, CN, CF ₃ or OCF ₃ .

[00177] In another embodiment, the invention features a compound of formula I-B-4 and the attendant definitions, wherein R ³ is H. In another embodiment, R ³ is halogen. In another embodiment, R ³ is CI. In another embodiment, R ³ is F. In another embodiment, R ³ is CN. In another embodiment, R ³ is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ³ is i-butyl. In another embodiment, R ³ is CF ₃ . In another embodiment, R ³ is CF ₂ CF ₃ .

[00178] In another embodiment, the invention features a compound of formula I-B-4 and the attendant definitions, wherein R ⁴ is H. In another embodiment, R ⁴ is halogen. In another embodiment, R ⁴ is CN. In another embodiment, R ⁴ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁴ is CF ₃ .

[00179] In another embodiment, the invention features a compound of formula I-B-4 and the attendant definitions, wherein R ¹ , R ² , R ³ , and R ⁴ is H.

[00180] In another embodiment, the invention features a compound of formula I-B-4 and the attendant definitions, wherein R ⁵ is halogen. In another embodiment, R ⁵ is CI. In another embodiment, R ⁵ is F. In another embodiment, R ⁵ is CN. In another embodiment, R ⁵ is -X-R ^x . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁵ is CH ₃ . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁵ is OCH ₃ , OCH ₂ CH ₃ , OCH2CH ₂ CH ₃ , or OCH(CH ₃ ) ₂ . In another embodiment, R ⁵ is OCH ₃ . In another embodiment, R ⁵ is CH ₂ OH. In another embodiment, R ⁵ is OCF ₃ . In another embodiment, R ⁵ is OCHF ₂ .

[00181] In another embodiment, the invention features a compound of formula I-B-4 and the attendant definitions, wherein R ⁷ is halogen. In another embodiment, R ⁷ is CI. In another embodiment, R ⁷ is F. In another embodiment, R ⁷ is CN. In another embodiment, R ⁷ is -X-R ^x . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen. In another embodiment, R ⁷ is CH ₃ , CH ₂ CH ₃ , CH ₂ CH ₂ CH ₃ or isopropyl. In another embodiment, R ⁷ is CF ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein two non-adjacent CH ₂ units of said Ci-C ₆ alkyl are replaced with -0-. In another embodiment, R ⁷ is OCH ₂ CH ₂ OCH ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁷ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , OC(CH ₃ ) ₃ , CH ₂ CH ₂ OCH ₃ . In another embodiment, R ⁷ is OCF ₃ , OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ . [00182] In another embodiment, the invention features a compound of formula I-B-4 wherein R ⁷ is -X-R ^x wherein X is a bond and R ^x is C3-C8 cycloaliphatic and said C3-C8 cycloaliphatic is substituted with 0-3 substituents selected from halogen and Q-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is a bond and R ^x is cyclopropyl.

[00183] In another embodiment, the invention features a compound of formula I-B-4 and the attendant definitions, wherein R ⁷ is -X-R ^x wherein X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -O- and R ^x is C ₃ -C ₈ cycloaliphatic and said C ₃ -C ₈ cycloaliphatic is substituted with up 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is OCH ₂ and R ^x is cyclopropyl.

[00184] In another embodiment, the invention features a compound of formula I-B-4 and the attendant definitions, wherein ring A is selected from:

[00185] In another aspect, the invention provides a compound of formula I-C:

I-C

or a pharmaceutically acceptable salt thereof,

wherein, independently for each occurrence:

Y is C or N;

m is an integer from 0 to 5 inclusive; W is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-,

R ^w is absent, H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , OCF ₃ , or a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R' is Ci-C ₆ alkyl;

R ¹ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen and wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ² is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ³ is H, halogen, CN, or C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁴ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁵ is H, halogen, CN, or -X-R ^x ;

R ⁵ is H, halogen, CN, or -X-R ^x ;

R ⁶ is H, halogen, CN, or -X-R ^x ;

R ^6' is H, halogen, CN, or -X-R ^x ;

R ⁷ is H, halogen, CN, or -X-R ^x ;

X is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-; and

R ^x is absent, H, or C ₃ -C ₈ cycloaliphatic, wherein up to two non-adjacent CH ₂ units of said C ₃ -C ₈ cycloaliphatic may be replaced with -O- and said C ₃ -C ₈ cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl.

[00186] In one embodiment, the invention features a compound of formula I-C and the attendant definitions, wherein Y is C. In another embodiment, Y is N.

[00187] In another embodiment, the invention features a compound of formula I-C and the attendant definitions, wherein m is zero. In another embodiment, m is an integer from 1 to 5. In another embodiment, m is 1. In another embodiment, m is 2. In another embodiment, m is 3. In another embodiment, m is 4. In another embodiment, m is 5.

[00188] In another embodiment, the invention features a compound of formula I-C and the attendant definitions, wherein W is a bond and R ^w is halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is a bond and R is halogen. In another embodiment, W is a bond and R ^w is OH. In another embodiment, W is a bond and R ^w is NH ₂ . In another embodiment, W is a bond and R ^w is NHR'. In another embodiment, W is a bond and R ^w is CN. In another embodiment, W is a bond and R ^w is CF ₃ . In another embodiment, W is a bond and R ^w is OCF ₃ .

[00189] In another embodiment, the invention features a compound of formula I-C and the attendant definitions, wherein W is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -O- - CO-,-S-, -SO-, or -SO2-; and R ^w is absent. In another embodiment, W is CH ₃ , CH ₂ CH ₃ ,

CH2CH2CH3, or isopropyl. In another embodiment, W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -SO2-; and R ^w is absent. In another embodiment, W is OCH3, OCH2CH3, OCH2CH2CH3, or O-isopropyl. In another embodiment, W is OCH ₂ CF ₃ , OCH2CH2CH2CF3, or OCHF ₂ . In another embodiment, W is OCH ₂ CH ₂ OCH ₃ , CH ₂ OH, OC(CH ₃ ) ₃ , or CH ₂ CH ₂ OCH ₃ .

[00190] In another embodiment, the invention features a compound of formula I-C and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl may be replaced with - 0-, -CO-, -S-, -SO-, -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -SO2-, and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, N¾, or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one C¾ unit of said Ci alkyl is replaced with -CO- and R ^w is N¾. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -SO2- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -SO2- and R ^w is H. In another embodiment, W is Ci alkyl wherein one C¾ unit of said Ci alkyl is replaced with -SO2- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NH ₂ . In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with [00191] In another embodiment, the invention features a compound of formula I-C and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -, and R ^w absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said C ₂ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -, and R ^w is absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is absent.

[00192] In another embodiment, the invention features a compound of formula I-C and the attendant definitions, wherein W is a bond and R ^w is a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is pyrrolyl, pyrazolyl, thiazolyl, thiadiazolyl, imidazolyl, oxazolyl, triazolyl, or tetrazolyl.

[00193] In another embodiment, the invention features a compound of formula I-C and the attendant definitions, wherein ring Ai is selected from:

[00194] In another embodiment, the invention features a compound of formula I-C and the attendant definitions, wherein R ¹ is H. In another embodiment, R ¹ is halogen. In another embodiment, R ¹ is CN. In another embodiment, R ¹ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ¹ is CF ₃ .

[00195] In another embodiment, the invention features a compound of formula I-C and the attendant definitions, wherein R ² is H. In another embodiment, R ² is halogen. In another embodiment, R ² is CI. In another embodiment, R ² is F. In another embodiment, R ² is CN. In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ² is CF ₃ . In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ² is OCF ₃ . In another embodiment, R ² is F, CI, CN, CF ₃ or OCF ₃ .

[00196] In another embodiment, the invention features a compound of formula I-C and the attendant definitions, wherein R ³ is H. In another embodiment, R ³ is halogen. In another embodiment, R ³ is CI. In another embodiment, R ³ is F. In another embodiment, R ³ is CN. In another embodiment, R ³ is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ³ is i-butyl. In another embodiment, R ³ is CF ₃ . In another embodiment, R ³ is CF ₂ CF ₃ .

[00197] In another embodiment, the invention features a compound of formula I-C and the attendant definitions, wherein R ⁴ is H. In another embodiment, R ⁴ is halogen. In another embodiment, R ⁴ is CN. In another embodiment, R ⁴ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁴ is CF3.

[00198] In another embodiment, the invention features a compound of formula I-C and the attendant definitions, wherein R ¹ , R ² , R ³ , and R ⁴ is H.

[00199] In another embodiment, the invention features a compound of formula I-C and the attendant definitions, wherein R ⁵ is H. In another embodiment, R ⁵ is halogen. In another embodiment, R ⁵ is CI. In another embodiment, R ⁵ is F. In another embodiment, R ⁵ is CN. In another embodiment, R ⁵ is -X-R ^x . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁵ is CH ₃ . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Q-C6 alkyl is replaced with -0-. In another embodiment, R ⁵ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or OCH(CH ₃ ) ₂ . In another embodiment, R ⁵ is OCH ₃ . In another embodiment, R ⁵ is CH ₂ OH. In another embodiment, R ⁵ is OCF ₃ . In another embodiment, R ⁵ is OCHF ₂ .

[00200] In another embodiment, the invention features a compound of formula I-C and the attendant definitions, wherein R ⁵ is H. In another embodiment, R ⁵ is halogen. In another embodiment, R ⁵ is CI. In another embodiment, R ⁵ is F. In another embodiment, R ⁵ is CN. In another embodiment, R ⁵ is -X-R ^x . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Q-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁵ is CH ₃ . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Q-C6 alkyl is replaced with -0-. In another embodiment, R ⁵ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or OCH(CH ₃ ) ₂ . In another embodiment, R ⁵ is OCH ₃ . In another embodiment, R ⁵ is CH ₂ OH. In another embodiment, R ⁵ is OCF ₃ . In another embodiment, R ⁵ is OCHF ₂ .

[00201] In another embodiment, the invention features a compound of formula I-C and the attendant definitions, R ⁶ is H. In another embodiment, R ⁶ is halogen. In another embodiment, R ⁶ is CI. In another embodiment, R ⁶ is F. In another embodiment, R ⁶ is CN. In another embodiment, R ⁶ is -X-R ^x . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁶ is CH ₃ . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said C1-C6 alkyl is replaced with -0-. In another embodiment, R ⁶ is OCH ₃ .

[00202] In another embodiment, the invention features a compound of formula I-C and the attendant definitions, wherein R ⁶ is H. In another embodiment, R ⁶ is halogen. In another embodiment, R ⁶ is CI. In another embodiment, R ⁶ is F. In another embodiment, R ⁶ is CN. In another embodiment, R ⁶ is -X-R ^x . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Q-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁶ is CH ₃ . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Q-C6 alkyl is replaced with -0-. In another embodiment, R ⁶ is OCH ₃ .

[00203] In another embodiment, the invention features a compound of formula I-C and the attendant definitions, wherein R ⁷ is H. In another embodiment, R ⁷ is halogen. In another embodiment, R ⁷ is CI. In another embodiment, R ⁷ is F. In another embodiment, R ⁷ is CN. In another embodiment, R ⁷ is -X-R ^x . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁷ is CH ₃ , CH ₂ CH ₃ , CH2CH2CH3 or isopropyl. In another embodiment, R ⁷ is CF3. In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein two non-adjacent CH ₂ units of said C1-C6 alkyl are replaced with -0-. In another embodiment, R ⁷ is OCH2CH2OCH3. In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁷ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , OC(CH ₃ ) ₃ , CH2CH2OCH3. In another embodiment, R ⁷ is OCF ₃ , OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF3, or OCHF ₂ .

[00204] In another embodiment, the invention features a compound of formula I-C wherein R ⁷ is -X-R ^x wherein X is a bond and R ^x is C3-C8 cycloaliphatic and said C3-C8 cycloaliphatic is substituted with 0-3 substituents selected from halogen and Q-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is a bond and R ^x is cyclopropyl.

[00205] In another embodiment, the invention features a compound of formula I-C and the attendant definitions, wherein R ⁷ is -X-R ^x wherein X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -O- and R ^x is C ₃ -C ₈ cycloaliphatic and said C ₃ -C ₈ cycloaliphatic is substituted with up 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is OCH ₂ and R ^x is cyclopropyl.

[00206] In another embodiment, the invention features a compound of formula I-C and the attendant definitions, wherein ring A is selected from:

[00207] In another aspect, the invention provides a compound of formula I-C-l:

I-C-l

or a pharmaceutically acceptable salt thereof,

wherein, independently for each occurrence:

Y is C or N;

m is an integer from 0 to 5 inclusive;

W is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -O- -CO-, -S-, -SO-, or -SO ₂ -;

R ^w is absent, H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , OCF ₃ , or a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R' is Ci-C ₆ alkyl;

R ¹ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen and wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ² is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-; R ³ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁴ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁵ is halogen, CN, or -X-R ^x ;

X is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-; and

R ^x is absent, H, or C ₃ -C ₈ cycloaliphatic, wherein up to two non-adjacent CH ₂ units of said C ₃ -C ₈ cycloaliphatic may be replaced with -O- and said C3-C8 cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl.

[00208] In one embodiment, the invention features a compound of formula I-C-l and the attendant definitions, wherein Y is C. In another embodiment, Y is N.

[00209] In another embodiment, the invention features a compound of formula I-C-l and the attendant definitions, wherein m is zero. In another embodiment, m is an integer from 1 to 5. In another embodiment, m is 1. In another embodiment, m is 2. In another embodiment, m is 3. In another embodiment, m is 4. In another embodiment, m is 5.

[00210] In another embodiment, the invention features a compound of formula I-C-l and the attendant definitions, wherein W is a bond and R ^w is halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF3. In another embodiment, W is a bond and R ^w is halogen. In another embodiment, W is a bond and R ^w is OH.. In another embodiment, W is a bond and R ^w is NH ₂ . In another embodiment, W is a bond and R ^w is NHR'. In another embodiment, W is a bond and R ^w is CN. In another embodiment, W is a bond and R ^w is CF ₃ . In another embodiment, W is a bond and R ^w is OCF ₃ .

[00211] In another embodiment, the invention features a compound of formula I-C-l and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is CH ₃ , CH ₂ CH ₃ ,

CH ₂ CH ₂ CH ₃ , or isopropyl. In another embodiment, W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or O-isopropyl. In another embodiment, W is OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ . In another embodiment, W is OCH ₂ CH ₂ OCH ₃ , CH ₂ OH, OC(CH ₃ ) ₃ , or CH ₂ CH ₂ OCH ₃ .

[00212] In another embodiment, the invention features a compound of formula I-C-l and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl may be replaced with - 0-, -CO-, -S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NH ₂ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NH ₂ . In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NHR'.

[00213] In another embodiment, the invention features a compound of formula I-C-l and the attendant definitions, wherein W is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-,-S-, -SO-, or -S0 ₂ -, and R ^w absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said C ₂ alkyl may be replaced with -O- -CO-,-S-, -SO-, or -S0 ₂ -, and R ^w is absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is absent.

[00214] In another embodiment, the invention features a compound of formula I-C-l and the attendant definitions, wherein W is a bond and R ^w is a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 1 -4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is pyrrolyl, pyrazolyl, thiazolyl, thiadiazolyl, imidazolyl, oxazolyl, triazolyl, or tetrazolyl.

[00215] In another embodiment, the invention features a compound of formula I-C-l and the attendant definitions, wherein ring Ai is selected from:

[00216] In another embodiment, the invention features a compound of formula I-C-l and the attendant definitions, wherein R ¹ is H. In another embodiment, R ¹ is halogen. In another embodiment, R ¹ is CN. In another embodiment, R ¹ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ¹ is CF ₃ .

[00217] In another embodiment, the invention features a compound of formula I-C-l and the attendant definitions, wherein R ² is H. In another embodiment, R ² is halogen. In another embodiment, R ² is CI. In another embodiment, R ² is F. In another embodiment, R ² is CN. In another embodiment, R ² is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ² is CF ₃ . In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ² is OCF ₃ . In another embodiment, R ² is F, CI, CN, CF ₃ or OCF ₃ .

[00218] In another embodiment, the invention features a compound of formula I-C-l and the attendant definitions, wherein R ³ is H. In another embodiment, R ³ is halogen. In another embodiment, R ³ is CI. In another embodiment, R ³ is F. In another embodiment, R ³ is CN. In another embodiment, R ³ is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ³ is i-butyl. In another embodiment, R ³ is CF ₃ . In another embodiment, R ³ is CF ₂ CF ₃ .

[00219] In another embodiment, the invention features a compound of formula I-C-l and the attendant definitions, wherein R ⁴ is H. In another embodiment, R ⁴ is halogen. In another embodiment, R ⁴ is CN. In another embodiment, R ⁴ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁴ is CF ₃ .

[00220] In another embodiment, the invention features a compound of formula I-C-l and the attendant definitions, wherein R ¹ , R ² , R ³ , and R ⁴ is H.

[00221] In another embodiment, the invention features a compound of formula I-C-l and the attendant definitions, wherein R ⁵ is halogen. In another embodiment, R ⁵ is CI. In another embodiment, R ⁵ is F. In another embodiment, R ⁵ is CN. In another embodiment, R ⁵ is -X-R ^x . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen. In another embodiment, R ⁵ is CH ₃ . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁵ is OCH ₃ , OCH ₂ CH ₃ ,

OCH ₂ CH ₂ CH ₃ , or OCH(CH ₃ ) ₂ . In another embodiment, R ⁵ is OCH ₃ . In another embodiment, R ⁵ is CH ₂ OH. In another embodiment, R ⁵ is OCF ₃ . In another embodiment, R ⁵ is OCHF ₂ .

[00222] In another embodiment, the invention features a compound of formula I-C-l and the attendant definitions, wherein ring A is selected from:

[00223] In another aspect, the invention provides a compound of formula I-C-2:

I-C-2

or a pharmaceutically acceptable salt thereof,

wherein, independently for each occurrence:

Y is C or N;

m is an integer from 0 to 5 inclusive;

W is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-,

R ^w is absent, H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , OCF ₃ , or a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R' is Ci-C ₆ alkyl;

R ¹ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen and wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ² is H, halogen, CN, or C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ³ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-; R ⁴ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁷ is halogen, CN, or -X-R ^x ;

X is a bond or C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-; and

R ^x is absent, H, or C ₃ -C ₈ cycloaliphatic, wherein up to two non-adjacent CH ₂ units of said C ₃ -C ₈ cycloaliphatic may be replaced with -O- and said C ₃ -C ₈ cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl.

[00224] In one embodiment, the invention features a compound of formula I-C-2 and the attendant definitions, wherein Y is C. In another embodiment, Y is N.

[00225] In another embodiment, the invention features a compound of formula I-C-2 and the attendant definitions, wherein m is zero. In another embodiment, m is an integer from 1 to 5. In another embodiment, m is 1. In another embodiment, m is 2. In another embodiment, m is 3. In another embodiment, m is 4. In another embodiment, m is 5.

[00226] In another embodiment, the invention features a compound of formula I-C-2 and the attendant definitions, wherein W is a bond and R ^w is halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is a bond and R ^w is halogen. In another embodiment, W is a bond and R ^w is OH. In another embodiment, W is a bond and R ^w is NH ₂ . In another embodiment, W is a bond and R ^w is NHR'. In another embodiment, W is a bond and R ^w is CN. In another embodiment, W is a bond and R ^w is CF ₃ . In another embodiment, W is a bond and R ^w is OCF ₃ .

[00227] In another embodiment, the invention features a compound of formula I-C-2 and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is CH ₃ , CH ₂ CH ₃ ,

CH ₂ CH ₂ CH ₃ , or isopropyl. In another embodiment, W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or O-isopropyl. In another embodiment, W is OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ . In another embodiment, W is OCH ₂ CH ₂ OCH ₃ , CH ₂ OH, OC(CH ₃ ) ₃ , or CH ₂ CH ₂ OCH ₃ .

[00228] In another embodiment, the invention features a compound of formula I-C-2 and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl may be replaced with - Ο-, -CO-, -S-, -SO-, or -SO ₂ -, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -SO ₂ -, and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NH ₂ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NH ₂ . In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NHR'.

[00229] In another embodiment, the invention features a compound of formula I-C-2 and the attendant definitions, wherein W is d-C ₆ alkyl wherein said d-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said d-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -, and R ^w absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said C ₂ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -, and R ^w is absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is absent.

[00230] In another embodiment, the invention features a compound of formula I-C-2 and the attendant definitions, wherein W is a bond and R ^w is a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 1 -4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is pyrrolyl, pyrazolyl, thiazolyl, thiadiazolyl, imidazolyl, oxazolyl, triazolyl, or tetrazolyl.

[00231] In another embodiment, the invention features a compound of formula I-C-2 and the attendant definitions, wherein ring Ai is selected from:

[00232] In another embodiment, the invention features a compound of formula I-C-2 and the attendant definitions, wherein R ¹ is H. In another embodiment, R ¹ is halogen. In another embodiment, R ¹ is CN. In another embodiment, R ¹ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ¹ is CF ₃ .

[00233] In another embodiment, the invention features a compound of formula I-C-2 and the attendant definitions, wherein R ² is H. In another embodiment, R ² is halogen. In another embodiment, R ² is CI. In another embodiment, R ² is F. In another embodiment, R ² is CN. In another embodiment, R ² is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ² is CF ₃ . In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ² is OCF ₃ . In another embodiment, R ² is F, CI, CN, CF ₃ or OCF ₃ .

[00234] In another embodiment, the invention features a compound of formula I-C-2 and the attendant definitions, wherein R ³ is H. In another embodiment, R ³ is halogen. In another embodiment, R ³ is CI. In another embodiment, R ³ is F. In another embodiment, R ³ is CN. In another embodiment, R ³ is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ³ is i-butyl. In another embodiment, R ³ is CF ₃ . In another embodiment, R ³ is CF ₂ CF ₃ .

[00235] In another embodiment, the invention features a compound of formula I-C-2 and the attendant definitions, wherein R ⁴ is H. In another embodiment, R ⁴ is halogen. In another embodiment, R ⁴ is CN. In another embodiment, R ⁴ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁴ is CF ₃ .

[00236] In another embodiment, the invention features a compound of formula I-C-2 and the attendant definitions, wherein R ¹ , R ² , R ³ , and R ⁴ is H.

[00237] In another embodiment, the invention features a compound of formula I-C-2 and the attendant definitions, wherein R ⁷ is halogen. In another embodiment, R ⁷ is CI. In another embodiment, R ⁷ is F. In another embodiment, R ⁷ is CN. In another embodiment, R ⁷ is -X-R ^x . In another embodiment, R is -X-R wherein R is absent. In another embodiment, R is -X-R wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen. In another embodiment, R ⁷ is CH ₃ , CH ₂ CH ₃ , CH2CH ₂ CH ₃ or isopropyl. In another embodiment, R ⁷ is CF ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein two non-adjacent CH ₂ units of said Ci-C ₆ alkyl are replaced with -0-. In another embodiment, R ⁷ is OCH ₂ CH ₂ OCH ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁷ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , OC(CH ₃ ) ₃ , CH ₂ CH ₂ OCH ₃ . In another embodiment, R ⁷ is OCF ₃ , OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ .

[00238] In another embodiment, the invention features a compound of formula I-C-2 wherein R ⁷ is -X-R ^x wherein X is a bond and R ^x is C ₃ -Cs cycloaliphatic and said C ₃ -Cs cycloaliphatic is substituted with 0-3 substituents selected from halogen and Q-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is a bond and R ^x is cyclopropyl.

[00239] In another embodiment, the invention features a compound of formula I-C-2 and the attendant definitions, wherein R ⁷ is -X-R ^x wherein X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -O- and R ^x is C ₃ -C ₈ cycloaliphatic and said C ₃ -C ₈ cycloaliphatic is substituted with up 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is OCH ₂ and R ^x is cyclopropyl.

[00240] In another embodiment, the invention features a compound of formula I-C-2 and the attendant definitions, wherein ring A is selected from:

[00241] In another aspect, the invention provides a compound of formula I-C-3:

I-C-3

or a pharmaceutically acceptable salt thereof,

wherein, independently for each occurrence:

Y is C or N; m is an integer from 0 to 5 inclusive;

W is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-,

R ^w is absent, H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , OCF ₃ , or a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R' is Ci-C ₆ alkyl;

R ¹ is H, halogen, CN, or Ci-C ₆ alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen and wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ² is H, halogen, CN, or C C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non -adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-;

R ³ is H, halogen, CN, or C C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁴ is H, halogen, CN, or C C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁶ is halogen, CN, or -X-R ^x ;

R ⁷ is halogen, CN, or -X-R ^x ;

X is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-; and

R ^x is absent, H, or C ₃ -C ₈ cycloaliphatic, wherein up to two non-adjacent CH ₂ units of said C ₃ -C ₈ cycloaliphatic may be replaced with -O- and said C ₃ -C ₈ cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl.

[00242] In one embodiment, the invention features a compound of formula I-C-3 and the attendant definitions, wherein Y is C. In another embodiment, Y is N.

[00243] In another embodiment, the invention features a compound of formula I-C-3 and the attendant definitions, wherein m is zero. In another embodiment, m is an integer from 1 to 5. In another embodiment, m is 1. In another embodiment, m is 2. In another embodiment, m is 3. In another embodiment, m is 4. In another embodiment, m is 5.

[00244] In another embodiment, the invention features a compound of formula I-C-3 and the attendant definitions, wherein W is a bond and R ^w is halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is a bond and R ^w is halogen. In another embodiment, W is a bond and R ^w is OH.. In another embodiment, W is a bond and R ^w is NH _2. In another embodiment, W is a bond and R is NHR'. In another embodiment, W is a bond and R is CN. In another embodiment, W is a bond and R ^w is CF ₃ . In another embodiment, W is a bond and R ^w is OCF ₃ .

[00245] In another embodiment, the invention features a compound of formula I-C-3 and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO ₂ -; and R ^w is absent. In another embodiment, W is CH ₃ , CH ₂ CH ₃ ,

CH ₂ CH ₂ CH ₃ , or isopropyl. In another embodiment, W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or O-isopropyl. In another embodiment, W is OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ . In another embodiment, W is OCH ₂ CH ₂ OCH ₃ , CH ₂ OH, OC(CH ₃ ) ₃ , or CH ₂ CH ₂ OCH ₃ .

[00246] In another embodiment, the invention features a compound of formula I-C-3 and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO ₂ -, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl may be replaced with - 0-, -CO-, -S-, -SO-, or -SO ₂ -, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NH ₂ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NH ₂ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -SO ₂ - and R ^w is NHR'.

[00247] In another embodiment, the invention features a compound of formula I-C-3 and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO2-, and R absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said C ₂ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -, and R ^w is absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is absent.

[00248] In another embodiment, the invention features a compound of formula I-C-3 and the attendant definitions, wherein W is a bond and R ^w is a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 1 -4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is pyrrolyl, pyrazolyl, thiazolyl, thiadiazolyl, imidazolyl, oxazolyl, triazolyl, or tetrazolyl.

[00249] In another embodiment, the invention features a compound of formula I-C-3 and the attendant definitions, wherein ring Ai is selected from:

[00250] In another embodiment, the invention features a compound of formula I-C-3 and the attendant definitions, wherein R ¹ is H. In another embodiment, R ¹ is halogen. In another embodiment, R ¹ is CN. In another embodiment, R ¹ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ¹ is CF3.

[00251] In another embodiment, the invention features a compound of formula I-C-3 and the attendant definitions, wherein R ² is H. In another embodiment, R ² is halogen. In another embodiment, R ² is CI. In another embodiment, R ² is F. In another embodiment, R ² is CN. In another embodiment, R ² is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ² is CF ₃ . In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ² is OCF ₃ . In another embodiment, R ² is F, CI, CN, CF ₃ or OCF ₃ .

[00252] In another embodiment, the invention features a compound of formula I-C-3 and the attendant definitions, wherein R ³ is H. In another embodiment, R ³ is halogen. In another embodiment, R ³ is CI. In another embodiment, R ³ is F. In another embodiment, R ³ is CN. In another embodiment, R ³ is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ³ is i-butyl. In another embodiment, R ³ is CF ₃ . In another embodiment, R ³ is CF ₂ CF ₃ .

[00253] In another embodiment, the invention features a compound of formula I-C-3 and the attendant definitions, wherein R ⁴ is H. In another embodiment, R ⁴ is halogen. In another embodiment, R ⁴ is CN. In another embodiment, R ⁴ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁴ is CF ₃ .

[00254] In another embodiment, the invention features a compound of formula I-C-3 and the attendant definitions, wherein R ¹ , R ² , R ³ , and R ⁴ is H.

[00255] In another embodiment, the invention features a compound of formula I-C-3 and the attendant definitions, R ⁶ is halogen. In another embodiment, R ⁶ is CI. In another embodiment, R ⁶ is F. In another embodiment, R ⁶ is CN. In another embodiment, R ⁶ is -X-R ^x . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁶ is CH ₃ . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Q-C6 alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁶ is OCH ₃ .

[00256] In another embodiment, the invention features a compound of formula I-C-3 and the attendant definitions, wherein R ⁷ is halogen. In another embodiment, R ⁷ is CI. In another embodiment, R ⁷ is F. In another embodiment, R ⁷ is CN. In another embodiment, R ⁷ is -X-R ^x . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen. In another embodiment, R ⁷ is CH ₃ , CH ₂ CH ₃ , CH2CH ₂ CH ₃ or isopropyl. In another embodiment, R ⁷ is CF ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein two non-adjacent CH ₂ units of said Ci-C ₆ alkyl are replaced with -0-. In another embodiment, R ⁷ is OCH2CH ₂ OCH ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁷ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , OC(CH ₃ ) ₃ , CH ₂ CH ₂ OCH ₃ . In another embodiment, R ⁷ is OCF ₃ , OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ .

[00257] In another embodiment, the invention features a compound of formula I-C-3 wherein R ⁷ is -X-R ^x wherein X is a bond and R ^x is C ₃ -Cs cycloaliphatic and said C ₃ -Cs cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is a bond and R ^x is cyclopropyl.

[00258] In another embodiment, the invention features a compound of formula I-C-3 and the attendant definitions, wherein R ⁷ is -X-R ^x wherein X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -O- and R ^x is C ₃ -C ₈ cycloaliphatic and said C ₃ -C ₈ cycloaliphatic is substituted with up 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is OCH ₂ and R ^x is cyclopropyl. [00259] In another embodiment, the invention features a compound of formula I-C-3 and the attendant definitions, wherein ring A is selected from:

[00260] In another aspect, the invention provides a compound of formula I-C-4:

I-C-4

or a pharmaceutically acceptable salt thereof,

wherein, independently for each occurrence:

Y is C or N;

m is an integer from 0 to 5 inclusive;

W is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -SO ₂ -;

R ^w is absent, H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , OCF ₃ , or a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R' is Ci-C ₆ alkyl;

R ¹ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen and wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ² is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ³ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-; R ⁴ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁵ is halogen, CN, or -X-R ^x ;

R ⁷ is halogen, CN, or -X-R ^x ;

X is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-; and

R ^x is absent, H, or C ₃ -C ₈ cycloaliphatic, wherein up to two non-adjacent CH ₂ units of said C ₃ -C ₈ cycloaliphatic may be replaced with -O- and said C ₃ -C ₈ cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl.

[00261] In one embodiment, the invention features a compound of formula I-C-4 and the attendant definitions, wherein Y is C. In another embodiment, Y is N.

[00262] In another embodiment, the invention features a compound of formula I-C-4 and the attendant definitions, wherein m is zero. In another embodiment, m is an integer from 1 to 5. In another embodiment, m is 1. In another embodiment, m is 2. In another embodiment, m is 3. In another embodiment, m is 4. In another embodiment, m is 5.

[00263] In another embodiment, the invention features a compound of formula I-C-4 and the attendant definitions, wherein W is a bond and R ^w is halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is a bond and R ^w is halogen. In another embodiment, W is a bond and R ^w is OH. In another embodiment, W is a bond and R ^w is NH ₂ . In another embodiment, W is a bond and R ^w is NHR'. In another embodiment, W is a bond and R ^w is CN. In another embodiment, W is a bond and R ^w is CF ₃ . In another embodiment, W is a bond and R ^w is OCF ₃ .

[00264] In another embodiment, the invention features a compound of formula I-C-4 and the attendant definitions, wherein W is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is CH ₃ , CH ₂ CH ₃ ,

CH ₂ CH ₂ CH ₃ , or isopropyl. In another embodiment, W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-,-S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or O-isopropyl. In another embodiment, W is OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ . In another embodiment, W is OCH ₂ CH ₂ OCH ₃ , CH ₂ OH, OC(CH ₃ ) ₃ , or CH ₂ CH ₂ OCH ₃ .

[00265] In another embodiment, the invention features a compound of formula I-C-4 and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl may be replaced with - 0-, -CO-, -S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -SO2-, and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NH ₂ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NH ₂ . In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NHR'.

[00266] In another embodiment, the invention features a compound of formula I-C-4 and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said d-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -, and R ^w absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said C ₂ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -, and R ^w is absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is absent.

[00267] In another embodiment, the invention features a compound of formula I-C-4 and the attendant definitions, wherein W is a bond and R ^w is a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 1 -4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is pyrrolyl, pyrazolyl, thiazolyl, thiadiazolyl, imidazolyl, oxazolyl, triazolyl, or tetrazolyl.

[00268] In another embodiment, the invention features a compound of formula I-C-4 and the attendant definitions, wherein ring Ai is selected from:

[00269] In another embodiment, the invention features a compound of formula I-C-4 and the attendant definitions, wherein R ¹ is H. In another embodiment, R ¹ is halogen. In another embodiment, R ¹ is CN. In another embodiment, R ¹ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ¹ is CF ₃ .

[00270] In another embodiment, the invention features a compound of formula I-C-4 and the attendant definitions, wherein R ² is H. In another embodiment, R ² is halogen. In another embodiment, R ² is CI. In another embodiment, R ² is F. In another embodiment, R ² is CN. In another embodiment, R ² is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ² is CF ₃ . In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ² is OCF ₃ . In another embodiment, R ² is F, CI, CN, CF ₃ or OCF ₃ .

[00271] In another embodiment, the invention features a compound of formula I-C-4 and the attendant definitions, wherein R ³ is H. In another embodiment, R ³ is halogen. In another embodiment, R ³ is CI. In another embodiment, R ³ is F. In another embodiment, R ³ is CN. In another embodiment, R ³ is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ³ is i-butyl. In another embodiment, R ³ is CF ₃ . In another embodiment, R ³ is CF ₂ CF ₃ .

[00272] In another embodiment, the invention features a compound of formula I-C-4 and the attendant definitions, wherein R ⁴ is H. In another embodiment, R ⁴ is halogen. In another embodiment, R ⁴ is CN. In another embodiment, R ⁴ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁴ is CF ₃ .

[00273] In another embodiment, the invention features a compound of formula I-C-4 and the attendant definitions, wherein R ¹ , R ² , R ³ , and R ⁴ is H.

[00274] In another embodiment, the invention features a compound of formula I-C-4 and the attendant definitions, wherein R ⁵ is halogen. In another embodiment, R ⁵ is CI. In another embodiment, R ⁵ is F. In another embodiment, R ⁵ is CN. In another embodiment, R ⁵ is -X-R ^x . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen. In another embodiment, R ⁵ is CH ₃ . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁵ is OCH ₃ , OCH ₂ CH ₃ ,

OCH ₂ CH ₂ CH ₃ , or OCH(CH ₃ ) ₂ . In another embodiment, R ⁵ is OCH ₃ . In another embodiment, R ⁵ is CH ₂ OH. In another embodiment, R ⁵ is OCF ₃ . In another embodiment, R ⁵ is OCHF ₂ .

[00275] In another embodiment, the invention features a compound of formula I-C-4 and the attendant definitions, wherein R ⁷ is H. In another embodiment, R ⁷ is halogen. In another embodiment, R ⁷ is CI. In another embodiment, R ⁷ is F. In another embodiment, R ⁷ is CN. In another embodiment, R is -X-R . In another embodiment, R is -X-R wherein R is absent. In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁷ is CH ₃ , CH ₂ CH ₃ , CH2CH2CH3 or isopropyl. In another embodiment, R ⁷ is CF ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein two non-adjacent CH ₂ units of said C1-C6 alkyl are replaced with -0-. In another embodiment, R ⁷ is OCH2CH2OCH3. In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁷ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , OC(CH ₃ ) ₃ , CH ₂ CH ₂ OCH ₃ . In another embodiment, R ⁷ is OCF ₃ , OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ .

[00276] In another embodiment, the invention features a compound of formula I-C-4 wherein R ⁷ is -X-R ^x wherein X is a bond and R ^x is C ₃ -Cs cycloaliphatic and said C ₃ -Cs cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is a bond and R ^x is cyclopropyl.

[00277] In another embodiment, the invention features a compound of formula I-C-4 and the attendant definitions, wherein R ⁷ is -X-R ^x wherein X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -O- and R ^x is C ₃ -C ₈ cycloaliphatic and said C ₃ -C ₈ cycloaliphatic is substituted with up 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is OCH ₂ and R ^x is cyclopropyl.

[00278] In another embodiment, the invention features a compound of formula I-C-4 and the attendant definitions, wherein ring A is selected from:

[00279] In another aspect, the invention provides a compound of formula I-D:

I-D

or a pharmaceutically acceptable salt thereof,

wherein, independently for each occurrence:

Y is C or N;

m is an integer from 0 to 5 inclusive;

W is a bond or C _\ -C(, alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C _\ -C _& alkyl may be replaced with -0-, -CO-,

R ^w is absent, H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , OCF ₃ , or a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R' is Ci-Ce alkyl;

R ¹ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen and wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ² is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ³ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁴ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁵ is H, halogen, CN, or -X-R ^x ;

R ⁵ is H, halogen, CN, or -X-R ^x ;

R ⁶ is H, halogen, CN, or -X-R ^x ;

R ⁶ is H, halogen, CN, or -X-R ^x ;

R ⁷ is H, halogen, CN, or -X-R ^x ; X is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-; and

R ^x is absent, H, or C ₃ -C ₈ cycloaliphatic, wherein up to two non-adjacent CH ₂ units of said C ₃ -C ₈ cycloaliphatic may be replaced with -O- and said C ₃ -C ₈ cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl.

[00280] In one embodiment, the invention features a compound of formula I-D and the attendant definitions, wherein Y is C. In another embodiment, Y is N.

[00281] In another embodiment, the invention features a compound of formula I-D and the attendant definitions, wherein m is zero. In another embodiment, m is an integer from 1 to 5. In another embodiment, m is 1. In another embodiment, m is 2. In another embodiment, m is 3. In another embodiment, m is 4. In another embodiment, m is 5.

[00282] In another embodiment, the invention features a compound of formula I-D and the attendant definitions, wherein W is a bond and R ^w is halogen, OH, NH ₂ , NHR', NO2, CN, CF ₃ , or OCF ₃ . In another embodiment, W is a bond and R ^w is halogen. In another embodiment, W is a bond and R ^w is OH. In another embodiment, W is a bond and R ^w is NH ₂ . In another embodiment, W is a bond and R ^w is NHR'. In another embodiment, W is a bond and R ^w is CN. In another embodiment, W is a bond and R ^w is CF ₃ . In another embodiment, W is a bond and R ^w is OCF ₃ .

[00283] In another embodiment, the invention features a compound of formula I-D and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is CH ₃ , CH ₂ CH ₃ ,

CH ₂ CH ₂ CH ₃ , or isopropyl. In another embodiment, W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or O-isopropyl. In another embodiment, W is OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ . In another embodiment, W is OCH ₂ CH ₂ OCH ₃ , CH ₂ OH, OC(CH ₃ ) ₃ , or CH ₂ CH ₂ OCH ₃ .

[00284] In another embodiment, the invention features a compound of formula I-D and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl may be replaced with - 0-, -CO-, -S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NH ₂ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NH ₂ . In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NHR'.

[00285] In another embodiment, the invention features a compound of formula I-D and the attendant definitions, wherein W is d-C ₆ alkyl wherein said d-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -, and R ^w absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said C ₂ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -, and R ^w is absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is absent.

[00286] In another embodiment, the invention features a compound of formula I-D and the attendant definitions, wherein W is a bond and R ^w is a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5-membered aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5-membered aromatic ring having 1 -4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is pyrrolyl, pyrazolyl, thiazolyl, thiadiazolyl, imidazolyl, oxazolyl, triazolyl, or tetrazolyl.

[00287] In another embodiment, the invention features a compound of formula I-D and the attendant definitions, wherein ring Aj is selected from:

[00288] In another embodiment, the invention features a compound of formula I-D and the attendant definitions, wherein R ¹ is H. In another embodiment, R ¹ is halogen. In another embodiment, R ¹ is CN. In another embodiment, R ¹ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ¹ is CF ₃ .

[00289] In another embodiment, the invention features a compound of formula I-D and the attendant definitions, wherein R ² is H. In another embodiment, R ² is halogen. In another embodiment, R ² is CI. In another embodiment, R ² is F. In another embodiment, R ² is CN. In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ² is CF ₃ . In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ² is OCF ₃ . In another embodiment, R ² is F, CI, CN, CF ₃ or OCF ₃ .

[00290] In another embodiment, the invention features a compound of formula I-D and the attendant definitions, wherein R ³ is H. In another embodiment, R ³ is halogen. In another embodiment, R ³ is CI. In another embodiment, R ³ is F. In another embodiment, R ³ is CN. In another embodiment, R ³ is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen. In another embodiment, R ³ is i-butyl. In another embodiment, R ³ is CF ₃ . In another embodiment, R ³ is CF ₂ CF ₃ .

[00291] In another embodiment, the invention features a compound of formula I-D and the attendant definitions, wherein R ⁴ is H. In another embodiment, R ⁴ is halogen. In another embodiment, R ⁴ is CN. In another embodiment, R ⁴ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁴ is CF ₃ .

[00292] In another embodiment, the invention features a compound of formula I-D and the attendant definitions, wherein R ¹ , R ² , R ³ , and R ⁴ is H.

[00293] In another embodiment, the invention features a compound of formula I-D and the attendant definitions, wherein R ⁵ is H. In another embodiment, R ⁵ is halogen. In another embodiment, R ⁵ is CI. In another embodiment, R ⁵ is F. In another embodiment, R ⁵ is CN. In another embodiment, R ⁵ is -X-R ^x . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁵ is CH ₃ . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Q-C6 alkyl is replaced with -0-. In another embodiment, R ⁵ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or OCH(CH ₃ ) ₂ . In another embodiment, R ⁵ is OCH ₃ . In another embodiment, R ⁵ is CH ₂ OH. In another embodiment, R ⁵ is OCF ₃ . In another embodiment, R ⁵ is OCHF ₂ .

[00294] In another embodiment, the invention features a compound of formula I-D and the attendant definitions, wherein R ⁵ is H. In another embodiment, R ⁵ is halogen. In another embodiment, R ⁵ is CI. In another embodiment, R ⁵ is F. In another embodiment, R ⁵ is CN. In another embodiment, R ⁵ is -X-R ^x . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Q-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁵ is CH ₃ . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said C1-C6 alkyl is replaced with -0-. In another embodiment, R ⁵ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or OCH(CH ₃ ) ₂ . In another embodiment, R ⁵ is OCH ₃ . In another embodiment, R ⁵ is CH ₂ OH. In another embodiment, R ⁵ is OCF ₃ . In another embodiment, R ⁵ is OCHF ₂ .

[00295] In another embodiment, the invention features a compound of formula I-D and the attendant definitions, R ⁶ is H. In another embodiment, R ⁶ is halogen. In another embodiment, R ⁶ is CI. In another embodiment, R ⁶ is F. In another embodiment, R ⁶ is CN. In another embodiment, R ⁶ is -X-R ^x . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen. In another embodiment, R ⁶ is CH ₃ . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said C1-C6 alkyl is replaced with -0-. In another embodiment, R ⁶ is OCH ₃ .

[00296] In another embodiment, the invention features a compound of formula I-D and the attendant definitions, wherein R ⁶ is H. In another embodiment, R ⁶ is halogen. In another embodiment, R ⁶ is CI. In another embodiment, R ⁶ is F. In another embodiment, R ⁶ is CN. In another embodiment, R ⁶ is -X-R ^x . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Q-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁶ is CH ₃ . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said C1-C6 alkyl is replaced with -0-. In another embodiment, R ⁶ is OCH ₃ .

[00297] In another embodiment, the invention features a compound of formula I-D and the attendant definitions, wherein R ⁷ is H. In another embodiment, R ⁷ is halogen. In another embodiment, R ⁷ is CI. In another embodiment, R ⁷ is F. In another embodiment, R ⁷ is CN. In another embodiment, R ⁷ is -X-R ^x . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁷ is CH ₃ , CH ₂ CH ₃ , CH ₂ CH ₂ CH ₃ or isopropyl. In another embodiment, R ⁷ is CF ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein two non-adjacent CH ₂ units of said C1-C6 alkyl are replaced with -0-. In another embodiment, R ⁷ is OCH ₂ CH ₂ OCH ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said C1-C6 alkyl is replaced with -0-. In another embodiment, R ⁷ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , OC(CH ₃ ) ₃ , CH ₂ CH ₂ OCH ₃ . In another embodiment, R ⁷ is OCF ₃ , OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ . [00298] In another embodiment, the invention features a compound of formula I-D wherein R ⁷ is -X-R ^x wherein X is a bond and R ^x is C3-C8 cycloaliphatic and said C3-C8 cycloaliphatic is substituted with 0-3 substituents selected from halogen and Q-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is a bond and R ^x is cyclopropyl.

[00299] In another embodiment, the invention features a compound of formula I-D and the attendant definitions, wherein R ⁷ is -X-R ^x wherein X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -O- and R ^x is C ₃ -C ₈ cycloaliphatic and said C ₃ -C ₈ cycloaliphatic is substituted with up 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is OCH ₂ and R ^x is cyclopropyl.

[00300] In another embodiment, the invention features a compound of formula I-D and the attendant definitions, wherein ring A is selected from:

[00301] In another aspect, the invention provides a compound of formula I-D-l:

I-D-l

or a pharmaceutically acceptable salt thereof,

wherein, independently for each occurrence:

Y is C or N;

m is an integer from 0 to 5 inclusive; W is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-,

R ^w is absent, H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , OCF ₃ , or a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R' is Ci-C ₆ alkyl;

R ¹ is H, halogen, CN, or C C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen and wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ² is H, halogen, CN, or C C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ³ is H, halogen, CN, or Ci-C ₆ alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen, wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁴ is H, halogen, CN, or C C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁵ is halogen, CN, or -X-R ^x ;

X is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-; and

R ^x is absent, H, or C ₃ -C ₈ cycloaliphatic, wherein up to two non-adjacent CH ₂ units of said C ₃ -C ₈ cycloaliphatic may be replaced with -O- and said C ₃ -C ₈ cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl.

[00302] In one embodiment, the invention features a compound of formula I-D-l and the attendant definitions, wherein Y is C. In another embodiment, Y is N.

[00303] In another embodiment, the invention features a compound of formula I-D-l and the attendant definitions, wherein m is zero. In another embodiment, m is an integer from 1 to 5. In another embodiment, m is 1. In another embodiment, m is 2. In another embodiment, m is 3. In another embodiment, m is 4. In another embodiment, m is 5.

[00304] In another embodiment, the invention features a compound of formula I-D-l and the attendant definitions, wherein W is a bond and R ^w is halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is a bond and R ^w is halogen. In another embodiment, W is a bond and R ^w is OH. In another embodiment, W is a bond and R ^w is NH _2. In another embodiment, W is a bond and R ^w is NHR'. In another embodiment, W is a bond and R ^w is CN. In another embodiment, W is a bond and R ^w is CF ₃ . In another embodiment, W is a bond and R ^w is OCF ₃ . [00305] In another embodiment, the invention features a compound of formula I-D-l and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is CH ₃ , CH ₂ CH ₃ ,

CH ₂ CH ₂ CH ₃ , or isopropyl. In another embodiment, W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or O-isopropyl. In another embodiment, W is OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ . In another embodiment, W is OCH ₂ CH ₂ OCH ₃ , CH ₂ OH, OC(CH ₃ ) ₃ , or CH ₂ CH ₂ OCH ₃ .

[00306] In another embodiment, the invention features a compound of formula I-D-l and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO ₂ -, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl may be replaced with - 0-, -CO-, -S-, -SO-, or -SO ₂ -, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NH ₂ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NH ₂ . In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -SO ₂ - and R ^w is NHR'.

[00307] In another embodiment, the invention features a compound of formula I-D-l and the attendant definitions, wherein W is d-C ₆ alkyl wherein said d-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said d-C ₆ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -, and R ^w absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said C ₂ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -, and R ^w is absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -SO2-, and R ^w is absent.

[00308] In another embodiment, the invention features a compound of formula I-D-l and the attendant definitions, wherein W is a bond and R ^w is a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 1 -4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is pyrrolyl, pyrazolyl, thiazolyl, thiadiazolyl, imidazolyl, oxazolyl, triazolyl, or tetrazolyl.

[00309] In another embodiment, the invention features a compound of formula I-D-l and the attendant definitions, wherein ring Ai is selected from:

[00310] In another embodiment, the invention features a compound of formula I-D-l and the attendant definitions, wherein R ¹ is H. In another embodiment, R ¹ is halogen. In another embodiment, R ¹ is CN. In another embodiment, R ¹ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ¹ is CF3.

[00311] In another embodiment, the invention features a compound of formula I-D-l and the attendant definitions, wherein R ² is H. In another embodiment, R ² is halogen. In another embodiment, R ² is CI. In another embodiment, R ² is F. In another embodiment, R ² is CN. In another embodiment, R ² is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ² is CF ₃ . In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ² is OCF ₃ . In another embodiment, R ² is F, CI, CN, CF ₃ or OCF ₃ .

[00312] In another embodiment, the invention features a compound of formula I-D-l and the attendant definitions, wherein R ³ is H. In another embodiment, R ³ is halogen. In another embodiment, R ³ is CI. In another embodiment, R ³ is F. In another embodiment, R ³ is CN. In another embodiment, R ³ is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ³ is i-butyl. In another embodiment, R ³ is CF ₃ . In another embodiment, R ³ is CF ₂ CF ₃ .

[00313] In another embodiment, the invention features a compound of formula I-D-l and the attendant definitions, wherein R ⁴ is H. In another embodiment, R ⁴ is halogen. In another embodiment, R ⁴ is CN. In another embodiment, R ⁴ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁴ is CF ₃ .

[00314] In another embodiment, the invention features a compound of formula I-D-l and the attendant definitions, wherein R ¹ , R ² , R ³ , and R ⁴ is H.

[00315] In another embodiment, the invention features a compound of formula I-D-l and the attendant definitions, wherein R ⁵ is halogen. In another embodiment, R ⁵ is CI. In another embodiment, R ⁵ is F. In another embodiment, R ⁵ is CN. In another embodiment, R ⁵ is -X-R ^x . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen. In another embodiment, R ⁵ is CH ₃ . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁵ is OCH ₃ , OCH ₂ CH ₃ ,

OCH ₂ CH ₂ CH ₃ , or OCH(CH ₃ ) ₂ . In another embodiment, R ⁵ is OCH ₃ . In another embodiment, R ⁵ is CH ₂ OH. In another embodiment, R ⁵ is OCF ₃ . In another embodiment, R ⁵ is OCHF ₂ .

[00316] In another embodiment, the invention features a compound of formula I-D-l and the attendant definitions, wherein ring A is selected from:

[00317] In another aspect, the invention provides a compound of formula I-D-2:

I-D-2

or a pharmaceutically acceptable salt thereof,

wherein, independently for each occurrence:

Y is C or N;

m is an integer from 0 to 5 inclusive;

W is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-,

-S-, -SO-, or -S0 ₂ -; R ^w is absent, H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , OCF ₃ , or a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R' is Ci-C ₆ alkyl;

R ¹ is H, halogen, CN, or C C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen and wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ² is H, halogen, CN, or C C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ³ is H, halogen, CN, or Ci-C ₆ alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen, wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁴ is H, halogen, CN, or C C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non -adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-;

R ⁷ is halogen, CN, or -X-R ^x ;

X is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-; and

R ^x is absent, H, or C ₃ -C ₈ cycloaliphatic, wherein up to two non-adjacent CH ₂ units of said C ₃ -C ₈ cycloaliphatic may be replaced with -O- and said C ₃ -C ₈ cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl.

[00318] In one embodiment, the invention features a compound of formula I-D-2 and the attendant definitions, wherein Y is C. In another embodiment, Y is N.

[00319] In another embodiment, the invention features a compound of formula I-D-2 and the attendant definitions, wherein m is zero. In another embodiment, m is an integer from 1 to 5. In another embodiment, m is 1. In another embodiment, m is 2. In another embodiment, m is 3. In another embodiment, m is 4. In another embodiment, m is 5.

[00320] In another embodiment, the invention features a compound of formula I-D-2 and the attendant definitions, wherein W is a bond and R ^w is halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is a bond and R ^w is halogen. In another embodiment, W is a bond and R ^w is OH.. In another embodiment, W is a bond and R ^w is NH _2. In another embodiment, W is a bond and R ^w is NHR'. In another embodiment, W is a bond and R ^w is CN. In another embodiment, W is a bond and R ^w is CF ₃ . In another embodiment, W is a bond and R ^w is OCF ₃ .

[00321] In another embodiment, the invention features a compound of formula I-D-2 and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is CH ₃ , CH ₂ CH ₃ , CH ₂ CH ₂ CH ₃ , or isopropyl. In another embodiment, W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or O-isopropyl. In another embodiment, W is OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ . In another embodiment, W is OCH ₂ CH ₂ OCH ₃ , CH ₂ OH, OC(CH ₃ ) ₃ , or CH ₂ CH ₂ OCH ₃ .

[00322] In another embodiment, the invention features a compound of formula I-D-2 and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO ₂ -, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl may be replaced with - 0-, -CO-, -S-, -SO-, or -SO ₂ -, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NH ₂ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NH ₂ . In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -SO ₂ - and R ^w is NHR'.

[00323] In another embodiment, the invention features a compound of formula I-D-2 and the attendant definitions, wherein W is d-C ₆ alkyl wherein said d-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said d-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -, and R ^w absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said C ₂ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -, and R ^w is absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is absent.

[00324] In another embodiment, the invention features a compound of formula I-D-2 and the attendant definitions, wherein W is a bond and R ^w is a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5-membered aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5-membered aromatic ring having 1 -4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is pyrrolyl, pyrazolyl, thiazolyl, thiadiazolyl, imidazolyl, oxazolyl, triazolyl, or tetrazolyl.

[00325] In another embodiment, the invention features a compound of formula I-D-2 and the attendant definitions, wherein ring Ai is selected from:

[00326] In another embodiment, the invention features a compound of formula I-D-2 and the attendant definitions, wherein R ¹ is H. In another embodiment, R ¹ is halogen. In another embodiment, R ¹ is CN. In another embodiment, R ¹ is alkyl wherein said alkyl is substituted with 0-6 halogen. In another embodiment, R ¹ is CF ₃ .

[00327] In another embodiment, the invention features a compound of formula I-D-2 and the attendant definitions, wherein R ² is H. In another embodiment, R ² is halogen. In another embodiment, R ² is CI. In another embodiment, R ² is F. In another embodiment, R ² is CN. In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ² is CF ₃ . In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ² is OCF ₃ . In another embodiment, R ² is F, CI, CN, CF ₃ or OCF ₃ .

[00328] In another embodiment, the invention features a compound of formula I-D-2 and the attendant definitions, wherein R ³ is H. In another embodiment, R ³ is halogen. In another embodiment, R ³ is CI. In another embodiment, R ³ is F. In another embodiment, R ³ is CN. In another embodiment, R ³ is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ³ is i-butyl. In another embodiment, R ³ is CF ₃ . In another embodiment, R ³ is CF ₂ CF ₃ .

[00329] In another embodiment, the invention features a compound of formula I-D-2 and the attendant definitions, wherein R ⁴ is H. In another embodiment, R ⁴ is halogen. In another embodiment, R ⁴ is CN. In another embodiment, R ⁴ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁴ is CF ₃ .

[00330] In another embodiment, the invention features a compound of formula I-D-2 and the attendant definitions, wherein R ¹ , R ² , R ³ , and R ⁴ is H.

[00331] In another embodiment, the invention features a compound of formula I-D-2 and the attendant definitions, wherein R ⁷ is halogen. In another embodiment, R ⁷ is CI. In another embodiment, R ⁷ is F. In another embodiment, R ⁷ is CN. In another embodiment, R ⁷ is -X-R ^x . In another embodiment, R is -X-R wherein R is absent. In another embodiment, R is -X-R wherein R ^x is absent and X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁷ is CH ₃ , CH ₂ CH ₃ , CH2CH2CH3 or isopropyl. In another embodiment, R ⁷ is CF ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein two non-adjacent CH ₂ units of said Ci-C ₆ alkyl are replaced with -0-. In another embodiment, R ⁷ is OCH2CH2OCH3. In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁷ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , OC(CH ₃ ) ₃ , CH ₂ CH ₂ OCH ₃ . In another embodiment, R ⁷ is OCF ₃ , OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ .

[00332] In another embodiment, the invention features a compound of formula I-D-2 wherein R ⁷ is -X-R ^x wherein X is a bond and R ^x is C ₃ -Cs cycloaliphatic and said C ₃ -Cs cycloaliphatic is substituted with 0-3 substituents selected from halogen and Q-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is a bond and R ^x is cyclopropyl.

[00333] In another embodiment, the invention features a compound of formula I-D-2 and the attendant definitions, wherein R ⁷ is -X-R ^x wherein X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -O- and R ^x is C ₃ -C ₈ cycloaliphatic and said C ₃ -C ₈ cycloaliphatic is substituted with up 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is OCH ₂ and R ^x is cyclopropyl.

[00334] In another embodiment, the invention features a compound of formula I-D-2 and the attendant definitions, wherein ring A is selected from:

[00335] In another aspect, the invention provides a compound of formula I-D-3:

I-D-3

or a pharmaceutically acceptable salt thereof,

wherein, independently for each occurrence:

Y is C or N;

m is an integer from 0 to 5 inclusive;

W is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-,

R ^w is absent, H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , OCF ₃ , or a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R' is Ci-C ₆ alkyl;

R ¹ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen and wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ² is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ³ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁴ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁶ is halogen, CN, or -X-R ^x ;

R ⁷ is halogen, CN, or -X-R ^x ;

X is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-; and R is absent, H, or C ₃ -C ₈ cycloaliphatic, wherein up to two non-adjacent CH ₂ units of said C ₃ -C ₈ cycloaliphatic may be replaced with -O- and said C ₃ -C ₈ cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl.

[00336] In one embodiment, the invention features a compound of formula I-D-3 and the attendant definitions, wherein Y is C. In another embodiment, Y is N.

[00337] In another embodiment, the invention features a compound of formula I-D-3 and the attendant definitions, wherein m is zero. In another embodiment, m is an integer from 1 to 5. In another embodiment, m is 1. In another embodiment, m is 2. In another embodiment, m is 3. In another embodiment, m is 4. In another embodiment, m is 5.

[00338] In another embodiment, the invention features a compound of formula I-D-3 and the attendant definitions, wherein W is a bond and R ^w is halogen, OH, NH ₂ , NHR', NO2, CN, CF ₃ , or OCF ₃ . In another embodiment, W is a bond and R ^w is halogen. In another embodiment, W is a bond and R ^w is OH.. In another embodiment, W is a bond and R ^w is NH ₂ . In another embodiment, W is a bond and R ^w is NHR'. In another embodiment, W is a bond and R ^w is CN. In another embodiment, W is a bond and R ^w is CF ₃ . In another embodiment, W is a bond and R ^w is OCF ₃ .

[00339] In another embodiment, the invention features a compound of formula I-D-3 and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO2-; and R ^w is absent. In another embodiment, W is CH ₃ , CH ₂ CH ₃ ,

CH ₂ CH ₂ CH ₃ , or isopropyl. In another embodiment, W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-,-S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or O-isopropyl. In another embodiment, W is OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ . In another embodiment, W is OCH ₂ CH ₂ OCH ₃ , CH ₂ OH, OC(CH ₃ ) ₃ , or CH ₂ CH ₂ OCH ₃ .

[00340] In another embodiment, the invention features a compound of formula I-D-3 and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl may be replaced with - 0-, -CO-, -S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NH ₂ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NH ₂ . In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NHR'.

[00341] In another embodiment, the invention features a compound of formula I-D-3 and the attendant definitions, wherein W is d-C ₆ alkyl wherein said d-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said d-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -, and R ^w absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said C ₂ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -, and R ^w is absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is absent.

[00342] In another embodiment, the invention features a compound of formula I-D-3 and the attendant definitions, wherein W is a bond and R ^w is a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is pyrrolyl, pyrazolyl, thiazolyl, thiadiazolyl, imidazolyl, oxazolyl, triazolyl, or tetrazolyl.

[00343] In another embodiment, the invention features a compound of formula I-D-3 and the attendant definitions, wherein ring Ai is selected from:

[00344] In another embodiment, the invention features a compound of formula I-D-3 and the attendant definitions, wherein R ¹ is H. In another embodiment, R ¹ is halogen. In another embodiment, R ¹ is CN. In another embodiment, R ¹ is C ₁ -C6 alkyl wherein said C ₁ -C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ¹ is CF ₃ . [00345] In another embodiment, the invention features a compound of formula I-D-3 and the attendant definitions, wherein R ² is H. In another embodiment, R ² is halogen. In another embodiment, R ² is CI. In another embodiment, R ² is F. In another embodiment, R ² is CN. In another embodiment, R ² is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ² is CF ₃ . In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ² is OCF ₃ . In another embodiment, R ² is F, CI, CN, CF ₃ or OCF ₃ .

[00346] In another embodiment, the invention features a compound of formula I-D-3 and the attendant definitions, wherein R ³ is H. In another embodiment, R ³ is halogen. In another embodiment, R ³ is CI. In another embodiment, R ³ is F. In another embodiment, R ³ is CN. In another embodiment, R ³ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ³ is i-butyl. In another embodiment, R ³ is CF ₃ . In another embodiment, R ³ is CF ₂ CF ₃ .

[00347] In another embodiment, the invention features a compound of formula I-D-3 and the attendant definitions, wherein R ⁴ is H. In another embodiment, R ⁴ is halogen. In another embodiment, R ⁴ is CN. In another embodiment, R ⁴ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁴ is CF ₃ .

[00348] In another embodiment, the invention features a compound of formula I-D-3 and the attendant definitions, wherein R ¹ , R ² , R ³ , and R ⁴ is H.

[00349] In another embodiment, the invention features a compound of formula I-D-3 and the attendant definitions, R ⁶ is halogen. In another embodiment, R ⁶ is CI. In another embodiment, R ⁶ is F. In another embodiment, R ⁶ is CN. In another embodiment, R ⁶ is -X-R ^x . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁶ is CH ₃ . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Q-C6 alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁶ is OCH ₃ .

[00350] In another embodiment, the invention features a compound of formula I-D-3 and the attendant definitions, wherein R ⁷ is halogen. In another embodiment, R ⁷ is CI. In another embodiment, R ⁷ is F. In another embodiment, R ⁷ is CN. In another embodiment, R ⁷ is -X-R ^x . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen. In another embodiment, R ⁷ is CH ₃ , CH ₂ CH ₃ , CH ₂ CH ₂ CH ₃ or isopropyl. In another embodiment, R ⁷ is CF ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein two non-adjacent CH ₂ units of said Ci-C ₆ alkyl are replaced with -0-. In another embodiment, R ⁷ is OCH ₂ CH ₂ OCH ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁷ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , OC(CH ₃ ) ₃ , CH ₂ CH ₂ OCH ₃ . In another embodiment, R ⁷ is OCF ₃ , OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ .

[00351] In another embodiment, the invention features a compound of formula I-D-3 wherein R ⁷ is -X-R ^x wherein X is a bond and R ^x is C ₃ -Cs cycloaliphatic and said C ₃ -Cs cycloaliphatic is substituted with 0-3 substituents selected from halogen and Q-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is a bond and R ^x is cyclopropyl.

[00352] In another embodiment, the invention features a compound of formula I-D-3 and the attendant definitions, wherein R ⁷ is -X-R ^x wherein X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -O- and R ^x is C ₃ -C ₈ cycloaliphatic and said C ₃ -C ₈ cycloaliphatic is substituted with up 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is OCH ₂ and R ^x is cyclopropyl.

[00353] In another embodiment, the invention features a compound of formula I-D-3 and the attendant definitions, wherein ring A is selected from:

[00354] In another aspect, the invention provides a compound of formula I-D-4:

I-D-4

or a pharmaceutically acceptable salt thereof,

wherein, independently for each occurrence:

Y is C or N;

m is an integer from 0 to 5 inclusive; W is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-,

R ^w is absent, H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , OCF ₃ , or a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R' is Ci-C ₆ alkyl;

R ¹ is H, halogen, CN, or C C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen and wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ² is H, halogen, CN, or C C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ³ is H, halogen, CN, or Ci-C ₆ alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen, wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁴ is H, halogen, CN, or C C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non -adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁵ is halogen, CN, or -X-R ^x ;

R ⁷ is halogen, CN, or -X-R ^x ;

X is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-; and

R ^x is absent, H, or C ₃ -C ₈ cycloaliphatic, wherein up to two non-adjacent CH ₂ units of said C ₃ -C ₈ cycloaliphatic may be replaced with -O- and said C ₃ -C ₈ cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl.

[00355] In one embodiment, the invention features a compound of formula I-D-4 and the attendant definitions, wherein Y is C. In another embodiment, Y is N.

[00356] In another embodiment, the invention features a compound of formula I-D-4 and the attendant definitions, wherein m is zero. In another embodiment, m is an integer from 1 to 5. In another embodiment, m is 1. In another embodiment, m is 2. In another embodiment, m is 3. In another embodiment, m is 4. In another embodiment, m is 5.

[00357] In another embodiment, the invention features a compound of formula I-D-4 and the attendant definitions, wherein W is a bond and R ^w is halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is a bond and R ^w is halogen. In another embodiment, W is a bond and R ^w is OH.. In another embodiment, W is a bond and R ^w is NH ₂ . In another embodiment, W is a bond and R ^w is NHR'. In another embodiment, W is a bond and R ^w is CN. In another embodiment, W is a bond and R ^w is CF ₃ . In another embodiment, W is a bond and R ^w is OCF ₃ . [00358] In another embodiment, the invention features a compound of formula I-D-4 and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is CH ₃ , CH ₂ CH ₃ ,

CH ₂ CH ₂ CH ₃ , or isopropyl. In another embodiment, W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-,-S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or O-isopropyl. In another embodiment, W is OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ . In another embodiment, W is OCH ₂ CH ₂ OCH ₃ , CH ₂ OH, OC(CH ₃ ) ₃ , or CH ₂ CH ₂ OCH ₃ .

[00359] In another embodiment, the invention features a compound of formula I-D-4 and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO ₂ -, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl may be replaced with - 0-, -CO-, -S-, -SO-, or -SO ₂ -, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NH ₂ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NH ₂ . In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -SO ₂ - and R ^w is NHR'.

[00360] In another embodiment, the invention features a compound of formula I-D-4 and the attendant definitions, wherein W is d-C ₆ alkyl wherein said d-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said d-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -, and R ^w absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said C ₂ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -, and R ^w is absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -SO2-, and R ^w is absent.

[00361] In another embodiment, the invention features a compound of formula I-D-4 and the attendant definitions, wherein W is a bond and R ^w is a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is a 5 -membered aromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, W is a bond and R ^w is pyrrolyl, pyrazolyl, thiazolyl, thiadiazolyl, imidazolyl, oxazolyl, triazolyl, or tetrazolyl.

[00362] In another embodiment, the invention features a compound of formula I-D-4 and the attendant definitions, wherein ring Ai is selected from:

[00363] In another embodiment, the invention features a compound of formula I-D-4 and the attendant definitions, wherein R ¹ is H. In another embodiment, R ¹ is halogen. In another embodiment, R ¹ is CN. In another embodiment, R ¹ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ¹ is CF3.

[00364] In another embodiment, the invention features a compound of formula I-D-4 and the attendant definitions, wherein R ² is H. In another embodiment, R ² is halogen. In another embodiment, R ² is CI. In another embodiment, R ² is F. In another embodiment, R ² is CN. In another embodiment, R ² is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ² is CF ₃ . In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ² is OCF ₃ . In another embodiment, R ² is F, CI, CN, CF ₃ or OCF ₃ .

[00365] In another embodiment, the invention features a compound of formula I-D-4 and the attendant definitions, wherein R ³ is H. In another embodiment, R ³ is halogen. In another embodiment, R ³ is CI. In another embodiment, R ³ is F. In another embodiment, R ³ is CN. In another embodiment, R ³ is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ³ is i-butyl. In another embodiment, R ³ is CF ₃ . In another embodiment, R ³ is CF ₂ CF ₃ .

[00366] In another embodiment, the invention features a compound of formula I-D-4 and the attendant definitions, wherein R ⁴ is H. In another embodiment, R ⁴ is halogen. In another embodiment, R ⁴ is CN. In another embodiment, R ⁴ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁴ is CF ₃ .

[00367] In another embodiment, the invention features a compound of formula I-D-4 and the attendant definitions, wherein R ¹ , R ² , R ³ , and R ⁴ is H.

[00368] In another embodiment, the invention features a compound of formula I-D-4 and the attendant definitions, wherein R ⁵ is halogen. In another embodiment, R ⁵ is CI. In another embodiment, R ⁵ is F. In another embodiment, R ⁵ is CN. In another embodiment, R ⁵ is -X-R ^x . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen. In another embodiment, R ⁵ is CH ₃ . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁵ is OCH ₃ , OCH ₂ CH ₃ , OCH2CH ₂ CH ₃ , or OCH(CH ₃ ) ₂ . In another embodiment, R ⁵ is OCH ₃ . In another embodiment, R ⁵ is CH ₂ OH. In another embodiment, R ⁵ is OCF ₃ . In another embodiment, R ⁵ is OCHF ₂ .

[00369] In another embodiment, the invention features a compound of formula I-D-4 and the attendant definitions, wherein R ⁷ is H. In another embodiment, R ⁷ is halogen. In another embodiment, R ⁷ is CI. In another embodiment, R ⁷ is F. In another embodiment, R ⁷ is CN. In another embodiment, R ⁷ is -X-R ^x . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁷ is CH ₃ , CH ₂ CH ₃ , CH ₂ CH ₂ CH ₃ or isopropyl. In another embodiment, R ⁷ is CF ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein two non-adjacent CH ₂ units of said C1-C6 alkyl are replaced with -0-. In another embodiment, R ⁷ is OCH ₂ CH ₂ OCH ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁷ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , OC(CH ₃ ) ₃ , CH ₂ CH ₂ OCH ₃ . In another embodiment, R ⁷ is OCF ₃ , OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ .

[00370] In another embodiment, the invention features a compound of formula I-D-4 wherein R ⁷ is -X-R ^x wherein X is a bond and R ^x is C ₃ -Cs cycloaliphatic and said C ₃ -Cs cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is a bond and R ^x is cyclopropyl.

[00371] In another embodiment, the invention features a compound of formula I-D-4 and the attendant definitions, wherein R ⁷ is -X-R ^x wherein X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -O- and R ^x is C ₃ -C ₈ cycloaliphatic and said C ₃ -C ₈ cycloaliphatic is substituted with up 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is OCH ₂ and R ^x is cyclopropyl. [00372] In another embodiment, the invention features a compound of formula I-D-4 and the attendant definitions, wherein ring A is selected from:

[00373] In another aspect, the invention provides a compound of formula I-E:

I-E

or a pharmaceutically acceptable salt thereof,

wherein, independently for each occurrence:

Y is C or N;

Ai and A ₂ , together, form an 8-9 membered aromatic, bicyclic ring, wherein each ring contains 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

m is an integer from 0 to 5 inclusive;

W is a bond or C _\ -C(, alkyl wherein said C ₁ -C6 alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -SO ₂ -;

R ^w is absent, H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , OCF ₃ , or a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R' is Ci-C ₆ alkyl;

R ¹ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen and wherein up to two non-adjacent CH ₂ units of said C ₁ -C6 alkyl may be replaced with -0-; R ² is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ³ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁴ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁵ is H, halogen, CN, or -X-R ^x ;

R ⁵ is H, halogen, CN, or -X-R ^x ;

R ⁶ is H, halogen, CN, or -X-R ^x ;

R ⁶ is H, halogen, CN, or -X-R ^x ;

R ⁷ is H, halogen, CN, or -X-R ^x ;

X is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C ₁ -C6 alkyl may be replaced with -0-; and

R ^x is absent, H, or C ₃ -C ₈ cycloaliphatic, wherein up to two non-adjacent CH ₂ units of said C ₃ -C ₈ cycloaliphatic may be replaced with -O- and said C ₃ -C ₈ cycloaliphatic is substituted with 0-3 substituents selected from halogen and C ₁ -C4 alkyl.

[00374] In one embodiment, the invention features a compound of formula I-E and the attendant definitions, wherein Y is C. In another embodiment, Y is N.

[00375] In another embodiment, the invention features a compound of formula I-E and the attendant definitions, wherein Ai is a 6 membered aromatic ring having 0-4 heteroatoms, independently selected from nitrogen, oxygen, or sulfur, and A ₂ is a 5-membered aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, Ai is phenyl and A ₂ is a 5-membered aromatic ring having 1 -3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In another embodiment, Ai is phenyl and A ₂ is pyrrolyl, pyrazolyl, thiazolyl, thiadiazolyl, imidazolyl, oxazolyl, or triazolyl.

[00376] In another embodiment, the invention features a compound of formula I-E and the attendant definitions, wherein Ai and A ₂ , together, are selected from:

[00377] In another embodiment, the invention features a compound of formula I-E and the attendant definitions, wherein m is zero. In another embodiment, m is an integer from 1 to 5. In another embodiment, m is 1. In another embodiment, m is 2. In another embodiment, m is 3. In another embodiment, m is 4. In another embodiment, m is 5.

[00378] In another embodiment, the invention features a compound of formula I-E and the attendant definitions, wherein W is a bond and R ^w is halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is a bond and R ^w is halogen. In another embodiment, W is a bond and R ^w is OH. In another embodiment, W is a bond and R ^w is NH ₂ . In another embodiment, W is a bond and R ^w is NHR'. In another embodiment, W is a bond and R ^w is CN. In another embodiment, W is a bond and R ^w is CF ₃ . In another embodiment, W is a bond and R ^w is OCF ₃ .

[00379] In another embodiment, the invention features a compound of formula I-E and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is CH ₃ , CH ₂ CH ₃ ,

CH ₂ CH ₂ CH ₃ , or isopropyl. In another embodiment, W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or O-isopropyl. In another embodiment, W is OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ . In another embodiment, W is OCH ₂ CH ₂ OCH ₃ , CH ₂ OH, OC(CH ₃ ) ₃ , or CH ₂ CH ₂ OCH ₃ .

[00380] In another embodiment, the invention features a compound of formula I-E and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO ₂ -, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl may be replaced with - 0-, -CO-, -S-, -SO-, or -SO ₂ -, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NH ₂ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -SO2- and R is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NH ₂ . In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with

[00381] In another embodiment, the invention features a compound of formula I-E and the attendant definitions, wherein W is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -, and R ^w absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said C ₂ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -, and R ^w is absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is absent.

[00382] In another embodiment, the invention features a compound of formula I-E and the attendant definitions, Aj and A ₂ , together with WR ^W , are selected from:

[00383] In another embodiment, the invention features a compound of formula I-E and the attendant definitions, wherein R ¹ is H. In another embodiment, R ¹ is halogen. In another embodiment, R ¹ is CN. In another embodiment, R ¹ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ¹ is CF _3.

[00384] In another embodiment, the invention features a compound of formula I-E and the attendant definitions, wherein R ² is H. In another embodiment, R ² is halogen. In another embodiment, R ² is CI. In another embodiment, R ² is F. In another embodiment, R ² is CN. In another embodiment, R ² is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ² is CF ₃ . In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said C1-C6 alkyl is replaced with -0-. In another embodiment, R ² is OCF ₃ . In another embodiment, R ² is F, CI, CN, CF ₃ or OCF ₃ .

[00385] In another embodiment, the invention features a compound of formula I-E and the attendant definitions, wherein R ³ is H. In another embodiment, R ³ is halogen. In another embodiment, R ³ is CI. In another embodiment, R ³ is F. In another embodiment, R ³ is CN. In another embodiment, R ³ is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ³ is i-butyl. In another embodiment, R ³ is CF ₃ . In another embodiment, R ³ is CF ₂ CF ₃ .

[00386] In another embodiment, the invention features a compound of formula I-E and the attendant definitions, wherein R ⁴ is H. In another embodiment, R ⁴ is halogen. In another embodiment, R ⁴ is CN. In another embodiment, R ⁴ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁴ is CF ₃ .

[00387] In another embodiment, the invention features a compound of formula I-E and the attendant definitions, wherein R ¹ , R ² , R ³ , and R ⁴ is H.

[00388] In another embodiment, the invention features a compound of formula I-E and the attendant definitions, wherein R ⁵ is H. In another embodiment, R ⁵ is halogen. In another embodiment, R ⁵ is CI. In another embodiment, R ⁵ is F. In another embodiment, R ⁵ is CN. In another embodiment, R ⁵ is -X-R ^x . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁵ is CH ₃ . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Q-C6 alkyl is replaced with -0-. In another embodiment, R ⁵ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or OCH(CH ₃ ) ₂ . In another embodiment, R ⁵ is OCH ₃ . In another embodiment, R ⁵ is CH ₂ OH. In another embodiment, R ⁵ is OCF ₃ . In another embodiment, R ⁵ is OCHF ₂ .

[00389] In another embodiment, the invention features a compound of formula I-E and the attendant definitions, wherein R ⁵ is H. In another embodiment, R ⁵ is halogen. In another embodiment, R ⁵ is CI. In another embodiment, R ⁵ is F. In another embodiment, R ⁵ is CN. In another embodiment, R ⁵ is -X-R ^x . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Q-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁵ is CH ₃ . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Q-C6 alkyl is replaced with -0-. In another embodiment, R ⁵ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or OCH(CH ₃ ) ₂ . In another embodiment, R ⁵ is OCH ₃ . In another embodiment, R ⁵ is CH ₂ OH. In another embodiment, R ⁵ is OCF ₃ . In another embodiment, R ⁵ is OCHF ₂ .

[00390] In another embodiment, the invention features a compound of formula I-E and the attendant definitions, R ⁶ is H. In another embodiment, R ⁶ is halogen. In another embodiment, R ⁶ is CI. In another embodiment, R ⁶ is F. In another embodiment, R ⁶ is CN. In another embodiment, R ⁶ is -X-R ^x . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen. In another embodiment, R ⁶ is CH ₃ . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said C1-C6 alkyl is replaced with -0-. In another embodiment, R ⁶ is OCH ₃ .

[00391] In another embodiment, the invention features a compound of formula I-E and the attendant definitions, wherein R ⁶ is H. In another embodiment, R ⁶ is halogen. In another embodiment, R ⁶ is CI. In another embodiment, R ⁶ is F. In another embodiment, R ⁶ is CN. In another embodiment, R ⁶ is -X-R ^x . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Q-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁶ is CH ₃ . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Q-C6 alkyl is replaced with -0-. In another embodiment, R ⁶ is OCH ₃ .

[00392] In another embodiment, the invention features a compound of formula I-E and the attendant definitions, wherein R ⁷ is H. In another embodiment, R ⁷ is halogen. In another embodiment, R ⁷ is CI. In another embodiment, R ⁷ is F. In another embodiment, R ⁷ is CN. In another embodiment, R is -X-R . In another embodiment, R is -X-R wherein R is absent. In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁷ is CH ₃ , CH ₂ CH ₃ , CH2CH ₂ CH ₃ or isopropyl. In another embodiment, R ⁷ is CF ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein two non-adjacent CH2 units of said C1-C6 alkyl are replaced with -0-. In another embodiment, R ⁷ is OCH2CH ₂ OCH ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁷ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , OC(CH ₃ ) ₃ , CH ₂ CH ₂ OCH ₃ . In another embodiment, R ⁷ is OCF ₃ , OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ .

[00393] In another embodiment, the invention features a compound of formula I-E wherein R ⁷ is -X-R ^x wherein X is a bond and R ^x is C ₃ -Cs cycloaliphatic and said C ₃ -Cs cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is a bond and R ^x is cyclopropyl.

[00394] In another embodiment, the invention features a compound of formula I-E and the attendant definitions, wherein R ⁷ is -X-R ^x wherein X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -O- and R ^x is C ₃ -C ₈ cycloaliphatic and said C ₃ -C ₈ cycloaliphatic is substituted with up 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is OCH ₂ and R ^x is cyclopropyl.

[00395] In another embodiment, the invention features a compound of formula I-E and the attendant definitions, wherein ring A is selected from:

[00396] In another embodiment ring A is selected from:

[00397] In another embodiment, the invention features a compound of formula I-E and the attendant definitions, wherein R ¹ , R ² , R ³ and R ⁴ are H.

[00398] In another embodiment, the invention features a compound of formula I-E and the attendant definitions, wherein R ⁵ and R ⁷ are each independently halogen, or -X-R ^x and R ⁵ , R ⁶ , and R ⁶ are each hydrogen. In another embodiment, R ⁵ and R ⁷ are each independently F, CI, CH ₃ , OCF ₃ , or OCH ₃ .

[00399] In another aspect, the invention provides a compound of formula I-F:

I-F

or a pharmaceutically acceptable salt thereof,

wherein, independently for each occurrence:

Y is C or N;

m is an integer from 0 to 5 inclusive; W is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-,

R ^w is absent, H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , OCF ₃ , or a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R' is Ci-C ₆ alkyl;

R ¹ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen and wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ² is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ³ is H, halogen, CN, or C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁴ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁵ is H, halogen, CN, or -X-R ^x ;

R ⁵ is H, halogen, CN, or -X-R ^x ;

R ⁶ is H, halogen, CN, or -X-R ^x ;

R ^6' is H, halogen, CN, or -X-R ^x ;

R ⁷ is H, halogen, CN, or -X-R ^x ;

X is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-; and

R ^x is absent, H, or C ₃ -C ₈ cycloaliphatic, wherein up to two non-adjacent CH ₂ units of said C ₃ -C ₈ cycloaliphatic may be replaced with -O- and said C ₃ -C ₈ cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl.

[00400] In one embodiment, the invention features a compound of formula I-F and the attendant definitions, wherein Y is C. In another embodiment, Y is N.

[00401] In another embodiment, the invention features a compound of formula I-F and the attendant definitions, wherein m is zero. In another embodiment, m is an integer from 1 to 5. In another embodiment, m is 1. In another embodiment, m is 2. In another embodiment, m is 3. In another embodiment, m is 4. In another embodiment, m is 5.

[00402] In another embodiment, the invention features a compound of formula I-F and the attendant definitions, wherein W is a bond and R ^w is halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is a bond and R is halogen. In another embodiment, W is a bond and R ^w is OH.. In another embodiment, W is a bond and R ^w is NH ₂ . In another embodiment, W is a bond and R ^w is NHR'. In another embodiment, W is a bond and R ^w is CN. In another embodiment, W is a bond and R ^w is CF ₃ . In another embodiment, W is a bond and R ^w is OCF ₃ .

[00403] In another embodiment, the invention features a compound of formula I-F and the attendant definitions, wherein W is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO2-; and R ^w is absent. In another embodiment, W is CH ₃ , CH ₂ CH ₃ ,

CH2CH2CH3, or isopropyl. In another embodiment, W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-,-S-, -SO-, or -SO2-; and R ^w is absent. In another embodiment, W is OCH3, OCH2CH3, OCH2CH2CH3, or O-isopropyl. In another embodiment, W is OCH ₂ CF ₃ , OCH2CH2CH2CF3, or OCHF ₂ . In another embodiment, W is OCH ₂ CH ₂ OCH ₃ , CH ₂ OH, OC(CH ₃ ) ₃ , or CH ₂ CH ₂ OCH ₃ .

[00404] In another embodiment, the invention features a compound of formula I-F and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl may be replaced with - 0-, -CO-, -S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -SO2-, and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, N¾, or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one C¾ unit of said Ci alkyl is replaced with -CO- and R ^w is N¾. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -SO2- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -SO2- and R ^w is H. In another embodiment, W is Ci alkyl wherein one C¾ unit of said Ci alkyl is replaced with -SO2- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NH ₂ . In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with [00405] In another embodiment, the invention features a compound of formula I-F and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -, and R ^w absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said C ₂ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -, and R ^w is absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is absent.

[00406] In another embodiment, the invention features a compound of formula I-F and the attendant definitions, wherein Ai and A ₂ , together with WR ^W , are selected from:

[00407] In another embodiment, the invention features a compound of formula I-F and the attendant definitions, wherein R ¹ is H. In another embodiment, R ¹ is halogen. In another embodiment, R ¹ is CN. In another embodiment, R ¹ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ¹ is CF3.

[00408] In another embodiment, the invention features a compound of formula I-F and the attendant definitions, wherein R ² is H. In another embodiment, R ² is halogen. In another embodiment, R ² is CI. In another embodiment, R ² is F. In another embodiment, R ² is CN. In another embodiment, R ² is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ² is CF ₃ . In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ² is OCF3. In another embodiment, R ² is F, CI, CN, CF3 or OCF3.

[00409] In another embodiment, the invention features a compound of formula I-F and the attendant definitions, wherein R ³ is H. In another embodiment, R ³ is halogen. In another embodiment, R ³ is CI. In another embodiment, R ³ is F. In another embodiment, R ³ is CN. In another embodiment, R ³ is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ³ is i-butyl. In another embodiment, R ³ is CF ₃ . In another embodiment, R ³ is CF ₂ CF ₃ .

[00410] In another embodiment, the invention features a compound of formula I-F and the attendant definitions, wherein R ⁴ is H. In another embodiment, R ⁴ is halogen. In another embodiment, R ⁴ is CN. In another embodiment, R ⁴ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁴ is CF ₃ .

[00411] In another embodiment, the invention features a compound of formula I-F and the attendant definitions, wherein R ¹ , R ² , R ³ , and R ⁴ is H. [00412] In another embodiment, the invention features a compound of formula I-F and the attendant definitions, wherein R ⁵ is H. In another embodiment, R ⁵ is halogen. In another embodiment, R ⁵ is CI. In another embodiment, R ⁵ is F. In another embodiment, R ⁵ is CN. In another embodiment, R ⁵ is -X-R ^x . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁵ is CH ₃ . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Q-C6 alkyl is replaced with -0-. In another embodiment, R ⁵ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or OCH(CH ₃ ) ₂ . In another embodiment, R ⁵ is OCH ₃ . In another embodiment, R ⁵ is CH ₂ OH. In another embodiment, R ⁵ is OCF ₃ . In another embodiment, R ⁵ is OCHF ₂ .

[00413] In another embodiment, the invention features a compound of formula I-F and the attendant definitions, wherein R ⁵ is H. In another embodiment, R ⁵ is halogen. In another embodiment, R ⁵ is CI. In another embodiment, R ⁵ is F. In another embodiment, R ⁵ is CN. In another embodiment, R ⁵ is -X-R ^x . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Q-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁵ is CH ₃ . In another embodiment, R ⁵ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Q-C6 alkyl is replaced with -0-. In another embodiment, R ⁵ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or OCH(CH ₃ ) ₂ . In another embodiment, R ⁵ is OCH ₃ . In another embodiment, R ⁵ is CH ₂ OH. In another embodiment, R ⁵ is OCF ₃ . In another embodiment, R ⁵ is OCHF ₂ .

[00414] In another embodiment, the invention features a compound of formula I-F and the attendant definitions, R ⁶ is H. In another embodiment, R ⁶ is halogen. In another embodiment, R ⁶ is CI. In another embodiment, R ⁶ is F. In another embodiment, R ⁶ is CN. In another embodiment, R ⁶ is -X-R ^x . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen. In another embodiment, R ⁶ is CH ₃ . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said C1-C6 alkyl is replaced with -0-. In another embodiment, R ⁶ is OCH ₃ .

[00415] In another embodiment, the invention features a compound of formula I-F and the attendant definitions, wherein R ⁶ is H. In another embodiment, R ⁶ is halogen. In another embodiment, R ⁶ is CI. In another embodiment, R ⁶ is F. In another embodiment, R ⁶ is CN. In another embodiment, R ⁶ is -X-R ^x . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent. In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁶ is CH ₃ . In another embodiment, R ⁶ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Q-C6 alkyl is replaced with -0-. In another embodiment, R ⁶ is OCH ₃ .

[00416] In another embodiment, the invention features a compound of formula I-F and the attendant definitions, wherein R ⁷ is H. In another embodiment, R ⁷ is halogen. In another embodiment, R ⁷ is CI. In another embodiment, R ⁷ is F. In another embodiment, R ⁷ is CN. In another embodiment, R is -X-R . In another embodiment, R is -X-R wherein R is absent. In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is alkyl wherein said alkyl is substituted with 0-6 halogen. In another embodiment, R ⁷ is CH ₃ , CH ₂ CH ₃ , CH2CH2CH3 or isopropyl. In another embodiment, R ⁷ is CF ₃ . In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein two non-adjacent CH2 units of said C1-C6 alkyl are replaced with -0-. In another embodiment, R ⁷ is OCH2CH2OCH3. In another embodiment, R ⁷ is -X-R ^x wherein R ^x is absent and X is C1-C6 alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -0-. In another embodiment, R ⁷ is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , OC(CH ₃ ) ₃ , CH ₂ CH ₂ OCH ₃ . In another embodiment, R ⁷ is OCF ₃ , OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ .

[00417] In another embodiment, the invention features a compound of formula I-F wherein R ⁷ is -X-R ^x wherein X is a bond and R ^x is C ₃ -Cs cycloaliphatic and said C ₃ -Cs cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is a bond and R ^x is cyclopropyl.

[00418] In another embodiment, the invention features a compound of formula I-F and the attendant definitions, wherein R ⁷ is -X-R ^x wherein X is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-C ₆ alkyl is replaced with -O- and R ^x is C ₃ -C ₈ cycloaliphatic and said C ₃ -C ₈ cycloaliphatic is substituted with up 0-3 substituents selected from halogen and C1-C4 alkyl. In another embodiment, R ⁷ is -X-R ^x wherein X is OCH ₂ and R ^x is cyclopropyl.

[00419] In another embodiment, the invention features a compound of formula I-F and the attendant definitions, wherein ring A is selected from:

[00420] In another aspect, the invention provides a compound of formula I-F-l :

I-F-l

or a pharmaceutically acceptable salt thereof,

wherein, independently for each occurrence:

Y is C or N;

m is an integer from 0 to 5 inclusive;

W is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-,

R ^w is absent, H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , OCF ₃ , or a 3-6 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R' is Ci-C ₆ alkyl;

R ¹ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen and wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ² is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ³ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁴ is H, halogen, CN, or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-;

R ⁵ is halogen, CN, or -X-R ^x ; X is a bond or Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-; and

R ^x is absent, H, or C ₃ -C ₈ cycloaliphatic, wherein up to two non-adjacent CH ₂ units of said C ₃ -C ₈ cycloaliphatic may be replaced with -O- and said C ₃ -C ₈ cycloaliphatic is substituted with 0-3 substituents selected from halogen and C1-C4 alkyl.

[00421] In one embodiment, the invention features a compound of formula I-F-l and the attendant definitions, wherein Y is C. In another embodiment, Y is N.

[00422] In another embodiment, the invention features a compound of formula I-F-l and the attendant definitions, wherein m is zero. In another embodiment, m is an integer from 1 to 5. In another embodiment, m is 1. In another embodiment, m is 2. In another embodiment, m is 3. In another embodiment, m is 4. In another embodiment, m is 5.

[00423] In another embodiment, the invention features a compound of formula I-F-l and the attendant definitions, wherein W is a bond and R ^w is halogen, OH, NH ₂ , NHR', NO2, CN, CF ₃ , or OCF ₃ . In another embodiment, W is a bond and R ^w is halogen. In another embodiment, W is a bond and R ^w is OH. In another embodiment, W is a bond and R ^w is NH ₂ . In another embodiment, W is a bond and R ^w is NHR'. In another embodiment, W is a bond and R ^w is CN. In another embodiment, W is a bond and R ^w is CF ₃ . In another embodiment, W is a bond and R ^w is OCF ₃ .

[00424] In another embodiment, the invention features a compound of formula I-F-l and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is CH ₃ , CH ₂ CH ₃ ,

CH ₂ CH ₂ CH ₃ , or isopropyl. In another embodiment, W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -; and R ^w is absent. In another embodiment, W is OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , or O-isopropyl. In another embodiment, W is OCH ₂ CF ₃ , OCH ₂ CH ₂ CH ₂ CF ₃ , or OCHF ₂ . In another embodiment, W is OCH ₂ CH ₂ OCH ₃ , CH ₂ OH, OC(CH ₃ ) ₃ , or CH ₂ CH ₂ OCH ₃ .

[00425] In another embodiment, the invention features a compound of formula I-F-l and the attendant definitions, wherein W is Ci-C ₆ alkyl wherein said Ci-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said Ci-C ₆ alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl may be replaced with - 0-, -CO-, -S-, -SO-, or -SO2-, and R ^w is H, halogen, OH, NH ₂ , NHR', N0 ₂ , CN, CF ₃ , or OCF ₃ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R is H, OH, NH ₂ , or NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NH ₂ . In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO- and R ^w is NHR'. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H, OH, NH ₂ , or NHR'. In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is H. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is OH. In another embodiment, W is Ci alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NH ₂ . In another embodiment, W is d alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -S0 ₂ - and R ^w is NHR'.

[00426] In another embodiment, the invention features a compound of formula I-F-l and the attendant definitions, wherein W is d-C ₆ alkyl wherein said d-C ₆ alkyl is substituted with 0-6 halogen, wherein up to two non-adjacent CH ₂ units of said C1-C6 alkyl may be replaced with -0-, - CO-, -S-, -SO-, or -S0 ₂ -, and R ^w absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said C ₂ alkyl may be replaced with -0-, -CO-, -S-, -SO-, or -S0 ₂ -, and R ^w is absent. In another embodiment, W is C ₂ alkyl wherein one CH ₂ unit of said Ci alkyl is replaced with -CO-, or -S0 ₂ -, and R ^w is absent.

[00427] In another embodiment, the invention features a compound of formula I-F-l and the attendant definitions, wherein Ai and A ₂ , together with WR ^W , are selected from:

[00428] In another embodiment, the invention features a compound of formula I-F-l and the attendant definitions, wherein R ¹ is H. In another embodiment, R ¹ is halogen. In another embodiment, R ¹ is CN. In another embodiment, R ¹ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ¹ is CF ₃ .

[00429] In another embodiment, the invention features a compound of formula I-F-l and the attendant definitions, wherein R ² is H. In another embodiment, R ² is halogen. In another embodiment, R ² is CI. In another embodiment, R ² is F. In another embodiment, R ² is CN. In another embodiment, R ² is C1-C6 alkyl wherein said Ci-d alkyl is substituted with 0-6 halogen. In another embodiment, R ² is CF ₃ . In another embodiment, R ² is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen wherein one CH ₂ unit of said Ci-d alkyl is replaced with -0-. In another embodiment, R ² is OCF ₃ . In another embodiment, R ² is F, CI, CN, CF ₃ or OCF ₃ . [00430] In another embodiment, the invention features a compound of formula I-F-l and the attendant definitions, wherein R ³ is H. In another embodiment, R ³ is halogen. In another embodiment, R ³ is CI. In another embodiment, R ³ is F. In another embodiment, R ³ is CN. In another embodiment, R ³ is C1-C6 alkyl wherein said Q-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ³ is i-butyl. In another embodiment, R ³ is CF ₃ . In another embodiment, R ³ is CF ₂ CF ₃ .

[00431] In another embodiment, the invention features a compound of formula I-F-l and the attendant definitions, wherein R ⁴ is H. In another embodiment, R ⁴ is halogen. In another embodiment, R ⁴ is CN. In another embodiment, R ⁴ is C1-C6 alkyl wherein said C1-C6 alkyl is substituted with 0-6 halogen. In another embodiment, R ⁴ is CF ₃ .