PYRIMIDINONE COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM The present invention relates to certain novel pyrimidinone compounds, processes for their preparation, intermediates useful in their preparation, pharmaceutical compositions containing them and their use in therapy, in particular in the treatment of atherosclerosis.

WO 95/00649 (SmithKline Beecham plc) describe the phospholipase A2 enzyme Lipoprotein Associated Phospholipase A (Lp-PLA), the sequence. isolation and purification thereof, isolated nucleic acids encoding the enzyme, and recombinant host cells transformed with DNA encoding the enzyme. Suggested therapeutic uses for inhibitors of the enzyme included atherosclerosis, diabetes, rheumatoid arthritis, stroke, myocardial infarction, reperfusion injury and acute and chronic inflammation. A subsequent publication from the same group further describes this enzyme (Tew D et al, Arterioscler Thromb Vas Biol 1996: 16 ; 591-9) wherein it is referred to as LDL-PLA. A later patent application (WO 95/09921, Icos Corporation) and a related publication in Nature (Tjoelker et al, vol 374,6 April 1995,549) describe the enzyme PAF-AH which has essentially the same sequence as Lp-PLA and suggest that it may have potential as a therapeutic protein for regulating pathological inflammatory events.

It has been shown that Lp-PLA2 is responsible for the conversion of phosphatidylcholine to lysophosphatidylcholine, during the conversion of low density lipoprotein (LDL) to its oxidised form. The enzyme is known to hydrolyse the sn-2 ester of the oxidised phosphatidylcholine to give lysophosphatidylcholine and an oxidatively modified fatty acid. Both products of Lp-PLAn action are biologically active with lysophosphatidylcholine, a component of oxidised LDL, known to be a potent chemoattractant for circulating monocytes. As such. lysophosphatidylcholine is thought play a significant role in atherosclerosis by being responsible for the accumulation of cells loaded with cholesterol ester in the arteries. Inhibition of the Lp-PLA enzyme would therefore be expected to stop the build up of these macrophage enriched lesions (by inhibition of the formation of lysophosphatidylcholine and oxidised free fatty acids) and so be useful in the treatment of atherosclerosis.

The increased lysophosphatidylcholine content of oxidatively modified LDL is also thought to be responsible for the endothelial dysfunction observed in patients with atherosclerosis. Inhibitors of Lp-PLA2 could therefore prove beneficial in the treatment of this phenomenon. An Lp-PLA inhibitor could also find utility in other disease states that exhibit endothelial dysfunction including diabetes, hypertension. angina pectoris and after ischaemia and reperfusion.

In addition, Lp-PLA2 inhibitors may also have a general application in any disorder that involves activated monocytes, macrophages or lymphocytes, as all of these cell types express Lp-PLA2. Examples of such disorders include psoriasis.

Furthermore, Lp-PLA2 inhibitors may also have a general application in any disorder that involves lipid peroxidation in conjunction with Lp-PLA2 activity to produce the two injurious products, lysophosphatidylcholine and oxidatively modified fatty acids. Such conditions include the aforementioned conditions atherosclerosis, diabetes, rheumatoid arthritis, stroke, myocardial infarction, reperfusion injury and acute and chronic inflammation. Further such conditions include various neuropsychiatric disorders such as schizophrenia (see Psychopharmacology Bulletin, 31,159-165,1995).

Patent applications WO 96/12963, WO 96/13484, W096/19451, WO 97/02242, W097/217675, W097/217676, WO 96/41098, and W097/41099 (SmithKline Beecham plc) disclose inter alia various series of 4-thionyl/sulfinyl/sulfonyl azetidinone compounds which are inhibitors of the enzyme Lp-PLA2. These are irreversible, acylating inhibitors (Tew et al, Biochemistry, 37,10087,1998).

GB 1 582 527 describes, as compounds of formula (7), a group of pyrimidone compounds of the formula (A): in which Alk is lower alkyl, Het is selected from 2-or 4-imidazolyl, 2-pyridyl, 2-thiazolyl, 3-isothiazolyl, 1.2,5-thiadiazolyl and n is from 1 to 4. These compounds are said to be useful as intermediates in the preparation of further compounds which are H2 antagonists.

A new class of pyrimidone compounds has now been identified which are inhibitors of the enzyme Lp-PLA.

Accordingly, the present invention provides compounds of formula (I):

in which: Z is a bond and R 1 is halogen; or Z is CR3R4, where R3 and R4 are each hydrogen or C 1-4)alkyl, or R3 and R4 together with the intervening carbon atom form a C(3-6)cycloalkyl ring; and RI is an aryl or heteroaryl group, optionally substituted by 1,2,3 or 4 substituents selected from C(1-18)alkylthio,arylC(1-18)alkoxy,oxo,C(1-18)akoxy, hydroxy, halogen, CN, CONR5R6,NR5COR6,SO2NR5R6,COOR5, NR5SO2R6, NR5R6, mono to perfluoro-C(1-4)alkyl and mono to perfluoro- C(1-4)alkoxy; XisOorS; Y is a group of formula-Al-A2-A3-in which A 1 and A3 each represent a bond or a straight chain or branched C(1-10)alkylene group and A2 represents a bond or O, S, SO, SO2, CO, C=CH2, CH=CH, C=C, CONH, NHCO, or CR5R6, providing that when A2 is O, S. SO, SO2or CONH, A3 contains at least two carbon atoms linking the A2 group and the CHo group in formula (I); R2 is an aryl or heteroaryl group, optionally substituted by 1,2,3 or 4 substituents selected from the substituents hereinbefore defined for R 1, as well as aryl and arylC (1 4) alkyl; W is a bond and R7 is hydrogen; or W is SO2 or a bond; and R7 is R1 or a hydrocarbyl group which hydrocarbyl group may be optionally interupted within the carbon chain by a group selected from O, COO, OCO, CO, CONR8, NR8CO, NR8CONR9, NR8COO, OCONR8, and NR8, and which hydrocarbyl group may also be optionally substituted by 1 or 2 substituents selected from mono to perfluoro- COOR8,CONR8R9,NR8COR9,NR8CONR9R10,NR8COOR9,C(1-4)alkyl,OR8, OCONR8R9 NRandR1 : R5 and R6 are independently hydrogen or C (1 20) alkyls for instance C 1-4)ALKYL (e. g. methyl or ethyl); R8, R9 and R10 are independently selected from hydrogen, C(1-20) alkyl (for instance C(1-15)alkyl), (which may optionally be fluorinated, including up to

perfluorinated on the terminal 1 to 3 carbon atoms), C(1-20) alkenyl (preferably arylC(1-10)alkyl,C(1-10)alkoxyC(1-10)alkyl,orC(12-18)alkenyl ),aryl, aryloxyCn. io) alkyl and in which an aryl group may have one or two substituents selected from halogen, C(1-20)alkyl, C (1-20)alkoxy, aryloxy and COOC (1 20) alkyl; and R11 and R12 are independently selected from one of the values hereinbefore defined for R8 and R9 or R 11 and R 12 together with the nitrogen atom to which they are attached form a 5-to 7 membered ring optionally containing one or two further heteroatoms selected from oxygen, nitrogen and sulphur, and optionally substituted by one or two substituents selected from hydroxy, oxo, C 1-4)alkyl, phenyl, or benzyl.

Preferably, Z is CH2.

Representative examples of R l when an aryl group include phenyl and naphthyl.

Representative examples of R l when a heteroaryl group include pyridyl, pyrimidyl, pyrazolyl, furyl, thienyl, thiazolyl, quinolyl, benzothiazolyl, pyridazolyl and pyrazinyl.

Preferably R I is a 5-or 6-membered, monocyclic heteroaryl group containing 1 or 2 nitrogen heteroatoms, preferably pyridyl, pyrimidyl or pyrazolyl, more preferably, pyrid- 4-yl or pyrimid-5-yl and optionally substituted by 1 or 2 substituents preferably selected from arylC(1-4)alkyl (e.g. benzyl), C(1-18)alkyl (e. g. methyl or ethyl), halogen (e. g. chlorine), oxo, hydroxy, C (1 4) alkoxy (e. g. methoxy) and arylC 1-4)alkoxy (e. g. benzyloxy). More preferably, R I is pyrimid-5-yl or a 2-oxo-pyrimid-5-yl group, optionally substituted at N-I by C (1-1 g) alkyl (e. g. undecyl, methyl or ethyl), or a 2- group.C(1-4)alkoxy-orarylC(1-4)alkoxy-pyrimid-5-yl Preferably, ZR1 is 2-oxo-pyrid-4-ylmethyl, pyrimid-5-ylmethyl or 2-oxo-pyrimid-5- ylmethyl in which the 2-oxo-pyrimid-5-yl moiety is as hereinbefore defined.

Preferably X is S.

Preferred compounds of formula (I) include those in which Y is a bond, i. e. A I, A2 and A3 each represent a bond. Other preferred examples of the groups Al and A3 are straight chain C (1 1o) alkylene groups. When A2 is other than a bond, Al is preferably a bond.

Preferred examples of A2 when other than a bond include CO, C=CH2 and O, the CO group being especially preferred. Other preferred examples of Y are (CH2) 7 and CO (CH2) 6.

Representative examples of R2 when an aryl group include phenyl and naphthyl.

Representative examples of R2 when a heteroaryl group include pyridyl, pyrimidinyl, pyrazolyl, furanyl, thienyl, thiazolyl, quinolyl, benzothiazolyl, pyridazolyl and pyrazinyl Preferrably, R2 is phenyl optionally substituted by 1,2 or 3 substituents selected from halogen (e. g. chlorine or fluorine), C(1-4)alkyl (e. g. methyl or ethyl) or Cn. 4) alkoxy (e. g. methoxy). Further optional substituents include phenyl and benzyl.

Representative examples of R2YCH2X include 4-fluorobenzylthiogroup, 4- chlorophenylheptylthio and 4-chlorophenyl-1-oxaheptylthio. Preferably, R2YCH2X is 4-fluorobenzylthio group.

Preferably W is a bond.

Representative examples of R7 when a hydrocarbyl group include C(1-20)alkyl, C (2-20) alkenyl, C(2-20)alkynyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-5)alkyl, or C (1-15)alkoxyC(1-10) alkyl each of which may be optionally substituted by 1 or 2 substituents as hereinbefore defined.

Preferably, W is a bond and R7 is C (I-20) alkyl, especially C(10-20)alkyl. Preferably, R7 is also Cn. ioalkyi, more preferably a C 5) alkyl which is substituted by one or two substituents selected from hydroxy, C(1-20)alkoxy (e. g. methoxy), COOC(1-10)alkyl (e. g. COOCH3, COOC2H5), CONR8R9, NR8CONR9R10, NHCOR8 (in which R8, R9 and RIO is each independently C (1 20) alkyl e. g. methyl). Further optional substituents include aryl, preferably phenyl which may be optionally substituted by COOC(1-6)alkyl (e. g methyl) and heteroaryl (for instance pyridyl, imidazolyl, furanyl, thienyl and 2-oxo pyrrolidinyl). Preferred examples of the substituent NR lRl2 include morpholino, piperidino or 2-oxo-pyrrolidino group.

A preferred sub-group of compounds of formula (I) are those in which W is a bond and R7 is a phenyl or a phenylC@ 1 alkyl group, for instance benzyl or phenethyl, substituted in the phenyl ring by 1 or 2 substituents selected from C (6 12) alkyl (for instance hexyl and decyl), C (6-l) alkoxy. COOH, COOC(6-12)alkyl and CONHC (6-l) alkyl.

Alternatively, R7 maybe heteroarylC 1-8)alkyl, preferably heteroarylC(1-3)alkyl in which the heteroaryl ring is monocyclic with 5 to 6 members and one or two heteroatoms selected from nitrogen, oxygen and sulphur, such as pyridyl, furanyl, thienyl and imidazolyl.

A further preferred subgroup of compounds of formula (I) are those in which W is a bond and R7 is a group of the formula (CH2) nBR13 where n is an integer from 1 to 6, preferably 1 to 4, B is selected from NR 14CO, CONR 14, NR 14CONR 15, NR 15COO (in which R 14 and R 15 are independently selected from hydrogen or C 6) alkyl, preferably hydrogen) and R13 is C(8-18)alkyl (which may optionally be fluorinated, including up to perfluorinated on the terminal 1 to 3 carbon atoms), C (g 1g) alkenyl, phenyl C (1 6) alkyl and phenylC(1-8)alkoxyC(1-6)alkyl in which phenyl may be optionally substituted by halogen or C (1 6) alkyl. Prefered examples of C (g 1g) alkyl are straight chains and include octyl, dodecyl and fatty alkyl groups such as lauryl and stearyl. Preferred values of C (g 1g) alkenyl include octadec-9- (Z)-en-lyl. Preferred examples of optionally substituted phenylCnalkyI and phenylC 1-8)alkoxyC(1-6)alkyl include 4- fluorophenylhexyl, 4-pentylphenylethyl and 4-fluorophenylhexoxyethyl. Particularly preferred compounds of formula (I) are those in which R12 is C (12 1g) alkyl or C (12- 1g) alkenyl. Such a long, lipophilic substituent is found to be especially beneficial for enzyme inhibition When used herein, the term'alkyl'and similar terms such as'alkoxy'includes all straight chain and branched isomers. Representative examples thereof include methyl, ethyl, n- propyl. iso-propyl, n-butyl, sec-butyl, iso-butyl, t-butyl, n-pentyl and n-hexyl.

When used herein, the term"hydrocarbyl"refers to a group having from 1 to 20 carbon atoms which may be in a straight chain or a branched chain and include a saturated carbocyclic ring having from 3 to 6 carbon atoms and which chain may contain unsaturation (double and/or triple carbon-carbon bonds).

When used herein, the term'aryl'refers to, unless otherwise defined, a mono-or bicyclic aromatic ring system containing up to 10 carbon atoms in the ring system, for instance phenyl or naphthyl.

When used herein, the terrn'heteroaryl'refers to a mono-or bicyclic heteroaromatic ring system comprising up to four, preferably 1 or 2, heteroatoms each selected from oxygen, nitrogen and sulphur. Each ring may have from 4 to 7, preferably 5 or 6, ring atoms. A bicyclic heteroaromatic ring system may include a carbocyclic ring. Representative examples include pyridyl, pyridyl N-oxide, pyrimidyl, pyrazolyl, furyl, thienyl, thiazolyl, pyridazolyl and pyrazinyl, quinolyl and benzothiazolyl.

When used herein. the terms'halogen'and'halo'include fluorine, chlorine, bromine and iodine and fluoro, chloro. bromo and iodo, respectively.

Compounds of formula (I) are inhibitors of Lp-PLA and as such are expected to be of use in treating atherosclerosis and the other disease conditions noted elsewhere. Such compounds are found to act as inhibitors of Lp-PLA2 in in vitro assays..

Particularly preferred compounds of formula (I) are 2- (4-Fluorobenzylthio)-5- ( (pyrimid-5-yl) methyl) pyrimidin-4-one; l-Methyl-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one; 1- (Tetradec-1-ylaminocarbonylmethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl)pyrimidin-4-one; 1- (N- (Dodec-1-yl)-N-methylaminocarbonylmethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one; and 1- (N-Methyl-N- (dodec-1-yl) aminocarbonylmethyl)-2- (4-fluorobenzyl) thio-5- (2- methoxypyrimid-5-ylmethyl) pyrimidin-4-one.

Since the compounds of the present invention, in particular compounds of formula (I), are intended for use in pharmaceutical compositions, it will be understood that they are each provided in substantially pure form, for example at least 50% pure, more suitably at least 75% pure and preferably at least 95% pure (% are on a wt/wt basis). Impure preparations of the compounds of formula (I) may be used for preparing the more pure forms used in the pharmaceutical compositions. Although the purity of intermediate compounds of the present invention is less critical, it will be readily understood that the substantially pure form is preferred as for the compounds of formula (I). Preferably, whenever possible, the compounds of the present invention are obtained in crystalline form.

When some of the compounds of this invention are allowed to crystallise or are recrystallised from organic solvents, solvent of crystallisation may be present in the crystalline product. This invention includes within its scope such solvates. Similarly, some of the compounds of this invention may be crystallised or recrystallised from solvents containing water. In such cases water of hydration may be formed. This invention includes within its scope stoichiometric hydrates as well as compounds containing variable amounts of water that may be produced by processes such as lyophilisation. In addition, different crystallisation conditions may lead to the formation of different polymorphic forms of crystalline products. This invention includes within its scope all polymorphic forms of the compounds of formula (I).

Compounds of the present invention are inhibitors of the enzyme lipoprotein associated phospholipase A-e (Lp-PLA) and as such are expected to be of use in therapy, in

particular in the treatment of atherosclerosis. In a further aspect therefore the present invention provides a compound of formula (I) for use in therapy.

The compounds of formula (I) are inhibitors of lysophosphatidylcholine production by Lp-PLA and may therefore also have a general application in any disorder that involves endothelial dysfunction, for example atherosclerosis, diabetes, hypertension, angina pectoris and after ischaemia and reperfusion. In addition, compounds of formula (I) may have a general application in any disorder that involves lipid peroxidation in conjunction with enzyme activity, for example in addition to conditions such as atherosclerosis and diabetes, other conditions such as rheumatoid arthritis, stroke, inflammatory conditions of the brain such as Alzheimer's Disease, myocardial infarction, reperfusion injury, sepsis, and acute and chronic inflammation. Further such conditions include various neuropsychiatric disorders such as schizophrenia (see Psychopharmacology Bulletin, 31, 159-165,1995).

Further applications include any disorder that involves activated monocytes, macrophages or lymphocytes, as all of these cell types express Lp-PLA,. Examples of such disorders include psoriasis.

Accordingly, in a further aspect, the present invention provides for a method of treating a disease state associated with activity of the enzyme Lp-PLA, which method involves treating a patient in need thereof with a therapeutically effective amount of an inhibitor of the enzyme. The disease state may be associated with the increased involvement of monocytes. macrophages or lymphocytes: with the formation of lysophosphatidylcholine and oxidised free fatty acids: with lipid peroxidation in conjunction with Lp PLA2 activity; or with endothelial dysfunction.

Compounds of the present invention may also be of use in treating the above mentioned disease states in combination with anti-hyperlipidaemic or anti-atherosclerotic or anti- diabetic or anti-anginal or anti-inflammatory or anti-hypertension agents. Examples of the above include cholesterol synthesis inhibitors such as statins, anti-oxidants such as probucol, insulin sensitisers, calcium channel antagonists, and anti-inflammatory drugs such as NSAIDs.

In therapeutic use, the compounds of the present invention are usually administered in a standard pharmaceutical composition. The present invention therefore provides, in a further aspect, a pharmaceutical composition comprising a compound of formula (I) and a pharmaceutically acceptable carrier.

Suitable pharmaceutical compositions include those which are adapted for oral or parenteral administration or as a suppository.

Suitable pharmaceutical compositions include those which are adapted for oral or parenteral administration or as a suppository. Compounds of formula (I) which are active when given orally can be formulated as liquids, for example syrups, suspensions or mulsions, tablets, capsules and lozenges. A liquid formulation will generally consist of a suspension or solution of the compound or pharmaceutically acceptable salt in a suitable liquid carrier (s) for example, ethanol, glycerine, non-aqueous solvent, for example polyethylene glycol, oils, or water with a suspending agent, preservative, flavouring or colouring agent. A composition in the form of a tablet can be prepared using any suitable pharmaceutical carrier (s) routinely used for preparing solid formulations. Examples of such carriers include magnesium stearate, starch, lactose, sucrose and cellulose. A composition in the form of a capsule can be prepared using routine encapsulation procedures. For example, pellets containing the active ingredient can be prepared using standard carriers and then filled into a hard gelatin capsule; alternatively, a dispersion or suspension can be prepared using any suitable pharmaceutical carrier (s), for example aqueous gums, celluloses, silicates or oils and the dispersion or suspension then filled into a soft gelatin capsule. Typical parenteral compositions consist of a solution or suspension of the compound of formula (I) in a sterile aqueous carrier or parenterally acceptable oil, for example polyethylene glycol, polyvinyl pyrrolidone, lecithin, arachis oil or sesame oil. Alternatively, the solution can be lyophilised and then reconstituted with a suitable solvent just prior to administration. A typical suppository formulation comprises a compound of formula (I) which is active when administered in this way, with a binding and/or lubricating agent such as polymeric glycols, gelatins or cocoa butter or other low melting vegetable or synthetic waxes or fats.

Preferably the composition is in unit dose form such as a tablet or capsule. Each dosage unit for oral administration contains preferably from 1 to 500 mg (and for parenteral administration contains preferably from 0.1 to 25 mg) of a compound of the formula (I).

The daily dosage regimen for an adult patient may be, for example, an oral dose of between 1 mg and 1000 mg, preferably between 1 mg and 500 mg, or an intravenous, subcutaneous, or intramuscular dose of between 0.1 mg and 100 mg, preferably between 0.1 mg and 25 mg, of the compound of the formula (I), the compound being administered 1 to 4 times per day. Suitably the compounds will be administered for a period of continuous therapy, for example for a week or more.

Compounds of formula (I) may be conveniently prepared from readily available starting materials by adapting synthetic methodology well known in the art for the preparation and derivatisation of pyrimidones by a process.

Accordingly, in a first aspect, the present invention provides a process for preparing a compound of formula (I) which process comprises: (a) treating a compound of formula (IIA):

in which R 1 and Z are as hereinbefore defined; with a compound of formula (III): R2YCH2L 1 (III) in which Y and R2 are as hereinbefore defined and L1 is a leaving group e. g. bromine or iodine; to give a compound of formula (IA):

in which Z, Y, R I and R2 are as hereinbefore defined and X is S; or (b) treating a compound of formula (IV):

in which Z and R1 are as hereinbefore defined and L2 is a leaving group, e. g. halogen such as chlorine or bromine, alkylthio such as methylthio. or-NHNO2, with a compound of formula (V): R2YCH2XH (V) in which X, Y and R2 are as hereinbefore defined; advantageously at an elevated temperature, in a solvent such as pyridine, to give a compound of formula (IA); and thereafter, and if so desired; treating a compound of formula (IA) form (a) or (b) above with a compound of formula (VI) : Ravi1 (VI) in which L 1, W and R7 are as hereinbefore defined; to give a compound of formula (1B): in which X, Y, Z, R 1 and R2 are as hereinbefore defined and WR7 is as hereinbefore defined, other than-H ; or (c) treating a compound of formula (IIB):

in which W is a bond, Z and Rl are as hereinbefore defined and R7 are as hereinbefore defined, other then H, with a compound of formula (III) as hereinbefore defined, to obtain a compound of formula (IB); and, thereafter and if so desired; treating a compound of formula (IA) or (IB) in which X is S with a compound of formula (V): R2YCH20H (VII) in which Y and R2 are as hereinbefore defined; to give a corresponding compound of formula (I) in which X is O.

In the above process, the reaction of the compounds of formulae (IIA/B) and (III) is advantageously effected in the presence of a base such as sodium ethoxide, potassium carbonate, preferably in a solvent such as ethanol or dimethylformamide, or a base such as di-isopropyl ethylamine, preferably in a solvent such as dichloromethane.

In the above process, the reaction of the compounds of formulae (IA) and (VI) is advantageously effected at a temperature of 20-100 degrees C, in the presence of sodium hydride in a solvent such as dimethylformamide; or by the compound of formula (IA) being pre-treated with tributyl tin chloride in the presence of di-isopropylethylamine, for example in a dichloromethane solvent at reflux temperature, followed by addition of (VI) Alternatively, the compound of formula (IA) may be treated directly with a compound of formula (VI) and di-isopropylethylamine in a dichloromethane solvent at room temperature.

In the above processes, the reaction of the compounds of formulae (IA/IB) and (VII) is conveniently effected in the presence of pyridine at an elevated temperature, containing a catalytic amount of 4-dimethylaminopyridine.

A compound of formula (I) in which Z is a bond and R represents halogen may be obtained by treating a compound of formula (VIII):

in which W, Y, R2, and R7 are as hereinbefore defined; with a halogenating agent, <BR> <BR> preferably with bromine to form a compound of formula (I) in which Z is a bond and ruz is bromine, the reaction being advantageously effected in a solvent such as dichloromethane.

A compound of formula (IIA) may be obtained from a compound of formula (IX): L30COCH2ZR1 (IX) in which L3 is C (1 6) alkyl, for instance methyl, and Z and R l are as hereinbefore defined; by the initial treatment thereof with a formylating agent such ethyl formate in the presence of a strong base such as potassium t-butoxide or sodium hydride, to give an enolate metal salt compound of formula (X): in which L3, Z and R are as hereinbefore defined and M is a metal cation, for instance sodium or potassium. Further treatment of a compound of formula (X) or a salt thereof with thiourea leads to a compound of formula (IIA). The two steps, starting form the compound of formula (IX) may conveniently be carried out as a"one-pot"process.

A compound of formula (IIB) may be obtained from a compound of formula (X), in a series of steps. In a first step. a compound of formula (X) is converted into the

corresponding methyl enol ether by treatment with a methylating agent such as dimethyl sulphate in the presence of a base such as potassium carbonate. The corresponding carboxylic acid may then be obtained by conventional hydrolysis, for instance basic hydrolysis, using, for instance aqueous sodium hydroxide. The acid may then be converted into the corresponding acyl chloride, by treatment with oxalyl chloride, and the acyl chloride treated with potassium thiocyanate in a solvent such as acetonitrile, to give an intermediate of the formula (XI): in which R and Z are as hereinbefore defined. Treatment of a compound of formula (XI) with a compound of formula (XII): <BR> <BR> <BR> <BR> R7WNH2<BR> <BR> (XII) in which R7 is as hereinbefore defined and W is a bond, followed by the addition of an organic base such as sodium ethoxide. leads to a compound of formula (IIB).

A compound of formula (IV) in which L2 is N (H) NOs can be conveniently prepared by reacting a compound of formula (X) above with a compound of formula (XIII): in which the reaction is carried out in a conventional manner.

A compound of formula (VIII) may be obtained by treating a 3,3-dialkoxypropionic ester of the formula (XIV): (L3) 02CCHsCH (oL3) 2

(XIV) in which L3 is as hereinbefore defined; with a thiourea of the formula (XV): R7NHCSNH2 (XV) in which R7 is as hereinbefore defined; in the presence of sodium hydride followed by aqueous acetic acid.

Compounds of formula (I) in which R7 comprises an amide moiety can be prepared from a precursor comprising an ester, for instance a methyl or ethyl ester, by first converting the ester to an acid, by hydrolysis and then treating the acid with an appropriate amine, under amide bond forming conditions. The acid may preferably be converted into an activated derivative, prior to amide bond formation.

Compounds of formula (I) in which R7 comprises a urea moiety can be prepared from a precursor comprising an amine moiety, by treating the amine with an isocyanate, under urea forming conditions, well known in the art.

The present invention will now be illustrated by the following examples.

Intermediate A1-8-Bromo-1- (4-chlorophenyl) octan-1-one To a stirring suspension of aluminium chloride (33.6g) in dry dichloromethane (474ml) was added 8-bromo-n-octanoyl chloride (67.8g) over 10min. Chlorobenzene (123ml) was then added over 10min and the mixture allowed to stir at 25°C for 74h and stood for 64h.

The mixture was poured into ice/water (540ml) and diethyl ether (1.3L). The organic layer was removed and was washed with water (540ml), saturated sodium hydrogen carbonate (540ml), water (400ml) and brine (400ml) and dried over magnesium sulfate.

Removal of the organic layer under reduced pressure and chromatography of the residue on silica gel using 5% ethyl acetate in hexane gave 8-bromo-1- (4-chlorophenyl) octan-1- one (35.5g).'H-NMR (CDCy § 1.2-1.6 (6H, m), 1.6-1.95 (4H, m), 2.95 (2H, t), 3.42 (2H, t), 7.43 (2H, m) and 7.90 (2H, m).

Intermediate A2-8-Hydroxy-1- (4-chlorophenyl) octan-1-one To 8-bromo-1- (4-chlorophenyl) octan-1-one (4.0g) in ethanol (170ml) was added 3% aqueous sodium hydroxide (70ml). The mixture was heated at reflux for 3h, cooled and evaporated to one third volume. Water (50ml) and dichloromethane (100ml) were added.

The organic layer was separated and the aqueous layer was re-extracted with dichloromethane (2x50ml). The combined extracts were washed with water (30ml) and dried over magnesium sulphate. The solvent was removed under reduced pressure and the residue was crystallised from 40-60°C petroleum ether to give 8-hydroxy-1- (4- chlorophenyl) octan-l-one (l. Og). lH-NMR (CDCl) õ 1.25-1.9 (10H, m), 2.94 (2H, t), 3.64 (2H, t), 7.43 (2H, m) and 7.89 (2H. m). (EI) Found M+=254. C14H19ClO2 requires 254.

Intermediate A3-8-Bromo-1- (4-methoxyphenyl) octan-1-one Prepared analogously to intermediate Al. lH-NMR (CDC13) õ 1.3-1.95 (10H, m), 2.91 (2H, t), 3.41 (2H, t), 3.87 (3H, s), 6.93 (2H, m) and 7.94 (2H, m).

Intermediate A4-8-Bromo-1- (4-bromophenyl) octan-1-one Prepared analogously to intermediate Al. IH-NMR (CDCl3) 6 1. 25-1.55 (6H, m), 1.65- 1.95 (4H, m), 2.93 (2H, t), 3.41 (2H, t), 7.60 (2H,m) and 7.83 (2H, t).

Intermediate8-Bromo-1-(2-thienyl)octan-1-one- Prepared analogously to intermediate A l, except using SnCl4 as catalyst in place of AlCl3. I H-NMR (CDC13) 8 1.3-1.55 (6H, m), 1.65-1.95 (4H. m), 2.90 (2H, t), 3.41 (2H, t), 7.13 (1H, dd), 7.63 (lH, dd) and 7.70 (lH, dd).

Intermediate A6-8-Bromo-1-(2-furyl) octan-1-one

Prepared analogously to intermediate A1, except using SnCl4 as catalyst in place of A1C13. 'H-NMR (CDCy 5 1.3-1.55 (6H, m), 1.6-1.95 (4H, m), 2.82 (2H, t), 3.41 (2H, t), 6.53 (1H, m), 7.18 (1H, m) and 7.58 (1H, m).

Intermediate A7-8-Bromo-1- (4-methylphenyl) octan-1-one Prepared analogously to intermediate Al. IH-NMR (CDC'3) 6 1.3-1.55 (6H, m), 1.65- 1.95 (4H, m), 2.41 (3H, s), 2.94 (2H, t), 3.41 (2H, t), 7.25 (2H, m) and 7.86 (2H, m).

Intermediate A8-8-Bromo-1-(4-fluorophenyl) octan-1-one Prepared analogously to intermediate Al. IH-NMR (CDC13) õ 1.3-1.6 (6H, m), 1.6-1.95 (4H. m), 2.94 (2H. t). 3.41 (2H, t), 7.13 (2H, m) and 7.98 (2H, m).

Intermediate A9-8-Bromo-1- (4-methyl-1-naphthyl) octan-1-one Prepared analogously to intermediate Al. 1H-NMR (CDCl3) # (6H, m), 1.7-1.95 (4H. m), 2.74 (3H. s), 3.03 (2H, t), 3.41 (2H, t), 7.32 (1H. m), 7.5-7.65 (2H, m), 7.76 (lH, d), 8.0-8.1 (1 H, m) and 8.55-8.7 (1 H, m).

Intermediate -1-Bromo-8-(2-thiazolinyl)octane10 To a solution of 2-methyl-2-thiazoline (1. 01g) in dry tetrahydrofuran at-70°C was added a solution of n-butyl lithium in hexanes (2.5M, 4.0ml) dropwise over 10min. After stirring at-70°C for 2h. 1,7-dibromoheptane (12. 9g) was added in one portion (temperature increased to-45°C). The mixture was cooled again to-70°C for lh and then allowed to warm to room temperature over lh. The mixture was cooled to 0°C and water (lOml) added, followed by dilute hydrochloric acid (to pH 2). The organic layer was separated and the aqueous layer extracted with diethyl ethyl (2x20ml). The organic layers were combined and washed with water and brine and dried over magnesium sulfate.

Evaporation under reduced pressure gave an oil that was chromatographed on silica gel using 40-60°C petroleum ether : ethyl acetate 5: 1 to give 1-bromo-8- (2-thiazolinyl) octane (1.06g). IH-NMR (CDCl3) õ 1.2-1.5 (6H, m), 1.5-1.75 (4H, m), 1.75-1.95 (2H, m), 2.50 (2H, t), 3.28 (2H, t), 3.40 (2H, t) and 4.21 (2H, dt).

Intermediate All-1-Bromo-8- (2-pyridyl) octane

Prepared analogously to intermediate Al0. IH-NMR (CDCl3) 6 1.2-1.55 (8H, m), 1.6- 1.95 (4H, m). 2.76 (2H, t), 3.41 (2H, t), 7.05-7.2 (2H, m), 7.5-7.65 (IH. m) and 8.52 (IH. m).

Intermediate A12-8- (3,4-Dichlorophenyl) oct-7-yn-1-ol A mixture of 3,4-dichloroiodobenzene (2.16g), oct-7-yn-1-ol (1.20g), tetrakis (triphenylphosphine) palladium (0) (0.185g), copper (I) iodide (0.046g) and triethylamine (15ml) was stirred at room temperature for 16h. The solid was filtered off and the filtrate evaporated under reduced pressure. The residual oil was dissolved in ethyl acetate (15ml) and washed with water (10ml), 2M hydrochloric acid (2xlOml) and brine (10ml). Drying over magnesium sulfate and removal of the solvent under reduced pressure gave an oil that was purified by flash chromatography on silica gel using dichloromethane as eluent.

This gave 8- (3, 4-dichlorophenyl) oct-7-yn-l-ol (1. 89g). 1H-NMR (CDCl3) # 1.2-1.75 (8H, m), 2.40 (2H, t), 3.66 (2H, t), 7.19 (IH. dd), 7.35 (1H, d) and 7.47 (1H, dd) Intermediate A13-8- (3,4-Dichlorophenyl) octan-1-ol To a solution of 8-(3,4-dichlorophenyl)-oct-7-yn-l-ol (0.70g) in methanol (20ml) was added platinum dioxide (0. 05g) and the mixture reacted under an atmosphere of hydrogen (initial pressure 50 psi). After Ih. the catalyst was filtered through Hyflo and washed with methanol. The combined methanol layers were evaporated under reduced pressure to give 8- (3,4-dichlorophenyl) octan-l-ol (0.69g).'H-NMR (CDCy § 1.1-1.8 (12H, m), 2.55 (2H, t), 3.64 (2H. m), 6.99 (lH, dd) and 7.2-7.4 (2H, m)

Intermediate A14-8-Bromo-l- (3, 4-dichlorophenyl)-l-octyne A solution of 8-(3,4-dichlorophenyl)-oct-7-yn-1-of (0.52g) in diethyl ether (2.5ml) was treated with phosphorous tribromide (0.23g) at 0°C (ice/salt bath). The solution was stirred at 0-5°C for 2h and allowed to warm to room temperature. Aqueous sodium hydrogen carbonate solution was added. The aqueous layer was extracted with further diethyl ether (2x5ml) and the combined organic layers were washed with brine (5ml) and dried over magnesium sulfate. Removal of the solvent under reduced pressure gave an oil that was chromatographed on silica gel using dichloromethane as eluent. This gave 8- bromo-l- (3, 4-dichlorophenyl)-l-octyne (0. 25g). 1H-NMR (CDCl3) # 1.35-1.7 (6H, m), 1.75-1.95 (2H, m), 2.33 (2H, t), 3.35 (2H, t), 7.13 (lH, dd), 7.27 (lH, d) and 7.40 (lH, d) Intermediate A15-1-Bromo-8- (3, 4-dichlorophenyl) octane A solution of 8- (3,4-dichlorophenyl) octan-1-ol (0.66g) in 48% hydrobromic acid (7ml) was stirred under reflux for 2h. Water (20ml) and diethyl ether (20ml) were added. The organic layer was separated and the aqueous layer reextracted with diethyl ether (10ml).

The combined organic extracts were washed with water (lOml), sodium hydrogen carbonate solution (10ml) and brine (10ml) and dried over magnesium sulfate. The solution was treated with charcoal, filtered and evaporated under reduced pressure to give 1-bromo-8- (3,4-dichlorophenyl) octane (0. 74g). 1H-NMR (CDCl3) # 1.2-1.8 (12H, m), 2.55 (2H, t), 3.41 (2H, t), 7.00 (lH, dd), 7.25 (lH, dd) and 7.33 (1H, d).

Intermediate A16-8- (3-Chlorophenvl) oct-7-vn-l-ol Prepared analogously to intermediate A 12. H-NMR (CDC13) b 1.25 (8H, m), 2.41 (2H, t), 3.66 (2H, t), 7.13-7.33 (3H, m) and 7.37 (lH, m) Intermediate A17-8- (3-Chlorophenyl) octan-l-ol Prepared analogously to intermediate Al3. lH-NMR (CDCl3) b 1. 1-1.8 (12H, m), 2.57 (2H, t), 3.64 (2H, t), 7.0-7.4 (4H. m) Intermediate A18-1-Bromo-8- (3-chlorophenvl) octane

Prepared analogously to intermediate A15. 1H-NMR (CDC13) b 1.05-1.9 (12H, m), 2.50 (2H, t), 3.33 (2H, t) and 6.9-7.25 (4H, m).

Intermediate A19-8- (4-Acetylphenyl) octan-1-ol Prepared analogously to intermediate A13. IH-NMR (CDC13) â 1.2-1.8 (12H, m), 2.59 (3H, s), 2.68 (2H, t), 3.63 (2H, t) 7.25 (2H, m) and 7.88 (2H, m) Intermediate A20-1-Bromo-8- (4-acetylphenyl) octane Prepared analogously to intermediate A15. IH-NMR (CDCl3) 8 1.2-1.75 (10H, m), 1.85 (2H, m), 2.59 (3H, s), 2.67 (2H, m), 3.40 (2H, t), 7.2-7.3 (2H, m) and 7.88 (2H, m).

Intermediate A21-1-Bromo-8- (4-fluorophenyl) octane Triethylsilane (30.5 g, 260 mmol) was added dropwise to 8-bromo-1- (4- fluorophenyl) octan-1-one (230 ml, 105 mmol) over 20 min, with cooling to keep the temperature at ca 30°C. After 2 hours stirring, a further 3.1 g (27 mmol) triethylsilane was added, and reaction continued for an additional 2 hours. The mixture was poured into ice-water (200 ml) and ether (300 ml), then the organic layer was washed with aqueous sodium hydroxide, dried and evaporated, finally at 65°C/0. 01 mm. The residue was filtered through silica gel, eluting with petroleum ether, then distilled, collecting the fraction at 122-140°C/0.5 mm (24.2 g). 1H-NMR (CDCl3) # 1.2-1.7 (lOH. m), 1.85 (2H, m), 2.57 (2H, t), 3.40 (2H, t), 6.9-7.05 (2H. m) and 7.05-7.2 (2H, m).

Intermediate A22-I-Bromo-8- (4-methoxyphenyl) octane Prepared as in reference 1 Intermediate A23-I-Bromo-8- (4-pyridvl) octane Prepared analogously to intermediate AlO. 'H-NMR (CDC13) a 1.2-1.95 (12H, m), 2.48 (2H. t), 3.42 (2H, t), 7.11 (2H, d) and 8.47 (2H, m).

Intermediate A24-1-Bromo-8- (4-chlorophenyl) octane

Prepared analogously to intermediate A21. 'H-NMR (CDC'3) 5 1.2-1.5 (8H, m), 1.5-1.7 (2H. m), 1.75-1.95 (2H, m), 2.56 (2H, t), 3.40 (2H, t), 7.08 (2H, m) and 7.23 (2H, m).

Intermediate A25-I-Bromo-6- (4-chlorobenzyloxy) hexane Sodium hydride (60%, 0.39g) was added to a mixture of 6-bromohexanol (1.78g) and 4- chlorobenzyl bromide (2.02g) in dry tetrahydrofuran (150ml). The mixture was stirred at 25°C for 5h and poured into 1M hydrochloric acid. Extraction with diethyl ether (3x), and washing the combined extracts with water and brine gave a solution that was dried over magnesium sulfate and evaporated under reduced pressure. The residue so obtained was chromatographed on silica gel using 40-60°C petroleum ether to 10% diethyl ether in 40-60°C petroleum ether as eluents. This gave l-bromo-6- (4-chlorobenzyloxy) hexane (1.7g). lH-NMR (CDCl3) å 1.3-1.55 (4H, m), 1.55-1.7 (2H, m), 1.75-1.95 (2H, m), 3.35- 3.55 (4H, m), 4.46 (2H, s) and 7.2-7.4 (4H, m).

Intermediate A26-I-Bromo-6- (4-fluorobenzyloxy) hexane Prepared analogously to intermediate A25. 'H-NMR (CDCy 5 1.3-1.5 (4H, m), 1.6 (2H. m), 1. 1. 9 (2H, m), 3.39 (2H, t), 3.45 (2H, t), 4.44 (2H, s), 7.0-7.1 (2H, m), 7.2-7.4 (2H, m).

Intermediate A27-1-Bromo-6-benzyloxyhexane Prepared as in reference 14.

Intermediate A28-1-Bromo-7-phenoxyheptane To a mixture of phenol (0.58g) and 1,7-dibromoheptane (4.76g) in dimethylformamide (5ml) was added potassium carbonate (4.3g) and the mixture was heated at 80°C for 6h.

The mixture was cooled and the solvent was removed under reduced pressure. Toluene (10ml) was added and removed under reduced pressure. The residue was chromatographed on silica gel using hexane as eluent. This gave 1-bromo-7- phenoxyheptane (1. 15g). 1H-NMR (CDCl3 # 1.3-1.7 (6H, m), 1.7-2.1 (4H, m), 3.41 (2H. t), 3.95 (2H, t), 6.8-7.0 (3H. m) and 7.2-7.4 (2H, m) Intermediate A29-I-Bromo-7- (4-chlorophenoxv) heptane Prepared analogously to intermediate A28. 1H-NMR (CDCl3) # 1.3-1.6 (6H, m), 1.7-2.0 (4H, m), 3.41 (2H, t), 3.91 (2H, t), 6.75-6.9 (2H, m) and 7.15-7.3 (2H, m).

Intermediate A30-I-Bromo-7- (4-chlorophenylthio) heptane To 1,7-dibromoheptane (23g) and potassium carbonate (lOg) in dry dimethylformamide (100ml) was added 4-chlorothiophenol (4.3g) dropwise with stirring at 25°C. After 6h, the mixture was filtered and the solvent removed under reduced pressure.

Chromatography of the residue on silica gel using hexane as eluent gave 1-bromo-7- (4- chlorophenylthio) heptane (9.6g). IH-NMR (CDCl3) â 1.2-1.55 (6H, m), 1.55-1.75 (2H, m), 1.8-2.0 (2H, m), 2.89 (2H, t), 3.40 (2H, t) and 7.2-7.4 (4H, m).

Intermediate 1-Bromo-7-(4-chlorophenylsulfinyl)heptane- A solution of 1-bromo-7- (4-chlorophenylthio) heptane (0.80g) in dichloromethane (10ml) was cooled to-78°C (cardice/acetone) and a slurry of metachloroperbenzoic acid (60%, 0.72g) in dichloromethane (5ml) was added over 20min. After 40min, the reaction was allowed to warm to room temperature and shaken with aqueous sodium sulfite/sodium hydrogen carbonate solution. The organic layer was dried over magnesium sulfate and evaporated under reduced pressure. The residue was chromatographed on silica gel using dichloromethane to 4% methanol in dichloromethane as eluents to give 1-bromo-7- (4- chlorophenylsulfinyl) heptane (IOH, m), 2.77 (2H, t), 3.39 (2H, t) and 7.4-7.7 (4H, m).

Intermediate A32-1-Bromo-7- (4-chlorophenvlsulfonyl) heptane To a solution of l-bromo-7- (4-chlorophenylthio) heptane (1.19g) in dichloromethane (20ml) at-20°C was added metachloroperbenzoic acid (60%, 2.23g) portionwise over 15min. The mixture was allowed to warm to room temperature over lh and was shaken with aqueous sodium sulfite/sodium hydrogen carbonate solution. The organic layer was dried over magnesium sulfate and evaporated under reduced pressure. The residue was chromatographed on silica gel using 50: 50 hexane: dichloromethane as eluent to give 1- bromo-7- (4-chlorophenylsulfonyl) heptane (1.17g). lH-NMR (CDCl3) å 1.2-2.0 (10H, m), 3.07 (2H, m), 3.38 (2H, t), 7.5-7.6 (2H, m) and 7.8-7.9 (2H, m).

Intermediate A33-1-Bromo-7-phenylthioheptane Prepared analogously to intermediate A30. 'H-NMR (CDC) 5 1.2-1.55 (6H, m), 1.6- 1.75 (2H, m). 1.75-1.95 (2H, m), 2.91 (2H, t), 3.40 (2H, t) and 7.1-7.4 (5H, m).

Intermediate A34-1-Bromo-7-phenylsulfinylheptane Prepared analogously to intermediate A31. IH-NMR (CDCl3) å 1.2-1.95 (IOH, m), 2.91 (2H, t), 3.40 (2H, m) and 7.1-7.4 (5H, m).

Intermediate A35-1-Bromo-7-phenylsulfonylheptane Prepared analogously to intermediate A32. lH-NMR (CDCl3) â 1.2-2.0 (lH, m), 3.09 (2H, m), 3.38 (2H, t), 7.5-7.8 (3H, m) and 7.85-8.0 (2H, m).

Intermediate A36-8-Bromo-l- (4-chlorophenyl)-l-hydroxyoctane To a solution of 8-bromo-1- (4-chlorophenyl) octan-l-one (0.95g) in industrial methylated spirit (10ml) was added sodium borohydride (O. 115g) at-10°C. After stirring for lh, glacial acetic acid (0.2g) was added and the mixture was poured into water (60ml) and extracted with diethyl ether. The diethyl ether layer was washed with brine and dried over magnesium sulfate. Removal of the solvent under reduced pressure gave an oil that was chromatographed on silica gel using dichloromethane as eluent. This gave 8-bromo- 1- (4-chlorophenyl)-l-hydroxyoctane(4-chlorophenyl)-l-hydroxyoc tane (0.70g). 1H-NMR (CDC13) 8 (12H, m), 3.40 (2H, t), 4.65 (1H, t) and 7.2-7.4 (4H, m).

Intermediate A37-9-Bromo-2- (4-fluorophenyl)-l-nonene To a solution of butyl lithium (2.5M, 3.2ml) in anhydrous tetrahydrofuran (75ml) was added triphenylmethylphosphonium bromide (2.86g) in portions over lOmin. The mixture was stirred at 25°C for 3h and a solution of 8-bromo-1- (4-fluorophenyl) octan-1- one (1.20g) in dry tetrahydrofuran (15ml) added dropwise over 5min. After stirring at 25°C for 1h, the mixture was heated at reflux for 24h. The mixture was evaporated under reduced pressure and partitioned between diethyl ether (70ml) and water (4x30ml). The organic layer was washed with brine and dried over magnesium sulfate. Removal of the solvent under reduced pressure gave an oil that was chromatographed on silica gel using 5% diethyl ether in hexane. This gave 9-bromo-2- (4-fluorophenyl)-l-nonene (0.75g).

'H-NMR (CDC13) 8 1.2-1.55 (8H, m), 1.80 (2H, m), 2.46 (2H, t), 3.39 (2H, t), 5.03 (lH, bs), 5.20 (lH, bs), 7.03 (2H. m) and 7.3-7.45 (2H, m).

Intermediate A38-1- (3-Chlorophenvl) hex-1-yn-6-ol Prepared analogously to intermediate A12. IH-NMR (CDCl3) 5 1.6-1.85 (4H, m), 2.45 (2H, bt), 3.71 (2H, t), 7.15-7.33 (3H, m) and 7.37 (lH, m) Intermediate A39-6- (3-Chlorophenyl) hexan-1-ol Prepared analogously to intermediate A13. 1H-NMR (CDCl3) # 1.2-1. 8 (8H, m), 2.58 (2H, t), 3.64 (2H, t) and 7.0-7.3 (4H, m) Intermediate A40-1-Bromo-6- (3-chlorophenyl) hexane Prepared analogously to intermediate A15. IH-NMR (CDCl3) 8 1.2-1.95 (8H, m), 2.59 (2H, t), 3.40 (2H, t) and 7.0-7.3 (4H, m) Intermediate A41-9-Bromo-1- (4-chlorophenyl) nonan-1-one 9-Bromononanoyl chloride was obtained from the carboxylic acid (reference 12) by treatment with thionyl chloride. 9-Bromo-1- (4-chlorophenyl) nonan-1-one was prepared analogously to intermediate Al. 'H-NMR (CDCy 8 1.2-2.0 (12H, m), 2.95 (2H, t), 3.41 (2H, t), 7.44 (2H, m) and 7.90 (2H. m).

Intermediate A42-N- (6- (4-Fluorophenyl) hexyl)-2-bromoacetamide To a solution of6- (4-fluorophenyl)-l-hexylamine (21. 8g) in dry dichloromethane (200ml) at 0°C under an argon atmosphere was added diisopropylethylamine (14.4g) followed by bromoacetyl bromide (22.5g) over 30min whilst maintaining the temperature between 0-5°C. The resulting orange solution was stirred at 0-5°C for 45min and evaporated to dryness. The residue was mixed with diethyl ether and the hydrobromide salt filtered off. The filtrate was evaporated under reduced pressure and the residue was chromatographed on silica gel using 5: 1 to 3: 2 40-60°C petroleum ether: ethyl acetate as eluents. This gave a yellow oil that was triturated with 40-60°C petroleum ether, filtered and dried to give N- (1- (4-fluorophenyl)-hexyl) bromoacetamide (24.8g). lH-NMR (CDCl3) 8 1.25-1.45 (4H. m), 1.45-1.75 (4H, m), 2.57 (2H, t), 3.28 (2H, q), 3.88 (2H, s), 6.5 (lH, bs), 6.85-7.05 (2H. m) and 7.05-7.2 (2H. m).

Intermediate A43-1-Bromo-4- (3-phenylpropyloxy) butane Prepared as in reference 13.

Intermediate A44-6- (4-Chlorobenzoylamino) hexan-l-ol To a solution of 6-amino-1-hexanol (12.9g) and diisopropylethylamine (11. 9g) in dry dichloromethane (100ml) at 5°C was added 4-chlorobenzoyl chloride (16.1g) in dry dichloromethane at such a rate to maintain the temperature below 10°C. After stirring for 16h, the mixture was poured into water and filtered. The solid was washed with water, 2M hydrochloric acid (150ml), water, dichloromethane and was dried under reduced pressure to give 6- (4-chlorobenzoylamino) hexan-1-ol (19.2g). IH-NMR (d6-DMSO) 8 1.25-1.65 (8H, m), 3.24 (2H, q), 3.38 (2H, t), 7.52 (2H, m), 7.84 (2H, m) and 8.54 (lH, bt) Intermediate A45-I-Bromo-6- (4-chlorobenzovlamino) hexane 6- (4-Chlorobenzoylamino) hexan-l-ol (17. 0g) was refluxed in 48% hydrobromic acid (260ml) for 2.5h. The mixture was cooled and added to water (450ml) and diethyl ether (450ml). The organic layer was washed with saturated sodium bicarbonate (450ml) and brine (450ml) and was dried over magnesium sulfate. Evaporation followed by recrystallisation from diethyl ether gave 1-bromo-6- (4-chlorobenzoylamino) hexane (8.6g).'H-NMR (CDCy 5 (8H, m), 3.35-3.55 (4H, m), 6.15 (lH, bs), 7.40 (2H, m) and 7.70 (2H. m).

Intermediate BI-Ethyl 3- (5-pyrimidinvl) acrylate A mixture of 5-bromopyrimidine (5.93g), ethyl acrylate (5.08g), palladium acetate (0.112g), triphenyl phosphine (0.23g) and triethylamine (4.5g) was stirred at 150°C in a pressure vessel for 6 hours. After cooling overnight, water (SOml) was added to the dark residue, and the product was extracted into toluene. Drying, charcoaling and evaporation gave a pale oil, which was triturated with pet. ether to obtain ethyl 3- (5- pyrimidyl) acrylate (4.78g). IH-NMR (CDCI3) 6 1.36 (3H, t), 4.27 (2H, q), 6.59 (lH, d), 7.62 (lH, d), 8.88 (2H, s), 9.20 (lH, s).

Intermediate B2-Ethyl 3- (5-pyrimidyl) propionate

To a solution of ethyl 3- (5-pyrimidyl) acrylate (4.75g) in ethanol (90ml) was added 5% palladium on charcoal (0.2g). The mixture was hydrogenated at an initial pressure of 50 psi, then filtered to remove catalyst and the solvent evaporated. Water was added, and the product extracted into ether. Drying, charcoaling and evaporation gave ethyl 3- (5- pyrimidyl) propionate (2.3g) as a yellow oil. 1H-NMR (CDC13) S 1.23 (3H, t), 2.69 (2H, t), 2.96 (2H, t), 4.14 (2H, q), 8.635 (2H, s) and 9.09 (lH, s).

Intermediate B3-Ethyl 2-formyl-3- (5-pyrimidvl) propionate A mixture of ethyl 3- (5-pyrimidyl) propionate (2.28g) and ethyl formate (1.41ml) dissolved in dry dimethoxyethane (5ml) was added dropwise over 30 min to a suspension of sodium hydride (60%, 4.0g) in DME (5 ml) under nitrogen, keeping the temperature below 0°C. Stirring was continued for a further 24h, then the mixture was poured onto ice and washed with ether. The aqueous layer was adjusted to pH 7, then evaporated and the residue extracted with acetone. Filtration and evaporation gave crude product, which was taken up in ethyl acetate, charcoaled, dried and evaporated to give ethyl 2-formyl-3- (5-pyrimidyl) propionate. Like other compounds of this type, this proved difficult to characterise and was used without further purification.

Intermediate B4-3- (5-Pyrimidyl) acrylic acid A mixture of 5-bromopyrimidine (lOOg), acrylic acid (48g), triphenylphosphine (2.5g) and palladium II acetate (O. lg) was refluxed in tri-n-butylamine (260ml) with overhead stirring for 4.5h at 145-160°C. The mixture was cooled and a 10% solution of potassium carbonate (2L) added followed by dichloromethane (500mL). The organic layer was separated and the aqueous phase extracted with diethyl ether (3 x 300ml). The aqueous layer was brought to pH 3 with concentrated hydrochloric acid (ice-cooling) and the solid so formed was filtered and dried in vacua to give 3- (5-pyrimidyl) acrylic acid (35g).'H- NMR (d6-DMSO) 8 6.82 (1H, d), 7.60 (1H. d) and 9.15 (3H, 2xs) Intermediate B5-Methyl 3- (5-pyrimidinvl) acrylate 3- (5-Pyrimidyl) acrylic acid (lOOg) was added to a mixture of dry methanol (2L) and 4M hydrogen chloride in dioxan (445ml) and allowed to stir at 60°C under argon for 18h.

The mixture was cooled, and the solvent removed under reduced pressure. The residue was partitioned between dichloromethane (500ml) and was washed with saturated sodium bicarbonate (300ml). The aqueous layer was extracted with dichloromethane and the combined dichloromethane layers were dried over magnesium sulfate and evaporated in

vacuo to give methyl 3- (5-pyrimidinyl) acrylate (85g). IH-NMR (d6-DMSO) 8 3.82 (3H, s), 7.03 (lH, d), 7.75 (lH, d) and 9.28 (3H, s) Intermediate B6-Methyl 3- (5-pyrimidyl) propionate To a solution of methyl 3- (5-pyrimidyl) acrylate (85g) in glacial acetic acid was added 10% palladium on charcoal (11.3g) and ammonium formate (74. 2g) under argon. The mixture was heated at 110°C for 20min, cooled and the solvent removed in vacuo. The resulting oil was dissolved in dichloromethane (1.5L) and washed with saturated sodium bicarbonate (750ml). The aqueous layer was extracted with further dichloromethane (200ml), the organic layers were combined and dried over magnesium sulfate. Removal of the solvent under reduced pressure gave an oil. This was distilled under reduced pressure to give methyl 3- (5-pyrimidyl) propionate (26g).'H-NMR (CDCl3) 8 2.69 (2H, t), 2.97 (2H. t), 3.70 (3H, s), 8.65 (2H, s) and 9.12 (lH, s) Intermediate B7-Methyl 2- (5-pyrimidyl) methyl)-3-methoxyacrylate A mixture of methyl 3- (5-pyrimidyl) propionate (13.1g) and methyl formate (7.1ml) dissolved in dry dimethoxyethane (20ml) was added portionwise to a suspension of sodium hydride (60%, 4.0g) in DME (10ml) under argon. Reaction initiated rapidly and was stirred for a further 2h, diluted with dry diethyl ether (50ml) and filtered. The solid so separated was washed with further diethyl ether (50ml) and was dried in vacuo to give a solid that was dissolved in dry dimethyl formamide (50ml) and potassium carbonate (11.3g) added under argon. A solution of dimethyl sulfate (7.0ml) was then added over 1 hour. The mixture was stirred for 18h and the solvent removed in vacuo. The residue was partitioned between ethyl acetate (200ml) and water (100ml). The aqueous layer was re-extracted with ethyl acetate (2 x 100ml) and the combined ethyl acetate layers washed with brine (50ml) and dried over sodium sulfate. The solvent was removed in vacuo to give methyl 2 ( (5-pyrimidyl) methyl)-3-methoxyacrylate (9.1g).

Intermediate B8-2- (5-Pyrimidyl) methyl)-3-methoxyacrylic acid To methyl 2- ( (5-pyrimidyl) methyl)-3-methoxyacrylate (9. Og) was added, with stirring, a solution of sodium hydroxide (3.5g) in water (43ml) at RT under argon. After 20h, the pH of the solution was brought to 3.5 with concentrated hydrochloric acid. Sonication of

the oil so formed gave 2- ( (5-pyrimidyl) methyl)-3-methoxyacrylic acid (5.4g) as a pale yellow solid.

Intermediate B9-5- (Pyrimid-5-ylmethyl)-2-thiouracil Sodium (0.25 g) was dissolved in ethanol (5 ml), thiourea (0.77 g) added, and the mixture stirred under reflux for 1 hour. A solution of ethyl 2-formyl-3- (5-pyrimidyl) propionate (1.99 g) in ethanol (5 ml) was added slowly, and reflux continued for 18 hours. The solvent was evaporated, and the residue taken up in water and washed with dichloromethane. The aqueous solution was acidified to pH 5, and the precipitate filtered off, washed with water and dried to obtain 5- (pyrimid-5-ylmethyl)-2-thiouracil (0.71 g).

'H-NMR (d6-DMSO) 8 3.58 (2H, s), 7.54 (lH, s), 8.70 (2H, s) and 9.02 (lH, s). MPt 265- 6°C IntermediateB10-5- ((1-Benzyl-2-oxo-pyrid-4-yl)((1-Benzyl-2-oxo-pyrid-4-yl) methyl)-2-thiouracil Prepared from methyl 2- (1-benzyl-2-oxo-pyrid-4-yl) methyl)-3-hydroxyacrylate (reference 7) analogously to intermediate B9. lH-NMR (d6-DMSO) 8 5.04 (2H, s), 6.15 (lH, dd), 6.21 (lH, bs), 7.2-7.4 (5H, m), 7.45 (lH, s) and 7.67 (lH, d); (EI) M=325. Cl7Hl5N30, S requires 325.

Intermediate B11-5-((1-Methyl-2-oxo-pyrid-4-yl) methyl)-2-thiouracil Prepared from methyl 2- (1-methyl-2-oxo-pyrid-4-yl) methyl)-3-hydroxyacrylate (reference 7) analogously to intermediate B9. IH-NMR (CD30D) 6 3.50,3.51 (5H, 2xs), 6.32 (lH, dd), 6.40 (lH, bs), 7.35 (lH, s) and 7.54 (1H. d).

Intermediate 5-((2,3-Dimethylpyrid-5-yl)methyl)-2-thiouracil- Prepared analogously to intermediate B9. IH-NMR (d6-DMSO) # 2.19 (3H, s), 2.35 (3H, s), 7.36 (2H, m) and 8.13 (lH, bs)

Intermediate B13-5- (Fur-2-ylmethyl)-2-thiouracil Prepared analogously to intermediate B9. IH-NMR (d6-DMSO) 8 3.58 (2H, s), 6.11 (1H, m), 6.35 (1H, m), 7.27 (lH, s), 7.52 (1H, m), 12 41 (2H, br. m). Mpt 205-7°C (dec) Intermediate B14-5- (Pyrazin-2-ylmethyl)-2-thiouracil Prepared from methyl 3- (2-pyrazinyl) propionate (reference 10) analogously to intermediate B9. lH-NMR (d6-DMSO) 8 3.77 (2H. s), 7.48 (1H, s), 8.46 (lH, d), 8.51 (IH. t) and 8.59 (1H, d). Mpt 265-7°C (dec) Intermediate B15-5- (Fur-3-ylmethyl)-2-thiouracil Prepared from methyl 3- (3-furyl) propionate (reference 9) analogously to intermediate B9.

IH-NMR (d6-DMSO) 8 3.33 (2H, s), 6.38 (1H, m), 7.19 (1H, s), 7.47 (1H, m), 7.56 (1H, m). Mpt 197-9°C (dec) Intermediate B16-5- (Quinolin-3-ylmethyl)-2-thiouracil Prepared analogously to intermediate B9. IH-NMR (d6-DMSO) 8 3.77 (2H, s), 7.54 (2H, m), 7.71 (1 H, m), 7.94 (2H, m), 8.14 (1H,m), 8.84 (1H,m) Mpt 274-9°C -5-(2-(Pyrid-4-yl)ethyl)-2-thiouracilIntermediateB17 Prepared analogously to intermediate B9. IH-NMR (d6-DMSO) # 2.53 (2H, t), 2.77 (2H, t), 7.20 (3H, m) and 8.45 (2H, m). MPt 265-7°C (dec) Intermediate 5-*Pyrid-2-ylmethyl)-2-thiouracil- Prepared as in reference 2.

Intermediate B19-5- (Pyrid-3-ylmethyl)-2-thiouracil Prepared as in reference 11.

Intermediate B20-5- (Pyrid-4-ylmethyl)-2-thiouracil

Prepared analogously to intermediate B9. 'H-NMR (d6-DMSO) 8 3.57 (2H, s), 7.25 (2H, m), 7.47 (1 H, s), 8.44 (2H, m), 12.43 (2H, br. m) Mpt >250°C Intermediate B21-5-((2-Methylpyrid-5-yl) methyl)-2-thiouracil Prepared as in reference 5.

Intermediate B22-5- (Thiazol-2-ylmethyl)-2-thiouracil

Prepared as in reference 2.

Intermediate B23-5-Benzyl-2-thiouracil Prepared as in reference 6.

Intermediate B24-5- (Pyrid-3-ylmethyl)-2- (nitroamino) pyrimidin-4-one Prepared as in reference 4.

Intermediate B25-5-(2-Methoxypyrid-4-ylmethyl)-2-(nitroamino) pyrimidin-4-one Prepared as in reference 3.

Intermediate B26-5- (4-Methoxypyrid-2-ylmethyl)-2- (nitroamino) pyrimidin-4-one Prepared as in reference 4.

Intermediate B27-5- ( (1-Butyl-2-oxo-pyrid-4-yl) methyl)-2- (nitroamino) pyrimidin- 4-one Prepared as in reference 7.

Intermediate B28-S- ( (1-Oxo-2-methylpyrid-5-yl) methyl)-2- (nitroamino) pyrimidin-4-one Prepared as in reference 3. Intermediate B29-5- ((2,4-Dimethylpyrid-5-yl) methyl)-2- (nitroamino) pyrimidin-4- one

Prepared as in reference 8.

Intermediate B30-3- (1-Methylpyrazol-4-yl) acrylic acid A mixture of 1-methylpyrazole-4-carboxaldehyde (made as in reference 15) (18.1 g), malonic acid (17.1 g), pyridine (15 ml) and piperidine (0.2 ml) was heated to 100°C for 1 hour. After cooling, water was added, followed by aqueous ammonia to obtain a clear solution, which was acidified to pH5 with hydrochloric acid. The resulting solid was filtered off. washed with water and dried to obtain 3- (1-methylpyrazol-4-yl) acrylic acid (18.9 g). IH-NMR (d6-DMSO) õ 3.83 (3H, s), 6.18 (lH, d), 7.44 (lH, d), 7.83 (lH, s), 8.07 (IH. s). (APCI) M+H=153. C7HgN202 requires 152.

Intermediate B31-Methyl 3- (1-methylpyrazol-4-yl) acrylate 3- (l-Methylpyrazol-4-yl) acrylic acid (18.86 g) was added to a solution of sulphuric acid (15 ml) in methanol (150 ml), and the mixture refluxed for 2 hours, cooled, and poured onto ice. The acid was neutralised with solid sodium carbonate and the product extracted into dichloromethane, which was dried and evaporated. Crystallisation from ether/petrol gave methyl 3- (1-methylpyrazol-4-yl) acrylate (16.0 g). IH-NMR (d6-DMSO) 5 3.77 (3H, s), 3.91 (3H, s), 6.16 (lH, d), 7.54 (lH, s), 7.56 (lH, d), 7.69 (lH, s). (APCI) requires166.M+H=167.C8H10N2O2

Intermediate B32-Methyl 3- (I-methylpyrazol-4-yl) propionate Prepared analogously to intermediate B6. IH-NMR (d6-DMSO) 8 2.56 (2H, t), 2.79 (2H, t), 3.67 (3H, s), 3.85 (3H, s), 7.17 (lH, s), 7.31 (3H, s). (APCI) M+H=169. C8H, 2N202 requires 168.

Intermediate B33-Methyl 2-formyl-3- (I-methylpyrazol-4-yl) propionate, sodium salt Sodium hydride (2.62 g, 60% in oil) was washed with petrol and suspended in dry dimethoxyethane (20 ml). Methyl 3- (1-methylpyrazol-4-yl) propionate (8.8 g) and methyl formate (4.87 ml) were dissolved in DME (20 ml), and a few drops of the mixture added to the sodium hydride suspension, which was warmed briefly to initiate the reaction before continuing dropwise addition at a rate which sustained controlled evolution of hydrogen. The mixture was stirred for a further 16 hours at room temperature, then diluted with ether. The solid was filtered off, washed with ether and immediately dried, and was used promptly without further purification.

Intermediate B34-5-((1-Methylpyrazol-4-yl) methyl)-2-thiouracil Prepared analogously to intermediate B9, except using the preformed sodium salt instead of adding sodium ethoxide. IH-NMR (d6-DMSO) õ 3.33 (3H, s), 3.75 (3H, s), 7.15 (lH, s), 7.23 (IH. s), 7.46 (IH, s), 12.2 (1H. br s), 12.4 (lH, br s). (APCI) M+H=223. C9H, oN40S requires 222.

Intermediate B35-Ethyl 3- (2-methoxypyrimidin-5-yl) acrylate A mixture of 2-methoxy-5-bromopyrimidine (75.43 g, 0.399 mol), ethyl acrylate (47.5 ml, 0.439 mol), palladium (II) acetate (1.07 g, 0.0048 mol), tri-o-tolylphosphine (2.92 g, 0.0096 mol) and triethylamine (84 ml) were heated at 135°C with stirring under argon for 12 h. After allowing to cool the solid mass was dissolved in water and ethyl acetate, filtered, and the aqueous phase separated and further extracted with ethyl acetate. The combined extracts were washed with saturated aqueous ammonium chloride, dried (MgSO4) and evaporated. The solid thus obtained was triturated with ether/light petrol (1: 3,350 ml), filtered, washed and dried, yield 52.41, (63%). IH-NMR (CDC13) 6 1.33

(3H, t), 4.06 (3H, s), 4.28 (2H, q), 6.45 (1H, d), 7.58 (1H, d), 8.67 (2H, s); MS (APCI+) found (M+H) = 209; C I OH I 2N203 requires 208.

Intermediate B36-Ethyl 3- (2-methoxypyrimidin-5-yl) propionate A suspension of ethyl 3- (2-methoxypyrimidin-5-yl) acrylate (52.4 g, 0.252 mol) in ethanol (400 ml) and triethylamine (50 ml) was treated with 10% palladium on carbon (3 g) and hydrogenated at 50 psi for 1.75 h. The catalyst was filtered off through hyflo and the filtrate evaporated. The residue was dissolved in dichloromethane, washed twice with saturated aqueous ammonium chloride, dried (MgS04) and evaporated to an oil, yield 41.2 g (78%). IH-NMR (CDC13) õ 1.23 (3H, t), 2.61 (2H, t), 2.87 (2H, t), 3.99 (3H, s), 4.13 (2H, q), 8.39 (2H, s); MS (APCI+) found (M+H) = 211; CloHI4N203 requires 210.

Intermediate B37-2- (Methoxymethylene)-3- (2-methoxypyrimidin-5-yl) propionic acid, mixed methyl/ethyl esters To a stirring suspension of sodium hydride (0.83 g of a 60% dispersion in oil) in anhydrous 1,2-dimethoxyethane (6 ml) was added dropwise a solution of methyl formate (1.54 ml) and ethyl 3- (2-methoxypyrimid-5-yl) propionate (3.5 g) in anhydrous 1,2- dimethoxyethane (6 ml) at such a rate as to maintain the reaction temperature at 25-30°C.

After 1 h, ether was added and the precipitated oil allowed to settle. The solution was decanted off and replaced with fresh ether, and the oil slowly solidified. The solid 2- (hydroxymethylene) derivative was filtered, washed and dried, yield 3.8 g. A 1.33 g portion was suspended in dimethyl formamide (10 ml) together with anhydrous potassium carbonate (1.15 g), and a solution of dimethyl sulphate (0.48 ml) in dimethylformamide (10 ml) was added dropwise with stirring over 30 min. After 16 h the solvent was evaporated and the residue treated with water and extracted with ethyl acetate. The extracts were washed with water, dried (MgSO4) and evaporated to give the product as an oil, yield 0.91 g. lH-NMR (CDCI3) õ 1.23 (3H, t), 3.46 (2H, s), 3.69 (3H, s, methyl ester), 3.88 (3H. s), 3.97 (3H, s), 4.16 (2H, q), 7.39 (1H, s), 8.40 (2H, s). 3: 2 ratio of methyl : ethyl esters. MS (APCI+) found (M+1) = 253,239 (ethyl and methyl esters); C12Hl6N204 requires 252. Ci lHI4N204 requires 238.

Intermediate B38-2- (Methoxymethylene)-3- (2-methoxypyrimidin-5-yl) propionic acid A suspension of the mixed esters of intermediate 5 (0. 9 g) in 2M aqueous sodium hydroxide (3.6 ml) was stirred at ambient temperature for 16 h to give a clear solution.

This was diluted with water, extracted with dichloromethane and evaporated to about half volume, then acidified to pH 3-4 (2M hydrochloric acid) when the product crystallised out. The white solid was filtered, washed with ice-cold water and dried, yield 0.46 g. IH- NMR (CDC13) b 3.43 (2H, s), 3.91 (3H, s), 3.99 (3H, s,), 7.49 (1H, s), 8.42 (2H, s); MS (APCI+) found (M+1) = 225, CloH12N204 requires 224.

Intermediate B39-5- (2-Methoxypyrimidin-5-ylmethyl)-2-thiouracil To an ice cooled solution of potassium t-butoxide (7.83 g, 0.07 mol) in anhydrous THF (60 ml) was added dropwise with stirring under argon over 1 hour to a solution of ethyl 3- (2-methoxypyrimidin-5-yl) propionate (5.87 g, 0.028 mol) and methyl formate (3.6 ml, 0.059 mol) in anhydrous ether (70 ml). After stirring for 16 h, the solvents were evaporated, thiourea (4.25 g, 0.056 mol) and propan-2-ol (80 ml) added and the mixture refluxed for 5 h. The solvent was evaporated and the residue dissolved in water, extracted twice with ether and acidified to pH 4.5 with acetic acid. The solid which precipitated was filtered, washed well with water and dried, yield 5.57 g (80%). lH-NMR (d6- DMSO) 5 3.47 (2H, s), 3.85 (3H, s), 7.43 (1H, s), 8.48 (2H, s), 12.25 (1H, br s), 12.46 (1H, br s); MS (APCI+) found (M+H) = 251; CloHloNaO ? S requires 250.

Intermediate B40-5- (2-Benzyloxypyrimid-5-ylmethyl)-2-thiouracil

To a solution of benzyl alcohol (20ml) in dry dimethylformamide (20ml) was added sodium hydride ( (60% in oil) 2.3g) over 0.5h under argon. A slurry of 2- methoxypyrimidyl thiouracil (3.6g) in dry dimethylformamide (10ml) was added in one portion and the solution heated to 80°C for 2.5h. After cooling, the solvent was removed under reduced pressure and the residue partitioned between diethyl ether and water. The aqueous layer was washed with further diethyl ether and then acidified to pH4 with glacial acetic acid. The solid so formed was filtered, washed with water and diethyl ether and dried in vacuo to give the desired material. IH-NMR (d6-DMSO) 8 3.49 (2H, s), 5.36 (2H, s), 7.2-7.5 (6H, m), 8.50 (2H, s); MS (APCI+) found (M+l) = 327; Cl6Hl4N402S requires 326.

Intermediate B41-Methyl 2-benzyl-3-methoxyacrylate Prepared analogously to intermediate B7.

Intermediate B42-2-Benzyl-3-methoxyacrylic acid Prepared analogously to intermediate B8. Intermediate B43-Methyl 2- (l-methyl-2-oxo-pyrid-4-yl) methyl)-3- methoxyacrylate Prepared from methyl 3- (1-methyl-2-oxo-pyrid-4-yl) propionate (reference 7) analogously to intermediate B7.

Intermediate B44-2 Methyl-2-oxo-pyrid-4-yl) methyl)-3-methoxyacrylic acid

Prepared analogously to intermediate B8.

Intermediate B45-1-(Pyrid-2-ylmethyl)-5-(pyrimid-5-ylmethyl)-2-thiouracil 2- ( (5-pyrimidyl) methyl)-3-methoxyacrylic acid (5.5g) was slurried in dry dichloromethane (100ml) and oxalyl chloride (4.3ml) added over 5min. After stirring at RT for 3h, the solvent was removed in vacuo and the residue triturated with toluene. The solvent was removed in vacuo to give a solid that was slurried in dry acetonitrile (100ml) under Ar. Dried powdered potassium thiocyanate (3.25g) was added in one portion at RT and the mixture was stirred for 15h. Removal of the solvent in vacuo gave a solid that was slurried with dry dimethylformamide (90ml). One ninth of the slurry was added to triethylamine (0.42ml) and 2-pyridylmethylamine (0.49g). The mixture was stirred for 19h under argon and a solution of sodium ethoxide (3M) in ethanol (1.5ml) was added in one portion. The mixture was heated on an oil bath (bath temp 101°C) for 2h, cooled and the solvent removed under reduced pressure. The residue was dissolved in water (12ml) and brought to pH 4 with glacial acetic acid. The solid so formed was filtered and dried in vacuo to give 1- (pyrid-2-ylmethyl)-5- (pyrimid-5-ylmethyl)-2-thiouracil (0.69g). lH- NMR (d6-DMSO) 8 3.63 (2H, s), 5.47 (2H, s), 7.2-7.4 (2H, m), 7.7-7.85 (lH, m), 8.04 (1H. s), 8.5 (lH, m), 8.7 (2H. s) and 9.04 (1H*s) ; (APCI) M+H=312. C15Hl3N50S requires 311.

Intermediate B46-1- (4-Hydroxycyclohexyl)-5- (pyrimid-5-ylmethyl)-2-thiouracil

Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) 8 1.0-2.0 (8H, m), 3.63 (2H, s), 8.10 (lH, s), 8.72 (2H, s) and 9.02 (lH, s); (ES-) Found (M-1) =317.

318.C15H18N4O2Srequires Intermediate B47-1- (3- (1-Imidazolyl) prop-1-yl)-5- (pyrimid-5-ylmethyl)-2- thiouracil Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) 8 2.22 (2H, m), 3.58 (2H, s), 4.13 (4H, m), 7.12 (1H, m), 7.36 (1H, m), 7.88 (1H, s), 8.08 (1H, s), 8.73 (2H, s), 9.05 (1H, s), 12.68 (1H, br s); (APCI+) Found (M+1) =329. C15Hl6N60S requires 328 Intermediate B48-1- (3- (1-Morpholino) prop-1-yl)-5- (pyrimid-5-ylmethyl)-2- thiouracil Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) õ 2.35-2.6 (6H+d5- DMSO. m), 3.4-3.8 (6H+HOD, m), 4.19 (2H, t), 7.96 (1H, s), 8.74 (2H, s) and 9.04); (APCI+) Found (M+1) =348. C16H21N5O2S requires 347.

Intermediate B49-1- (3- (2-Oxo-l-pyrrolidino) prop-1-yl)-5- (pyrimid-5-ylmethyl)-2- thiouracil Prepared analogously to intermediate B45. 1H-NMR (d6-DMSO) # 1. 91 (4H, m), 2.20 (2H, t), 3.24 (2H, t), 3.37 (2H, t), 3.58 (2H, s), 4.09 (2H, t), 7.97 (1H, s), 8.74 (2H, s), 9.04 (lH, s); (APCI+) Found (M+l) =346. C16H19N5O2S requires 345 Intermediate B50-1- (3-Ethoxycarbonylprop-1-yl)-5- (pyrimid-5-ylmethyl)-2- thiouracil

Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) 8 1.17 (1H, t), 1.98 (2H, m), 2.34 (2H. t), 3.59 (2H, s), 4.04 (2H, q), 4.16 (2H, t), 7.90 (lH, s), 8.75 (2H, s) and 9.03 (lH, s); (ES+) Found (M+1) =335. C15H18N4O3S requires 334.

Intermediate B51-1- (3-Dimethylaminoprop-1-yl)-5- (pyrimid-5-ylmethyl)-2- thiouracil Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) õ 2.21 (6H, s), 3.60 (2H, s), 4.15 (2H, t), 7.91 (lH, s), 8.72 (2H, s), 9.03 (lH, s); (APCI+) Found (M+1) =306.

C14H19N5O2 S requires 305.

Intermediate B52-1- (3-Hydroxyprop-1-yl)-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) õ 1.85 (2H, m), 3.45 (2H, b). 3.61 (2H, s), 4.19 (2H, t). 4.65 (lH, bs), 7.85-8.0 (2H, m), 8.71 (2H, s) and 9.04 (lH. s); (APCI) M+H=279. Cl, H14N4O2S requires 278.

Intermediate B53-1- (3-Hydroxvprop-l-vl)-5-benzyl-2-thiouracil Prepared analogously to intermediate B45. lH-NMR (d6-DMSO) õ 1.85 (2H, m), 3.46 (2H. m), 3.56 (2H, s), 4.19 (2H, t), 4.65 (1H, t), 7.1-7.4 (5H, m) and 7.81 (1H, s); (FAB) requires276.M+H=277.C14H16N2O2S Intermediate B54-1- (3-Methoxyprop-1-yl)-5- (pyrimid-5-ylmethyl)-2-thiouracil

Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) 6 1.94 (2H, m), 3.21 (3H, s), 8.55 (2H, s), 4.20 (2H, t), 7.88 (1H, s), 8.72 (2H, s) and 9.03 (1H, s); (ES-) Found (M-1) =291. Cl9H22BrCINO,, S requires 292.

Intermediate B55-1- (3-Phenylprop-1-yl)-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. 'H-NMR (d6-DMSO) 6 2.04 (2H, m), 2.63 (2H, t), 3.58 (2H. s), 4.18 (2H, t), 7.1-7.35 (5H, m), 7.92 (lH, s), 8.72 (2H, s) and 9.03 (lH, s); (APCI+) Found (M+1) =339. Cl8Hl8N40S requires 338.

Intermediate B56-1- (5-Hydroxypent-1-yl)-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) õ (HOAc salt) 1.79 (3H, s), 3.59 (2H, s), 4.13 (2H, t), 7.96 (1H, s), 8.72 (2H, s) and 9.02 (1H, s); (APCI+) Found (M+1) =307. Ci4HigN402S requires 306.

Intermediate 1-(pyrid-2-ylmethyl)-5-benzyl-2-thiouracil- Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) 8 3.59 (2H, s), 5.49 (2H, s), 7.1-7.45 (7H, m), 7.79 (1H, m), 7.95 (1H, s) and 8.51 (1H, m); MPt 171-4°C ; (EI) M=309. C17H15N3OS requires 309.

Intermediate B58-1-(Pyrid-3-ylmethyl)-5-((1-methyl-2-oxo-pyrid-4-yl) methyl)-2- thiouracil Prepared analogously to intermediate B45. 'H-NMR (d6-DMSO) b 3.11 (3H, s), 3.15 (2H, s), 5.21 (2H, s), 5.86 (1H, m), 5.95 (1H, m), 7.15 (1H, m), 7.34 (1H, m), 7.52 (1H,

m), 7.80 (1H, s), 8.26 (1H, m), 8.34 (1H, m), 12.55 (1H, br. s); (APCI+) Found (M+1) = 341. C17H16N4O2S requires 340 Intermediate B59-1- (Pyrid-3-ylmethyl)-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. 'H-NMR (d6-DMSO) 8 3.49 (2H, s), 5.33 (2H, s), 7.28 (1H, m), 7.64 (1H,m), 7.97 (1H, s), 8.42 (2H, m), 8.59 (2H, s), 8.88 (1H, m), 12.70 (1H, br. s) Mpt >250°C Intermediate B60-1- (Pyrid-3-ylmethyl)-5-benzyl-2-thiouracil Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) 8 3.57 (2H, s), 5.46 (2H, s), 7.1-7.35 (5H,m), 7.40 (1H, m), 7.75 (1H, s), 8.02 (lH, s), 8.51 (lH, m) and 8.59 (1H, m). MPt 236-8°C; (EI) M=309. Cl7Hl5N30S requires 309.

Intermediate B61-1-(Pyrid-4-ylmethyl)-5-((1-methyl-2-oxo-pyrid-4-yl) methyl)-2- thiouracil Prepared analogously to intermediate B45. 1H-NMR (d6-DMSO) # 3.39 (3H, s), 5.45 (2H, s), 6.11 (lH, dd), 6.21 (1H. m), 7.25 (2H. m), 7.58 (lH, d), 7.96 (lH, s) and 8.54 (2H, m). MPt 181-3°C; (EI) M=340. Cl7Hl6N40, S requires 340.

Intermediate 1-(Pyrid-4-ylmethyl)-5-(pyrimid-5-ylmethyl)-2-thiouracil- Prepared analogously to intermediate B45. 'H-NMR (d6-DMSO) 8 3.64 (2H, s), 5.45 (2H, s), 7.28 (2H, m), 8.00 (1H, s), 8.55 (2H, m), 8.73 (2H, m), 9.05 (1H, m), 12.85 (1H, Mpt>250°Cbrs)

Intermediate1-(Pyrid-4-ylmethyl)-5-benzyl-2-thiouracil- Prepared analogously to intermediate B45. 'H-NMR (d6-DMSO) 8 3.58 (2H, s), 5.46 (2H, s), 7.1-7.4 (7H, m), 7.93 (1H, s) and 8.54 (2H, m); MPt 174-6°C; (EI) M=309.

C17Hl5N30S requires 309.

Intermediate 1-(Pyrid-4-ylmethyl)-2-thiouracil- Prepared from 3-methoxyacrylic acid, analogously to intermediate B45. IH-NMR (d6- DMSO) 5 5.45 (2H, s), 6.03 (2H, d), 7.23 (2H, m), 7.94 (2H, d) and 8.54 (2H, m); MPt 267- 70°C; (EI) M=219. CloH9N30S requires 219.

Intermediate B65-1-(2-(Pyrid-2-yl) ethyl)-5-(pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) õ 3.22 (2H, t), 3.51 (2H, s), 4.51 (2H, t), 7.25 (2H, m), 7.7 (2H, m), 8.47 (1H,m), 8.61 (2H, s) and 9.03 (1H, s); (APCI+) Found (M+l) =326. C16H15N5OS requires 325.

Intermediate B66-1-(2-(Pyrid-3-yl) ethyl)-5-((1-methyl-2-oxo-pyrid-4-yl) methyl)-2- thiouracil Prepared analogously to intermediate B45. 1H-NMR (d6-DMSO) # 3.08 (2H, t), 3.29 (2H, s), 3.37 (3H, s), 4.38 (2H, t), 5.96 (1H, m), 6.13 (1H, m), 7.34 (1H, m), 7.60 (1H, m), 7.67 (1H, m), 7.71 (lH, s), 8.46 (2H, m), 12.73 (1H, br. s); (APCI+) Found (M+l) = 355. Cl8Hl8N40S requires 354

Intermediate B67-1- (2- (Pyrid-3-yl) ethyl)-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. 1H-NMR (d6-DMSO) 8 3.08 (2H, t), 3.53 (2H, s), 4.36 (2H, t), 7.3 (1H, m), 7.65 (lH, m), 7.78 (lH, s), 8.45 (2H, bs), 8.65 (2H, s) and 9.05 (1H, s); (APCI+) Found (M+l) =326. C16H15N5OS requires 325.

Intermediate B68-1-(2-(Pyrid-4-yl) ethyl)-5-((1-methyl-2-oxo-pyrid-4-yl) methyl)-2- thiouracil Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) 8 3.07 (2H, t), 3.30 (2H, s), 3.37 (3H, s), 4.39 (2H, t), 5.94 (1H, m), 6.15 (1H, m), 7.27 (2H, m), 7.56 (1H, m), 7.72 (1H, s), 8.48 (2H, m), 12.72 (1H, br. s); (APCI+) Found (M+1) = 355.

354C18H18N4O2Srequires Intermediate B69-1-(2-(Pyrid-4-yl) ethyl)-5-(pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) õ 3.16 (2H, t), 3.54 (2H, s), 4.45 (2H, t), 7.48 (2H. d), 7.82 (1H, s), 8.60 (2H, d), 8.67 (2H, s) and 9.05 (1H, s); (ES+) Found (M+l) =326. Cl6HlsN50S requires 325.

Intermediate B70-1-(2-Phenylethyl)-5-((1-methyl-2-oxo-pyrid-4-yl) methyl)-2- thiouracil

Prepared analogously to intermediate B45. 'H-NMR (d6-DMSO) 8 3.04 (2H, t), 3.27 (3H, s), 4.35 (2H, t), 5.93 (1H, m), 6.12 (lH, bs), 7.1-7.45 (5H, m), 7.56 (1H, d) and 7.67 (1H, s); MPt 230-3°C; (APCI) M+H=354. C19H19N3O2S requires 353.

Intermediate B71-Benzyl-5-((1-methyl-2-oxo-pyrid-4-yl) methyl)-2-thiouracil Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) 8 3.38 (s), 5.44 (2H, s), 6.07 (1H, m), 6.18 (1H, m), 7.1-7.5 (5H, m), 7.57 (1H, d) and 7.96 (lH, s). (EI) M=339.

CigHi7N302S requires 339.

Intermediate B72-1,5-Dibenzyl-2-thiouracil Prepared analogously to intermediate B45. IH-NMR (CDC13) 8 3.63 (2H, s), 5.35 (2H, s), 6.84 (1H, s) and 7.05-7.45 (10H, m). MPt 151-2°C; (EI) M=308. C18H16N2OS requires 308.

Intermediate B73-1-(2-Thienylmethyl)-5-(pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. 'H-NMR (d6-DMSO) 8 3.60 (2H, s), 5.58 (2H, s), 7.03 (1 H, m), 7.26 (1H, m), 7; 50 (1H, m), 8.08 (1H, s), 8.69 (2H, s), 9.04 (1 H, s), 12.18 (lH, br s) (APCI+) Found (M+l) =317. Cl4Hl2N40S2 requires 316 Intermediate 1-(2,2-Dimethylprop-1-yl)-5-(pyrimid-5-ylmethyl)-2-thoiuraci l- Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) õ 0.96 (9H, s), 3.62 zip s), 4.17 (2H, s), 7.77 (1H, s), 8.73 (2H, s) and 9.04 (1H, s); (APCI+) Found requires290.(M+1)=291.C14H18N4OS Intermediate B75-1- (2- (1-Piperidino) ethyl)-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. lH-NMR (d6-DMSO) õ 1.28-1.72 (6H, m), 2.50 (4H, m), 2.73 (2H, t), 3.61 (2H, s), 4.29 (2H, t), 7.80 (1H, s), 8.73 (2H, s), 9.05 (1H, s), 12.71 (1H, br s); (APCI+) Found (M+1) =332. C16HZ1NSOS requires 331 Intermediate B76-1- (2-Acetylaminoethyl)-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. 'H-NMR (d6-DMSO) 8 1.75 (3H, s), 3.43 (2H, m), 3.61 (2H, s), 4.18 (2H, t), 7.78 (1H, s), 8.03 (1H, bt), 8.73 (2H, s) and 9.03 (1H, s); (ES+) Found requires305.C13H15N5O2S

Intermediate1-(2-Hydroxyethyl)-5-(pyrimid-5-ylmethyl)-2-thio uracil- Prepared analogously to intermediate B45. 'H-NMR (d6-DMSO) 6 3.60 (2H, s), 3.72 (2H, bq), 4.21 (2H, t), 4.99 (1H, t), 7.83 (1H, s), 8.73 (2H, s) and 9.03 (1H.s) ; (ES+) Found requires264.(M+1)=265.C11H12IN4O2 Intermediate B78-1- (2-Hydroxyethyl)-5-benzyl-2-thiouracil Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) õ 3.55 (2H, s), 3.71 (2H, bm), 4.20 (2H, t), 4.99 (lH. bs), 7.1-7.45 (5H, m) and 7.70 (1H, s); MPt 171-3°C; (FAB) M+H=263. C13H14N2O2 requires 262.

Intermediate B79-1-Dimethylaminocarbonylmethyl-5-(pyrimid-5-ylmethyl)-2- thiouracil Prepared analogously to intermediate B45. 'H-NMR (d6-DMSO) 8 2.86 (3H, s), 3.02 (3H, s), 3.61 (2H, s), 5.09 (2H, s), 7.76 (1H, s), 8.71 (2H, s), 9.05 (1H, s); (APCI+) Found (M+l) =306. Cl3Hl5N50, S requires 305 Intermediate 1-Ethoxycarbonylmethyl-5-(pyrimid-5-ylmethyl)-2-thiouracil- Prepared analogously to intermediate B45. 'H-NMR (d6-DMSO) 8 1.19 (3H, t), 3.62 (2H, s), 4.16 (2H, q), 4.94 (2H, s), 7.88 (1H, s), 8.73 (2H, s), 9.06 (1H, s); (APCI+) Found (M+1) =307. C13H14N4O3S requires 306 Intermediate B81-1-(Fur-2-ylmethyl)-5-(pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. lH-NMR (d6-DMSO) õ 3.62 (2H, s), 5.43 (2H, s), 6.47 (2H, m), 7.66 (1H, m), 7.98 (1H, s), 8.70 (2H, s), 9.04 (1H, s), 12.75 (1H, br s); (APCI+) Found (M+1)=301. C14H12N4O2S requires 300 Intermediate 1-(Fur-2-ylmethyl)-5-benzyl-2-thiouracil- Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) 8 3.57 (2H, s), 5.43 (2H. s), 6.45 (2H, s), 7.1-7.4 (5H, m), 7.66 (lH, m) and 7.85 (lH, s); MPt 153-5°C; (FAB) M+H=299. 298.requires Intermediate B83-1-Methyl-5-((1-methyl-2-oxo-pyrid-4-yl) methyl)-2-thiouracil

Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) 8 3.57 (3H, s), 6.12 (1H, m), 6.20 (lH, bs), 7.57 (lH, d) and 7.87 (lH, s); (EI) M=263. C12H13N3O2S requires 263.

Intermediate B84-1-Methyl-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) õ 3.33 (3H, s), 7.93 (1H, s) 8.73 (2H, s) and 9.02 (lH, s); (APCI) M+H=235. C10H10N4OS requires 234.

Intermediate B85-1-Methyl-5-benzyl-2-thiouracil Prepared analogously to intermediate B45. 'H-NMR (CDCy § 3.55 (2H, s), 3.57 (3H, s), 7.1-7.4 (5H, m) and 7.84 (1H, s); MPt 143-6°C; (EI) M=232. C12H12N2OS requires 232.

Intermediate B86-1-Phenyl-5-((1-methyl-2-oxo-pyrid-4-yl) methyl)-2-thiouracil Prepared analogously to intermediate B45. IH-NMR (CDC13) 6 3.51 (3H + MeOH, s), 6.16 (1H. m), 6.48 (1H. m), 7.1-7.45 (4H. m) and 7.45-7.65 (3H. m); (EI) M=325; 325.C17H15N3O2Srequires Intermediate B87-1-(2-Methoxyethyl)-5-(pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. 'H-NMR (CDC) § 3.26 (3H, s), 3.60 (2H, s), 3.65 (2H, t), 4.33 (2H.t), 7.83 (IH. s), 8.70 (2H, s), 9.04 (lH, s) ; (ES+) M+H=279; CIHl4N40, S requires 278.

Intermediate 1-(2-Methylprop-1-yl)-5-(pyrimid-5-ylmethyl)-2-thiourcil-

Prepared analogously to intermediate B45. (APCI) M-H=275. C13Hl6N40S requires 276.

Intermediate B89-1-Ethyl-5-(pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) õ 1.23 (3H, t), 3.60 (2H, s), 4.19 (2H, q), 7.95 (lH, s) 8.73 (2H, s) and 9.04 (1H, s); (APCI) M-H=247.

CI lHl2N40S requires 248.

Intermediate B90-1- (8-Phenyloctyl)-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) 8 1.15-1.4 (8H, m), 1.45-1.8 (4H, m), 2.56 (2H, t), 3.6 (2H, s), 4.11 (2H, t), 7.1-7.35 (5H, m), 7.94 (lH, s), 8.73 (2H, s) and 9.02 (lH, s). (APCI) M+H=409. C23H28N4OS requires 408.

Intermediate B91-1- (9-Phenylnonyl)-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) õ 1.15-1.4 (8H,m). 1.45- 1.8 (4H, m), 2.55 (2H, t), 3.58 (2H, s), 4.12 (2H. t), 7.1-7.35 (5H, m), 7.95 (1H, s), 8.72 (2H, s) and 9.02 (1H. s). (APCI) M+H=421. C-. requires 422.

Intermediate B92-1-Undecyl-5- (2-ethoxypyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. iH-NMR (d6 DMSO) 5 0.8-0.95 (3H, m), 1.05-1.5 (19H, m), 1.6-1.8 (2H, m), 3.49 (2H, s), 4.11 (2H, t), 4.31 (2H, q), 8.48 (2H, s); MS (APCI+) found (M+l) = 418; C22H34N4O2S requires 417.

Intermediate B93-1- (2-Phenylethyl)-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. Solid. IH-NMR (DMSO) 6 3.00-3.10 (2H, t), 3.50 (2H, s), 4.29-4.40 (2H, t), 7.10-7.33 (5H, m), 7.71 (1H, s), 8.68 (2H, s), 9.00 (1H, s), 12.62-12.75 (1H, br. s); MS (APCI-) found (M-1) = 323; C17H16N40S requires 324.

Intermediate B94-1-Benzyl-5-(pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. Solid. lH-NMR (DMSO) 8 3.57 (2H, s), 4.46 (2H, s), 7.10-7.44 (6H, m), 7.91 (1H, s), 8.69 (2H, s), 9.01 (1H, s); MS (APCI+) found requires310.(M+1)=311;C16H14N4OS Intermediate B95-1-Undecyl-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. Solid. lH-NMR (DMSO) 8 0.79-0.93 (3H, t), 1.12-1.44 (16H, m), 1.60-1.79 (2H, t), 3.59 (2H, s), 4.05-4.20 (2H, t), 7.96 (1H, s), 8.70 (2H. s), 9.01 (1H, s), 12.61 (lH, s) ; MS (APCI-) found (M-1) = 373; C2oH3oN40S requires 374.

Intermediate B96-1-Dodecyl-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. Solid. lH-NMR (DMSO) 8 0.79-0.94 (3H, t), 1.13-1.47 (18H, s), 1.60-1.80 (2H, br. t), 3.59 (2H, s), 4.06-4.20 (2H, t), 7.96 (1H, s), 8.71 (2H, s), 9.03 (1H, s); MS (ES-) found (M-1) = 387; C2lH32N40S requires 388.

Intermediate B97-1- (2- (Thien-2-yl) ethyl)-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. Solid. lH-NMR (DMSO) 8 3.17-3.47 (2H, t), 3.52 (2H, s), 4.30-4.43 (2H, t), 6.80-7.04 (2H, m), 7.27-7.40 (1H, m), 7.73 (1H, s), 8.62 (2H, s), 9.03 (1H, s) 11.97-12.5 (1H, br. s); MS (APCI-) found (M-1) = 329; ClsHl4N40S, requires 330.

Intermediate B98-1- (5-Methylfuran-2-ylmethyl)-5- (pyrimid-5-ylmethyl)-2- thiouracil Prepared analogously to intermediate B45. Solid. lH-NMR (DMSO) 5 2.24 (3H, s), 3.63 (2H, s), 5.37 (2H, s), 6.01-6.08 (1H, d), 6.30-6.38 (1H, d), 7.92 (1H, s), 8.72 (2H, s), 9.04 (1H, s) 12.73 (1H, s), MS (ES-) found (M-1) = 313; C15Hl4N402S requires 314.

Intermediate B99-1- (4-Fluorobenzyl)-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. Solid. lH-NMR (DMSO) 8 3.60 (2H, s), 5.41 (2H, s), 7.13-7.25 (2H, m), 7.35-7.47 (2H, m), 8.02 (1H, s), 8.70 (2H, s), 9.03 (1H, s), 12.78 (lH, s) ; MS found (M-1) = 327; C6Hl3FN40S requires 328.

Intermediate B100-1-(2-(2-Chlorophenyl) ethyl)-5-(Pyrimid-5-ylmethyl)-2- thiouracil Prepared analogously to intermediate B45. Solid. lH-NMR (DMSO) 8 3.12-3.22 (2H, t), 3.49 (2H, s), 4.34-4.46 (2H, t), 7.14-7.43 (4H, m), 7.52 (1H, s), 8.57 (2H, s), 9.04 (1H, s), 11.40-11.85 (1H, br. s); MS (APCI-) found (M-1) = 357; C17H15ClN4OS requires 358.

Intermediate B101-1- (2-Phenoxyethyl)-5- (Pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. Solid. lH-NMR (DMSO) # 3.63 (2H, s), 4.25-4.37 (2H, t), 4.50-4.60 (2H, t), 6.84-7.00 (3H, m), 7.20-7.33 (2H, t), 7.94 (1H, s), 8.71 (2H, s), 9.06 (1H, s), 12.78 (1H, s); MS (ES+) found (M+1) = 341; Cl7Hl6N402S requires 340.

Intermediate B102-1- (5-Ethoxycarbonylpent-1-yl)-5- (Pyrimid-5-ylmethyl)-2- thiouracil Prepared analogously to intermediate B45. Solid. lH-NMR (DMSO) 5 1.10-1.20 (3H, t), 1.21-1.39 (2H, m), 1.45-1.80 (4H, m), 2.22-2.38 (2H, m), 3.59 (2H, s), 3.96-4.19 (4H, m), 7.94 (1 H, s), 8.70 (2H, s), 9.03 (1 H, s), 12.12-12.35 (1H, br. s); MS (ES-) found (M-1) 361; C17H22N4O3S requires 362.

Intermediate B103-1- (l-Ethoxycarbonylethyl)-5- (pyrimid-5-ylmethyl)-2- thiouracil Prepared analogously to intermediate B45. Solid. lH-NMR (DMSO) 8 1.06-1.30 (3H, t), 1.58-1.70 (3H, d), 3.67 (2H, d), 4.02-4.27 (2H, m), 6.02-6.19 (1H, q), 8.05 (1H, s), 8.70 (2H, s), 9.03 (1H, s), 12.80 (1H, s); MS (APCI+) found (M+l) = 321; C14H16N4O3S requires 320.

Intermediate B104-1- (1-Methylethyl)-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. Solid. lH-NMR (DMSO) 8 1.26-1.45 (6H, d), 3.65 (2H, s), 5.53-5.74 (1H,m), 8.10 (1 h, s), 8.72 (2H, s), 9.02 (1 H, s), 12.60 (1H, s); MS (APCI-) found (M+l) = 261; C12H14N4OS requires 262.

Intermediate B105-1-Cyclopropyl-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. Solid. 'H-NMR (DMSO) 8 0.92-1.10 (4H, m), 3.37-3.43 (1H, m), 3.60 (2H, s), 7.89 (1H, s), 8.71 (2H, s), 9.02 (1H, s), 12.60 (1H, s); MS (APCI-) found (M-1) = 259; C12Hl2N40S requires 260.

Intermediate B106-1- (1-Ethoxycarbonylcycloprop-1-yl)-5- (pyrimid-5-ylmethyl)- 2-thiouracil Prepared analogously to intermediate B45. Solid. 1H-NMR (DMSO) 8 1.05-1.20 (3H, t), 1.40-1.95 (4H, m), 3.61 (2H, s), 4.02-4.18 (2H, q), 7.98 (1H, s), 8.72 (2H, s), 9.04 (1H, s), 12.04 (1H, s); MS (APCI+) found (M+1) = 333; C15Hl6N40S requires 332.

Intermediate B107-1- (4-Ethoxycarbonylbenzyl)-5- (pyrimid-5-ylmethyl)-2- thiouracil Prepared analogously to intermediate B45. Solid. lH-NMR (DMSO) 5 1.23-1.38 (3H, t), 3.60 (2H, s), 4.24-4.40 (2H, q), 5.50 (2H, s), 7.35-7.47 (2H, m), 7.86-8.00 (2H, m), 8.04 (1H, s), 8.70 (2H, s), 9.03 (1H, s), 12.07-12.40 (1H. br. s); MS (APCI-) found (M-1) = 381; Cl9Hl8N403S requires 382. <BR> <BR> <P>Intermediate B108-1- (4-Methoxycarbonylcyclohex-1-yl)-5- (pyrimid-5-ylmethyl)- 2-thiouracil Prepared analogously to intermediate B45. Solid. lH-NMR (DMSO) 8 1.32-1.92 (6H, m), 2.10-2.30 (2H, m), 2.67-2.80 (1H, m), 3.64 (3H, s), 3.69 (2H, s), 5.17-5.34 (1H, br. s), 7.87 (lH, s), 8.70 (2H, s), 9.01 (1H, s), 12.63 (1H, s) ; MS (APCI-) found (M-1) = 359; 360.C17H20N4O3Srequires

Intermediate B109-1- (2- (6- (4-Fluorophenyl) hex-1-yloxy) ethyl)-5- (pyrimid-5- ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. Solid. lH-NMR (DMSO) 5 1.14-1.60 (12H, m), 3.60 (2H, s), 3.62-3.70 (2H, t), 4.26-4.35 (2H, t), (2H, t), 7.14-7.24 (2H, m), 7.80 (1H, s), 8.70 (2H, s), 9.00 (lH, s), 12.64-12.77 (1H, br. s); MS (APCI-) found (M-1) = 441; C23H27FN402S requires 442.

Intermediate B110-1-Undecyl-5- (l-methyl-2-oxopyrid-4-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45.1H-NMR (CDCl3) 8 0.88 (3H, t), 1.26 (14H, m), 1.32 (2H, t), 1.75 (2H, m), 3.48 (2H, s), 3.52 (3H, s), 4.11 (2H, t), 6.10 (1H, m), 6.40 (1H, s), 7.08 (1H, s), 7.22 (1H, d), 9.56 (1H, bs); MS (APCI+) M+1=404, C22H33N302S requires 403. MPt 137-140°C (cream solid) Intermediate B111-1- (3-Ethoxycarbonylpropyl)-5- (1-methyl-2-oxopyrid-4- ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. tH-NMR (d6-DMSO) å 1.17 (3H, t), 1.95 (2H, m), 2.35 (2H, m), 3.34 (5H, m), 4.03 (2H, q), 4.17 (2H, m), 6.11 (1H, m), 6.20 (1H, s), 7.57 (1H, d), 7.83 (1H, s), 12.63 (1H, bs); MS (APCI+) M+1=3642, C17H"IN304S requires 363. MPt 168-170°C (cream solid).

Intermediate B112-1- (2- (4-Pent-1-ylphenyl) ethyl)-5- (pyrimid-5-ylmethyl)-2- thiouracil Prepared analogously to intermediate B45. 'H-NMR (d6-DMSO) 8 0.85 (3H, m), 1. 25 (4H, m), 1.53 (2H, m), 2.52 (2H, m), 2.99 (2H, m), 3.49 (2H, s), 4.33 (2H, m), 7.03-7.24

(4H, m) 7.71 (1H, s), 8.59 (2H, s), 9.03 (1H, s), 12.70 (1H, bs); MS (APCI+) M+1=395, C22H26N4OS requires 394. (light brown solid) <BR> <BR> Intermediate B113-1- (2- (4-Pent-2-en-1-ylphenyl) ethyl)-5- (pyrimid-5-ylmethyl)-2- thiouracil Prepared analogously to intermediate B45.1H-NMR (d6-DMSO) 8 0.89 (3H, m), 1.30- 1.60 (2H, m), 2.24 (2H, m), 3.03 (2H, m), 3.51 (2H, s), 4.35 (2H, m), 5.63 (1H, m), 6.33 (1H, s), 7.10-7.33 (4H, m), 7.76 (lH, s), 8.61 (2H, s), 9.03 (1H, s), 12.70 (1H, bs); MS (APCI+) M+1=393, C22H24N40S requires 392. (light brown solid) Intermediate B114-1- (2- (4-Bromophenyl) ethyl)-5- (pyrimid-5-ylmethyl)-2- thiouracil Prepared analogously to intermediate B45. 'H-NMR (d6-DMSO) 8 3.02 (2H, t), 3.53 (2H, s), 4.33 (2H, t), 7.22 (2H, m), 7.49 (2H, m), 7.77 (1H, s), 8.60 (2H, s), 9.02 (1H, s), 12.7 (1H, bs), MS (APCI+) M+l=403, C17Hl5BrN40S requires 402 Intermediate B115-1- (4-Bromobenzyl)-5- (pyrimid-5-ylmethyl)-2-thiouracil SB- 296961- Prepared analogously to intermediate B45. lH-NMR (d6-DMSO) õ 3.60 (2H, s), 5.39 (2H, s), 7.29 (2H, d), 7.57 (2H, d), 8.01 (1H, s), 8.70 (2H, s), 9.03 (1H, s), 12.75 (1H, bs), MS (APCI+) M+1=389, C16Hl3BrN40S requires 388

Intermediate B116-1- (2- (3-Pent-1-ylphenyl) ethyl)-5- (pyrimid-5-ylmethyl)-2- thiouracil Prepared analogously to intermediate B45. IH-NMR (CDCl3) 6 0.89 (3H, m), 1.30 (4H, m), 1.55 (2H, m), 2.53 (2H, t), 3.10 (2H, t), 3.42 (2H, s), 4.35 (2H, t), 6.49 (1H, s), 6.91- 7.22 (4H, m), 8.44 (2H, s), 9.11 (1H, s), 9.60 (1H, bs) MS (APCI+) M+1=395, C, requires 394. MPt 137.5°C (colourless solid) Intermediate 1-(2-(2-Pent-1-ylphenyl)ethyl)-5-(pyrimid-5-ylmethyl)-2-- thiouracil Prepared analogously to intermediate B45. IH-NMR (CDCl3) 8 0.88 (3H, t), 1. 28 (4H, m), 1.49 (2H, m), 2.50 (2H, t), 3.15 (2H, t), 3.42 (2H, s), 4.34 (2H, t), 6.41 (1H, s), 7.03- 7.21 (4H, m), 8.50 (2H, s), 9.12 (1H, s), 9.70 (1H, bs); MS (APCI+) M+1=395, C2, requires 394. MPt 181.6°C (pale orange solid) Intermediate B118-1- (3-Ethoxycarbonylphenyl)- 5- (pyrimid-5-ylmethyl)-2- thiouracil Prepared analogously to intermediate B45. I H NMR (CDC'3) 41 (t, 3H), 3. (t, 3H), 2H), 4.41 (q, 2H), 7.30 (s, 1H), 7.35 (m, 1H), 7.60 (m, 2H), 7.98 (m, 1H), 8.15 (d, 1H), 8.71 (s, 2H), 9.10 (s, 1H). MS (ES+) Found (M+l) = 369; C18N16N4O3S requires 368.

Intermediate B 119-1-(4-Ethoxycarbonylphenyl)-2-(4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl)-2-thiouracil

Prepared analogously to intermediate B45. 1H NMR (CDCl3) 5: 1.41 (t, 3H), 3.69 (s, 2H), 4.39 (q, 2H), 7.30 (s, 1H), 7.46 (d, 2H), 8.21 (d, 2H), 8.72 (s, 2H), 9.10 (s, 1H). MS (ES+) Found (M+1) = 369; C18H16N4O3S requires 368.

Intermediate B120-1-(5-(Ethoxycarbonyl) fur-2-yl)-2-(4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. 1H NMR (CDCl3) 8: 1.39 (t, 3H), 3.69 (s, 2H), 4.39 (q, 2H), 6.69 (d, 1H), 7.28 (d, 1H), 7.41 (s, 1H), 8.72 (s, 2H), 9.12 (s, 1H). MS (APCI+) Found (M+l) = 359; C16Hl4N404S requires 358.

Intermediate B121-1-Phenyl-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl)-2- thiouracil Prepared analogously to intermediate B45. 1H NMR (CDC13) b: 3.69 (s, 2H), 7.30 (m, 3H), 7.50 (m, 3H), 8.72 (s, 2H), 9.10 (s, 1H). MS (ES+) Found (M+1) = 297; 296.C15H12N4OSrequires Intermediate B122-1- (4- (tert-Butoxycarbonylamino) but-1-yl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. in NMR (DMSO-d6) 5: 1.37 (s, 9H), 1.4 (m, 2H), 1.65 (m, 2H), 2.93 (m, 2H), 3.59 (s, 2H), 4.13 (t, 2H), 6.81 (br s, 1H), 7.94 (s, 1H), 8.70 (s. 2H), 9.04 (s, 1H), 13.45 (br s, 1H). MS (ES+) Found (M+l) = 392; C18H25N5O3S requires 391.

Intermediate B123-1- (3- (Ethoxycarbonylamino) prop-1-yl)-2- (4-fluorobenzyl) thio- 5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45 as a pale buff solid. 1H NMR (DMSO-d6) 8: 1.15 (t, 3H), 1.85 (m, 2H), 3.02 (m, 2H), 3.59 (s, 2H), 4.01 (q, 2H), 4.14 (t, 2H), 7.12 (br s, 1H), 7.93 (s, 1H), 8.69 (s, 2H), 9.00 (s, 1H), 13.55 (br s, 1H). MS (APCI+) Found (M+1) = 350; Cl5HlgN503S requires 349.

Intermediate B124-1- (1-Undecyl)- 5- (2-methoxypyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45, except using sodium methoxide in place of ethoxide.'H-NMR (CDC13) 8 0.8-0.95 (3H, t), 1.1-1.85 (18H, m), 3.59 (2H, s), 4.01 (3H, s), 4.11 (2H, t), 7.04 (lH, s), 8.43 (2H, s); MS (APCI+) found (M+1) = 405; C2lH32N402S requires 404. <BR> <BR> <P>Intermediate B125-1- (4- (Dec-1-yl) phenyl)-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. The ethoxide cyclisation step failed to go to completion, but the crude thiouracil was used in the next step without purification.

Intermediate B126-1- (4- (Non-1-yloxyphenyl))-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B125

Intermediate B127-1-(4-(Hex-1-yl) phenyl)-5-(pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B125 Intermediate B128-1- (3- (Non-1-yloxy) phenyl)-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B 125 Intermediate B129-1- (3- (Dec-1-yl) phenyl)-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B 125 Intermediate B130-1- (4-Iodophenyl)-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B 125 Intermediate B131-1- (2-Fluorobenzyl)-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. 1H NMR (d6-DMSO) # NMR (d6-DMSO) (2H, s), 5. (2H, (2H, s), 7.1-7.4 (4H, m), 7.98 (1H, s), 8.70 (2H, s), 9.04 (1H, s), 12.8 (1H, bs), MS (APCI-) requires328M-1=327,C16H13FN4OS

-(S)-1-(Tetrahydrofur-2-ylmethyl)-5-(pyrimid-5-ylmethyl)-2-I ntermediateB132 thiouracil Prepared analogously to intermediate B45. IH NMR (d6-DMSO) 8 1.5-1.65 (lH, m), 1.75-2.05 (3H, m), 3.62 (2H, s), 3.65 (lH, m), 3.79 (lH, m), 3.95 (lH, m), 4.24 (1H, m), 4.47 (1H, dd), 7.83 (1H, s), 8.70 (2H, s), 9.04 (1H, s), 12.7 (1H, bs), MS (APCI-) M- 3041=303,C14H16N4O2Srequires -(R)-1-(Tetrahydrofur-2-ylmethyl)-5-(pyrimid-5-ylmethyl)-2-I ntermediateB133 thiouracil Prepared analogously to intermediate B45. 1H NMR (d6-DMSO) 5 1.5-1.65 (lH, m), 1.75-2.05 (3H, m), 3.62 (2H, s), 3.65 (lH, m), 3.79 (lH, m), 3.95 (lH, m), 4.24 (1H, m), 4.47 (IH. dd), 7.83 (1H, s), 8.70 (2H, s), 9.04 (1H, s), 12.7 (1H, bs), MS (APCI-) M- 1=303, C14H16N4O2S requires 304 Intermediate B134-1- (2- (4-Methoxyphenyl) ethyl)-5- (pyrimid-5-ylmethyl)-2- thiouracil Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) 5 2.97 (2H, t), 3.51 (2H, s), 3,74 (3H. s), 4.31 (2H, t), 6.85 (2H, m), 7.49 (2H, m), 7.14 (1H, s), 8.59 (2H, s), 9.03 (1H, s), 12.7 (1H, bs), MS (APCI+) M+l=355, C18H18N4O2S requires 354 Intermediate B135-1- (Undec-1-yl)-5- (2-methylpyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45, except using sodium methoxide in place of ethoxide. 1H-NMR (CDCl3) # 0. 8-0.9 (3H, t), 1.2-1.35 (16H, m), 1.75 (2H, m), 2.73

(3H, s), 3.62 (2H, s), 4.11 (2H, t), 7.05 (lH, s), 8.57 (2H, s), 9.7-9.8 (lH, br s); MS (APCI+) found (M+1) = 389; C2lH32N40S requires 388.

Intermediate B136-1- (4-Acetylphenyl)-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B 125.

Intermediate B137-1- (trans-4- (Methoxycarbonyl) cyclohex-1-ylmethyl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl)-2-thiouracil Prepared analogously to intermediate B45. 'H-NMR (d6-DMSO) 8 1.0-1.4 (4H, m), 1.65 (2H, m), 1.92 (2H, m), 2.15-2.35 (1H, m), 3.58 (3H, s), 3.60 (2H, s), 4.01 (2H, m), 7.88 (1H, s), 8.70 (2H, s), 9.06 (1H, s), 12.6 (1H, br s); MS (APCI-) found (M-1) = 373; C18H22N403S requires 374.

Intermediate B138-1- (2- (t-Butoxycarbonylamino) ethyl)-5- (pyrimid-5-ylmethyl)-2- thiouracil Prepared analogously to intermediate B45. lH-NMR (d6-DMSO) 5 1.34 (9H, s), 3.32 (2H, m), 3.58 (2H, s), 4.19 (2H, m), 6.99 (lH, t), 7.69 (1H, s), 8.71 (2H, s), 9.03 (1H, s), 12.6 (1H, br s); MS (APCI-) found (M-l) = 362; C16H21N5O3S requires 363. <BR> <BR> <P>IntermediateB139-1-(3-(5-Phenylpent-l-yloxy) prop-l-yl)-5-(pyrimid-5-ylmethyl)- 2-thiouracil Prepared analogously to intermediate B45. IH-NMR (d6-DMSO) b 1.33 (2H, m), 1.4-1.7 (4H, m), 1.95 (2H, m), 2.55 (2H, t), 3.2-3.5 (4H, m), 3.60 (2H, s), 4.18 (2H, t), 7.1-7.3

(SH, m), 7.86 (1H, s), 8.71 (2H, s), 9.03 (1H, s), 12.6 (1H, br s); MS (APCI+) found (M+1) = 425; C23H28N40, S requires 424.

General method A: S-Alkylation of thiouracils A1 (N1-unsubstituted thiouracils). Sodium (2.2 equiv) was dissolved in ethanol to give a ca. O. 5M solution of sodium ethoxide. The appropriate thiouracil (1 equiv) was added, usually giving a clear solution, then the appropriate alkyating agent was added (1.0-1.25 equiv were used in various preparations, but no consistent advantage was seen with higher amounts) and the mixture was stirred at room temperature overnight. The ethanol was removed by evaporation, the residue was taken up in water, and the solution adjusted to pH 5 with acetic acid. In many cases the product precipitated, and was filtered off, washed with water and dried. When necessary, the aqueous solution was extracted with ethyl acetate, the organic layers dried and evaporated, and the residue triturated with ether or pet. ether to obtain the product.

A2. A mixture of thiouracil (1 equiv), the appropriate alkylating agent (1-1.1 equiv) and diisopropylethylamine (1-1. 1 equiv) was stirred overnight at room temperature in dichloromethane (12ml/mmol). The solution was diluted with dichloromethane and washed with saturated sodium bicarbonate solution. The organic layer was added directly to a silica gel column. Elution (ethyl acetate to methanol: ethyl acetate) gave the desired product.

A3. A mixture of thiouracil (1 equiv), the appropriate alkylating agent (1-1.1 equiv) and diisopropylethylamine (1-1. 1 equiv) was stirred for lh at between 64 and 72°C in 1, 2- dichloroethane (12ml/mmol). The solution was diluted with dichloromethane and washed with saturated sodium bicarbonate solution. The organic layer was added directly to a silica gel column. Elution (ethyl acetate to methanol: ethyl acetate) gave the desired product.1 A4. A mixture of the appropriate thiouracil (1 equiv), the appropriate alkylating agent (1.1 equiv) and potassium carbonate (2-3 equiv) in dry dimethylformamide (ca 4 ml/mmol) was heated at 65°C for 2.5h. The mixture was cooled, the solvent was removed under reduced pressure and the residue partitioned between dichloromethane (50ml) and 3% aqueous potassium carbonate solution. The organic layer was applied directly to a SepPak cartridge (lOg, Silica) and elution was continued with 2% to 8% methanol in ethyl acetate as eluent. This gave 1- (4-hydroxycyclohexyl)-2- (8- (4- chlorophenyl)-8-oxooct-1-yl)thio-5- (pyrimid-5-ylmethyl)pyrimidin-4-one (0.18g) AS. Array synthesis. This proceeded essentially as in method A 1, except that parallel reactions were carried out in screw-capped polypropylene tubes. The appropriate thiouracil (1 equiv) was weighed into each tube, then O. 5M ethanolic sodium ethoxide (2 equiv) and the appropriate alkyl halide (1 equiv) as an O. 5M ethanol solution were dispensed in by pipette and the tubes capped and vortexed at room temperature overnight

on an orbital shaker. After removal of solvent in a vacuum centrifuge, individual products were worked up in the usual way.

General method B: Displacement of 2- (nitroamino) pyrimidones with thiols The appropriate 2- (nitroamino) pyrimidone (1 equiv) and thiol (2 equiv) in pyridine (ca 2ml per mmol) were stirred at reflux for 2 days, then the pyridine was evaporated.

Trituration with an appropriate solvent, as described in the individual examples, gave the desired product.

General method C: N1-Alkylation of pyrimidin-4-ones Cl. To a stirred solution of the pyrimidinone (1 equiv) in dry DMF (20ml) was added sodium hydride (1 equiv). The mixture was stirred at room temperature for 30 min, then the appropriate alkylating agent (1-1.1 equiv) was added in portions over 15 min, and the mixture was stirred overnight. Ethyl acetate and dilute hydrochloric acid were added, the organic layer was separated and washed with water and brine, dried and evaporated.

Flash chromatography (silica, 1-10% methanol in dichloromethane) gave first a mixture of the 3-alkyl and 4-alkoxypyrimidine byproducts, then the desired 1-alkylpyrimidin-4- one.

C2. A mixture of pyrimidinone (1 equiv), the appropriate alkylating agent (1-1.1equiv) and diisopropylethylamine (1-1. 5 equiv, usually 1. 25-1. 3 equiv) was stirred for between 20-72h at room temperature in dichloromethane (12ml/mmol) (if the pyrimidinone was only partially soluble in dichloromethane, dimethylformamide (2ml/mmol) was also added). The solution was diluted with dichloromethane containing up to 2% methanol (if dimethylformamide was used, the solvent was first removed under reduced pressure) and washed with saturated ammonium chloride solution and sodium bicarbonate solution. The organic layer was separated and added directly to a silica gel column. Elution (ethyl acetate to methanol: dichloromethane: ethyl acetate) gave the desired product.

C3. Similar to method C2. except that the solvent was 1,2-dichloroethane in place of dichloromethane, and the pyrimidone was treated with tributyltin chloride (1 equiv) and stirred overnight to form the silyl ether before addition of the alkylating agent.

General method D: Ester hydrolysis To a solution of the ester (1 equiv) in 1,4 dioxane (9ml/mmol) under argon was added a solution of sodium hydroxide (0.95-1 equiv) in water (2-4. 5ml/mmol) whilst keeping the temperature below 25°C. After stirring for between 2-20h at room temperature (the reaction was checked for completion), 75% of the solvent was removed under reduced pressure at <25°C. The residue was diluted with water and brought to pH3 with 5% aqueous sodium bisulphate. The solid so formed was filtered and dried in vacuo to give the desired material.

General method E: Amide coupling To a slurry/solution of the carboxylic acid (1 equiv) in dichloromethane (or dimethylformamide) (12ml/mmol) was added hydroxybenzotriazole (O. lequiv), the amine (1 equiv) and 1- (3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1. OSeq).

After stirring under argon for 24h, (the solvent removed under reduced pressure if dimethylformamide) the mixture was diluted with dichloromethane and washed with saturated sodium bicarbonate. Addition of the organic layer directly to a silica gel column and elution (ethyl acetate to methanol: ethyl acetate) gave the desired product.

Alternatively, the crude product could be purified by solid phase extraction on a BondElut SCX cartridge, eluted with dichloromethane/methanol.

General method F: Urea synthesis The appropriate BOC-protected amine was dissolved in neat TFA (ca 5ml/g) at room temperature. After 5min the solution was concentrated to a brown gum and re-evaporated from ethyl acetate. The crude amine salt in dichloromethane (ca 15ml/g) was treated with the isocyanate (1.1 equiv.) in dichloromethane, followed by the addition of triethylamine and the reaction mixture shaken overnight. The reaction mixture was centrifuged to remove any solid material and the supernatent washed with water. The organic layer was dried over anhydrous magnesium sulfate and the solution concentrated. The crude material was then purified by silica gel chromatography.

Example 1-2-(8-Phenyloct-1-yl) thio-S-((1-benzyl-2-oxo-pyrid-4- yl) methyl) pyrimidin-4-one Prepared from intermediate B 10 by general method A1 as a white solid. MPt 124- 129°C; IH-NMR (d6 DMSO) 8 1.2-1.5 (8H, m), 1.5-1.8 (4H, m), 2.59 (2H, t), 3.13 (2H, t), 3.54 (2H, s), 5.10 (2H, s), 6.14 (lH, dd), 6.50 (lH, bs), 7.15-7.4 (1 lH, m) and 7.68 (lH, s).

Example 2-2-(8-(4-Fluorophenyl) oct-1-yl) thio-5-((1-benzyl-2-oxo-pyrid-4- yl) methyl) pyrimidin-4-one Prepared from intermediate B 10 and A21 by general method A5 as a white solid. MPt 147-151°C ; IH-NMR (CDC13) 8 1.2-1.5 (8H, m), 1.5-1.8 (4H, m), 2.58 (2H, t), 3.15 (2H. t), 3.55 (2H, s), 5.10 (2H, s), 6.15 (lH, dd), 6.47 (lH, m), 6.95 (2H, t), 7.05-7.2 (3H, m), 7.25-7.45 (5H, m) and 7.67 (lH, s); MS (EI) M=531; C31H34FN3O2S requires 531.

Example 2-(8-(4-Chlorophenyl)oct-1-yl)thio-5-((1-benzyl-2-oxo-pyrid- 4-- yl) methyl) pyrimidin-4-one Prepared from intermediates B 10 and A24 by general method A5 as a white solid. MPt 160-164°C; 1H-NMR (CDCl3) # 1.2-1.8 (12H. m), 2.56 (2H, t), 3.13 (2H, t), 3.55 (2H, s), 5.10 (2H, s), 6.15 (1H, m), 6.48 (IH. bs), 7.0-7.45 (1OH, m) and 7.67 (lH, s); MS (EI) M=547; C31H34CIN3O2S requires 547.

Example 4-2-(8-(4-Chlorophenyl)-8-oxooct-1-yl) thio-5-((1-benzyl-2-oxo-pyrid-4- yl) methyl) pyrimidin-4-one Prepared from intermediates B 10 and Al by general method A5 as a white solid. MPt 147-151°C; 1H-NMR (CDCl3) # 1.2-1.8 (10H, m), 2.93 (2H, t), 3.13 (2H, t), 3.55 (2H, s), 5.10 (2H, s), 6.15 (lH, dd), 6.49 (lH, bs), 7.05-7.5 (8H, m), 7.68 (lH, s) and 7.89 (2H, d); MS (EI) M=561; C3iH32ClN303S requires 561.

Example 5-2-(8-(4-Fluorophenyl)-8-oxooct-1-yl) thio-5-((1-benzyl-2-oxo-pyrid-4- yl) methyl) pyrimidin-4-one Prepared from intermediates B 10 and A8 by general method A5 as a white solid. MPt 125-133°C; 1H-NMR (CDCl3) # 1.2-1.8 (1OH), 2.93 (2H, t), 3.13 (2H, t), 3.55 (2H, s), 5.10 (2H, s), 6.15 (lH, m), 6.48 (lH, bs), 7.05-7.45 (8H, m), 7.68 (lH, s) and 7.97 (2H, m); MS (EI) M=545; C31H32FN3O3S requires 545.

Example 2-(9-Phenylnon-1-yl)thio-5-((1-benzyl-2-oxo-pyrid-4-- yl) methyl) pyrimidin-4-one Prepared from intermediate B 10 by general method A5 as a white solid. MPt 127- 132°C; 1H-NMR (CDCl3) # 1.2-1.9 (14H, m), 2.58 (2H, t), 3.14 (2H, t), 3.55 (2H, s), 5.10 (2H, s), 6.15 (1H, dd), 6.48 (1H, bd), 7.05-7.4 (lOH. m) and 7.67 (lH, s); MS (EI) M=527; C32H37N302S requires 527.

Example 7-2-(6-Phenylhex-1-yl) thio-5-((1-methyl-2-oxo-pyrid-4- yl) methyl) pyrimidin-4-one Prepared from intermediate B 11 by general method A5. IH-NMR (d6-DMSO) 8 1.3 (4H. m). 1.6 (4H. m). 2.55 (2H. t). 3.08 (2H, t), 3.35 (3H, s), 3.41 (2H, s), 6.10 (lH, dd), 6.16 (1H, d). 7.1-7.3 (5H, m), 7.55 (lH, d), 7.78 (lH, s).

Example 2-(7-Phenylhept-1-yl)thio-5-((1-methyl-2-oxo-pyrid-4-- yl) methyl) pyrimidin-4-one Prepared from intermediate B 11 by general method AS. lH-NMR (d6-DMSO) â 1.3 (6H. m), 1.6 (4H, m), 2.55 (2H. t), 3.07 (2H, t), 3.35 (3H, s), 3.41 (2H, s), 6.10 (lH, dd), 6.15 (H, d), 7.1-7.3 (5H, m), 7.55 (IH, d), 7.77 (lH, s).

Example 9-2-(8-Phenyloct-1-yl) thio-5-((1-methyl-2-oxo-pyrid-4- yl) methyl) pyrimidin-4-one Prepared from intermediate B 11 by general method A5. 1H-NMR (d6-DMSO) # 1.3 (8H, m), 1.6 (4H, m), 2.55 (2H, t), 2.97 (2H, t), 3.40 (3H, s), 3.42 (2H, s), 6.25 (lH, dd), 6.29 (lH, d), 7.1-7.3 (5H, m), 7.52 (lH, d), 7.58 (lH, s).

Example 10-2-(9-Phenylnon-1-yl) thio-5-((1-methyl-2-oxo-pyrid-4- yl) methyl) pyrimidin-4-one Prepared from intermediate B 11 by general method A5. IH-NMR (d6-DMSO) å 1.3 (10H. m), 1.6 (4H, m), 2.55 (2H, t), 3.06 (2H, t), 3.34 (3H, s), 6.10 (lH, dd), 6.15 (lH, d), 7.1- 7.3 (5H, m), 7.55 (lH, d), 7.75 (lH, s).

Example 11-2-(6-Benzyloxyhex-1-yl) thio-5-((1-methyl-2-oxo-pyrid-4- yl) methyl) pyrimidin-4-one Prepared from intermediates B 11 and A27 by general method A5.'H-NMR (d6-DMSO) 5 1.3 (4H, m), 1.5 (2H, m), 1.6 (2H, m), 3.08 (2H, t), 3.40 (2H, t), 3.64 (2H, s), 4.43 (2H, s), 6.09 (lH, dd), 6.15 (1H, d), 7.1-7.3 (5H, m), 7.55 (lH, d), 7.75 (lH, s).

Example 2-(8-(4-Chlorophenyl)-8-oxooct-1-yl)thio-5-((1-methyl-2-oxo- pyrid-4-- yl) methyl) pyrimidin-4-one Prepared from intermediates B 11 and A 1 by general method A5 as a white solid. MPt 125-127°C ; lH-NMR (d6-DMSO) â 1.3 (6H, m), 1.6 (4H, m), 3.00 (2H, t), 3.08 (2H, t), 3.35 (3H, s), 3.41 (2H, s), 6.10 (lH, m), 6.15 (lH, s), 7.57 (3H, m), 7.79 (lH, s), 7.97 (2H, d).

Example 13-2-(8-Phenyloct-1-yl) thio-5-((1-butyl-2-oxo-pyrid-4- yl) methyl) pyrimidin-4-one

Prepared from intermediate B27 by general method B as a white solid from pet. ether.

1H-NMR (d6-DMSO) 8 0.87 (3H, t), 1.26 (10H, m), 1.5-1.7 (6H, m), 2.55 (2H, t), 3.08 (2H, t), 3.42 (2H, s), 3.79 (2H, t), 6.1 (2H, m), 7.2 (3H, m), 7.3 (2H, m), 7.54 (lH, d), 7.81 (lH, s), 12.8 (lH, br s).

Example 14-2-(8-Phenyloct-1-yl) thio-5-((2,3-dimethylpyrid-5- yl) methyl) pyrimidin-4-one Prepared from intermediate B 12 by general method A 1 as a light brown solid. MPt 111- 113°C; IH-NMR (d6-DMSO) 8 1.3 (8H, m), 1.6 (4H, m), 2.18 (3H, s), 2.35 (3H, s), 2.51 (2H. t), 3.05 (2H, t), 3.52 (2H, s), (5H, m), 7.34 (lH, d), 7.74 (lH, s), 8.14 (lH, d).

Example 15-2-(6-Benzyloxyhex-1-yl) thio-5-((2,3-dimethylpyrid-5- yl) methyl) pyrimidin-4-one Prepared from intermediates B 12 and A27 by general method A1 as a light brown solid.

MPt 100-102°C ;H-NMR (d6-DMSO) 8 1.3 (4H, m), 1.5 (2H, m), 1.6 (2H, m), 2.18 (3H, s), 2.35 (3H, s), 3.06 (2H, t), 3.36 (2H, t), 3.52 (2H, s), 4.43 (2H, s), 7.3 (6H, m), 7.74 (lH, s), 8.14 (lH, d).

Example 16-2-(8-Phenyloct-1-vl) thio-5-((2, 4-dimethylpyrid-5- yl) methyl) pyrimidin-4-one Prepared from intermediate B29 by general method B as a beige solid from ether/pet. ether. MPt 73-75°C ; iH-NMR (d6-DMSO) â 1.2 (8H, m), 1.6 (4H, m), 2.21 (3H, s), 2.37 (3H, s), 2.57 (2H, t), 3.06 (2H, t), 3.57 (2H, s), 6.83 (lH, s), 7.1-7.3 (5H, m), 7.51 (lH, s), 8.15 (1 H. s), 12.8 (1 H, br s).

Example 17-2- (5-Phenylpent-1-yl) thio-5-((2-methylpyrid-5-yl) methyl) pyrimidin- 4-one Prepared from intermediate B21 by general method A1 as a white solid. MPt 113- 117°C; IH-NMR (d6-DMSO) 8 1.35 (2H. m), 1.6 (4H, m), 2.40 (3H, s), 2.55 (2H, t), 3.07 (2H, t), 3.57 (2H, s), 7.1-7.3 (6H, m), 7.52 (lH, dd), 7.78 (lH, s), 8.33 (lH, d).

Example 18-2- (N- (6- (4-Fluorophenyl) hexyl) carboxamidomethyl) thio-5- ( (2- methylpyrid-5-yl) methyl) pyrimidin-4-one Prepared from intermediates B21 and A42 by general method A1. MPt 159-161°C : IH- NMR (d6-DMSO) 5 1.2 (4H, m), 1.4 (2H, m), 1.5 (2H, m), 2.40 (3H, s), 2.52 (2H, t), 3.04 (2H, m), 3.57 (2H, s), 3.81 (2H, s), 7.0-7.2 (5H, m), 7.49 (lH, dd), 7.75 (lH, s), 8.15 (lH, t), 8.33 (lH, dd).

Example 2-(6-Benzyloxyhex-1-yl)thio-5-((2-methylpyrid-5-- yl) methyl) pyrimidin-4-one Prepared from intermediates B21 and A27 by general method A1. MPt 93-95°C ; IH- NMR (d6-DMSO) 5 1.3 (4H, m), 1.5 (2H, m), 1.6 (2H, m), 2.40 (3H, s), 3.07 (2H, t), 3.40 (2H, t), 3.57 (2H, s), 4.43 (2H, s), 7.13 (lH, d), 7.3 (5H, m), 7.51 (lH, dd), 7.80 (lH, s), 8.34 (1H,d).

Example 20-2- (8-Phenyloct-1-yl) thio-5-((2-methylpyrid-5-yl) methyl) pyrimidin-4- one Prepared from intermediate B21 by general method A5 as a white solid. MPt 92-94°C; 'H-NMR (d6-DMSO) 5 1.3 (8H, m), 1.6 (4H. m), 2.40 (3H, s), 2.55 (2H, t), 3.02 (2H, t), 3.54 (2H, s), 7.11 (lH, d), 7.16 (3H, m), 7.25 (2H, m), 7.50 (IH. m), 7.69 (lH, s), 8.33 (lH, d).

Example 21-2- (7-Phenylhept-1-yl) thio-5-((2-methylpyrid-5-yl) methyl) pyrimidin- 4-one Prepared from intermediate B21 by general method A5 as a white solid. MPt 101- 103°C; lH-NMR (d6-DMSO) å 1.3 (6H, m), 1.6 (4H, m), 2.40 (3H, s), 2.55 (2H, t), 3.02 (2H, t), 3.54 (2H, s), 7.11 (1H, d), 7.16 (3H, m), 7.25 (2H, m), 7.50 (lH, m), 7.68 (lH, s), 8.33 (lH, d).

Example 22 - 2-(6-Phenylhex-1-yl)thio-5-((2-methylpyrid-5-yl) methyl) pyrimidin-4- one Prepared from intermediate B21 by general method A1 as a white solid. MPt 104- 106°C; IH-NMR (d6-DMSO) 8 1.3 (4H, m), 1.6 (4H, m), 2.40 (3H, s), 2.55 (2H, t), 3.05 (2H, t), 3.57 (2H, s), 7.1-7.3 (6H, m), 7.50 (lH, m), 7.78 (lH, s), 8.33 (lH, d).

Example 23-2- (9-Phenylnon-1-yl) thio-5- ( (2-methylpyrid-5-yl) methyl) pyrimidin-4- one Prepared from intermediate B21 by general method A1 as a white solid. MPt 112- 114°C; lH-NMR (d6-DMSO) õ 1.3 (IOH, m), 1.6 (4H, m), 2.40 (3H, s), 2.54 (2H, t), 3.05 (2H, t), 3.55 (2H, s), 7.1-7.3 (6H, m), 7.50 (lH, m), 7.88 (lH, s), 8.33 (lH, d).

Example 24-2- (6- (4-Chlorobenzyloxy) hex-1-yl) thio-5- ( (2-methylpyrid-5- yl) methyl) pyrimidin-4-one Prepared from intermediates B21 and A25 by general method A1 as a white solid. MPt 93-95°C ; lH-NMR (d6-DMSO) õ 1.3 (4H, m), 1.5 (2H, m), 1.6 (2H, m), 2.51 (3H, s), 3.13 (2H. t), 3.44 (2H.t), 3.70 (2H. s), 4.45 (2H, s), 7.06 (lH, d), 7.3 (3H, m), 7.53 (lH, dd), 7.64 (1H,d).(1H,s),8.43 Example 25-2-(6-(4-Fluorobenzyloxy) hex-1-yl) thio-5-((2-methylpyrid-5- yl) methyl) pyrimidin-4-one Prepared from intermediates B21 and A26 by general method A1 as a white solid. MPt 90-92°C ; lH-NMR (d6-DMSO) õ 1.3 (4H, m), 1.5 (2H, m), 1.6 (2H, m), 2.51 (3H, s), 3.13 (2H, t), 3.45 (2H, t), 3.70 (2H, s), 4.44 (2H, s), 7.0 (3H, m), 7.3 (2H, m), 7.53 (lH, dd), 7.64 (1H,d).(1H.s),8.43

Example 26-2- (8- (4-Methoxyphenyl)-8-oxooct-1-yl) thio-5- ( (2-methylpyrid-5- yl) methyl) pyrimidin-4-one Prepared from intermediates B21 and A3 by general method A1 as a white solid. MPt 114-116°C ; IH-NMR (d6-DMSO) S 1.3 (6H, m), 1.6 (4H, m), 2.40 (3H, s), 2.93 (2H, t), 3.08 (2H, t), 3.57 (2H, s), 3.83 (3H, s), 7.02 (2H, d), 7.13 (lH, d), 7.51 (lH, dd), 7.79 (lH, s), 7.93 (2H, d), 8.34 (lH, d), 12.7 (lH, br s).

Example 27-2- (8- (4-Methoxyphenyl) oct-1-yl) thio-5- ( (2-methylpyrid-5- yl) methyl) pyrimidin-4-one Prepared from intermediates B21 and A22 by general method A1 as a white solid. MPt 103-105°C; 1H-NMR (d6-DMSO) 8 1.3 (8H, m), 1.4-1.7 (4H, m), 2.40 (3H, s), 2.48 (2H, t), 3.07 (2H, t), 3.57 (2H, s), 3.84 (3H, s), 6.82 (2H, d), 7.07 (2H, d), 7.12 (lH, d), 7.51 (lH, dd), 7.78 (lH, s), 8.34 (lH, d), 12.7 (lH, br s).

Example 28-2-(8-(4-Fluorophenyl) oct-1-yl) thio-5-((2-methylpyrid-5- yl) methyl) pyrimidin-4-one Prepared from intermediates B21 and A21 by general method A1. lH-NMR (d6-DMSO) 5 1.3 (8H, m), 1.6 (4H. m), 2.40 (3H, s), 2.53 (2H. t), 3.06 (2H, t), 3.56 (2H, s), 7.0-7. 2 (5H, m), 7.5 (IH. m), 7.77 (lH, s), 8.33 (lH, m).

Example 29-2- (8- (4-Fluorophenyl)-8-oxooct-1-yl) thio-5- ( (2-methylpyrid-5- yl) methyl) pyrimidin-4-one Prepared from intermediates B21 and A8 by general method Al. IH-NMR (d6-DMSO) 8 1.3 (6H, m), 1.6 (4H, m), 2.40 (3H, s), 3.00 (2H, t), 3.08 (2H, t), 3.57 (2H, s), 7.13 (lH, d), 7.34 (2H, m), 7.51 (lH, dd), 7.80 (lH, s), 8.04 (2H, m), 8.34 (lH, d), 12.7 (lH, br s).

Example 30-2- (8- (4-Chlorophenyl) oct-1-yl) thio-5- ( (2-methylpyrid-5- yl) methyl) pyrimidin-4-one Prepared from intermediates B21 and A24 by general method A1 as a white solid. MPt 100-102°C ; IH-NMR (d6-DMSO) 5 1.3 (8H, m), 1.6 (4H, m), 2.40 (3H, s), 2.57 (2H, t), 3.06 (2H, t), 3.56 (2H, s), 7.12 (lH, d), 7.20 (2H, d), 7.31 (2H, d), 7.50 (lH, dd), 7.76 (lH, s), 8.33 (1H, d).

Example 31-2- (8- (4-Chlorophenyl)-8-oxooct-1-yl) thio-5- ( (2-methylpyrid-5- yl) methyl) pyrimidin-4-one Prepared from intermediates B21 and A1 by general method A1 as a white solid. MPt 90 -92°C; lH-NMR (d6-DMSO) õ 1.3 (6H, m), 1.6 (4H, m), 2.40 (3H, s), 3.00 (2H, t), 3.07 (2H, t), 3.56 (2H, s), 7.12 (lH, d), 7.51 (lH, dd), 7.58 (2H, d), 7.86 (lH, s), 7.97 (2H, d), 8.34 (lH, d).

Example 32-2- (8-Phenyl-8-oxooct-1-yl) thio-5- ( (2-methylpyrid-5- yl) methyl) pyrimidin-4-one Prepared from intermediate B21 by general method Al as a white solid. MPt 72-74°C lH-NMR (d6-DMSO) õ 1.3 (6H, m). 1.6 (4H. m), 2.40 (3H, s), 3.00 (2H, t), 3.08 (2H, t), 3.57 (2H, s), 7.13 (lH, m), 7.5 (3H. m). 7.6 (lH, m), 7.80 (lH, s), 7.94 (lH, m), 8.33 (1H, d), 12.6 (lH, brs).

Example 33-2- (8- (4-Chlorophenyl)-8-hydroxyoct-1-yl) thio-5- ( (2-methylpyrid-5- yl) methyl) pyrimidin-4-one Prepared from intermediates B21 and A36 by general method Al. IH-NMR (d6-DMSO) 8 1.3 (8H. m), 1.6 (4H, m), 2.40 (3H. s), 3.08 (2H, t), 3.58 (2H, s), 4.5 (lH, br t), 4.9 (lH, br s), 7.10 (1H, m), 7.31 (4H, m), 7.48 (1H, m), 7.71 (1H, s), 8.32 (1H, m), 12.4 (1H, br s).

Example 34-2-(8-(4-Methylphenyl)-8-oxooct-1-yl) thio-5-((2-methylpyrid-S- yl) methyl) pyrimidin-4-one Prepared from intermediates B21 and A7 by general method Al as a white solid. MPt 115-116°C ; IH-NMR (CDCl3) 8 1.2-1.8 (10H, m), 2.41 (3H, s), 2.51 (3H, s), 2.93 (2H, t), 3.13 (2H, t), 7.06 (lH, m), 7.25 (2H, m), 7.26 (lH, s), 7.54 (lH, m), 7.85 (2H, m) and 8.43 (lH, d); MS (EI) M=449; C26H31N30S requires 449.

Example 35-2- (4-Phenylbut-1-yl) thio-5-((2-methylpyrid-S-yl) methyl) pyrimidin-4- one Prepared from intermediate B21 by general method Al. Mpt 129-30°C; IH-NMR (d6- DMSO) 5 1.6 (4H, m), 2.40 (3H, s), 2.58 (2H, m), 3.11 (2H, m), 3.57 (2H, s), 7.1-7.3 (6H, m), 7.52 (lH, dd), 7.80 (lH, s), 8.33 (lH, d).

Example 2-(8-Phenyloct-1-yl)thio-5-((1-oxo-2-methylpyrid-5-- yl) methyl) pyrimidin-4-one Prepared from intermediate B28 by general method B. Trituration with ether and recrystallisation from ethyl acetate gave the product as an off-white solid. MPt 93 - 95°C ; IH-NMR (d6-DMSO) 8 1.3 (8H. m), 1.6 (4H, m), 2.55 (2H, t), 3.07 (2H, t), 3.56 (2H, s), 7.1- 7.3 (6H. m), 7.52 (IH, dd), 7.78 (lH, s), 8.33 (lH, d).

Example 37-2- (8-Phenyloct-1-yl) thio-5-((2-methoxypyrid-4-yl) methyl) pyrimidin- 4-one Prepared from intermediate B25 by general method B as a beige solid from ethanol. MPt 70-72°C; 1H-NMR (d6-DMSO) # 1.3 (8H, m), 1.6 (4H, m), 2.55 (2H, t), 3.08 (2H, t), 3.58 (2H, s), 3.80 (3H, s), 6.64 (lH, s), 6.84 (lH, d), 7.1-7.3 (5H, m), 7.80 (lH, s), 8.02 (lH, d).

Example 38-2- (8- (4-Chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrazin-2- ylmethyl) pyrimidin-4-one Prepared from intermediates B 14 and Al by general method Al as a white solid. MPt 122.5-124°C; IH-NMR (d6 DMSO) 8 1.2-1.5 (6H, m), (4H, m), 3.00 (2H, t), 3.10 (2H, t), 3.81 (2H, s), 7.59 (2H, d), 7.8 (lH, bs), 7.97 (2H, d), 8.46 (1H, m), 8.50 (1H. m) and 8.58 (lH, m); MS (FAB) M+1=457; C23H25C1N402S requires 456.

Example 39-2- (8-Phenyloct-1-yl) thio-S- (pyrid-2-ylmethyl) pyrimidin-4-one Prepared from intermediate B 18 by general method Al. 1H-NMR (d6-DMSO) # 1. 3 (8H, m), 1.6 (4H, m), 2.55 (2H, t), 3.09 (2H, t), 3.76 (2H, s), 7.1-7.3 (7H, m), 7.67 (lH, m), 7.74 (lH, s), 8.44 (lH, m), 12.7 (lH, br s).

Example 40-2- (8- (4-Chlorophenyl)-8-oxooct-1-yl) thio-5- (thiazol-2- ylmethyl) pyrimidin-4-one Prepared from intermediates B22 and A1 by general method A1 as a pale buff solid. MPt 112-114°C; 1H-NMR (CDCl3) # (lOH. m), 2.92 (2H, t), 3.15 (2H, t), 4.17 (2H, s), 7.22 (1H.d), 7. 42 (2H. m), 7.69 (1 H. d) and 7.8-8.0 (3H. m); MS (EI) M=461; C"H. ClN30, S, requires 461.

Example 42-2-(6-Phenylhex-1-yl) thio-S-(pyrid-3-ylmethyl) pyrimidin-4-one Prepared from intermediate B 19 by general method A5. 1H-NMR (d6-DMSO) # 1.3 (4H, m). 1.6 (4H. m), 2.55 (2H, t), 3.07 (2H, t), 3.62 (2H, s), 7.1-7.3 (5H, m), 7.63 (1H, m), 7.81 (1H, s), 8.39 (lH, m), 8.48 (1H, d).

Example 43-2- (7-Phenylhept-1-yl) thio-5- (pyrid-3-ylmethyl) pyrimidin-4-one

Prepared from intermediate B 19 by general method A5. IH-NMR (d6-DMSO) 8 1.3 (6H, m), 1.6 (4H, m), 2.55 (2H, t), 3.07 (2H, t), 3.62 (2H, s), 7.1-7.3 (SH, m), 7.63 (lH, m), 7.82 (lH, s), 8.39 (lH, m), 8.48 (lH, d).

Example 44-2- (8-Phenyloct-1-yl) thio-5- (pyrid-3-ylmethyl) pyrimidin-4-one Prepared from intermediate B 19 by general method A5. IH-NMR (d6-DMSO) 8 1.3 (8H, m), 1.6 (4H, m), 2.55 (2H, t), 2.97 (2H, t), 3.62 (2H, s), 7.1-7.3 (5H, m), 7.63 (lH, m), 7.82 (lH, s), 8.39 (lH, m), 8.48 (lH, d).

Example 45-2- (9-Phenylnon-1-yl) thio-5- (pyrid-3-ylmethyl) pyrimidin-4-one Prepared from intermediate B 19 by general method AS. IH-NMR (d6-DMSO) 6 1.3 (10H, m), 1.6 (4H, m), 2.55 (2H, t), 3.07 (2H, t), 3.62 (2H, s), 7.1-7.3 (5H, m), 7.63 (lH, m), 7.81 (lH, s), 8.39 (lH, m), 8.48 (lH, d).

Example 46-2- (6-Benzyloxyhex-1-yl) thio-S- (pyrid-3-ylmethyl) pyrimidin-4-one Prepared from intermediates B 19 and A27 by general method A5. IH-NMR (d6-DMSO) 8 1.3 (4H, m), 1.5 (2H, m), 1.6 (2H, m), 3.08 (2H, t), 3.40 (2H, t), 3.62 (2H, s), 4.43 (2H, s), 7.1-7.3 (5H. m), 7.64 (6H, m), 7.82 (lH, s), 8.39 (lH, m), 8.49 (lH, d).

Example 47-2- (8- (4-Chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrid-3-ylmethyl)- pyrimidin-4-one Prepared from intermediates B 19 and Al by general method Al as a white solid. MPt 105-107°C ; IH-NMR (d6-DMSO) 8 1.3 (6H, m), 1.6 (4H, m), 3.00 (2H, t), 3.08 (2H, t), 3.62 (2H, s), 7.3 (lH, m), 7.58 (2H. d), 7.6 (1H, m), 7.82 (lH, s), 7.97 (2H. d), 8.39 (lH, m), 8.48 (lH, m).

Example 48-2- (8- (4-Fluorophenyl) non-8-en-1-yl) thio-5- (pyrid-3- ylmethyl) pyrimidin-4-one Prepared from intermediates B 19 and A37 by general method A1 as a white powder. MPt 70-75°C ; IH-NMR (d6 DMSO) 5 1.2-1.8 (10H. m), 2.45 (2H, t), 3.06 (2H, m), 3.62 (2H, s), 5.04 (lH, s), 5.26 (lH, s), 7.16 (2H, t), 7.29 (lH, dxd), 7.4-7.55 (2H, m), 7.81 (lH, s), 8.38 (lH, m) and 8.48 (lH, d); MS (EI) Found M=437; C25H28FN3OS requires 437.

Example 49-2- (6- (4-Chlorobenzoylamino) hex-1-yl) thio-5- (pyrid-3- ylmethyl) pyrimidin-4-one Prepared from intermediate B 19 and A45 by general method A 1 as a white solid. MPt 135-139°C ; IH-NMR (d6 DMSO) 8 1.2-1.8 (8H, m), 3.09 (2H, t), 3.23 (2H, q), 3.61 (2H, s), 7.28 (lH, s), 7.51 (2H, m), 7.62 (lH, m), 7.84 (3H, m), 8.38 (lH, m), 8.48 (lH, bs) and 8.53 (lH, bt).

Example 50-2- (8- (4-Bromophenyl)-8-oxooct-1-yl) thio-5- (pyrid-3- ylmethyl) pyrimidin-4-one Prepared from intermediate B 19 and A4 by general method A 1 as a white solid. MPt 132 -137°C ; IH-NMR (d6 DMSO) 8 (6H, m), 1.5-1.8 (4H, m), 2.98 (2H, t), 3.08 (2H, t), 3.62 (2H, t), 7.28 (lH, m), 7.5-7.95 (6H, m), 8.38 (1H, m) and 8.48 (lH, bd).

Example 51-2- (7- (4-Chlorophenoxy) hept-1-yl) thio-5- (pyrid-3- ylmethyl) pyrimidin-4-one Prepared from intermediate B 19 and A29 by general method A1. IH-NMR (d6 DMSO) 8 1.2-1.5 (6H. m), 1.5-1.8 (4H, m), 3.09 (2H, t), 3.62 (2H, s), 3.93 (2H, t), 6.94 (2H, m), 7.29 (2H, m), 7.63 (lH, m), 7.83 (lH, bs), 8.38 (lH, m) and 8.48 (lH, bd).

Example 52-2- (7-Phenoxyhept-1-yl) thio-5- (pyrid-3-ylmethyl) pyrimidin-4-one

Prepared from intermediate B 19 and A28 by general method Al. IH-NMR (d6DMSO) 8 1. 2-1. 5 (6H, m), 1.5-1.8 (4H, m), 3.09 (2H, t), 3.62 (2H, s), 3.93 (2H, t), 6.90 (3H, m), 7.27 (3H, m), 7.63 (IH. m), 7.82 (lH, s), 8.39 (lH, m) and 8.48 (lH, m).

Example 53-2- (7-Phenylthiohept-1-yl) thio-5- (pyrid-3-ylmethyl) pyrimidin-4-one Prepared from intermediate B 19 and A33 by general method Al. 1H-NMR (d6DMSO) # 1.2-1.5 (6H, m), 1.5-1.8 (4H, m), 2.94 (2H, t), 3.06 (2H, t), 3.62 (2H, s), 7.16 (lH, m), 7.20- 7.35 (5H, m), 7.62 (lH, m), 7.81 (lH, s), 8.38 (lH, m) and 8.48 (lH, bs).

Example 54-2- (7- (4-Chlorophenylthio) hept-1-yl) thio-5- (pyrid-3- ylmethyl) pyrimidin-4-one Prepared from intermediate B 19 and A30 by general method Al. IH-NMR (d6 DMSO) 8 1.2-1.5 (6H, m), 1.5-1.8 (4H, m), 2.94 (2H, t), 3.07 (2H, t), 3.62 (2H, s), 7.2-7.5 (5H, m), 7.62 (IH. m), 7.82 (lH, s), 8.38 (lH, m) and 8.48 (lH, bs).

Example 55-2- (6- (3-Chlorophenyl) hex-1-yl) thio-5- (pyrid-3-ylmethyl) pyrimidin-4- one Prepared from intermediate B 19 and A40 by general method Al as a white solid. MPt 84 -85°C;'H-NMR (CDCy § 1.2-1.8 (8H, m), 2.57 (2H, t), 3.13 (2H, t), 3.74 (2H, s), 7.03 (lH. m), 7.15-7.25 (4H. m), 7.65 (2H. m), 8.47 (lH, m), and 8.56 (lH, d); MS (EI) M=413; 413.C22H24ClN3OSrequires Example 56-2- (7-Phenylsulflnvlhept-1-yl) thio-5- (pyrid-3-ylmethyl) pyrimidin-4- one Prepared from intermediate B 19 and A34 by general method Al. 1H-NMR (d6 DMSO) # 1.2-1.5 (6H, m), 1.5-1.8 (4H, m), 2.6-3.0 (4H. m), 3.55 (2H, s), 7.25 (lH, m), 7.45-7.7 (7H, m), 8.35 (lH, m) and 8.46 (IH, m).

Example 57-2- (7- (4-Chlorophenylsulfinyl) hept-1-yl) thio-5- (pyrid-3-ylmethyl)- pyrimidin-4-one Prepared from intermediate B 19 and A31 by general method Al. 'H-NMR (d6 DMSO) 8 (6H, m), 1.5-1.8 (4H, m), 2.7-3.2 (4H, m), 3.61 (2H, s), 7.28 (lH, m), 7.55-7.75 (5H, m), 7.80 (lH, s), 8.38 (lH, m) and 8.47 (lH, bs).

Example 58-2- (7-Phenylsulfonylhept-1-yl) thio-5- (pyrid-3-ylmethyl) pyrimidin-4- one Prepared from intermediate B 19 and A35 by general method Al. IH-NMR (d6 DMSO) 5 (6H, m), 1.5-1.8 (4H, m), 3.05 (2H, t), 3.29 (2H, t), 3.62 (2H, s), 7.29 (lH, m), 7.6- 8.0 (7H, m), 8.44 (lH, m) and 8.49 (lH, m).

Example 59-2- (7- (4-Chlorophenylsulfonyl) hept-1-yl) thio-5- (pyrid-3- ylmethyl) pyrimidin-4-one Prepared from intermediate B19 and A32 by general method A1. lH-NMR (d6 DMSO) 6 1.2-1.5 (6H. m), 1.5-1.8 (4H. m), 3.05 (2H, t), 3.62 (2H, s), 7.28 (lH, m), 7.6-80 (6H, m), 8.44 (1 H. m) and 8.48 (1H. m).

Example 60-2-(8-(3-Chlorophenyl) oct-1-yl) thio-5-(pyrid-3-ylmethyl) pyrimidin-4- one Prepared from intermediate B 19 and A 18 by general method A 1 as a white solid. MPt 68 -70°C;'H-NMR (CDCy 8 1.2-1.5 (8H, m), 1.5-1.8 (4H, m), 2.56 (2H, t), 3.13 (2H, t), 3.74 (2H. t), 7.05 (1H, m), 7.15-7.25 (4H. m), 7.65 (2H, m), 8.46 (1H,m) and 8.57 (lH, m); MS (EI) M=441; C24H28CIN3OS requires 441.

Example 61-2- (8- (3,4-Dichlorophenyl) oct-l-yl) thio-5- (pyrid-3- ylmethyl) pyrimidin-4-one

Prepared from intermediate B 19 and A 15 by general method A 1 as a white solid. MPt 96 -99°C; IH-NMR (CDCl3) õ 1.2-1.5 (8H, m), 1.5-1.8 (4H, m), 2.54 (2H, t), 3.13 (2H, t), 3.74 (2H, s), 7.0 (lH, m), 7.2-7.35 (3H, m), 7.65 (2H. m), 8.46 (lH, m) and 8.56 (1H, d); MS (EI) M=475; C24H27Cl2N3O requires 475.

Example 62-2- (8- (2-Thienyl)-8-oxooct-1-yl) thio-5- (pyrid-3-ylmethyl) pyrimidin-4- one Prepared from intermediate B 19 and A5 by general method Al as a light brown solid.

MPt 101-102°C ;'H-NMR (d6 DMSO) 8 1.2-1.45 (6H, m), 1.5-1.75 (4H, m), 2.79 (2H, t), 3.07 (2H, t), 3.61 (2H, s), 6.69 (1 H. dd), 7.2-7.3 (1H, m), 7.45 (1H, d), 7.6-7.7 (1H, m), 7.81 (lH, s), 7.97 (lH, s), 8.3-8.4 (lH, m) and 8.47 (lH, d).

Example 63-2- (8- (2-Furyl)-8-oxooct-1-yl) thio-5- (pyrid-3-ylmethyl) pyrimidin-4- one Prepared from intermediate B 19 and A6 by general method Al as a light brown solid.

MPt 104-107°C; IH-NMR (d6 DMSO) 8 1.2-1.45 (6H. m) 1.5-1.8 (4H, m), 2.79 (2H, t), 3.07 (2H, t), 3.61 (2H, s), 6.69 (lH, m), 7.28 (lH, m), 7.45 (1H, m), 7.63 (1H, m), 7.81 (lH, m), 7.97 (lH, m), 8.38 (1H, m) and 8.48 (lH, m).

Example 64-2- (8- (2-Pyridyl) oct-1-yl) thio-5- (pyrid-3-ylmethyl) pyrimidin-4-one Prepared from intermediate B 19 and A 11 by general method A 1 as a light brown solid.

MPt 76-79°C ; lH-NMR (d6 DMSO) S 1.2-1.5 (8H, m), 1.55-1.8 (4H, m), 2.69 (2H, t), 3.07 (2H, t), 3.62 (2H, s), 7.05-7.4 (3H, m), 7.55-7.75 (2H, m), 7.82 (lH, s) and 8.35-8.55 (3H, m).

Example 65-2- (9- (4-Chlorophenyl)-9-oxonon-1-yl) thio-5- (pyrid-3-ylmethyl)- pyrimidin-4-one Prepared from intermediate B 19 and A 1 by general method Al as a white solid. MPt 112 -114°C;'H-NMR (CDCy 5 1.2-1.8 (14H), 2.92 (2H, t), 3.11 (2H, t), 3.74 (2H, s), 7.2

(lH, m), 7.42 (2H, d), 7.6-7.75 (2H, m), 7.88 (2H, m), 8.45 (lH, m) and 8.55 (lH, m); MS (EI) M=469; C25H28ClN3O2S requires 469.

Example 66-2- (8- (3,4-Dichlorophenyl) oct-7-yn-1-yl) thio-5- (pyrid-3-ylmethyl)- pyrimidin-4-one Prepared from intermediate B 19 and A 14 by general method Al as a white solid. MPt 92 -94°C ;1H@NMR (CDCl3) # 1.4-1.9 (8H, m), 2.39 (2H, t), 3.15 (2H, t), 3.74 (2H, s), 7.1-7.4 (5H, m), 7.6-7.75 (2H, m), 8.45 (1H, m) and 8.57 (1H, m); MS (EI) M=471; C24H23C12N30S requires 471.

Example 67-2- (8- (4-Acetylphenyl) oct-1-yl) thio-5- (pyrid-3-ylmethyl) pyrimidin-4- one Prepared from intermediate B 19 and A20 by general method Al as a white solid. MPt 81 -84°C; lH-NMR (CDCl3) b 1.2-1.8 (12H, m), 2.58 (3H, s), 2.65 (2H, t), 3.13 (2H, t), 3.74 (2H, s), 7.1-7.35 (3H, m), 7.6-7.75 (2H, m), 7.87 (2H, d) and 8.3-8.7 (2H, bd); MS (EI) M=449; C26H31N3O2S requires 449.

Example 68-2- (8- (4-Methylnaphth-1-yl)-8-oxooct-1-yl) thio-5- (pyrid-3-ylmethyl)- pyrimidin-4-one Prepared from intermediate B 19 and A9 by general method Al as a white solid. MPt 102 -104°C; IH-NMR (CDCl3) å (6H, m), 1.5-1.8 (4H, m), 2.73 (3H, s), 3.02 (2H, t), 3.13 (2H, t), 3.73 (2H, s), 7. 25 (1H,m), 7.28 (lH, d), 7.45-7.75 (4H, m), 7.75 (lH, d), 8.02 (1H, m), 8.45 (IH. m) and 8.5-8.7 (2H, m); MS (EI) M=485; C., 9H3lN302S requires 485.

Example 69-2-(8-(4-Pyridyl) oct-1-yl) thio-5-(pyrid-3-ylmethyl) pyrimidin-4-one Prepared from intermediate B 19 and A23 by general method A 1 as a white solid. MPt 86 -88°C; lH-NMR (d6 DMSO) 8 (8H, m), 1.5-1.8 (4H, m), 2.57 (2H, t), 3.07 (2H, t), 3.62 (2H, s), 7.21 (2H, d), 7.25 (1H, m), 7.81 (1H, s) and 8.3-8.6 (4H, m).

Example 70-2- (8- (4-Chlorophenyl) oct-1-yl) thio-5- (pyrid-3-ylmethyl) pyrimidin-4- one Prepared from intermediate B19 and A24 by general method Al. 1H-NMR (d6DMSO) # 1.2-1.5 (6H, m), 1.5-1.8 (4H, m), 2.54 (2H, t), 3.07 (2H, t), 3.61 (2H, s), 7.1-7.4 (5H, m), 7.63 (lH, m), 7.80 (lH, s), 8.38 (lH, m) and 8.47 (lH, bs).

Example 71-2- (4- (3-Phenylprop-1-yloxy) but-1-yl) thio-5- (pyrid-3-ylmethyl)- pyrimidin-4-one Prepared from intermediate B19 and A43 by general method A1. IH-NMR (d6-DMSO) 5 1.5-1.9 (6H, m), 2.59 (2H, t), 3.12 (2H, t), 3.3 (4H, m), 3.61 (2H, s), 7.1-7.3 (6H, m), 7.6 (1H, m), 7.81 (1H, s), 8.38 (lH, m), 8.48 (lH, d).

Example 72-2- (6-Benzyloxyhex-1-yl) thio-5- (quinolin-3-ylmethyl) pyrimidin-4-one Prepared from intermediate B 19 and A27 by general method A 1 as a light brown solid.

MPt 120-122°C ; lH-NMR (d6-DMSO) â 1.3 (4H, m), 1.5 (2H, m), 1.6 (2H, m), 3.08 (2H, t), 3.39 (2H. t), 3.82 (2H, s), 4.42 (2H, s), 7.3 (5H, m), 7.56 (lH, m), 7.70 (lH, m), 7.9- 8.0 (3H, m), 8.13 (1 H, d), 8.85 (1H, d), 12.7 (1H, br s).

Example 73-2- (8-Phenyloct-1-yl) thio-5- (quinolin-3-ylmethyl) pyrimidin-4-one Prepared from intermediate B 16 by general method Al as a light brown solid. MPt 124- 126°C; 1H-NMR (d6-DMSO) # 7. 1-7.3 (5H, m), 7.56 (lH, m), 7.68 (lH, m), 7.9-8.0 (3H, m), 8.12 (1H, d), 8.85 (1H, d).

Example 74-2-(8-Phenyloct-1-yl) thio-5-((4-methoxypyrid-2-yl) methyl) pyrimidin- 4-one Prepared from intermediate B26 by general method B as a brown solid after trituration with ether and recrystallisation from ethyl acetate. MPt 58-60°C ; IH-NMR (d6-DMSO)

8 1.3 (8H, m), 1.6 (4H, m), 2.55 (2H, t), 3.07 (2H, t), 3.69 (2H, s), 3.78 (3H, s), 6.8 (2H, m), 7.1-7.3 (5H, m), 7.70 (lH, s), 8.25 (lH, d).

Example 75-2- (8-Phenyloct-1-yl) thio-5- (2-oxopyrid-4-ylmethyl) pyrimidin-4-one A mixture of 2- (8-phenyloct-1-yl) thio-5- (2-methoxypyrid-4-ylmethyl) pyrimidin-4-one (0.40 g, 0.9 mmol), chlorotrimethylsilane (0. 23 ml, 1.8 mmol) and sodium iodide (0.27 g, 1.8 mmol) in acetonitrile (30 ml) was heated at reflux for 6 hours. The solvent was evaporated, the residue taken up in dichloromethane, and washed with water and aqueous sodium thiosulphate. Evaporation of the solvent and trituration with ether gave 2- (8- phenyloct-1-yl) thio-5- (2-oxopyrid-4-ylmethyl) pyrimidin-4-one as a white solid (0.03 g).

IH-NMR (d6-DMSO) å 1.3 (8H, m), 1.6 (4H, m), 2.55 (2H, t), 3.07 (2H, t), 6.07 (2H, m), 7.1-7.3 (6H, m), 7.77 (lH, s); MPt indeterminate.

Example 76-2- (8-Phenyloct-1-yl) thio-5- (pyrid-4-ylmethyl) pyrimidin-4-one Prepared from intermediate B20 by general method Al as a beige solid. MPt 124- 125°C;'H-NMR (d6-DMSO) b 1.3 (8H, m), 1.6 (4H. m), 2.55 (2H, t), 3.08 (2H, t), 3.63 (2H, s), 7.1-7.3 (7H, m), 7.83 (lH, s), 8.42 (2H, d).

Example 77-2-(6-Benzyloxyhex-1-yl) thio-5-(pyrid-4-ylmethyl) pyrimidin-4-one Prepared from intermediate B20 and A27 by general method A1 as a white solid. MPt 111-113°C ;H-NMR (d6-DMSO) 5 7.23 (2H, d), 7.3 (5H, m), 7.83 (lH, s), 8.43 (2H, d), 1. 28 (l H, br s).

Example 78-2-(8-(4-Chlorophenyl)-8-oxooct-1-yl) thio-5-(pyrimid-5-ylmethyl)- pyrimidin-4-one Prepared from intermediate B9 and Al by general method Al as a white solid. MPt 129- 130°C; lH-NMR (CDCI3) â 1.2-1.5 (6H, m), 1.5-1.8 (4H, m), 2.93 (2H, t), 3.15 (2H, t), 3.71 (2H, s), 7.43 (2H, d), 7.78 (1H, s), 7.89 (2H, d), 8.72 (2H, s) and 9.07 (lH, s); MS (EI) M=456; C23H25ClN4O2 requires 456.

Example 79-2- (8-Phenyloct-1-yl) thio-5- (fur-2-ylmethyl) pyrimidin-4-one Prepared from intermediate B 13 by general method A l as a light brown solid. MPt 79- 81°C ; lH-NMR (d6-DMSO) å 1.3 (8H, m), 1.6 (4H, m), 2.55 (2H, t), 3.07 (2H, t), 3.64 (2H, s), 6.08 (lH, m), 6.34 (lH, m), 7.1-7.3 (5H, m), 7.51 (lH, m), 7.67 (lH, s).

Example 80-2- (6-Benzyloxyhex-1-yl) thio-5- (fur-2-ylmethyl) pyrimidin-4-one Prepared from intermediate B 13 and A27 by general method A1 as a brown solid. MPt 63-65°C; 1H-NMR (d6-CMSO) # 1.3 (4H, m), 1.5 (2H, m), 1.6 (2H, m), 3.08 (2H, t), 3.40 (2H, t). 3.64 (2H, s), 4.43 (2H, s), 6.08 (lH, m), 6.34 (lH, m), 7.3 (5H, m), 7.51 (1H, m), 7.68 (1H,s).

Example 81-2- (6-Benzyloxyhex-1-yl) thio-5- (fur-3-ylmethyl) pyrimidin-4-one Prepared from intermediatee B 15 and A27 by general method A1 as a white solid. MPt 58-60°C ; lH-NMR (d6-DMSO) b 1.3 (4H, m), 1.5 (2H, m), 1.6 (2H, m), 3.08 (2H, t), 3.4 (4H, m), 4.43 (2H, s), 6.37 (1H, m), 7.3 (5H, m), 7.44 (lH, m), 7.55 (lH, m), 7.68 (lH, s).

Example 82-2- (8-Phenyloct-1-yl) thio-5- (fur-3-ylmethyl) pyrimidin-4-one Prepared from intermediatee B 15 by general method A1 as a white solid. MPt 78-80°C; 'H-NMR (d6-DMSO) S 6.37 (lH, s), 7.1-7.3 (5H, m), 7.44 (lH, m), 7.55 (lH, m), 7.65 (1H,s) Example 83-2-Benzylthio-5- ((1-methyl-2-oxo-pyrid-4-yl) methyl) pyrimidin-4-one Prepared from intermediate B 11 by general method Al as a white solid. MPt 194- 196°C; lH-NMR (d6-DMSO) â 3.35 (3H, s), 3.44 (2H, s), 4.39 (2H, s), 6.10 (lH, m), 6.16 (lH, s), 7.56 (lH, d), 7.86 (lH, s), 12.8 (lH, br s).

Example 84-2-Benzylthio-5- (fur-2-ylmethyl) pyrimidin-4-one Prepared from intermediate B 13 by general method A5.1H-NMR (d6-DMSO) 8. 366 (2H, s), 4.38 (2H, s), 6.09 (lH, m), 6.35 (lH, m), 7.2-7.4 (5H, m), 7.52 (lH, m), 7.74 (lH, s).

Example 85-2- (3-Chlorobenzyl) thio-5- (fur-2-ylmethyl) pyrimidin-4-one Prepared from intermediate B 13 by general method A5. 1H-NMR (d6-DMSO) # 3. 66 (2H, s), 4.39 (2H, s), 6.09 (lH, m), 6.35 (lH, m), 7.3-7.4 (5H, m), 7.50 (lH, m), 7.74 (lH, s).

Example 86-2- (4-Chlorobenzyl) thio-5- (fur-2-ylmethyl) pyrimidin-4-one Prepared from intermediate B 13 by general method AS. lH-NMR (d6-DMSO) â 3.63 (2H, s), 4.33 (2H, s), 6.07 (1H, m), 6.34 (lH, m), 7.35 (2H, d), 7.42 (2H, d), 7.50 (lH, m), 7.64 (1 H, s).

Example 87-2-Benzylthio-5-((2-methylpyrid-5-yl) methyl) pyrimidin-4-one Prepared from intermediate B21 by general method Al as a white solid. MPt 226- 228°C ; IH-NMR (d6-DMSO) å 2.40 (3H, s), 3.59 (2H, s), 4.38 (2H, s), 7.14 (lH, d), 7.2-7.5 (5H, m), 7.52 (lH, dd), 7.84 (lH, s), 8.34 (lH, d).

Example 2-Benzylthio-5-((2-methoxypyrid-4-yl)methyl)pyrimidin-4-one- Prepared from intermediate B25 by general method B as a white solid. MPt 193-5°C ;1H- NMR (d6-DMSO) 8 3.60 (2H, s), 3.81 (3H, s), 4.39 (2H, s), 6.65 (1 H, s), 6.85 (1H, m), 7.25-7.42 (5H, m), 7.87 (1H, s), 8.03 (1H, m).

Example 89-2-Benzylthio-5-(pyrazin-2-ylmethyl) pyrimidin-4-one Prepared from intermediate B 14 by general method Al as a white solid. MPt 174- 175°C;'H-NMR (d6 DMSO) 8 3.84 (2H, s), 4.40 (2H, s), 7.1-7.5 (5H, m), 7.89 (lH, bs), 8.47 (lH, d), 8.51 (lH, t) and 8.59 (lH, d); MS (FAB) M+1=311; C16H14N4OS requires 310.

Example 2-Benzylthio-5-(thiazol-2-ylmethyl)pyrimidin-4-one- Prepared from intermediate B22 by general method A1 as light brown crystals; lH-NMR (d6 DMSO) 4.02 (2H, s). 4.41 (2H, s), 7.2-7.45 (6H, m), 7.55 (lH, d), 7.67 (lH, d) and 7.95 (lH, bs); MS (EI) M=315; CisHi3N30S2 requires 315.

Example 91-2- (4-Chlorobenzyl) thio-5- (pyrid-3-ylmethyl) pyrimidin-4-one Prepared from intermediate B 19 by general method A5. IH-NMR (d6-DMSO) 5 3.59 (2H, s), 4.30 (2H, s), 7.26 (1H, m), 7.31 (2H, d), 7.41 (2H, d), 7.63 (lH, m), 7.72 (lH, s), 8.37 (1H, m), 8.47 (1H, m).

Example 92-2-Benzylthio-5- (pyrid-3-ylmethyl) pyrimidin-4-one Prepared from intermediate B 19 by general method A5. 1H-NMR (d6-DMSO) # 3.61 (2H, s), 4.33 (2H, s), 7.2-7.4 (5H, m), 7.64 (1H. m), 7.78 (lH, s), 8.38 (lH, m), 8.49 (lH, m).

Example 93-2-(3, 4-Dichlorobenzyl) thio-5-(pyrid-3-ylmethyl) pyrimidin-4-one Prepared from intermediate B 19 by general method A5. 1H-NMR (d6-DMSO) # 3. 60 (2H, s), 4.31 (2H, s), 7.26 (lH, m), 7.39 (IH. m), 7.53 (1H, d), 7.65 (lH, m), 7.75 (lH, s), 8.37 (1H, m), 8.48 (lH. m).

Example2-Benzylthio-5-(pyrid-4-ylmethyl)pyrimidin-4-one- Prepared from intermediate B20 by general method Al as a white solid. MPt 183- 185°C; IH-NMR (d6-DMSO) â 3.64 (2H, s), 4.39 (2H, s), 7.24 (2H, d), 7.3-7.4 (5H, m), 7.89 (1H, s), 8.43 (2H, d).

Example 95-2- (4-Chlorobenzyl) thio-5- (pyrid-4-ylmethyl) pyrimidin-4-one Prepared from intermediate B20 by general method A5. 'H-NMR (d6-DMSO) 8 3.65 (2H. s), 4.38 (2H, s), 7.24 (2H. d), 7.37 (2H, d), 7.44 (2H, d), 7.88 (lH, s), 8.43 (2H, d).

Example 96-2- (3,4-Dichlorobenzyl) thio-5- (pyrid-4-ylmethyl) pyrimidin-4-one Prepared from intermediate B20 by general method A5. IH-NMR (d6-DMSO) 8 3.66 (2H, s), 4.39 (2H, s), 7.25 (2H, d), 7.42 (lH, dd), 7.57 (1H, d), 7.69 (lH, d), 7.89 (1H, s), 8.44 (2H, d).

Example 97-2-Benzylthio-5-(pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B9 by general method Al as a white solid. MPt 239-241°C; IH-NMR (d6-DMSO) â 3.65 (2H, s), 4.39 (2H, s), 7.1-7.5 (5H, m), 7.95 (lH, bs), 8.71 (2H. s) and 9.02 (lH, s); MS (EI) M=310 ; Cl6Hl4N40S requires 310.

Example 98-2-Benzylthio-5- (2-(pyrid-4-yl) ethyl) pyrimidin-4-one Prepared from intermediate B 17 by general method A1 as a white solid. MPt 209- 2105°C ;1H-NMR (d6-DMSO) # 2.61 (2H, t), 2.81 (2H, t), 4.36 (2H, s), 7.1-7.5 (7H, m), 7.69 (lH, s) and 8.45 (2H, d); MS (FAB) M+1=324; ClgHl7N30S requires 323.

Example 99-2-Benzylthio-5-benzylpyrimidin-4-one Prepared from intermediate B23 by general method Al as a brown solid. MPt 156- 158°C; 1H-NMR (d6-DMSO) # 3.62 (2H, s), 4.38 (2H, s), 7.1-7.5 (IOH, m), 7.8 (lH, s), 12.8 (1 H, br s).

Example 100-2- (8-Phenyloct-1-yl) oxy-5- (pyrid-3-ylmethyl) pyrimidin-4-one A mixture of 8-phenyl-1-octanol (1.5g), 2-nitroamino-5- (pyrid-3-ylmethyl) pyrimidin-4- one (1. Og) and pyridine (5ml) was stirred at reflux for 24 hours, then the pyridine was removed by evaporation. Water was added, and the product extracted into dichloromethane, which was dried and evaporated. The residue was purified by chromatography (silica, 0-5% methanol in dichloromethane) and recrystallisation from ether to give 2- (8-phenyloct-1-yl) oxy-5- (pyrid-3-ylmethyl) pyrimidin-4-one as a pale buff solid (O. lg). MPt 53-55°C ;H-NMR (CDC13) 8 1.32 (8H, m), 1.60 (2H, m), 1.74 (2H, m), 2.58 (2H, t), 3.72 (2H, t), 4.31 (2H, t), 7.1-7.3 (6H, m), 7.54 (lH, m), 7.63 (lH, m), 8.45 (lH, m) and 8.55 (lH, d); MS (EI) Found M=391; C24H29N30, requires 391.

Example 101-2- (8- (4-Chlorophenyl)-8-oxooct-1-yl) oxy-5- (pyrid-3-ylmethyl)- pyrimidin-4-one Prepared from intermediates B24 and A2 analogously to example 100. Recrystallisation from acetonitrile/ether gave the product as an off-white solid. MPt 116-7°C; I H-NMR (CDCl3) 8 1.39 (6H, m), 1.74 (4H, m), 2.93 (2H, t), 3.72 (2H, t), 4.31 (2H, t), 7.2 (lH, m), 7.42 (2H, d), 7.55 (lH, s), 7.62 (lH, d), 7.88 (2H, d), 8.45 (lH, m) and 8.54 (1H, d); MS (FAB) M+1=440; C24H26ClN3O2 requires 439.

Example 102-2- (4-Phenylbut-1-yl) oxy-5-((2-methylpyrid-5-yl) methyl) pyrimidin- 4-one Finely ground cyanamide (1.68 g, 0.04 mol) and cyanamide dihydrochloride (2.26 g, 0.02 mol) were treated with 4-phenyl-1-butanol (3.24 g, 0.02 mol), occasionally stirring with a glass rod over a 20 day period. The white paste was dissolved in water, extracted with chloroform and the aqueous layer adjusted to pH 13 (conc. sodium hydroxide) with ice cooling. The oil which precipitated was extracted into ethyl acetate, dried (MgS04) and the solvent evaporated to give the isourea as a clear oil (3.88 g). A portion of this material (2.44 g) was converted to the hydrochloride salt by treatment with HCl/ethanol/ether, the solvents evaporated and the residue washed several times with ether and dried under high vacuum to yield 1.47 g.

This material (1.47 g, 0.00646 mol) was dissolved in ethanol (40 ml) together with ethyl 2-formyl-3- (6-methylpyrid-3-yl) propionate (0.95 g, 0.00431 mol) and triethylamine and heated under reflux for 6 h. The solvent was evaporated and the residue treated with water and extracted with ethyl acetate, dried (MgS04) and evaporated to an oil.

Purification by chromatography (silica, methanol/chloroform) followed by crystallisation from ethyl acetate-petrol gave 2- (4-phenylbut-1-yl) thio-5- ( (2-methylpyrid-5-yl) methyl)- pyrimidin-4-one, yield 0.09 g (6%). MPt 88-90°C; lH-NMR (CDCl3) õ 1.75 (4H, m), 2.49 (3H, s), 2.65 (2H, t), 3.64 (2H, s), 4.32 (2H, t), 6.90-7.60 (8H, m), 8.38 (1H, m).

Example 103-2- (2-Phenylethyl) thio-5-((2-methylpyrid-5-yl) methyl) pyrimidin-4- one Prepared from intermediate B21 by general method B as white crystals; MPt 158-160°C.

'H-NMR (d6-DMSO) 8 2.41 (3H, s), 2.93 (2H, t), 3.3 (2H+H., O, t), 3.58 (2H, s), 7.14 (lH, d), 7. 2-7.3 (5H, m), 7.52 (lH, dd), 7.83 (lH, s), 8.34 (lH, d), 12.7 (lH, br s).

Example 104 - 2-(2-Phenylethyl)thio-5-((2-methoxypyrid-4-yl) methyl) pyrimidin-4- one Prepared from intermediate B25 by general method B as white crystals; MPt 139-140°C.

1H-NMR (d6-DMSO) 5 2.94 (2H, t), 3.3 (2H+H, O, t), 3.59 (2H, s), 3.81 (3H, s), 6.65 (lH, s), 6.86 (1H, dd), 7.2-7.3 (5H, m), 7.85 (1 H. br s), 8.03 (1H, d) Example 105-2-Benzylthio-5- ( (l-methylpyrazol-4-yl) methyl) pyrimidin-4-one Prepared from intermediate B34 by general method Al as a white crystalline solid. 1H- NMR (d6-DMSO) 8 3.37 (2H, s), 3.71 (3H. s), 4.33 (2H, s), 7.2-7.4 (6H, m), 7.41 (lH, s), 7.67 (lH, brs), 12.7 (IH, br s); (APCI) M+H=313. Cl6Hl6N40S requires 312.

Example 106-2- (4-Fluorobenzylthio)-5-((pyrimid-5-yl) methyl) pyrimidin-4-one

Prepared from intermediate B9 by general method A4. IH-NMR (d6-DMSO) 6 3.65 (2H, s), 4.38 (2H, s), 7.05-7.2 (2H, m), 7.35-7.5 (2H. m), 7.94 (lH, bs), 8.71 (2H, s), 9.06 (lH, s); MS (APCI-) found (M-1)=327; C16-H13FN4OS requires 328.

Example 107-2- (3, 4-Difluorobenzylthio)-5- ( (2-methoxypyrimid-5- yl) methyl) pyrimidin-4-one Prepared from intermediate B39 by general method A4. IH-NMR (d6-DMSO) 8 3.57 (2H, s), 3.87 (3H, s), 4.37 (2H, s), 7.24-7.53 (3H, m), 7.88 (1H, br. s), 8.49 (2H, s), 12.88 (1H, br s); MS (APCI+) found (M+1) = 377; C17H20F2N4O2S requires 376.

Example 108-2- (4-Fluorobenzylthio)-5- ( (2-methoxypyrimid-5- yl) methyl) pyrimidin-4-one Prepared from intermediate B39 by general method A4. IH-NMR (d6 DMSO) 8 3.55 (2H, s), 3.85 (3H, s), 4.36 (2H, s), 7.0-7.2 (2H, m), 7.35-7.5 (2H, m), 7.86 (lH, bs), 8.48 (2H, s) 12.81 (lH, b); MS (APCI+) found (M+1) = 359; C17Hl5FN402S requires 358.

Example 109-2-(4-Fluorobenzylthio)-5-((2-benzyloxypyrimid-5- yl) methyl) pyrimidin-4-one Prepared from intermediate B40 by general method A4. lH-NMR (d6-DMSO) 6 3.57 (2H, s), 4.38 (2H, s), 5.35 (2H, s), 7.0-7.2 (2H, m), 7.25-7.5 (7H, m), 7.87 (lH, bs), 8.51 (2H, s); MS (APCI+) found (M+1)=435; C23H19FN4O2S requires 434.

Example 110-1- (4-Hydroxycyclohexyl)-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5-ylmethyl)pyrimidin-one Prepared from intermediates B46 and A1 by general method A4.'H-NMR (CDC) § 1. 1-2. 3 (18H, m), 2.94 (2H, t), 3.24 (2H, t), 3.6-3.8 (3H, m), 4.2 (lH. m), 7.12 (1h, s),

7.45 (2H, m), 7.90 (2H, m), 8.71 (2H, s) and 9.09 (lH, s); MS (APCI+) found (M+1) =555; 554.C29H35CIN4O3Srequires Example 111-1- (2-Methoxyethyl)-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B87 by general method A4. 1H-NMR (CDCl3) # 1.25- 1.85 (10H, m), 2.93 (2H, t), 3.26 (2H, t), 3.32 (3H, s), 3.62 (2H, t), 3.69 (2H, s), 3.98 (2H, t), 7.08 (1H, s), 7.43 (2H, m), 7.90 (2H, m), 8.70 (2H, s) and 9.09 (lH, s); MS (APCI+) found (M+1) =515 ; C26H31ClN403S requires 514.

Example 112-1-(3-(1-Imidazolyl) prop-l-yl)-2-(8-(4-chlorophenyl)-8-oXooct-1- yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B47 and A1 by general method A4, as a yellow oil. lH-NMR (CDCl3) 8 1.38 (6H, m), 1.70 (4H, m), 2.25 (2H, m), 2.91 (2H, t), 3.25 (2H, t), 3.69 (2H, s), 3.77 (2H, t), 4.07 (2H, t), 6.81 (1H, s), 6.92 (1H, s), 7 13 (1H, s), 7.43 (2H, d), 7.50 (1H, s), 7.89 (2H, d), 8.70 (2H, s), 9.10 (1H, s); MS APCI+) found (M+1) =565; 564.C29H33ClN6O2Srequires Example 113-1- (3- (1-Morpholino) prop-1-yl)-2- (8- (4-chlorophenyl)-8-oxooct-1- yl) thio-5-(pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B48 and Al by general method A4, as a thick gum. 1H-NMR (CDC13) 5 1.2-1.8 (10H, m), 1.93 (2H, m), 2.25-2.5 (6H, m), 2.93 (2H, t), 3.25 (2H, t), 3.55- 3.8 (6H, m), 3.90 (2H, t), 7.07 (1H, s), 7.45 (2H, m), 7.90 (2H, m), 8.72 (2H, s) and 9.12 (1H, s); MS (APCI+) found (M+l) =584 ; C3oH3gClN503S requires 583.

Example 114-1- (3- (2-Oxo-l-pyrrolidino) prop-1-yl)-2- (8- (4-chlorophenyl)-8- oxooct-1-yl) thio-5-(pyrimid-5-ylmethyl) pyrimidin-4-one

Prepared from intermediate B49 and A1 by general method A4, as a yellow oil. 1H-NMR (CDCl3) 5 1.38 (6H, m), 1.74 (4H, m), 1. 98 (2H, m), 2.10 (2H, m), 2.43 (2H, t), 2.93 (2H, m), 3.25 (2H, t), 3.34 (2H, t), 3.41 (2H, t), 3.70 (2H, s), 3.82 (2H, t), 7.43 (2H, m), 7.54 (1H, s), 7.89 (2H, m), 8.74 (2H, s), 9.07 (1H, s); MS APCI+) found (M+1) =582; C3oH36CIN503S requires 581.

Example 115-1- (3-Dimethylaminoprop-1-yl)-2- (8- (4-chlorophenyl)-8-oxooct-1- yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B51 and Al by general method A4, as a thick gum. lH-NMR (CDCl3) 8 1.2-1.8 (10H, m), 1.8-2.05 (4H, m), 2.14 (3H, s), 2.19 (3H, s), 2.93 (2H, t), 3.24 (2H, t), 3.70 (2H, s), 7.42 (2H, m), 7.88 (2H, m) 8.72 (2H, s) and 9.09 (lH, s); MS (APCI+) found (M+l) =542; C28H36CIN502S requires 541.

Example 116-1- (3-Hydroxyprop-1-yl)-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B52 and Al by general method A4. lH-NMR (CDC13) õ 1.3- 1.55 (6H, m), 1.6-1.85 (4H), 1.95-2.1 (2H, m), 2.93 (2H, t), 3.25 (2H, t), 3.6-3.8 (4H, m), 4.01 (2H, t), 7.11 (1H, s) 7.45 (2H, d), 7.89 (2H, d), 8.70 (2H, m) and 9.08 (1H, s); MS (APCI+) found (M+l) =515; C26H31ClN4O3S requires 514.

Example 117-1- (3-Hydroxyprop-1-yl)-2- (8- (4-chlorophenyl) oct-1-yl) thio-5- benzylpyrimidin-4-one

Prepared from intermediate B52and A24 by general method A4, as a colourless powder.

MPt 76-77°C ; IH-NMR (CDC13) 6 1. 2-2.0 (14H, m), 2.56 (2H, t), 3.25 (2H, t), 3.61 (2H, t), 3.73 (2H, s), 3.88 (2H, t), 6.76 (lH, s), 7.09 (lH, d) and 7.15-7.4 (7H, m); MS (FAB) found M+H=499; C., H35ClN., O., S requiresH35ClN., O., S requires 498.

Example 118-1- (3-Methoxyprop-1-yl)-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B54 and A1 by general method A4. 'H-NMR (CDC'3) 6 1.2- 1.85 (10H, m), 2.00 (2H, m), 2.94 (2H, t), 3.2-3.4 (7H, m), 3.70 (2H, s), 3.92 (2H, t), 6.99 (1H, s), 7.44 (2H. m), 7.90 (2H, m), 8.71 (2H, s) and 9.10 (lH, s); MS (APCI+) found (M+1) =529; C27H33C1N403S requires 528.

Example 119-1- (3-Phenylprop-1-yl)-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B55 and A1 by general method A4. 1H-NMR (CDC13) 8 1.2- 1.85 (10H. m), 2.11 (2H, quintet), 2.69 (2H. t), 2.93 (2H, t), 3.24 (2H, t), 3.67 (2H, s), 3.78 (2H, t), 6.84 (1H, s), 7.1-7.5 (7H. m), 7.90 (2H, m), 8.70 (2H, s) and 9.10 (1H, s); MS (APCI+) found (M+1) =575; C32H35ClN4O2S requires 574.

Example 120-1- (5-Hydroxypent-1-yl)-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B56 and A1 by general method A4. IH-NMR (CDCI3) õ 1.3- 1.9 (16H. m), 2.94 (2H, t), 3.25 (2H, t), 3.6-3.75 (4H, m), 3.80 (2H, t), 6.96 (lH, m), 7.44 (2H, m), 7.90 (2H. m), 8.71 (2H. s) and 9.09 (1H, s); MS (APCI+) found (M+1) =543; C28H35ClN4O3S requires 542.

Example 121-1-(Pyrid-2-ylmethyl)-2-(8-(4-chlorophenyl)-8-oxooct-1-yl ) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one

Prepared from intermediate B45 and Al by general method A4, as a white solid. IH- NMR (CDCl3) 8 1.3-1.5 (6H, m), 1.6-1.8 (4H, m), 2.92 (2H, t), 3.25 (2H, t), 3.71 (2H, s), 5.06 (2H, s), 7.2-7.35 (3H, m), 7.6-7.8 (1H, m), 8.5-8.6 (1H, m), 8.70 (2H, s) and 9.10 (1H, s); MS (APCI+) found (M+1) =548; C, 9H30CIN502S requires 547.

Example 122-1- (Pyrid-2-ylmethyl)-2- (8- (4-chlorophenyl) oct-1-yl) thio-5- benzylpyrimidin-4-one Prepared from intermediate B57 and A24 by general method A4, as a pale brown oil. 1H- NMR (CDC13) 8 1.2-1.5 (8H, m), 1.5-1. 85 (4H, m), 2.55 (2H, t), 3.24 (2H, t), 3.77 (2H, s), 5.00 (2H, s), 6.88 (1H, s), 7.09 (2H, d), 7.25-7.4 (9H, m), 7.68 (1H, m) and 8.57 (1H, m); MS (EI) found M=531; C31H34C1N30S requires 531.

Example 123-1-(Pyrid-3-ylmethyl)-2-(8-(4-chlorophenyl)-8-oxooct-1-yl ) thio-5-((1- methyl-2-oxo-pyrid-4-yl) methyl) pyrimidin-4-one Prepared from intermediate B58 and Al by general method A4, as a buff coloured solid.

MPt 105-106°C ; IH-NMR (CDCl3) 8 1.36 (6H, m), 1.71 (4H, m), 2.96 (2H, t), 3.26 (2H, t), 3.49 (3H, s), 3.53 (2H, s), 5.02 (2H, s), 6.14 (1H, m), 6.34 (1H, s), 6.99 (1H, s), 7.17 (1H, m), 7.25-7.55 (4H, m), 7.91 (2H, d), 8.52 (1H, s), 8.64 (1H, m); MS (APCI+) found (M+l) = 577; C3lH33ClN403S requires 576.

Example 124-1- (Pyrid-3-ylmethyl)-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one

Prepared from intermediate B59 and Al by general method A4, as a white solid. MPt 80 -83°C;'H-NMR (CDC13) § 1.40 (6H, m), 1.69 (4H, m), 2.93 (2H, t), 3.26 (2H, t), 3.69 (2H, s), 5.04 (2H, s), 7.04 (lH, s), 7.30-7.56 (4H, m), 7.91 (2H, d), 8.55 (1H, m), 8.68 (3H, m), 9.10 (1H, s); MS (APCI+) found (M+l) = 548; C29H3oClN50., S requires 547.

Example 125-1- (Pyrid-3-ylmethyl)-2- (8- (4-chlorophenyl) oct-1-yl) thio-5- benzylpyrimidin-4-one Prepared from intermediate B60 and A24 by general method A4, as a pale brown oil. 1H- NMR (CDCl3) 5 1.2-1.5 (8H, m), 1.5-1.85 (4H, m), 2.56 (2H, t), 3.26 (2H, t), 3.75 (2H, s), 4.92 (2H, s), 6.66 (1H, s), 7.09 (lH, d), 7.15-7.5 (9H, m), 8.45 (lH, m) and 8.59 (1H, m); MS (EI) found 531; C3IH34ClN30S requires 531.

Example 126-1-(Pyrid-4-ylmethyl)-2-(8-(4-chlorophenyl) oct-1-yl) thio-5-((1- methyl-2-oxo-pyrid-4-yl) methyl) pyrimidin-4-one Prepared from intermediate B61 and A24 by general method A4, as an orange gum. IH- NMR (CDCl3) 8 1.2-1.5 (8H, m), 1.5-1.75 (4H, m), 2.55 (2H, t), 3.24 (2H, t), 3.49 (3H, s), 3.55 (2H, s), 5.01 (2H, s), 6.16 (1H, m), 6.35 (1H, bs), 6.9-7.35 (8H, m) and 8.63 (2H, m); MS (FAB) M+1=563; C3lH35ClN402S requires 562.

Example 1-(Pyrid-4-ylmethyl)-2-(8-(4-chlorophenyl)-8-oxooct-1-yl)thi o-5-((1-- methyl-2-oxo-pyrid-4-yl) methyl) pyrimidin-4-one Prepared from intermediate B61 and Al by general method A4, as an off-white solid.

MPt 113-114°C; lH-NMR (CDCl3) õ 1.29 (6H, m), 1.63 (4H, m), 2.86 (2H, t), 3.19 (2H, t), 3.43 (3H, s), 3.49 (2H, s), 4.95 (2H, s), 6.09 (1H, m), 6.29 (1H, m), 6.89 (1H, s), 6.99 (2H, m), 7.12 (1H, d), 7.36 (2H, d), 7.83 (2H, d), 8.58 (2H, m).

Example 128-1- (Pyrid-4-ylmethyl)-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B62 and A1 by general method A4, as a buff coloured solid.

MPt 75-77°C ; lH-NMR (CDC13) 6 1.35 (6H, m), 1.67 (4H, m), 2.92 (2H, t), 3.27 (2H, t), 3.72 (2H, s), 5.02 (2H, s), 6.99 (1H, s), 7.05 (2H, m), 7.43 (2H, d), 7.89 (2H, d), 8.64 (4H, m), 9.09 (1H, s); MS (APCI+) found (M+l) = 548; C29H30ClN5OS requires 547.

Example 129-1- (Pyrid-4-ylmethyl)-2- (8- (4-chlorophenyl) oct-1-yl) thio-5- benzylpyrimidin-4-one Prepared from intermediate B63 and A24 by general method A4, as a buff powder. MPt 108-110°C ; IH-NMR (CDCI3) õ 1.2-1.8 (12H, m), 2.55 (2H, t), 3.25 (2H, t), 3.77 (2H, s), 4.91 (2H, s), 6.62 (lH, s), 6.68 (2H, d), 7.08 (2H, d), 7.15-7.4 (7H, m) and 8.5-8.7 (2H, m); MS (EI) found M=531; C3IH34C1N30S requires 531.

Example 130-1- (Pyrid-4-ylmethyl)-2- (8- (4-chlorophenyl) oct-1-yl) thiopyrimidin-4- one Prepared from intermediate B64 and A24 by general method A4, as a brown gum. lH- NMR (CDCl3) # 1.2-1.5 (8H, m), 1.5-1.8 (4H, m), 2.55 (2H, t), 3.24 (2H, t), 5.04 (2H, s), 6.11 (lH, d), 7.0-7.4 (7H, m) and 8.65 (2H, m); MS (EI) M=441; C24H28ClN30S requires 441.

Example 131-1-(2-(Pyrid-2-yl) ethyl)-2-(8-(4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B65 and Al by general method A4. 1H-NMR (CDCl3) # 1.2- 1.8 (1IOH, m), 2.94 (2H. t), 3.2-3.35 (4H. m), 3.53 (2H, s), 4.32 (2H, t), 6.74 (lH, s), 7.04 (lH, m),

7.20 (1H, m), 7.43 (2H, m), 7.57 (lH. m), 7.88 (2H. m), 8.4-8.55 (3H, m) and 9.09 (1H, s); MS (APCI+) found (M+1) =562; C3oH32C1N50., S requires 561.

Example 132-1- (2- (Pyrid-3-yl) ethyl)-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- ( (1-methyl-2-oxo-pyrid-4-yl) methyl) pyrimidin-4-one Prepared from intermediate B66 and A1 by general method A4, as a cream coloured crystalline solid. MPt 121 - 123°C 1H-NMR (CDCl3) # 1.42 (6H, m), 1.7 (4H, m), 2.94 (2H, t), 3.07 (2H, t), 3.29 (2H, t), 3.45 (2H, s), 3.51 (3H, s), 4.01 (2H, t), 6.05 (1H, m), 6.28 (1H, m), 6.64 (1H, s), 7.16 (1H, d), 7.26 (1H, m), 7.45 (3H, m), 7.89 (2H, d), 8.45 (1H, m), 8.54 (1H, m); MS (APCI+) found (M+l) = 591; C32H35C1N403S requires 590.

Example 133-1- (2- (Pyrid-3-yl) ethyl)-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B67 and Al by general method A4. 1H-NMR (CDCl3) # 1.3- 1.9 (10H, m), 2.94 (2H, t), 3.08 (2H. t), 3.58 (2H. s), 4.03 (2H, t), 6.57 (1H, s), 7.43 (2H, m), 7.90 (2H, m), 8.44 (lH, m), 8.55 (3H. m) and 9.09 (lH, m) ; MS (APCI+) found (M+l) =562 ; C3oH32ClN50, S requires 561.

Example 134-1- (2- (Pyrid-4-yl) ethyl)-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- ( (1-methyl-2-oxo-pyrid-4-yl) methyl) pyrimidin-4-one Prepared from intermediate B68 and Al by general method A4, as a cream coloured crystalline solid. MPt 129-130°C ; 1H-NMR (CDCl3) # 1.40 (6H, m), 1.70 (4H, m), 2.95 (2H, t), 3.06 (2H, t), 3.30 (2H, t), 3.44 (2H, s), 3.51 (3H, s), 4.04 (2H, t), 5.95 (1H, m), 6.29 (1H, m), 6.56 (1H, s), 7.08 (2H, m), 7.17 (1H, d), 7.44 (2H, d), 7.90 (2H, d), 8.53 (2H, m); MS (APCI+) found (M+l) = 591; C32H35CIN403S requires 590.

Example 135-1- (2- (Pyrid-4-yl) ethyl)-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediates B69 and Al by general method A4. lH-NMR (CDCl3) 6 (lOH, m), 2.91 (2H, t), 3.06 (2H, t), 3.29 (2H, t), 3.59 (2H, s), 4.04 (2H, t), 6.62 (lH, s), 7.07 (2H, m), 7.43 (2H, m), 7.90 (2H, m), 8.45-8.7 (4H, m) and 9.10 (lH, s); MS (APCI+) found (M+l) =562 ; C3oH32ClN502S requires 561.

Example 1-(2-Phenylethyl)-2-(8-(4-chlorophenyl)oct-1-yl)thio-5-((1-m ethyl-2-- oxo-pyrid-4-yl) methyl) pyrimidin-4-one Prepared from intermediate B70 and A24 by general method A4, as a pale brown gum.

1H-NMR (d6-DMSO) # 1.2-1.5 (8H, m), 1.5-1.8 (4H, m), 2.54 (2H, t), 3.01 (2H, t), 3.11 (2H, t), 3.26 (2H, s). 3.35 (3H+HOD), 4.09 (2H, t), 5.94 (1H, dd), 6.10 (lH, d), 7.1-7.4 (9H, m) and 7.54 (2H. m).

Example 1-(2-Phenylethyl)-2-(8-(4-chlorophenyl)oct-1-yl)thio-5-(pyri d-3-- ylmethyl) pyrimidin-4-one Prepared from Example 70 by general method Cl, as a brown/green gum. I H-NMR (CDC13) 5 1.2-1.8 (12H, m), 2.56 (2H. t), 3.01 (2H, t), 3.26 (2H, t), 3.51 (2H, t), 3.97 (2H, t), 6.27 (1H, s), 7.0-7.5 (l IH. m), 8.30 (1H, m) and 8.46 (1H, m); MS (FAB) M+1=546; C32H36C1N30S requires 545.

Example 138-1- (2-Methylprop-1-yl)-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B88 and Al by general method A4.'H-NMR (d6-DMSO) 8 0.88 (6H, d), 1.2-1.4 (6H, m), 2.5-2.7 (4H, m), 2.08 (lH, m), 3.00 (2H, t). 3.11 (2H, t), 3.57 (2H, s), 3.69 (2H, d), 7.58 (2H, d), 7.82 (lH, s), 7.97 (2H, d), 8.70 (2H, s), 9.01 (lH, s); MS (APCI) M=513; C27H33CIN402S requires 513.

Example 139-1-Phenylsulfonyl-2- (8- (4-chlorophenyl) oct-1-yl) thio-5- (pyrid-3- ylmethyl) pyrimidin-4-one Benzenesulfonyl chloride (41mg) was added to a solution of 2- (8- (4-chlorophenyl) oct-1- yl) thio-5- (pyrid-3-ylmethyl) pyrimidin-4-one (103mg) in pyridine (O. 5ml), and the mixture stirred overnight. Evaporation of the pyridine followed by chromatography (silica, 0-2% methanol in dichloromethane) gave 1-phenylsulfonyl-2- (8- (4- chlorophenyl) oct-1-yl) thio-5- (pyrid-3-ylmethyl) pyrimidin-4-one (25mg). IH-NMR (CDCl3) S 1.2-1.5 (8H, m), 1.5-1.8 (4H, m), 2.56 (2H, t), 2.92 (2H, t), 3.87 (2H, s), 7.08 (2H, d), 7.15-7.8 (7H, m). 7.95 (2H, m), 8.29 (lH, s) and 8.35-8.7 (2H, bm).

Example 140-1-Benzyl-2-(8-(4-chlorophenyl) oct-1-yl) thio-5-((1-methyl-2-oxo- pyrid-4-yl) methyl) pyrimidin-4-one Prepared from intermediate B71 and A24 by general method A4, as a yellow/orange gum.

'H-NMR (CDCl3) 8 1.2-1.5 (8H, m), 1.5-1.8 (4H, m), 2,56 (2H, t), 3.25 (2H, t), 3.49 (3H, s), 3.52 (2H, s), 4.99 (2H, s), 6.16 (lH. dd), 6.34 (1H, m), 6.95 (1H, s) and 7.0-7.5 (10H, m); MS (EI) M=561; C32H36C1N30 ; S requires 561.

Example 141-1-Benzyl-2-(8-(4-chlorophenyl)-8-oxooct-1-yl) thio-5-((1-methyl-2- oxo-pyrid-4-yl) methyl) pyrimidin-4-one Prepared from intermediate B71 and A1 by general method A4, as a pale brown solid.

'H-NMR (CDC13) 8 1.38 (6H, m), 1.73 (4H, m), 2.93 (2H, t), 3.26 (2H, t), 3.49 (3H, s), 3.52 (2H, s), 4.99 (2H, s), 6.16 (1H, m), 6.33 (1H, m), 6.96 (1H, s), 7.16 (3H, m), 7.27- 7.45 (5H, m), 7.90 (2H, d).

Example 142-1-Benzyl-2-(8-(4-chlorophenyl) oct-1-yl) thio-5-((2-methylpyrid-5- yl) methyl) pyrimidin-4-one Prepared from Example 30 by general method Cl, as a pale yellow gum. 1H-NMR (CDC13) 5 1.2-1.8 (12H, m), 2.5-2.65 (5H, m), 3.25 (2H, t), 3.68 (2H, s), 4.95 (2H, s), 6.78 (1H, s), 7.0-7.6 (1 lH, m) and 8. 31(1H, d); MS (EI) found M=546; C32H36C1N30S requires 546.

Example 143-1-Benzyl-2-(8-phenyloct-1-yl) thio-5-((2-methylpyrid-S- yl) methyl) pyrimidin-4-one Prepared from Example 21 by general method Cl, as a pale yellow oil. I H-NMR (CDCl3) 8 1.2-1.5 (8H, m), 1.5-1.8 (4H, m), 2.53 (3H, s), 2.59 (2H, t), 3.24 (2H, t), 3.68 (2H, s), 4.95 (2H, s), 6.78 (1H, s), 7.0-7.5 (1 lHsm), 7.52 (1H, m) and 8.31 (lH, bs); MS (FAB) M+1=512; C32H37N30S requires 511.

Example 144-1-Benzyl-2-(8-phenyloct-1-yl) thio-5-((2-methoxypyrid-4- yl) methyl) pyrimidin-4-one Prepared from Example 37 by general method Cl, as a thick gum. IH-NMR (CDCI3) õ 1.2-1.8 (10H.m), 2.59 (2H, t), 3.26 (2H, t), 3.66 (2H, s), 3.91 (3H, s), 4.95 (2H, s), 6.56 (lH, bs),

6.73 (lH, m), 6.78 (lH, s), 7.05-7. 45 (10H, m) and 8.03 (1H, m); MS (APCI+) Found (M+1) =528. C32H37N302S requires 527.

Example 145-1-Benzyl-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrid-3- ylmethyl) pyrimidin-4-one Prepared from Example 47 by general method Cl, as a colourless oil. IH-NMR (CDCl3) b 1.25-1.5 (6H, m), (4H, m), 2.93 (2H, t), 3.25 (2H, t), 3.71 (2H, s), 4.96 (2H, s), 6.83 (1H, s), 7.05-7.5 (8H, m), 7.60 (1H, txd), 7.88 (2H, d) and 8.4-8.55 (2H, m); MS (EI) found M=545; C31H37ClN3O2S requires 545.

Example 147-1- (2-Thienylmethyl)-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediates B73 and A1 by general method A4, as a white crystalline solid. MPt 68-70°C; IH-NMR (CDCl3) 8 1.38 (6H, m), 1.69 (4H, m), 2.93 (2H, t), 3.29 (2H, t), 3.67 (2H, s), 5.14 (2H, s), 7.04 (3H, m), 7.37 (1H, m), 7.43 (2H, m), 7.90 (2H, m), 8.67 (2H, s), 9.01 (1H, s); MS APCI+) found (M+l) =553; C98H29CIN40S2 requires 552.

Example 148-1- (2, 2-Dimethylprop-1-yl)-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio- 5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediates B74 and Al by general method A4. IH-NMR (CDCI3) â 0.98 (9H, s), 1.2-1.85 (10H.m), 2.93 (2H, t), 3.24 (2H, t), 3.65 (2H, s), 3.70 (2H, s), 6.89 (1H, s), 7.43 (2H, m), 7.90 (2H, m), 8.69 (2H, s) and 9.09 (1H*s); MS (APCI+) found (M+1) =527; 526.C28H35ClN4O2Srequires

Example 149-1-(2-(1-Piperidino) ethyl)-2-(8-(4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediates B75 and Al by general method A4, as a yellow oil. lH- NMR (CDC13) 5 1.34-1.90 (16H, m), 2.30-2.55 (6H, m), 2.93 (2H, t), 3.25 (2H, t), 3.71 (2H, s), 4.40 (2H, m), 7.02 (1H, s), 7.42 (2H, m), 7.89 (2H, m), 8.70 (2H, s), 9.09 (1H, s); MS APCI+) found (M+1) =568; C3oH3gClN502S requires 567.

Example 150-1- (2-Hydroxyethyl)-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediates B77 and A1 by general method A4. lH-NMR (CDCl3) â 1.3-1.8 (10H, m), 2.93 (2H, t), 3.25 (2H, t), 3.66 (2H, s), 3.99 (4H, m), 7.20 (lH, s), 7.43 (2H, m), 7.89 (2H, m), 8.68 (2H.s) and 9.05 (1H, s); MS (APCI+) found (M+1) =501 ; C25H29C1N403S requires 500.

Example 151-1-(2-Hydroxyethyl)-2-(8-(4-chlorophenyl) oct-1-yl) thio-5- benzylpyrimidin-4-one Prepared from intermediates B78 and A24 by general method A4, as a colourless gum.

'H-NMR (CDCl3) b 1.2-1.5 (8H, m), 1.5-1.8 (4H, m), 2.54 (2H, t), 3.21 (2H, t), 3.64 (2H, s), 3.8-4.15 (4H, m), 5.23 (1H, bs), 6.97 (1H, s), 7.08 (2H, d) and 7.1-7.45 (7H, m).

Example 152-1-Ethyl-2-(8-(4-chlorophenyl)-8-oxooct-1-yl) thio-5-(pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediates B89 and Al by general method A4. lH-NMR (d6-DMSO) å 1.2-1.4 (9H. m), 2.5-2.7 (4H,m). 2.84 (2H, t). 3.11 (2H, t), 3.56 (2H, s), 3.89 (2H, q), 7.58

(2H. d), 7.85 (lH, s), 7.97 (2H, d), 8.70 (2H, s), 9.01 (1H, s); MS (APCI) M=485; C25H29C1N402S requires 485.

Example 153-1- (Fur-2-ylmethyl)-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediates B81 and Al by general method A4, as a light brown oil. 1H- NMR (CDCl3) 5 1.38 (6H, m), 1.70 (4H, m), 2.93 (2H, t), 3.27 (2H, t), 3.69 (2H, s), 4.94 (2H, s), 6.40 (2H, m), 7.06 (1H, s), 7.44 (3H, m), 7.90 (2H, m), 8.68 (2H, s), 9.09 (1H, s); MS APCI+) found (M+1) =537; C28H29ClN403S requires 536.

Example 154-1- (Fur-2-ylmethyl)-2- (8- (4-chlorophenyl) oct-1-yl) thio-5- benzylpyrimidin-4-one Prepared from intermediates B82 and A24 by general method A4, as a pale brown gum.

1H-NMR (CDCl3) 8 1.2-1.5 (8H, m), 1.5-1.8 (4H, m), 2.56 (2H, t), 3.27 (2H, t), 3.73 (2H, s), 4.85 (2H, s), 6.33 (2H, s), 6.73 (1H, s), 7.09 (2H, d) and 7.2-7.5 (8H, m); MS (FAB) M+1=521; C30H33ClN202S requires 520.

Example 155-1-Methyl-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- bromopyrimidin-4-one 1-Methyl-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thiopyrimidin-4-one was prepared from 1- methyl-2-thiouracil by general method A4. A solution of bromine (O. 05ml) in dichloromethane (lml) was added to a slurry of 1-methyl-2-(8-(4-chlorophenyl)-8- oxooct-1-yl) thiopyrimidin-4-one (0.38g) in dichloromethane (20ml), and the mixture was stirred for 24 hours. The solution was washed with aqueous sodium carbonate, dried and evaporated. Chromatography (silica, 1-4% methanol in dichloromethane) gave 1-methyl- 2- (8- (4-chlorophenyl)-8-oxooct-l-yl) thio-5-bromopyrimidin-4-one (0.18g), as a white solid. lH-NMR (CDCI3) õ 1.3-1.5 (6H, m), 1.65-1.8 (4H, m), 2.94 (2H, t), 3.26 (2H, t), 3.56 (3H, s), 7.45 (2H, d), 7.56 (1H, s) and 7.90 (2H, d); MS (APCI+) found (M+l) =459; ClgH, BrClN20, S requires 458.

Example 156-1-Methyl-2-(8-(4-chlorophenyl) oct-1-yl) thio-5-((1-methyl-2-oxo- pyrid-4-yl) methyl) pyrimidin-4-one Prepared from intermediates B83 and A24 by general method A4, as a colourless solid.

IH-NMR (CDCl3) 8 1.2-1.5 (8H, m), 1.5-1.8 (4H, m), 2.56 (2H, t), 3.25 (2H, t), 3.49 (3H, s), 3.51 (3H, s), 3.54 (2H, s), 6.19 (1H, m), 6.38 (lH, m), 6.93 (lH, s) and 7.0-7.35 (5H, m); MS (EI) M=485 ; C26H32ClN302S requires 485.

Example 157-1-Methyl-2-(8-(4-chlorophenyl)-8-oxooct-1-yl) thio-5-((1-methyl-2- oxo-pyrid-4-yl) methyl) pyrimidin-4-one Prepared from intermediates B83 and A1 by general method A4, as a cream coloured crystalline solid. MPt 90-5°C ;1H-NMR (CDCl3) # 1.38 (6H, m), 1.72 (4H, m), 2.91 (2H, t), 3.26 (2H, t), 3.49 (3H, s), 3.51 (3H, s), 3.54 (2H, s), 6.19 (1H, m), 6.38 (1H, s), 6.93 (1H, s), 7.19 (1H, m), 7.43 (2H, d), 7.90 (2H, d); MS (APCI+) Found (M+1) = 500; 499.C26H30N3O3Srequires Example 158-1-Methyl-2- (8- (4-chlorophenyl) oct-1-yl) thio-5- (pyrid-3- ylmethyl) pyrimidin-4-one Prepared from Example 70 by general method Cl, as a pale yellow oil.'H-NMR (CDCl3) 5 1.2-1.8 (12H, m), 2.56 (2H, t), 3.22 (2H, t), 3.46 (3H, s), 3.74 (2H, s), 6.77 (lH, s), 7.08 (2H, d), 7.15-7.35 (4H, m), 7.66 (1H, txd) and 8.49 (2H, bs); MS (EI) found M=455; C, 5H30CIN30S requires 455.

Example 159-1-Methyl-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediates B84 and A1 by general method A4, as a white solid. IH- NMR (CDCl3) 8 1.3-1.55 (6H, m), 1.6-1.85 (4H, m), 2.93 (2H, t), 3.26 (2H, t), 3.51 (3H, s), 3.70 (2H, s), 6.94 (1H, s), 7.45 (2H, d), 7.89 (2H, d), 8.70 (2H, s) and 9.1 (lH, s); MS (APCI+) found (M+l) =471; C24H27ClN4O2S requires 470.

Example 160-1-Methyl-2- (8- (4-chlorophenyl) oct-1-yl) thio-5-benzylpyrimidin-4- one Prepared from intermediates B85 and A24 by general method A4, as a colourless powder.

MPt 92-93°C : IH-NMR (CDC13) å 1.2-1.8 (12H, m), 2.56 (2H, t), 3.26 (2H, t), 3.40 (3H, s), 3.76 (2H, s), 6.59 (1H, s), 7.09 (2H, d) and 7.15-7.45 (7H, m); MS (EI) found M=454; C26H31CIN, OS requires 454.

Example 1-Phenyl-2-(8-(4-chlorophenyl)oct-1-yl)thio-5-((1-methyl-2-o xo-- pyrid-4-yl) methyl) pyrimidin-4-one Prepared from intermediates B86 and A24 by general method A4, as a yellow/orange solid. IH-NMR (CDCI3) å 1.2-1.5 (8H, m), 1.5-1.8 (4H, m), 2.54 (2H, t), 3.14 (2H, t), 3.49 (3H, s), 3.57 (2H, s), 6.22 (lH, m), 6.38 (lH, m), 7.00 (lH, s), 7.08 (2H, d), 7.15-7.4 (5H, m) and 7.5-7.6 (3H, m); MS (EI) M=547; C31H34ClN30, S requires 547.

Example 162-1-Methylsulfonyl-2- (8- (4-chlorophenyl) oct-1-yl) thio-5- (pyrid-3- ylmethyl) pyrimidin-4-one Prepared from Example 70, analogously to example 139. IH-NMR (CDC13) õ 1.2- 1.8 (12H, m), 2.56 (2H, t), 3.10 (2H, t), 3.55 (3H, s), 4.03 (2H, s), 7.09 (2H, m), 7.15-7.3 (2H, m), 7.61 (1H, m), 7.96 (1H. m), 8.45 (1H, s) and 8.60 (2H, m).

Example 163-1-Benzyl-2- (8-phenyloct-1-yl) oxy-5- (pyrid-3-ylmethyl) pyrimidin-4- one Prepared from Example 100 by general method Cl, as a pale buff solid. MPt 74-78°C ; 'H-NMR (CDCl3) 8 1.2-1.5 (8H, m), 1.5-1.85 (4H. m), 2.58 (2H, t), 3.72 (2H, s), 4.40 (2H, t), 4.83 (2H, s), 6.76 (1H, s), 7.0-7.4 (1 lH, m), 7.6-7.7 (1H, m) and 8.46 (2H, m); IR 1655,1621 cm-1.

Example 164-1-(2-Methoxyethyl)-2-benzylthio-5-(pyrimid-5-ylmethyl) pyrimidin- 4-one Prepared from intermediate B87 by general method A4. 'H-NMR (CDC) 5 3.31 (3H, s), 3.59 (2H, t), 3.71 (2H, s), 4.51 (2H, s), 7.10 (1H, s), 7.2-7.45 (5H, m), 8.72 (2H, s) and 9. 10(1H, s); MS (APCI+) found (M+1) =369; C19H20N4O2S requires 368.

Example 165-1- (3-Phenylprop-1-yl)-2-benzylthio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B55 by general method A4. 1H-NMR (CDCl3) 8 2.08 (2H, quintet), 2.65 (2H, t), 3.68 (2H, s), 3.75 (2H, t), 4.49 (2H, s), 5.30 (2H, s), 6.84 (1H, s), 7.10 (2H, m), 7.15-7.5 (8H, m), 8.69 (2H, s) and 9.10 (1 H, s); MS (APCI+) found (M+1) =429; C'-15H24N40S requires 428.

Example 166-1- (5-Hydroxypent-1-yl)-2-benzylthio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B56 by general method A4. lH-NMR (CDCI3) õ 1.3- 1.9 (6H, m), 3.64 (2H, t), 3.7-3.9 (4H. m), 4.50 (2H, s), 6.98 (lH, m), 7.2-7.5 (5H, m), 8.72 (2H, s) and 9.10 (lH, s); MS (APCI+) found (M+1) =397; C21H24N4O2S requires 396.

Example 1-(Pyrid-2-ylmethyl)-2-benzylthio-5-(pyrimid-5-- ylmethyl) pyrimidin-4-one Prepared from intermediate B45 by general method A4. 1H-NMR (CDCl3) # 3.73 (2H, s), 4.49 (2H, s), 5.03 (2H, s), 7.1-7.4 (8H, m), 7.69 (lH, m), 8.57 (1H, m), 8.71 (2H, s) and 9.09 (1H, s); MS (APCI+) found (M+1) =402 : C22HlgN50S requires 401.

Example 168-I-(Pyrid-3-ylmethyl)-2-benzylthio-5-((1-methyl-2-oXo-pyr id-4- yl) methyl) pyrimidin-4-one Prepared from intermediate B58 by general method A4, as a buff coloured solid, 1H- NMR (CDCl3) b 3.5 (3H, s), 3.55 (2H, s), 4.51 (2H, s), 4.99 (2H, s), 6.27 (1H, m), 6.26 (1H, s), 7.01 (1H, s), 7.15-7.50 (8H, m), 8.50 (1H, s), 8.62 (1H, m); MS (APCI+) found (M+l) = 431; C24H22N402S requires 430.

Example 169-1- (Pyrid-4-ylmethyl)-2-benzylthio-5-benzylpyrimidin-4-one Prepared from intermediate B63 by general method A4, as a brown gum. IH-NMR (CDCl3) 8 3.78 (2H, s), 4.50 (2H, s), 4.89 (2H, s), 6.64 (1H, s), 6.94 (2H, d), 7.1-7.5 (10H, m) and 8.58 (2H, d); MS (EI) found M=399; C24H2lN30S requires 399.

Example 170-1-(2-(Pyrid-2-yl) ethyl)-2-benzylthio-5-(pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B65 by general method A4. 'H-NMR (CDCL,) § 3.20 (2H, t), 3.55 (2H. s), 4.30 (2H, t), 4.53 (2H, s), 6.75 (1H, s), 6.96 (1H, m), 7.17 (lH, m), 7.25-7.5 (5H, m), 7.56 (1H, m), 8.4-8.55 (3H, m) and 9.10 (lH, s), ; MS (APCI+) found (M+1) =416; 2321 N508 requires 415.

Example 171-1- (2- (Pyrid-3-yl) ethyl)-2-benzylthio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one

Prepared from intermediate B67 by general method A4. 1H-NMR (CDC13) # 3.05 (2H, t), 3.60 (2H, s), 4.00 (2H, t), 4.54 (2H, s), 6.57 (1H, s), 7.1-7.5 (6H, m), 8.43 (lH, m), 8.5- 8.65 (3H, m) and 9.10 (lH, s); MS (APCI+) found (M+1) =416; C23H2lN50S requires 415.

Example 172-1-(2-(Pyrid-4-yl) ethyl)-2-benzylthio-5-(pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B68 by general method A4, as a buff coloured solid. IH- NMR (CDC13) 8 3.02 (2H, t), 3.45 (2H, s), 3.52 (3H, s), 4.00 (2H, t), 4.55 (2H, s), 5.95 (I H, m), 6.30 (1H, s), 6.57 (1H, s), 7.02 (2H, m), 7.18 (1H, m), 7.19-7.44 (5H, m), 8.50 (2H, m); MS (APCI+) Found (M+1) = 445; C2sH24N402S requires 444.

Example 173-1- (2- (Pyrid-4-yl) ethyl)-2-benzylthio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B69 by general method A4. 1H-NMR (CDC13) 8 3.03 (2H, t), 3.60 (2H, s), 4.01 (2H, t), 4.54 (2H, s), 6.61 (lH, s), 7.01 (2H, m), 7.25-7.5 (5H, m), 8.45- 8.65 (4H. m) and 9. 11(1H, s); MS (APCI+) found (M+1) =416 ; C23H21N50S requires 415.

Example 1-(2-Phenylethyl)-2-benzylthio-5-((2-methoxypyrid-4-- yl) methyl) pyrimidin-4-one Prepared from Example 88 by general method Cl. 1H-NMR (CDCl3) # 3. 01 (2H, t), 3.57 (2H, s), 3.95 (5H, m), 4.53 (2H, m), 6.27 (1H, s), 6.45 (lH, s), 6.55 (1H, m), 7.0 (2H, m), 7.1- 7.5 (8H, m) and 8.02 (lH, d); MS (APCI+) found M+H=444; C26H25N3O2S requires 443.

Example 175-1-Benzyl-2-benzylthio-5- ((2-methoxypyrid-4-yl) methyl) pyrimidin-4- one Prepared from intermediate Example 88 by general method Cl, as a colourless stiff gum.

'H-NMR (CDCl3) 8 3.67 (2H, s), 3.90 (3H, s), 4.51 (2H, s), 4.93 (2H, s), 6.57 (1H, s), 6.73 (1H, m), 6.81 (1H, s), 7.10 (1H, m), 7.25-7.45 (9H, m) and 8.04 (1H, d); MS (EI) M=429; C'SHz3N3OS requires 429.

Example 176-1-(2-Thienylmethyl)-2-benzylthio-5-(pyrimid-5-ylmethyl) pyrimidin- 4-one Prepared from intermediate B73 by general method A4, as a pale yellow crystalline solid.

MPt 110-112°C; 1H-NMR (CDCl3) # 3.69 (2H, s), 4.54 (2H, s), 5.11 (2H, s), 7.02 (3H, m). 7.30-7.42 (6H, m), 8.65 (2H, s), 9.09 (1H, s); MS APCI+) found (M+l) = 407; 406.C21H18N4OS2requires Example 177-1-(2, 2-Dimethylprop-l-yl)-2-benzylthio-5-(pyrimid-S- ylmethyl) pyrimidin-4-one Prepared from intermediate B74 by general method A4. IH-NMR (CDC13) å 0.96 (9H, s), 3.62 (2H, s). 3.72 (2H, s), 4.49 (2H, s), 6.91 (1H, s), 7.25-7.45 (5H, m), 8.70 (2H, s) and 9.11 (1H, s); MS (APCI+) found (M+1) =381; CI-lOS requires 380.

Example 1-(Fur-2-ylmethyl)-2-benzylthio-5-(pyrimid-5-ylmethyl)pyrimi din-- 4-one Prepared from intermediate B81 by general method A4, as a brown oil. 1H-NMR (CDCl3) 8 3.70 (2H, s), 4.52 (2H, s), 4.91 (2H, s), 6.40 (2H, m), 7.06 (1H, s), 7.26-7.42

(6H, m), 8.70 (2H, s), 9.10 (1H, s); MS APCI+) found (M+1) =391; C21H18N4O2S requires 390.

Example 179-1-Methyl-2-benzylthio-5- ((2-methoxypyrid-4-yl) methyl) pyrimidin- 4-one Prepared from Example 88 by general method Cl, as a pale cream powder. MPt 119- 120°C; IH-NMR (CDCl3) õ 3.44 (3H, s), 3.69 (2H, s), 3.93 (3H, s), 4.52 (2H, s), 6.62 (1H, bs), 6.78 (2H, m), 7.2-7.5 (5H, m) and 8.10 (1H, m); MS (EI) M=353; Cl9Hl9N302S requires 353.

Example 180-1-Benzyl-2- (8- (4-chlorophenyl) oct-1-yl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B94 by general method A4. I H-NMR (CDC'3) 8 1.2-1.8 (12H, m), 2.55 (2H, t), 3.25 (2H, t), 3.67 (2H, s), 5.00 (2H, s), 6.8-7.4 (10H, m), 8.7 (2H, s), 9.07 (lH, s); (APCI) M+H=533. C3oH33ClN40S requires 532.

Example 181-1- (2-Phenylethyl)-2- (8- (4-chlorophenyl) oct-1-yl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B93 by general method A4, as a white crystalline solid. IH- NMR (CDCl3) 8 1.2-1.5 (8H, m), 1.5-1.8 (4H, m), 2.56 (2H, t), 3.05 (2H, t), 3.29 (2H, t), 3.50 (2H, s), 4.02 (2H, t), 6.36 (1H, s), 7.0-7.1 (4H, m), 7.2-7.3 (5H, m), 8.47 (2H, s) and 9.07 (lH, s) ; (APCI) M+H=547. C31H35ClN4OS requires 546.

Example 182-1-Methyl-2- (8- (4-chlorophenyl) oct-1-yl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B84 by general method A4 as a white crystalline solid. 1H- NMR (CDCl3) 8 1.2-1.5 (8H, m), 1.5-1.8 (4H, m), 2.56 (2H. t), 3.25 (2H, t), 3.50 (3H, st),

3.70 (2H, s), 6.94 (lH, s), 7.09 (2H, m), 7.23 (2H. m), 8.69 (2H, s) and 9.09 (lH, s); (APCI) M+H=457. C4H29ClN40S requires 456.

Example 183-1-Benzyl-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrid-4- yl) pyrimidin-4-one 1-Benzyl-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-pyrimidin-4-one was prepared from 1-benzyl-2-thiouracil and intermediate A1 by general method A4, then iodinated with iodine (1.2 equiv) and silver trifluoromethanesulfonate (1 equiv) in chloroform at room temperature overnight, giving 1-benzyl-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- iodopyrimidin-4-one in 27% yield after chromatography. This compound (1 equiv) and 4-pyridylboronic acid (2 equiv) were suspended in dimethoxyethane, 2M aqueous sodium carbonate added, followed by tetrakis (triphenylphosphine) palladium (0.05 equiv). The mixture was refluxed for 16 hours, then the solvent evaporated. Aqueous workup, chromatography and crystallisation from ether gave the title compound as a white crystalline solid. IH-NMR (CDC13) 6 1.3-1.5 (6H, m), 1.6-1.8 (4H, m), 2.94 (2H, t), 3.32 (2H, t), 5.13 (2H, s), 7.27 (2H, d), 7.4 (6H, m), 7.55 (2H, d), 7.90 (2H, d); (APCI) M+H-532. 531.requires Example 184-1-Benzyl-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B94 by general method A4. IH-NMR (CDC13) õ 1.3-1.5 (4H. m), 1.6-1.8 (4H. m) 2.93 (2H, t), 3.26 (2H, t), 3.67 (2H, s), 5.01 (2H, s), 6.98 (lH, s), 7.1- 7.2 (2H, m), 7.4-7.5 (5H, m), 7.90 (2H, d), 8.7 (2H, s), 9.07 (lH, s); (APCI) M+H=547.

C3oH3iClN40 ; S requires 546.

Example 185-1-(2-Phenylethyl)-2-(8-(4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one

Prepared from intermediate B93 by general method A4 as a cream coloured crystalline solid. 'H-NMR (CDC'3) 8 1.3-1.5 (6H, m), 1. 6-1. 8 (4H, m), 2.94 (2H, t), 3.05 (2H, t), 3.30 (2H, t), 3.50 (2H, s), 4.03 (2H, t), 6.37 (lH, s), 7.05 (2H, m), 7.3 (3H. m), 7.43 (2H, d), 7.89 (2H, d), 8.47 (2H, s), 9.08 (lH, s); (APCI) M+H=561. C31H33ClN4O2S requires 560.

Example 186-1- (Fur-2-ylmethyl)-2- (2-phenylethyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B81 by general method A4. lH-NMR (CDCl3) 6 3.02 (2H, t), 3.54 (2H, t), 3.69 (2H, s), 4.91 (2H, s), 6.38 (2H, m), 7.06 (lH, s), 7.2-7.35 (5H, m), 7.4 (lH, m), 8.7 (2H, s), 9.09 (lH, s); (APCI) M+H=405. C22H2oN402S requires 404.

Example 187-1- (2-Fluorobenzyl)-2-benzylthio-5- (pyrimid-5-ylmethyl) pyrimidin- 4-one Prepared from intermediate B 131 by general method A4. lH-NMR (CDC13) 6 3.70 (2H, s), 4.51 (2H, s), 5.01 (2H, s), 7.08 (lH, s), 7.1-7.2 (3H, m), 7.2-7.4 (6H, m), 8.7 (2H, s), 9.09 (lH, s); (APCI) M+H=419. C23H19FN4OS requires 418.

Example 188-1-(8-Phenyloctyl)-2-benzylthio-5-(pyrimid-5-ylmethyl) pyrimidin-4- one Prepared from intermediate B90 by general method A4. lH-NMR (CDC13) 6 1.2- 1.4 (8H, m), 1.5-1.8 (4H, m), 2.59 (2H, t), 3.6-3.8 (4H, m), 4.50 (2H, s), 6.93 (lH, s), 7.1- 7.5 (10H, m), 8.70 (2H, s) and 9.10 (1H, s); (APCI) M+H=499. C30H34N40S requires 498.

Example 189-1-(9-Phenylnonyl)-2-benzylthio-5-(pyrimid-5-ylmethyl) pyrimidin-4- one

Prepared from intermediate B91 by general method A4 as a thick oil. 1H-NMR (CDCl3) 8 1.2-1.4 (10H, m), 1.5-1.85 (4H, m), 2.59 (2H, t), 3.6-3.8 (4H, m), 4.50 (2H, s), 6.94 (lH, s), 7.1-7.45 (lH, m), 8.69 (2H, s) and 9.10 (lH, s); (APCI) M+H=513. C3lH36N40S requires 512.

Example 190-1-Benzyl-2-benzylthio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B94 by general method A4. lH-NMR (CDC13) 6 3.68 (2H, s), 4.51 (2H, s), 4.97 (2H, s), 7.00 (lH, s), 7.1 (2H, m), 7.2-7.4 (2H, m), 8.7 (2H, s) and 9.08 (lH, s); (APCI) M+H=401. (C23H20N4OS requires 400.

Example 191-1-Benzyl-2-benzylthio-5- ((1-methylpyrazol-4-yl) methyl) pyrimidin- 4-one Prepared from Example 105 by general method C3, as a pale brown oil. lH-NMR (CDC13) b 3.57 (2H, s), 3.84 (3H, s), 4.52 (2H, s), 4.93 (2H, s), 6.90 (lH, s), 7.1 (2H, s), 7.2- 7.4 (10H, m); (APCI) M+H=403. C23H22N40S requires 402.

Example 192-1-Benzyl-2-(4-fluorobenzyl) thio-5-(pyrimid-5-ylmethyl) pyrimidin- 4-one Prepared from intermediate B94 by general method A4. lH-NMR (CDCl3) 6 3.68 (2H, s), 4.48 (2H, s), 4.97 (2H, s), 7.0 (3H, m), 7.1 (2H, m), 7.3-7.4 (5H, m), 8.7 (2H, s), 9.08 (lH, s); (APCI) M+H=419. C, 3Hl9FN40S requires 418.

Example 193-1- (2, 2-Dimethylprop-1-yl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one

Prepared from intermediate B74 by general method A4 as a oil. 1H-NMR (CDCl3) # 0.96 (9H, s), 3.61 (2H, s), 3.72 (2H, s), 4.46 (2H, s), 6.85-7.1 (3H, m), 7.3-7.45 (2H, m), 8.70 (2H, s) and 9.11 (lH, s); (APCI) M+H=399. C21H23FN4OS requires 398.

Example 1-(2-Phenylethyl)-2-benzylthio-5-(pyrimid-5-ylmethyl)pyrimid in-4-- one Prepared from intermediate B93, by general method A4, as a cream coloured crystalline solid. 'H-NMR (CDCy § 3.02 (2H, t), 3.51 (2H, s), 4.00 (2H, t), 4.55 (2H, s), 6.37 (lH, s), 7.0 (2H, m), 7.2-7.4 (8H, m), 8.47 (2H, s), 9.09 (lH, s); (APCI) M+H=415. C24H22N40S requires 414.

Example 195-1-(Fur-2-ylmethyl)-2-(4-methylbenzyl) thio-5-(pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B81 by general method A4. 1H-NMR (CDCl3) # 2.33 (3H, s), 3.70 (2H, s), 4.49 (2H, s), 4.90 (2H. s), 6.3-6.4 (2H. m), 6.84 (lH, s), 7.08 (2H, d), 7.33 (2H, d), 7.41 (lH, m), 8.7 (2H, s), 9.10 (lH, s); (APCI) M+H=405. CHzOzS requires 404.

Example 196-1-(Fur-2-ylmethyl)-2-(2-fluorobenzyl) thio-5-(pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B93 by general method A4. IH-NMR (CDC13) 8 3.70 (2H, s), 4.56 (2H, s), 4.90 (2H, s), 6.37 (1H, m), 6.41 (IH. m), 7.1 (3H, m), 7.3 (lH, m), 7.41 (lH, m), 7.55 (1H, m), 8.7 (2H, s), 9.10 (1H, s); (APCI) M+H=409. C21H17FN4O2S requires 408.

Example 197-1- (Fur-2-ylmethyl)-2- (4-chlorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B81 by general method A4. I H-NMR (CDC13) 6 3.69 (2H, s), 4.48 (2H, s), 4.90 (2H, s), 6.38 (2H, m), 7.06 (lH, m), 7.28 (2H. d), 7.35 (2H, d), 7.42 (lH, m), 8.7 (2H, s), 9.10 (lH, s); (APCI) M+H=425,2M+H=849. C21H17CIN4O2 S requires 424.

Example 198-1- (Fur-2-ylmethyl)-2- (3-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B81 by general method A4. 'H-NMR (CDCy 5 3.70 (2H, s), 4.51 (2H, s), 4.90 (2H, s), 6.38 (lH, m), 6.41 (lH, m), 7.0 (lH, m), 7.1-7.3 (5, m), 7.42 (lH, m), 8.7 (2H, s), 9.10 (lH, s); (APCI) M+H=409. C2iHpFN402S requires 408.

Example 199-1- (Fur-2-ylmethyl)-2- (3-chlorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B81 by general method A4, as an orange oil. 1H-NMR (CDCl3) 5 3.69 (2H. s), 4.47 (2H, s), 4.93 (2H, s), 6.38 (lH, m), 6.41 (lH, m), 7.12 (lH, s), (5H, m), 8.7 (2H, s), 9.08 (lH, s); (APCI) M+H=425. C2lHl7ClN402S requires 424.

Example 200-1-Methyl-2-benzylthio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B84 by general method A4, as an off-white crystalline solid.

I H-NMR (CDC'3) 8 3.49 (3H, s), 3.71 (2H, s), 4.51 (2H, s), 6.96 (lH, s), 7.2-7.5 (5H, m), @ 8.70 (2H, s), 9.10 (lH, s); (APCI) M+H=325. C17Hl6N40S requires 324.

Example 201-1-((R)-Tetrahydofuran-2-ylmethyl)-2-benzylthio-5-(pyrimi d-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B 133 by general method A4. White solid. 1H-NMR (CDCl3) 8 1.37-1.60 (1H, m), 1.81-2.14 (3H, m), 3.53-3.87 (5H, m), 3.99-4.18 (2H, m), 4.50 (1H, s), 7.18 (1H, s), 7.28-7.44 (5H, m), 8.72 (2H, s), 9.09 (1H, s); MS (APCI+) found (M+1) = 395 CHOSrequires 394.

Example 1-((S)-Tetrahydrofuran-2-ylmethyl)-2-benzylthio-5-(pyrimid-5 -- ylmethyl) pyrimidin-4-one Prepared from intermediate B 132 by general method A4, as a white solid. I H-NMR (CDCl3) 8 1.37-1.58 (1H, m), 1.8-2.12 (3H, m), 3.55-3.88 (5H, m), 3.98-4.19 (2H, m), 4.5 (2H, s), 7.17 (1H, s), 7.29-7.44 (5H, m), 8.70 (2H, s), 9.02 (1H, s); MS (APCI+) found (M+1) = 395; C21H22N4O2S requires 394.

Example 203-1- (4-Fluorobenzyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one

Prepared from intermediate B99 by general method A2. as an orange solid.'H-NMR (CDCl3) 5 3.68 (2H, s), 4.47 (2H, s), 4.94 (2H, s), 6.92-7.20 (7H, m), 7. 28-7.41 (2H, m), 8.66 (2H, s), 9.08 (1H, s); MS (APCI+) found (M+l) = 437; C23H18F2N4OS requires 436.

Example 204-1- (4-Bromobenzyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B 115 by general method A2. 1H-NMR (CDCl3) # 3.68 (2H, s), 4.46 (2H, s), 4.91 (2H, s), 7.01 (5H, m), 7.35 (2H, m), 7.50 (2H, m), 8.70 (2H, s), 9.09 (1H, s), MS (APCI+) M+1=497, C23HIgBrFN40S requires 496. MPt 162.2°C (cream solid). MPt. 162.2 Example 205-1- (2- (6- (4-Fluorophenyl) hex-1-yloxy) ethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B 109 by general method A2 as an oil. 1H-NMR (CDCl3) 8 1.15-1.72 (8H, m), 2.50-2.63 (2H, t), 3.28-3.30 (2H, t), 3.55-3.64 (2H, t), 3.69 (2H, s), 3.89-3.98 (2H, t), 4.47 (2H, s), 6.88-7.43 (9H, m), 8.69 (2H, s), 9.08 (1H, s); MS (APCI+) found (M+l) = SS1; C30H32F2N4O2S requires 550.

Example 206-1- (2-Phenoxyethyl)-2- (3,4-difluorobenzyl) thio-5-(pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B 101 by general method A2 as a solid. lH-NMR (CDCl3) 8 3.72 (2H, s), 4.10-4.29 (4H, m), 4.47 (2H. s), 6.70-6.80 (2H, d), 6.95-7.39 (7H, m), 8.70 (2H, s), 9.12 (1H. s); MS (ES+) found (M+1) = 467; C24H20F2N4O2S requires 466.

Example 207-1- (3- (5-Phenylpent-1-yloxy) prop-1-yl)-2-benzylthio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B 139 by general method A2. 'H-NMR (CDC) § 1.35 (2H, m), 1.59 (4H, m), 1.95 (2H, m), 2.60 (2H, t), 3.32 (4H, m), 3.68 (2H, s), 3.87 (2H, t), 4.50 (2H, s), 7.01 (1H, s), 7.14-7.38 (10H, m), 8.68 (2H, s) 9.08 (1H, s); MS (APCI+) found 514.(M+1)=515;C30H34N4O2Srequires Example 208-1- (9-Phenylnonyl)-2-furfurylthio-5- (pyrimid-5-ylmethyl) pyrimidin- 4-one Prepared from intermediate B91 by general method A2. 1H-NMR (CDCl3) # 1.28 (10H, m), 1.65 (4H, m), 2.60 (2H, t), 3.69 (4H, m), 4.56 (2H, s), 6.30 (1H, m), 6.40 (1H, m), 6.98 (1H, s), 7.14-7.36 (6H, m), 8.69 (2H, s), 9.10 (1H, s); MS (APCI+) found (M+1) = 503; C29H34N402S requires 502.

Example 209-1-(9-Phenylnonyl)-2-(thiazol-2-ylmethyl) thio-5-(pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B91 by general method A2. 'H-NMR (CDC) 5 1.28 (10H, m), 1.65 (4H, m), 2.60 (2H, t), 3.72 (2H, s), 3.75 (2H, t), 4.85 (2H, s), 6.97 (1H, s), 7.14- 7.30 (6H, m), 7.71 (1H, d). 8.71 (2H, s), 9.11 (1H, s); MS (APCI+) found (M+1) = 520; C28H33NSOS2 requires 519.

Example 210-1-(9-Phenylnonyl)-2-(thien-2-ylmethyl) thio-S-(pyrimid-5- ylmethyl) pyrimidin-4-one

Prepared from intermediate B91 by general method A9. lH-NMR (CDC13) 6 1.28 (10H, m), 1.64 (4H, m), 2.60 (2H, t), 3.75 (4H, m), 4.73 (2H, s), 6.94 (2H, m), 7.09 (1H, m), 7.15-7.27 (6H, m), 8.73 (2H, s), 9.10 (1H, s); MS (APCI+) found (M+1) = 519; C29H34N40S2 requires 518.

Example 211-1- (9-Phenylnonyl)-2- (3,4-difluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B91 by general method A2. 1H-NMR (CDC13) 6 1.28 (10H m), 1.60 (4H, m), 2.59 (2H, t), 3.71 (4H, m), 4.44 (2H, s), 6.95 (lH, s), 7.10-7.27 (8H, m), 8.70 (2H, s), 9.10 (1H, s); MS (APCI+) found (M+1) = 549; C3iH34F2N40S requires 548. <BR> <BR> <P>Example 212-1- (2- (2-Pent-1-ylphenyl) ethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B 117 by general method A2. 1H-NMR (CDCl3) # 0.87 (3H, t), 1.25 (4H, m), 1.45 (2H, m), 2.39 (2H, t), 3.04 (2H, t), 3.50 (2H, s), 3.97 (2H, t), 4.52 (2H, s), 6.31 (1H, s), 6.94-7.21 (8H, m), 7.40 (2H, m), 8.50 (2H, s), 9.09 (1H, s), MS(APCI+) M+1=503, C29H31FN4OS requires 502. MPt 112.3°C (colourless solid).

Example 213-1- (2- (3-Pent-1-ylphenyl) ethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B 116 by general method A2. 1H-NMR (CDC13) b 0.89 (3H, m), 1.30 (4H, m), 1.50 (2H, m), 2.52 (2H, t), 2.98 (2H, t), 3.51 (2H, s), 3.98 (2H, t), 4.51 (2H, s), 6.41 (1H, s), 6.80-7.16 (6H, m), 7.41 (2H, m), 8.49 (2H, s), 9.08 (1H, s), MS(APCI+) M+1=503, C29H31FN4OS requires 502. MPt 93.2°C (colourless solid).

Example 214-1- (2- (4-Bromophenyl) ethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B 114 by general method A2. I H-NMR (CDC'3) 8 2.97 (2H, t), 3.59 (2H, s), 3.95 (2H, t), 4.49 (2H, s), 6.50 (1H, s), 6.89-7.05 (4H, m), 7.35-7.44 (4H, m), 8.58 (2H, s), 9.11 (1H, s), MS(APCI+)M+1=511, C24H20BrFN4OS requires 510.

MPt 151.6°C (cream solid).

Example 215-1- (5-Methylfuran-2-ylmethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B98 by general method A2 as a pale yellow solid. lH-NMR (CDCl3) 8 1.64 (3H, s), 3.70 (2H, s), 4.49 (2H, s), 4.83 (2H, s), 5.95 (1H, d), 6.28 (1H, d), 6.94-7.09 (3H, m), 7.33-7.45 (2H, m), 8.69 (2H, s), 9.09 (1H, s), MS (APCI+) found (M+1) = 423; C22HlgFN402S requires 422.

Example 216-1- (2- (2-Chlorophenyl) ethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B 100 by general method A2 as a pale yellow solid. lH-NMR (CDCl3) 8 3.10-3.23 (2H, t), 3.51 (2H, s), 4.00-4.12 (2H, t), 4.51 (2H, t), 6.42 (1H, s), 6.90-7.48 (8H, m), 8.48 (2H, s), 9.09 (1H, s); MS (APCI+) found (M+1) = 467; C24H2oClFN40S requires 466.

Example 217-1- (2- (Thien-2-yl) ethyl)-2- (3,4-difluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B97 by general method A2. 1H-NMR (CDC13) 8 3.26 (2H, t), 3.55 (2H, s), 4.02 (2H, t), 4.48 (2H, s), 6.51 (1H, s), 6.67 (1H, m), 6.91 (1H, m), 7.05- 7.27 (4H, m), 8.53 (2H, s) 9.09 (1H, s); MS (APCI+) found (M+1) = 457; C22H18F2N4OS2 requires 456.

Example 218-1- (2-Phenylethyl)-2- (2,3,4-trifluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B93 by general method A3 as a pale yellow foam IH-NMR (CDCl3) 5 3.02 (2H, t), 3.51 (2H, s), 3.99 (2H, t), 4.55 (2H, s), 6.42 (1H, s), 6.8-7.1 (3H, m), 7.2-7.45 (4H. m), 8.48 (2H, s), 9.09 (lH, s); MS (APCI+) found (M+1) = 469; C24Hl9F3N40S requires 468.

Example 219-1- (2-Phenylethyl)-2- (2,3,5-trifluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B93 by general method A3 as a white solid IH-NMR (CDCl3) 8 3.02 (2H, t), 3.52 (2H, s), 3.99 (2H, t), 4.51 (2H, s), 6.40 (lH, s), 6.85-7.1 (3H, m), 7.2- 7.35 (3H, m), 7.4-7.55 (lH, m), 8.5 (2H, s), 9.09 (lH, s); MS (APCI+) found (M+1) =469; 468.C24H19F3N4OSrequires

Example 220-1- (2-Phenylethyl)-2- (2,4, 6-trifluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B93 by general method A3 as a white solid 1H-NMR (CDCl3) 8 3.02 (2H, t), 3.51 (2H, s), 3.99 (2H, t), 4.60 (2H, s), 6.38 (lH, s), 6.6-6.8 (2H, m), 7.0-7.1 (2H, m), 7.2-7.3 (3H, m), 8.48 (2H, s), 9.09 (lH, s); MS (APCI+) found (M+1) = 469; C24HlgF3N40S requires 468.

Example 22-1-(2-Phenylethyl)l-2-(2, 4-difluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B93 by general method A2 as a pale yellow solid. lH-NMR (CDCl3) 8 2.95-3.08 (2H, t), 3.51 (2H, s), 3.94-4.05 (2H, t), 4.54 (2H, s), 6.39 (1H, s), @ 6.74-6.91 (2H, m), 6.95-7.06 (2H, m), 7.18-7.34 (3H, m), 7.52-7.67 (1H, m), 8.48 (2H, s), 9.09 (1H, s); MS (APCI+) found (M+l) = 451; C24H2oF2N40S requires 450.

Example 222-1-(2-Phenylethyl)-2-(2-fluorobenzyl) thio-5-(pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B93 by general method A2. IH-NMR (CDC13) õ 2.95-3.09 (2H, t), 3.49 (2H, s), 3.92-4.06 (2H, t), 4.59 (2H, s), 6.38 (1H, s), 6.94-7.37 (8H, m), 7.50- 7.63 (1H, t), 8.49 (2H, s), 9.08 (1H, s) ; MS (APCI+) found (M+1) = 433; C24H21FN40S requires 432.

Example 223-1- (2-Phenylethyl)-2-furfurylthio-5- (pyrimid-5-ylmethyl) pyrimidin- 4-one Prepared from intermediate B93 by general method A2. 'H-NMR (CDCy 5 3.03 (2H, t), 3.51 (2H, s), 4.00 (2H, t), 4.62 (2H, s), 6.41 (3H, m), 7.03 (2H, m), 7.27 (3H, m), 7.38 (1H, m), 8.46 (2H, s), 9.09 (1H, s); MS (APCI+) found (M+1) = 405; C22H2oN402S requires 404.

Example 224-1- (2-Phenylethyl)-2- (thien-2-ylmethyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B93 by general method A2. IH-NMR (CDC13) 8 3.03 (2H, t), 3.51 (2H, s), 3.99 (2H, t), 4.78 (2H, s), 6.36 (1H, s), 6.93-7.02 (3H, m), 7.12 (1H, m), 7.22-7.28 (4H, m), 8.48 (2H, s), 9.09 (1H, s); MS (APCI+) found (M+1) = 421; 420.C22H20N4OS2requires Example 225-1- (2-Phenylethyl)-2- (3,4,5-trifluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B93 by general method A3 as a pale yellow foam. IH-NMR (CDCl3) 8 3.03 (2H, t), 3.52 (2H, s), 4.02 (2H, t), 4.45 (2H, s), 6.46 (lH, s), 6.95-7. 2 (4H, m), 7.2-7.4 (3H, m), 8.49 (2H, s), 9.09 (lH, s); MS (APCI+) found (M+l) = 469; C, 4HI9F3N40S requires 468.

Example 226-1- (2-Phenylethyl)-2- (3,4-difluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B93 by general method A2. 1H-NMR (CDCl3) # 2. 95-3.10 (2H, t), 3.52 (2H, s), 3.95-4.07 (2H, t), 4.49 (2H, s), 6.39 (1H, s), 6.96-7.36 (8H, m), 8.48 (2H, s), 9.09 (1H, s); MS (APCI+) found (M+1) =451; C24H2oF2N40S requires 450.

Example 227-1- (2-Phenylethyl)-2- (3,5-difluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B93 by general method A2 as a pale yellow solid. IH-NMR (CDCl3) 8 2.97-3.10 (2H, t), 3.52 (2H, s), 3.95-4.16 (2H, t), 4.51 (2H, s), 6.40 (1H, s), 6.66-6.80 (1H, m), 6.89-7.08 (4H, m), 7.18-7.37 (3H, m), 8.49 (2H, s), 9.09 (1H, s); MS (APCI+) found (M+l) = 451; C24H20F2N4OS requires 450.

Example 228-1- (2-Phenylethyl)-2- (3-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B93 by general method A2 as a pale yellow solid. 1H-NMR (CDC13) 5 2.95-3.09 (2H, s), 3.52 (2H, s), 3.94-4.07 (2H, t), 4.53 (2H, s), 6.39 (1H, s), 6.90-7.38 (9H, m), 8.48 (2H, s), 9.09 (1H, s); MS (APCI+) found (M+1) = 433; C24H2) FN40S. requires 432.

Example 229-1-(2-Phenylethyl)-2-(4-fluorobenzyl) thio-5-(pyrimid-5- ylmethyl) pyrimidin-4-one

Prepared from intermediate B93 by general method A2 as a pale yellow solid. lH-NMR (CDCl3) b 2.98-3.10 (2H, t), 3.49 (2H, s), 3.94-4.06 (2H, s), 4.51 (2H, s), 6.39 (1H, s), 6.94-7.08 (4H, m), 7.20-7.33 (3H, m), 7.36-7.48 (2H, m), 8.48 (2H, s), 9.09 (1H, s); MS (APCI+) found (M+1) = 433; C24H21FN40S requires 432.

Example 230-1- (2-Phenylethyl)-2- (l-phenylethyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B93 by general method A2 as a pale yellow solid. lH-NMR (CDCl3) 8 1.82 (2H, t), 2.99 (2H, t), 3.50 (2H, s), 3.85-4.1 (2H, m), 5.35 (lH, q), 6.34 (lH, s), 6.9-7.05 (2H, m), 7.15-7.5 (8H, m), 8.49 (2H, s), 9.09 (lH, s); MS (APCI+) found (M+l) = 429; C2sH24N40S requires 428.

Example 231-1-(2-(4-Methoxyphenyl) ethyl)-2-(3, 4-difluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B 134 by general method A2 as a white solid. lH-NMR (CDCI3) 5 2.91-3.02 (2H, t), 3.59 (2H, s), 3.84 (3H, s), 3.90-4.02 (2H, t), 4.48 (2H, s), 6.42 (1H, s), 6.73-7.31 (7H, m), 8.51 (2H, s), 9.10 (1H, s); MS (APCI+) found (M+l) = 481; C25H22F2N4O2S requires 480.

Example 232-1- (2- (4-Pent-1-ylphenyl) ethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B 112 by general method A2. 1H-NMR (CDC13) 8 0.88 (3H, t), 1.32 (4H, m), 1.60 (2H, m), 2.60 (2H, m), 2.97 (2H, m), 3.52 (2H, s), 3.97 (2H, t), 4.51 (2H, s), 6.46 (1H, s), 6.84-7.11 (6H, m), 7.40 (2H, m), 8.50 (2H, s), 9.08 (1H, s); MS(APCI+)M+1=503, C29H31FN4OS requires 502. MPt 98.7°C (colourless solid).

Example 233-1- (Cycloprop-1-yl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl)- pyrimidin-4-one Prepared from intermediate B 105 by general method A2. 1H-NMR (CDCl3) # 0.94-1.32 (4H, m), 3.03-3.18 (1H, m), 3.69 (2H, s), 4.42 (2H, s), 6.93-7.07 (2H, t), 7.14 (1H, s), 7.31-7.45 (2H, m), 8.70 (2H, s), 9.10 (1H, s); MS (APCI+) found (M+1) = 369; Cl9Hl7FN40S requires 368.

Example 234-1- (Dodec-1-yl)-2- (3,4-difluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B96 by general method A2 as an oil. 1H-NMR (CDC13) 5 0.78-0.85 (3H, t), 1.13-1.70 (20H, m), 3.65-3.80 (4H, m), 4.45 (2H, s), 6.92-7.27 (4H, s), 8.70 (2H, s), 9.11 (1H, s); MS (APCI+) found (M+1) = 515; C28H36FN40S requires 514.

Example 235-1-Ethyl-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4- one Prepared from intermediate B89 by general method A2 as a solid. lH-NMR (CDCl3) 8 1.30-1.44 (3H, t). 3.72 (2H, s), 3.75-3.90 (2H, q), 4.47 (2H, s), 6.94-7.17 (3H, m), 7.33- 7.45 (2H, m), 8.70 (2H, s), 9.10 (1H, s); MS (APCI+) found (M+1) = 357; C18H17FN4OS requires 356.

Example 236-1- (l-Methylethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one

Prepared from intermediate B 104 by general method A2 as a solid. 1H-NMR (CDCl3) 8 1.32-1.45 (6H, d), 3.73 (2H, s), 4.46 (2H, s), 4.49-4.65 (1H, m), 6.94-7.05 (2H, t), 7.17 (1H, s), 7.33-7.45 (2H, m), 8.72 (2H, s), 9.10 (1H, s); MS (APCI+) found (M+1) = 371; Cl9Hl9FN40S requires 370.

Example 237-1-Methyl-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin- 4-one Prepared from intermediate B84 by general method A2 as a solid. lH-NMR (CDC13) 83.49 (3H, s), 3.71 (2H, s), 4.48 (2H, s) 6.93-7.07 (3H, m), 7.32-7.44 (2H, m), 8.70 (2H, s), 9.10 (1H, s); MS (APCI+) found (M+l) = 343; C 17H I 5FN40S requires 342.

Example 238-1- (Undec-1-yl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B95 by general method A2 as an oil. IH-NMR (CDC13) 8 0.82-0.98 (3H, t), 1.13-1.80 (18H, m), 3.65-3.79 (4H, m), 4.47 (2H, s), 6.90-7.07 (3H, m), 7.31-7.43 (2H, m), 8.70 (2H, s), 9.10 (1H, s); MS (APCI+) found (M+l) = 483; C27H35FN40S requires 482.

Example 239-1- (Undec-1-yl)-2- (4-fluorobenzyl) thio-5- (2-oxopyrimid-5- ylmethyl) pyrimidin-4-one To a solution of either Example 243 or 244 (0.2g) in dry methylene chloride (4ml) at 4°C was added boron tribromide (1M in methylene chloride, 2ml). The mixture was stirred

under argon for 24h and poured into a mixture of ice (50ml) and 0.880 ammonia (15ml) with stirring. Extraction with 5% methanol : methylene chloride was followed by filtration through kieselguhr and drying the organic layer over sodium sulphate. Removal of the solvent in vacuo gave the desired material as a grey solid (O. 15g). 1H-NMR (CDCl3) # 0.8-0.95 (3H, m), (16H, m), 1.6-1.85 (2H, m), 3.49 (2H, s), 3.79 (2H, t), 4.45 (2H, s), 6.9-7.1 (2H, m), 7.2-7.45 (3H, m), 8.32 (2H, s); MS (APCI+) found (M+l) = 499; C27H35FN402S requires 498.

Example 240-1-Benzyl-2-benzylthio-5- (2-methoxypyrimid-5-ylmethyl) pyrimidin- 4-one Prepared from Example B39 by alkylation with benzyl bromide using general method A4, followed by N-alkylation using general method C2. IH-NMR CDCl3) 5 3.62 (2H, s), 3.98 (3H, s), 4.51 (2H, s), 4.96 (2H, s), 6.92 (1H, s), 7.10 (1H, m), 7.23-7.40 (9H, m), 8.41 (2H, s) ; MS (APCI+) found (M+l) = 431; C24H22N402S requires 430.

Example 241-1- (2-Phenylethyl)-2- (3,4-difluorobenzyl) thio-5- (2-methoxypyrimid- 5-ylmethyl) pyrimidin-4-one Prepared from Example 107 by general method C3. 'H-NMR (CDCy § 3.01 (2H, t), 3.46 (2H, s), 3.99 (2H, t), 4.01 (3H. s), 4.49 (2H, s), 6.33 (1H, s), 6.99-7.29 (8H, m), 8.22 (2H, s) : MS (APCI+) found (M+1)=481 ; C25H22F2N40, S requires 480.

Example 242-1- (Furan-2-ylmethyl)-2- (3, 4-difluorobenzyl) thio-5- (2- methoxypyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 107 by general method C3. 1H-NMR (CDCl3) â 3.63 (2H, s), 4.00 (3H, s), 4.46 (2H, s), 4.90 (2H, s), 6.38 (2H, m), 7.01 (1 H, s), 7.07-7.26 (3H, m), 7.42 (1H, m), 8.44 (2H, s) ; MS (APCI+) found (M+1) = 457; ¬N4038 requires 456.

Example 243-1- (Undec-1-yl)-2- (4-fluorobenzyl) thio-5- (2-methoxypyrimid-5- ylmethyl) pyrimidin-4-one

Prepared from intermediate B 124 by general method A2. 1H-NMR (CDC13) 8 0.88 (3H, t), 1.25 (16H, m), 1.68 (2H, m), 3.64 (2H, s), 3.71 (2H, t), 4.00 (3H, s), 4.47 (2H, s), 6.87 (1H, s), 7.00 (2H, m), 7.36 (2H, m), 8.46 (2H, s); MS (APCI+) found (M+1) = 513; C2gH37N402S requires 512.

Example 244-1- (Undec-1-yl)-2- (4-fluorobenzyl) thio-5- (2-ethoxypyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B92 by general method A3 as an off-white solid. lH-NMR (CDCL3) 5 0.8-0.95 (3H, m), 1.15-1.4 (16H, m), 1.43 (3H, t), 1.55-1.8 (2H, m), 3.68 (2H, s), 3.71 (2H, t), 4.41 (2H, q), 4.47 (2H, s), 6.86 (lH, s), 6.9-7.1 (2H, m), 7.3-7.45 (2H, m), 8.45 (2H, d); MS (APCI+) found (M+1) = 527; C,9H39FN402S requires 526.

Example 245-1- (Undec-1-yl)-2- (4-fluorobenzyl) thio-5- (2-methylpyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B 135 by general method A2. 'H-NMR (CDCy 5 0.88 (3H, t), 1.25 (16H, m), 1.68 (2H, m), 2.72 (3H, s), 3.68 (2H, s), 3.72 (2H, t), 4.47 (2H, s), 6.89 (1H, s), 6.97 (2H, m), 7.38 (2H, m), 8.58 (2H, s); MS (APCI+) found (M+1) = 497; 496.C28H37N4OSrequires Example 246-1-(2-Phenvlethyl)-2-(4-fluorobenzyl) thio-5-((1-methyl-2-oxo-pyrid- 4-yl) methyl) pyrimidin-4-one Prepared from intermediate B70 by general method A2. 'H-NMR (CDCy § 3.01 (2H, t), 3.40 (2H, s), 3.51 (3H, s), 3.97 (2H, t), 4.51 (2H, s), 6.02 (1H, m), 6.24 (1H, s), 6.49 (1H,

s), 6.98-7.43 (10H. m); MS (APCI+) M+1=462; C26H24FN302S requires 461. MPt 69- 75°C (cream solid).

Example -1-(Undec-1-yl)-2-(4-fluorobenzyl)thio-5-((1-methyl-2-oxo-py rid-4- yl) methyl) pyrimidin-4-one Prepared from intermediate B 110 by general method A2. 1H-NMR (CDCl3) â 0.88 (3H, t), 1.25 (16H, m), 1.69 (2H, m), 3.50 (3H, s), 3.55 (2H, s), 3.71 (2H, t), 4.78 (2H, s), 6.17 (1H, m), 6.38 (1H, d), 6.84 (1H, s), 6.96 (2H, m), 7.19 (1H, m), 7.39 (2H, m); MS (APCI+) M+1=512, C29H38F3,2S requires 511. MPt 78-79°C (colourless solid).

Example 248-1- (Undec-1-yl)-2- (4-fluorobenzyl) thio-5- (1-methyl-2-oxopyrimid-5- ylmethyl) pyrimidin-4-one Prepared from Example 239 by treatment with methyl iodide (1 equiv) and potassium carbonate (2 equiv) in DMF. The misture was stirred at room temperature for 16 hours, then at 50°C for 1 hour. Evaporation of the solvent, aqueous workup and chromatography gave the title compound in 72% yield. IH-NMR (CDC13) õ (3H, m), 1.15-1.4 (16H. m), 1.6-1.85 (2H. m), 3.43 (2H. bs), 3.54 (3H, s), 3.78 (2H, t), 4.46 (2H, s), 6.9-7.1 (2H, m), 7.19 (lH, s), 7.25-7.45 (2H, m), 8.01 (lH, bd), 8.46 (lH, m).

Example 249-1-(Undec-1-yl)-2-(4-fluorobenzyl) thio-5-(1-benzyl-2-oxopyrimid-5- ylmethyl) pyrimidin-4-one Prepared from Example 239 analogously to Example 248, using benzyl bromide in place of methyl iodide. 1H-NMR (CDCl3) # (3H, m), 1.15-1.4 (16H, m), 1.6-1.85 (2H, m), 3.39 (2H, s), 3.74 (2H, t), 4.46 (2H, s), 5.08 (2H, s), 6.9-7.1 (3H, m), 7.25-7.45 (7H, m), 7.94 (lH, d), 8.43 (1H. d); MS (APCI+) found (M+l) = 589; C34H4, FN402S requires 588.

Example 250-1- (Undec-1-yl)-2-benzylthio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B95 by general method A4. 1H-NMR (CDC13) 8 0.88 (3H, t), 1.25 (16H, brs), 1.71 (2H, m), 3.71 (2H, s), 3.74 (2H, m), 4.49 (2H, s), 7.04 (1H, s), 7.26- 7.41 (SH. m), 8.69 (2H, s), 9.09 (lH, s); MS (APCI) found (M+H) = 465; C27H36N40S requires 464. <BR> <BR> <P>Example 251-1-Methyl-2- (4-fluorobenzyl) thio-5- (2-methoxypyrimid-5-ylmethyl)- pyrimidin-4-one Prepared from Example 108 by general method C2. IH-NMR (CDCl3) 8 3.47 (3H, s), 3.64 (2H, t), 3.99 (3H, s), 4.47 (2H, s), 6.88 (lH, s), 6.9-7.1 (2H, m), 7.3-7.5 (2H, m), 8.44 (2H, s); MS (APCI+) found (M+1) = 373; C18Hl7FN401S requires 372.

Example 252-1-Methyl-2-(4-fluorobenzyl) thio-5-(2-oxopyrimid-5- ylmethyl) pyrimidin-4-one To a solution of Example 251 (Sg) in dry methylene chloride was added a solution of boron tribromide 1M in dichloromethane (50ml) at 5°C under argon with stirring. After O. 5h, the mixture was allowed to warm to room temperature and was allowed to stir at room temperature for 72h. The mixture was decanted into a mixture of ice (50ml) and 0.880 ammonia (50ml). The solid remaining in the flask was treated with some of the aqueous mixture and 10% methanol in methylene chloride. The entire mixture was filtered through kieselguhr and the organic layer was separated. The aqueous layer was reduced to one quarter volume in vacuo and the solid formed filtered off, washed with water and dried in vacuo to give the desired product (2.2g). IH-NMR (d6 DMSO) 8 3.30 (2H, s), 3.47 (3H, s), 4.41 (2H, s), 7.05-7. 25 (2H, m), 7.4-7.55 (2H, m), 7.65 (lH, s), 7.85-8.3 (2H, b): MS (APCI+) found (M+l) = 359; Cl7HlsFN402S requires 358.

Example 253-1- (4-Acetylphenyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl)- pyrimidin-4-one

Prepared from intermediate B 136 by general method A4. 1H-NMR (CDCl3) 8 2.64 (3H, s), 3.79 (2H, s), 4.39 (2H, s), 6.95 (2H, m), 7.05 (1H, s), 7.29 (2H, m), 7.43 (2H, d, j=8. 5Hz), 8.08 (2H, d, j=8. 5), 8.75 (2H, s), 9.09 (lH, s): MS (APCI) found (M+H) = 447; C24HI9FN402S requires 446.

Example 254-1-(3-(Non-1-yloxy) phenyl)-2-(4-fluorobenzyl) thio-5-(pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B 128 by general method A2. 1H-NMR (CDCl3) # 9. 08 (1H, s), 8.73 (2H, s), 7.41-7.28 (3H, m), 7.09 (1H, s), 7.03-6.78 (5H, m), 4.36 (2H, s), 3.95 (2H, t), 3.73 (2H, s), 1.78 (2H, quintet), 1.47-1.23 (12H, m), 0.88 (3H, t); MS (APCI+) found (M+l) = 547, C3 H35FN40., S requires 546.

Example 255-1- (3- (Dec-1-yl) phenyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B 129 by general method A2. 'H-NMR (CDCy 5 9.08 (l H, s), 8.73 (2H, s), 7.40-7.27 (4H, m), 7.11-7.08 (3H, m), 6.94 (2H, t), 4.35 (2H, s), 3.73 (2H, s), 2.65 (2H, t), 1.67-1.56 (2H, m), 1.30-1.22 (14H, m), 0.88 (3H, t); MS (APCI+) found (M+l) = 545, C32H37FN40S requires 544.

Example 256-1-Methyl-2- (4-fluorobenzyl) thio-5- (1-undecyl-2-oxopyrimid-5- ylmethyl) pyrimidin-4-one

Prepared from Example 252 and undecyl iodide by the method of Example 248. 1H- NMR (CDC13) 6 0.88 (3H, s), 1.2-1.4 (16H. m), 1.77 (2H, m), 3.43 (2H, s), 3.53 (3H, s), 3.86 (2H, t), 4.47 (2H, s), 6.9-7.1 (2H, m), 7.20 (lH, s), 7.3-7.45 (2H, m), 7.96 (lH, d), 8.44 (lH, d); MS (APCI+) found (M+1) = 513; C28H37FN4O2S requires 512.

Example 257-1-Phenyl-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin- 4-one Prepared from intermediate B 121 by general method A2. IH NMR (CDCl3) b: 3.74 (s, 2H), 4.36 (s, 2H), 6.95 (t, 2H), 7.06 (s, 1H), 7.30 (m, 4H), 7.55 (m, 3H), 8.72 (s, 2H), 9.10 (s, 1H). MS (APCI+) Found (M+1) = 405; C, 2HI7FN40S requires 404.

Example 258-1-Phenyl-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B 121 by general method A2. IH NMR (CDCl3) 8: 1.35 (m, 6H), 1.65 (m, 4H), 2.91 (t, 2H), 3.14 (t, 2H), 3.76 (s, 2H), 7.04 (s, 1H), 7.3 (m, 2H), 7.43 (d, 2H), 7.55 (m, 3H), 7.89 (d, 2H), 8.72 (s, 2H), 9.10 (s, 1H). MS (APCI+) Found (M+1) = 533/535; C29H29CIN4O2S requires 533.

Example 259-1-(4-(Non-1-yloxyphenyl))-2-(4-fluorobenzyl) thio-5-(pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B 126 by general method A2. I H-NMR (CDC'3) 8 9.07 (1 H, s), 8.73 (2H, s), 7.30 (2H, dd), 7.21 (2H, d), 7.13 (1H, s), 6.95 (2H, d), 6.94 (2H, t), 4.33 (2H, s), 3.97 (2H, t), 3.73 (2H. s). 1.79 (2H, quintet), 1.47-1. 23 (12H, m), 0.88 (3H, t); MS (APCI+) found (M+l) = 547, C31H35FN4O2S requires 546.

Example 260-1- (4-Iodophenyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B 130 by general method A2.1H-NMR (CDCl3 + CD30D) 8 9.08 (1H, s), 8.72 (2H, s), 7.85 (2H, d), 7.33-7.26 (2H, m), 7.07 (1H, s), 7.05 (2H, d), 6.98 (2H, t), 4.35 (2H, s), 3.73 (2H, s); MS (APCI+) found (M+I) = 531, C22HI6FIN40S requires 530.

Example 261-1- (4- (Hex-1-yl) phenyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B 127 by general method A2. 1H-NMR (CDCl3) # 9.08 (1H, s), 8.73 (2H, s), 7.33-7.27 (4H, m), 7.19 (2H, d), 7.09 (1H, s), 6.94 (2H, t), 4.35 (2H, s), 3.73 (2H, s), 2.66 (2H, t), 1.62 (2H, quintet), 1.39-1.27 (6H, m), 0.87 (3H, t); MS (APCI+) found (M+1) = 489, C2sH29FN40S requires 488.

Example 262-1- (4- (Dec-1-yl) phenyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B 125 by general method A2. 1H-NMR (CDCl3) # 9. 08 (1H, s), 8.73 (2H, s), 7.33-7.27 (4H, m), 7.19 (2H, d), 7.10 (1H, s), 6.94 (2H, t), 4.35 (2H, s), 3.73 (2H, s), 2.65 (2H, t), 1.67-1.56 (2H, m), 1.34-1.22 (14H, m), 0.88 (3H, t); MS (APCI+) found (M+1) = 545, C32H37FN40S requires 544.

Example 263-1-Ethoxycarbonylmethyl-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio- 5- (pyrimid-5-ylmethyl)(pyrimid-5-ylmethyl) pyrimidin-4-one

Prepared from intermediates B80 and Al by general method A4, as a light brown crystalline solid. MPt 100-102°C; 1H-NMR (CDCl3) # 1.30 (3H, t), 1.37 (6H, m), 1.70 (4H, m), 2.93 (2H, t), 3.26 (2H, t), 3.71 (2H, s), 4.28 (2H, q), 4.50 (2H, s), 6.90 (1H, s), 7.44 (2H, m), 7.90 (2H, m), 8.71 (2H, s), 9.10 (1H, s); MS APCI+) found (M+1) = 543; C27H31ClN404S requires 542. <BR> <BR> <BR> <BR> <BR> <BR> <P>Example 264-1- (3-Ethoxycarbonylprop-1-yl)-2- (8- (4-chlorophenyl)-8-oxooct-l- yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediates B50 and A1 by general method A4, as a brown oil. lH- NMR (CDC13) 8 1.27 (3H, t), 1.38 (6H, m), 1. 69 (4H, m), 2.05 (2H, m), 2.38 (2H, t), 2.93 (2H, t), 3.25 (2H, t), 3.70 (2H, s), 3.88 (2H, t), 4.12 (2H, q), 7.05 (1H, s), 7.42 (2H, d), 7.91 (2H, d), 8.72 (2H, s), 9.09 (1H, s); MS (APCI+) found (M+1) = 571; C, 9H35ClN404S requires 570.

Example 265-1- (3-Ethoxycarbonylprop-1-yl)-2-benzylthio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B50 by general method A4, as a brown oil. IH-NMR (CDCl3) 8 1.24 (3H, t), 2.01 (2H, m), 2.35 (2H, m), 3.71 (2H, s), 3.86 (2H, t), 4.12 (2H, q), 4.50 (2H, s), 7.07 (1H, s), 7.27-7.41 (5H, m), 8.72 (2H, s), 9.12 (1H, s); MS (APCI+) found (M+1) = 425; C ; ; H24N403S requires 424.

Example 266 - 1-(3-Ethoxycarbonylprop-1-yl)-2-(3, 4-difluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B50 by general method A2 as an oil.'H-NMR (CDC13) 5 1.17-1.30 (3H, m), 1.96-2.12 (2H, m), 2.30-2.41 (2H, t), 3.70 (2H, s), 3.80-3.90 (2H, t), 4.06-4.20 (2H, q), 4.49 (2H, s), 7.01-7.26 (4H, m), 8.72 (2H, s), 9.10 1H, s); MS (ES+) found (M+1) = 461; C22H22F2N403S requires 460.

Example-1-(3-Ethoxycarbonylprop-1-yl)-2-(4-fluorobenzyl)t hio-5-(pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B50 by general method A2. 1H-NMR (CDCl3) # 1.26 (3H, t), 2.03 (2H, m), 2.35 (2H, t), 3.70 (2H, s), 3.85 (2H, t), 4. 12 (2H, m), 4.47 (2H, s), 6.71- 7.07 (3H, m), 7.35-7.41 (2H, m), 8.70 (2H, s), 9.10 (1H, s); MS (APCI+) M+1=443, C22H23FN4O3S requires 442 (orange oil).

Example 268-1- (5-Ethoxycarbonylpent-1-yl)-2- (3,4-difluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B 102 by general method A2 as an oil. IH-NMR (CDC13) 8 1.14-1.87 (9H, m), 2.25-2.37 (2H, m), 3.63-3.82 (4H, m), 4.04-4.19 (2H, q), 4.45 (2H, s), 6.97-7.30 (4H, m), 8.70 (2H, s), 9.10 (1H, s); MS (ES+) found (M+1) = 489; C24H26F2N403S requires 488.

Example -1-(1-(Ethoxycarbonyl)cycloprop-1-yl)-2-(4-fluorobenzyl)thio -5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B 106 by general method A2 as a foam. 1H-NMR (CDC13) 5 1.08-1.20 (3H, t), 1.38-1.54 (1H. m), 1.58-1.85 (2H, m), 1.94-2.10 (1H, m), 3.71 (2H, s), 4.04-4.28 (2H, m), 4.35-4.52 (2H, q), 6.90-7.05 (2H, t), 7.08 (1H, s), 7.29-7.42 (2H, m), 8.70 (2H, s), 9.10 (1H, s); MS (APCI+) found (M+1) = 44; C22H21FN4O3S requires 440.

Example 270-1-(4-Fluorobenzyloxycarbonylmethyl)-2-(4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B80 by alkaline hydrolysis as in general method D, followed by alkylation with 4-fluorobenzyl bromide by general method A2. 1H-NMR (CDCl3) # 3.71 (2H, s), 4.46 (4H, m), 5.16 (2H, s), 6.87 (1H. s), 6.94-7.06 (4H, m), 7.25-7.35 (4H,

m), 8.68 (2H, s), 9.10 (1H. s); MS (APCI+) M+1=495, C25H2QF2N403S requires 494.

MPt 184-186°C (colourless solid). MPt. 184-186 Example -1-Ethoxycarbonylmethyl-2-(4-fluorobenzyl)-thio-5-(pyrimid-5 - ylmethyl) pyrimidin-4-one Prepared from intermediate B80 by general method A2. 1H-NMR (CDCl3) # 1.26 (3H, t), 3.71 (2H. s), 4.26 (2H, q), 4.46 (2H, s), 4.48 (2H, s), 6.91 (1H, s), 6.98 (2H, m), 7.35 (2H, m), 8.70 (2H, s), 9.09 (1H, s); MS(APCI+) M+1=415, C20H29FN4O3S requires 414.

MPt 145.1°C (yellow solid).

Example 272-1-(1-(Methoxycarbonyl) ethyl)-2-(4-fluorobenzyl) thio-S-(pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B 103 by general method A2 as a solid. 1H-NMR (CDC13) 8 1.68 (3H, d), 3.70 (2H, s), 3.78 (3H, s), 4.38-4.58 (2H, br. q), 4.98-5.10 (1H, q), 6.95- 7.07 (2H, t), 7.19 (1H, s), 7.30-7.42 (2H, m), 8.72 (2H, s), 9.10 (1H, s); MS (APCI+) found (M+1) = 429; C20HlgFN403S requires 428.

Example 273-1- (trans-4- (Methoxycarbonyl) cyclohex-1-ylmethyl)-2- (4- fluorobenzyl) thio-5-(pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B 137 by general method A2 as a solid. IH-NMR (CDCl3) 5 (2H, m), 1.30-1.54 (2H, m), 1.60-1.82 (4H, m), 1.94-2.13 (1H, m), 2.14-2.34 (1H, m), 3.53-3.74 (7H, m), 4.46 (2H, s), 6.90 (1H, s), 6.94-7.08 (2H, t), 7.30-7.44 (2H, m), 8.70 (2H, s), 9.11 (1H, s); MS (APCI+) found (M+1) = 483; C25H7FN403S requires 482.

Example 274-1- (trans-4- (Methoxycarbonyl) cyclohex-1-yl)-2- (4-fluorobenzyl) thio- 5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B 108 by general method A2 as a solid. lH-NMR (CDC13) b 1.54-1.97 (6H, m), 2.22-2.39 (2H, d), 2.68-2.79 (1H, br. s), 3.70 (2H, s), 3.73 (3H, s), 4.03-4.25 (1H, m), 4.45 (2H, s), 6.93-7.08 (2H, m), 7.21 (1H, s), 7.30-7.43 (2H, m), 8.71 (2H, s), 9.08 (1H, s); MS (APCI+) found (M+1) = 469; C24H25FN4O3S requires 468.

Example 275-1-(3-Ethoxycarbonylprop-1-yl)-2-(4-fluorobenzyl) thio-5-((1-methyl- 2-oxo-pyrid-4-yl) methyl) pyrimidin-4-one Prepared from intermediate B 111 by general method A2. 1H-NMR (CDCl3) # 1.25 (3H, t), 2.02 (2H, m), 2.35 (2H, t), 3.50 (3H, s), 3.54 (2H, s), 3.83 (2H, t), 4.12 (2H, q), 4.47 (2H, s), 6.19 (1H, m), 6.37 (1H, s), 6.84-7.41 (6H, m); MS (APCI+) M+1=472, C,,4H26FN304S requires 471. MPt 109-111°C (colourless solid). MPt. 109-111 Example 276-1- (Ethoxycarbonylmethyl)-2- (4-fluorobenzyl) thio-5- (2- methoxypyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 108 by general method C2. 1H-NMR (CDC13) 6 1.26 (3H, t), 3.66 (2H, s), 3.99 (3H, s), 4.23 (2H, q), 4.47 (2H, s), 4.48 (2H, s), 6.84 (1H, s), 6.98 (2H, m), 7.34 (2H, m), 8.44 (2H, s); MS (APCI+) found (M+1) = 445; C21H21FN4O4S requires 444.

Example 277-1-(4-(Ethoxycarbonyl) benzyl)-2-(4-fluorobenzyl) thio-S-(pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B 107 by general method A2 as a solid. 1H-NMR (CDCl3) 8 1.35-1.47 (3H, t), 3.70 (2H, s), 3.93 (1H, s), 4.32-4.52 (3H, m), 5.02 (2H, s), 6.90-7.06

(3H, m), 7.13-7.40 (4H, m), 7.98-8.10 (2H, d), 8.67 (2H, s), 9.09 (1H, s); MS (APCI+) found (M+ 1) = 491; C26H23FN403S requires 490.

Example 278-1- (4-Methoxycarbonylbenzyl)-2- (8- (4-chlorophenyl) oct-1-yl) thio-5- (pyrid-3-ylmethyl) pyrimidin-4-one Prepared from Example 70 by general method Cl. 1H-NMR (CDCl3) # 1.2-1. 45 (8H, m), 1.45-1.75 (4H, m), 2.55 (2H, t), 3.24 (2H, t), 3.73 (2H, s), 3.92 (3H, s), 5.01 (2H, s), 6.81 (1H. s), 7.05-7.3 (7H, m), 7.61 (1H. txd), 8.03 (2H, d) and 8.46 (2H, bs); MS (EI) found M=589; C33H36C1N303S requires 589.

Example 279-1- (3-Carboxyprop-1-yl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from Example 267 by general method D. 1H-NMR (d6-DMSO) 5 1.93 (2H, m), 2.29 (2H, t), 3.58 (2H, s), 3.87 (2H, t), 4.40 (2H, s), 7.14 (2H, m), 7.48 (2H, m), 7.81 (1H, s), 8.70 (2H, s), 9.02 (1H, s); MS (APCI-) M-1=413, C20H19FN403S requires 414. MPt 188-190°C (colourless solid).

Example 280-1-Carboxymethyl-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from Example 271 by general method D. IH-NMR (d6-DMSO) õ 3.59 (2H, s), 4.41 (2H, s), 4.67 (2H, s), 7.11 (2H, m), 7.45 (2H, m), 7.72 (1H, s), 8.70 (2H, s), 9.03 (1H, s), 13.55 (1H, bs); MS (APCI-) M-1=385, Cl8HlsFN403S requires 386. MPt 206- 207°C (colourless solid).

Example 1-(3-Carboxyprop-1-yl)-2-(4-fluorobenzyl)thio-5-((1-methyl-2 -oxo-- pyrid-4-yl) methyl) pyrimidin-4-one

Prepared from Example 275 by general method D. IH-NMR (d6-DMSO) õ 1.90 (2H, m), 2.28 (2H, t), 3.37 (SH, m), 3.86 (2H, t), 4.41 (2H, s), 6.12 (1H, m), 6.18 (1H, s), 7.14 (2H, m), 7.50 (3H, m), 7.73 (1H, s), 12.2 (1H, bm): MS (APCI+) M+1=444, C22H22FN304S requires 443. MPt 245-249°C (colourless solid).

Example 282-1- (3-Carboxyprop-1-yl)-2- (3,4-difluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from Example 266 by general method D as a white solid. lH-NMR (DMSO) 8 1.83-2.03 (2H, m), 2.24-2.37 (2H, t), 3.58 (2H, s), 3.81-3.93 (2H, t), 4.41 (2H, s), 7.23- 7.59 (3H, m), 7.81 (1H, s), 8.71 (2H, s), 9.02 (1H, s), 12.13-12.20 (1H, s); MS (APCI-) found (M-1) = 431; C20H18F2N4O3S requires 432.

Example 283-1- (5-Carboxypent-1-yl)-2- (3, 4-difluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from Example 268 by general method D as a white solid. IH-NMR (DMSO) 8 1.18-1.81 (6H, m), 2.14-2.29 (2H, t), 3.59 (2H, s), 3.76-3.90 (2H, t), 4.41 (2H, s), 7.23- 7.60 (3H, m), 7.85 (1H, s), 8.70 (2H, s), 9.02 (1H, s), 11.92-12.10 (1H, s); MS (APCI-) found (M-1) = 459;¬NN4038 requires 460.

Example 284-1-(4-Carboxybenzyl)-2-(4-fluorobenzyl) thio-5-(pyrimid-5- ylmethyl)-2-thiouracil Prepared from Example 277 by general method D. IH-NMR (DMSO) 8 3.60 (2H, s), 4.39 (2H, s), 5.21 (2H, s), 7.03-7.19 (2H, t), 7. 26-7.49 (4H, m), 7.38-8.02 (3H, m), 8.72 (2H, s), 9.03 (1H, s), 12.92-13.10 (1H, br. s); MS (APCI+) found (M+1) = 463; C24Hl9FN403S requires 462.

Example 285-1- (4-Carboxycyclohex-1-yl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl)-2-thiouracil Prepared from Example 274 by general method D. IH-NMR (DMSO) 8 1.57-1.88 (6H, m), 2.13-2. 26 (2H, d), 2.60 (1H, s), 3.62 (2H, s), 3.98-4.10 (1H, m), 4.40 (2H, s), 7.09- 7.19 (2H, t), 7.44-7.53 (2H, m), 8.00 (1H, s), 8.72 (2H, s), 9.00 (1H, s), 12.27 (1H, s); MS (APCI+) found (M+1) = 455; C23H23FN403S requires 454.

Example 286-1- (3-Ethoxycarbonylphenyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate B 118 by general method A2. 1 H NMR (CDCl3) 8: 1.41 (t, 3H), 3.75 (s, 2H), 4.37 (s, 2H), 4.41 (q, 2H), 6.95 (t, 2H), 7.05 (s, 1H), 7.30 (m, 2H), 7.50 (m, 1H), 7.60 (t, 1H), 7.97 (m, 1H), 8.21 (d, 1H), 8.72 (s, 2H), 9.10 (s, 1H). MS (APCI+) Found (M+1) = 477; C25H21FN4O3S requires 476.

Example 287-1- (3-Ethoxycarbonylphenyl)-2- (8- (4-chlorophenyl)-8-oxooct-1- yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B 118 by general method A4. I H NMR (CDC'3) 6: 1.3 (m, 6H), 1.42 (t, 3H), 1.65 (m, 4H), 2.91 (t, 2H), 3.15 (t, 2H), 3.73 (s, 2H), 4.42 (q, 2H), 7.03 (s, 1H), 7.42 (d, 2H), 7.5 (m, 1H), 7.62 (t, 1H), 7.88 (d, 2H), 7.98 (s, 1H), 8.22 (d, 1H), 8.72 (s, 2H), 9.09 (s, 1H). MS (APCI+) Found (M+l) = 605/607; C32H33ClN404S requires 605.

Example 288-1- (3-Carboxyphenyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one

Prepared from Example 286 by general method D as a white solid, m. p 157-160°. 1H NMR (DMSO-d6) 8: 3.62 (s, 2H), 4.31 (s, 2H), 7.10 (t, 2H), 7.40 (m, 2H), 7.70 (t, 1H), 7.87 (d, 1H), 7.94 (s, 1H), 8.10 (m, 2H), 8.77 (s, 2H), 9.01 (s, 1H), 13.4 (br s, 1H). MS (APCI+) Found (M+1) = 449; C23HI7FN403S requires 448.

Example 289-1- (3-Carboxyphenyl)-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 287 by general method D as a white solid, m. p 109-112°. 1H NMR (DMSO-d6) 8: 1.3 (m, 6H), 1.65 (m, 4H), 2.9-3.1 (m, 4H), 3.60 (s, 2H), 7.57 (d, 2H), 7.71 (t, 1H), 7.8-8.0 (m, 4H), 8.13 (m, 2H), 8.75 (s, 2H), 9.02 (s, 1H) 13.35 (br s, 1H). MS (APCI+) Found (M+1) = 557/579: C30H29CIN4O4S requires 577.

Example 290-1- (4-Ethoxycarbonylphenyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from intermediate Bol 19 by general method A2.-H NMR (CDC) § NMR (CDC'3) 40 (t, 3H), 3.74 (s, 2H), 4.37 (s, 2H). 4.41 (q, 2H), 6.95 (t, 2H), 7.05 (s, 1H), 7.30 (m, 2H), 7.40 (d, 2H), 8.20 (d, 2H), 8.72 (s, 2H), 9.11 (s, 1H). MS (APCI+) Found (M+1) = 477; C, 5H, lFN403S requires 476.

Example 291-1- (4-Ethoxycarbonylphenyl)-2- (8- (4-chlorophenyl)-8-oxooct-1- yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate Bol 19 by general method A4. 1H NMR (CDC13) 5: 1.3 (m, 6H), 1.42 (t, 3H), 1.65 (m, 4H), 2.91 (t, 2H), 3.15 (t, 2H), 3.73 (s, 2H), 4.44 (q, 2H), 7.03 (s, 1H), 7.4 (m, 4H), 7.88 (d, 2H), 8.20 (d, 2H), 8.71 (s, 2H), 9.10 (s, 1H). MS (APCI+) Found (M+1) = 605/607; C32H33CIN4O4S requires 605.

Example 292-1- (4-Carboxyphenyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from Example 290 by general method D as a white solid, m. p. 258-262° dec. 1H NMR (DMSO-d6) 5: 3.63 (s, 2H), 4.31 (s, 2H), 7.10 (t, 2H), 7.40 (m, 2H), 7.74 (d, 2H), 7.95 (s, 1H), 8.10 (d, 2H), 8.77 (s, 2H), 9.01 (s, 1H), 13.3 (br s, 1H). MS (APCI+) Found (M+1) = 449; C23Hl7FN403S requires 448.

Example 293-1- (4-Carboxyphenyl)-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 291 by general method D as a white solid, m. p 92-96°. lH (DMSO-d6) b: 1.3 (m, 6H), 1.6 (m, 4H), 2.9-3.1 (m, 4H), 3.61 (s, 2H), 7.57 (d, 2H), 7.74 (d, 2H), 7.95 (m, 3H), 8.10 (d, 2H), 8.75 (s, 2H), 9.02 (s, 1H) 13.35 (br s, 1H). MS (APCI+) Found (M+1) = 577/579; C3oH29ClN404S requires 577.

Example 294-1- (5- (Ethoxycarbonyl) fur-2-yl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl)pyrimidin-4-one Prepared from intermediate B 120 by general method A2.'H NMR (CDCl3) 8: 1.38 (t, 3H), 3.72 (s, 2H), 4.38 (s, 2H), 4.39 (q, 2H), 6.60 (d, 1H), 6.97 (t, 2H), 7.08 (s, 1H), 7.20 (d, 1H), 7.3 (m, 2H), 8.71 (s, 2H), 9.11 (s, 1H). MS (APCI+) Found (M+1) = 467; C, 3HI9FN404S requires 466.

Example 295-1-(3-Ethoxycarbonyl-4-iodobenzyl)-2-(4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one

Prepared from Example 106 by general method C2 as a yellow solid.'H-NMR (250MHz, DMSO) 9.03 (s, 1H), 8.82 (s, 2H), 8.00 (m, 2H), 7.57 (s, 1H), 7.42 (m, 2H), 7.11 (m, 3H), 5.14 (s, 2H), 4.39 (s, 2H), 3.87 (s, 3H), 3.62 (s, 2H). MS (AP+) 603 (M+H+, 100%).

Example 296-1- (3- (Hept-1-yloxy)-4-methoxycarbonylbenzyl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 106 by general method C2 as a yellow solid. IH-NMR (400MHz, CDC13) 9. 00 (s, 1H), 8.61 (s, 2H), 7.53 (d, 1H), 7.30 (d, 1H), 7.28 (d, 1H), 7.15 (dd, 1H), 6.90 (m, 4H), 4.82 (s, 2H), 4.40 (s, 2H), 3.96 (t, 2H), 3.82 (s, 3H), 3.60 (s, 2H), 1.73 (m, 2H), 1.42 (m, 2H), 1.29 (m, 6H), 0.83 (t, 3H). MS (AP+) 591 (M+H+, 100%).

Example 297-1- (3- (Hept-1-yloxy)-4-methoxycarbonylbenzyl)-2- (4- fluorobenzyl) thio-5-(pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 106 by general method C2 as a yellow solid. 1H-NMR (400MHz, CDCl3) 9.00 (s, 1H). 8.59 (s, 2H), 7.68 (d, 1H), 7.29 (d, 1H), 7.28 (d, 1H), 6.91 (m. 3H), 6.59 (s, 2H), 4.88 (s, 2H), 4.40 (s, 2H), 3.81 (m, 5H), 3.62 (s, 2H), 1.72 (m, 2H), 1.40 (m, 2H), 1.28 (6H) 0.83 (t, 3H). MS (AP+) 591 (M+H+, 100%).

Example 298-1-(3-Carboxy-4-(hept-1-yloxy) benzyl)-2-(4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 296 by general method D as a colourless solid. IH-NMR (250MHz, CDCl3) 9.05 (s, 1H), 8.75 (s, 2H), 8.65 (br s, 1H), 8.02 (d, 1H), 7.32 (m, 4H), 6.98 (m, 3H), 4.99 (s, 2H), 4.40 (s. 2H), 4.21 (t, 2H), 3.70 (s, 2H), 1.88 (m, 2H), 1.50- 1.20 (m, 8H), 0.87 (t, 3H). MS (AP+) 577 (M+H+, 100%).

Example 299-1- (3- (Hept-1-yloxy)-4-carboxybenzyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one

Prepared from Example 297 by general method D as a colourless solid. IH-NMR (400MHz, CDCl3) 9.04 (s, 1H), 8.67 (s, 2H), 8.11 (d, 1H), 7.33 (d, 1H), 7.31 (d, 1H), 7.05 (s, 1H), 6.95 (t, 2H), 6.82 (d, 1H), 6.68 (s, 1H), 4.99 (s, 2H), 4.44 (s, 2H), 4.05 (t, 2H), 3.69 (s, 2H), 1.87 (m, 2H), 1.50-1.25 (m, 8H), 0.87 (t, 3H). MS (AP+) 577 (M+H+, 55%).

Example 300-1- (3-Methoxycarbonyl-4-hydroxybenzyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one

Prepared from Example 106 by general method C2 as a yellow solid. 1H-NMR (250MHz, CDC13) 10.82 (s, 1H) 9.03 (s, 1H), 8.64 (s, 2H), 7.77 (d, 1H), 7.30 (m, 2H), 6.93 (m, 3H), 6.68 (d, 1H), 6.53 (dd, 1H), 4.88 (s, 2H), 4.41 (s, 2H), 3.91 (s, 3H), 3.64 (s, 2H).

Example 301-1- (3-Methoxycarbonylbenzyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from Example 106 by general method C2 as a yellow solid. 1H-NMR (400MHz, CDC13) 9. 10 (s, 1H), 8.71 (s, 2H), 8.07 (d, 1H), 7.86 (s, 1H), 7.50 (t, 1H), 7.30 (m, 3H), 7.07 (s, 1H), 7.01 (t, 2H), 5.05 (s, 2H), 4.50 (s, 2H), 3.97 (s, 3H), 3.72 (s, 2H).

MS (AP+) 477 (M+H+, 25%).

Example 302-1-(3-CarboXvbenzyl)-2-(4-íluorobenzyl) thio-5-(pyrimid-5-ylmethyl)- pyrimidin-4-one Prepared from Example 301 by general method D as colourless crystals. 1H-NMR (400MHz, DMSO) 13.20 (br s, 1H), 9.07 (s, 1H), 8.78 (s, 2H), 8.06 (s, 1H), 7.95 (d, 1H), 7.85 (s, 1H), 7.50 (m, 4H), 7.16 (t, 2H), 5.26 (s, 2H), 4.44 (s, 2H), 3.68 (s, 2H).

Example 303-1- (3, 4-Di- (methoxycarbonyl) benzyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one

Prepared from Example 106 by general method C2 as a yellow solid. 1H-NMR (250MHz, CDC13) 9.05 (s, 1H), 8.65 (s, 2H), 7.69 (m, 1H), 7.44 (s, 1H), 7.27 (m, 3H), 6.96 (m, 3H), 4.99 (s, 2H), 4.62 (s, 2H), 4.09 (s, 6H), 3.87 (s, 2H). MS (AP+) 535 (M+H+, 100%).

Example 304-1-Carboxamidomethyl-2- (8- (4-chlorophenyl) oct-1-yl) thio-5- (pyrid- 3-ylmethyl) pyrimidin-4-one Prepared from example 7U by general method Cl, as a buff powder. MPt 147-152UC; 'H-NMR (d6 DMSO) 8 1. 2-1.5 (8H, m), 1.5-1.8 (4H, m), 2.54 (2H, t), 3.08 (2H, t), 3.56 (2H, s), 4.53 (2H, s), 7.1-7.9 (9H, m), 8.38 (1H, m) and 8.48 (lH, bs); MS (EI) M=498; C, 6H31 ClN402S requires 498.

Example 305-1-Dimethylaminocarbonylmethyl-2- (8- (4-chlorophenyl)-8-oxooct-1- yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediates B79 and A1 by general method A4, as a light brown crystalline solid. MPt 57-59°C ; IH-NMR (CDC13) 6 1.37 (6H, m), 1.69 (4H, m), 2.92 (2H, t), 3.01 (3H, s), 3.16 (3H, s), 3.68 (2H, s), 4.43 (2H, m), 5.06 (2H, s), 7.11 (1H, s), 7.42 (2H, m), 7.89 (2H, m), 8.71 (2H, s), 9.11 (1H, s).

Example 306-1-Carboxamidomethyl-2-benzylthio-5-((2-methoxypyrid-4- yl) methyl) pyrimidin-4-one Prepared from Example 88 by general method Cl, as a cream solid. MPt 126-132°C; IH-NMR (d6 DMSO) b 3.53 (2H, s), 3.81 (3H, s), 4.40 (2H, s), 4.53), 6.66 (1H, s), 6.85 (lH, dd), 7.2-7.5 (6H, m), 7.63 (lH, s), 7.75 (lH, bs) and 8.03 (1H, d); MS (EI) found M=396; C20H20N403S requires 396.

Example 307-1- (3- (Octadec-lylaminocarbonyl) prop-1-yl)-2- (4-fluorobenzyl) thio- 5- (pyrimid-5-ylmethyl) pyrimidin-4-one

Prepared from Example 279 by general method E. IH-NMR (CDC13) 6 0.88 (3H, m), 1.25 (30H, m), 1.47 (2H, m), 2.05 (2H, m), 2.18 (2H, m), 3.21 (2H, m), 3.69 (2H, s), 3.92 (2H, m), 4.46 (2H, s), 5.42 (1H, m), 6.98 (2H, m), 7.27 (1H, m), 7.37 (2H, m), 8.71 (2H, s), 9.09 (1H, s), MS (APCI+) M+1=666, C38H56FN502S requires 665. MPt 115.1°C (colourless solid).

Example 308-1- (3- (Octadec-9- (Z)-en-lylaminocarbonyl) prop-1-yl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 279 by general method E. 'H-NMR (CDC13) õ 0.88 (3H, m), 1.27 (22H, m), 1.47 (2H, m), 1.99-2.20 (8H, m), 3.20 (2H, m), 3.69 (2H, s), 3.92 (2H, m), 4.46 (2H, s), 5.32 (2H, m), 5.42 (1H, m), 6.99 (2H, m), 7.26 (1H, s), 7.37 (2H, m), 8.71 (2H, s), 9.08 (1H, s), MS(APCI+)M+1=664, C38H54FN5O2S requires 663 (waxy solid).

Example 309-1- (3- (Octadec-9- (E)-en-lylaminocarbonyl) prop-1-yl)-2- (4- fluorobenzyl) thio-5-(pyrimid-5-vlmethyl) pyrimidin-4-one Prepared from Example 279 by general method E. I H-NMR (CDC'3) 8 0.88 (3H, t), 1.27 (22H, m), 1.47 (2H, m), 1.99-2.20 (8H, m), 3.20 (2H, m), 3.69 (2H, s), 3.92 (2H, m), 4.46 (2H, s), 5.37 (2H, m), 5.44 (1H, m), 6.99 (2H, m), 7.26 (1H, s), 7.37 (2H, m), 8.71 (2H, s), 9.08 (1H, s), MS(APCI+)M+1=664, C38H54FN5O2S requires 663. MPt 108.4°C (colourless solid).

Example 310-1- (3- (N-Dodec-lyl-N-methylaminocarbonyl) prop-1-yl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 279 by general method E. IH-NMR (CDCl3) õ 0.88 (3H, m), 1.26 (18H, m), 1.49 (2H, m), 2.02 (2H, m), 2.30 (2H, m), 2.90 (3H, s), 3.17,3.32 (each 1H, m), 3.69 (2H, s), 3.92 (2H, t), 4.46 (2H, s), 6.98 (2H, m), 7.24 (1H, m), 7.35 (2H, m), 8.70 (2H, s), 9.08 (1H, s), MS (APCI+) M+1=596, C33H46FN502S requires 595. MPt 76.9°C (colourless solid).

Example 311-1- (3- (N-Non-1-yl-N-methylaminocarbonyl) prop-1-yl)-2- (4- fluorobenzyl) thio-5-(pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 279 by general method E. 1H-NMR (CDCl3) # 0.88 (3H, m), 1.26 (8H, m), 1.48 (2H, m), 2.05 (2H, m), 2.30 (2H, m), 2.90 (3H, s), 3.18,3.32 (each 1H, m), 3.69 (2H, s), 3.91 (2H, t), 4.46 (2H, s), 6.99 (2H, m), 7.25 (1H, m), 7.35 (2H, m), 8.71 (2H, s), 9.08 (1H, s), MS (APCI+) M+1=526, C2gH36FN50 S requires 525. (coloured oil).

Example 312-1-(4-(Pent-1-ylaminocarbonyl) benzyl)-2-(4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 284 by general method E as a solid. 'H-NMR (CDCy § 0.82- 1.05 (3H, t), 1.21-1.48 (3H, m), 1.52-1.77 (3H, m), 3.38-3.54 (2H, q), 3.69 (2H, s), 4.49 (2H, s), 5.01 (2H, s), 6.14-6.27 (1H, br. t), 6.90-7.05 (3H, m), 7.10-7.21 (2H, d), 7.28-7.39 (2H, m), 7.70-7.80 (2H, d), 8.65 (2H, s), 9.07 (1H, s); MS (APCI+) found (M+1) = 532; 531.C29H30FN5O2Srequires Example 315-1-(1-(6-(4-Fluorophenvl) hex-1-ylaminocarbonyl) ethyl)-2-(4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one

Prepared from Example 272 by hydrolysis using general method D, followed by amide coupling using general method E. 1H-NMR (CDCl3) # 1.15-1.72 (11H, m), 2.47-2.60 (2H, t), 3.17-3.35 (2H, m), 3.52-3.70 (2H, m), 4.25-4.49 (2H, br. q), 4.74-4.89 (1H, q), 6.53-6.66 (1H, br. t), 6.87-7.16 (6H, m), 7.21-7.40 (2H, m), 7.53 (1H, s), 8.69 (2H, s), 9.08 (1H, s); MS (APCI+) found (M+1) = 578; C3lH33F2N50,, S requires 577. <BR> <BR> <BR> <BR> <BR> <BR> <P>Example 316-1- (3- (11-Dimethylaminoundec-1-ylaminocarbonyl) prop-1-yl)-2- (4- fluorobenzyl) thio-5-(pyrimid-5-ylmethyl) pyrimidin-4-one Prepared trom Example 279 by general method E 1H-NMR (CDCl3) # 1.27 (10H, m) 1.47 (4H, m), 1.99-2. 20 (4H, m), 2.30 (6H, m), 3.20 (2H, m), 3.69 (2H, s), 3.92 (2H, m), 4.46 (2H, s), 5.49 (1H, bm), 6.99 (2H, m), 7.26 (1H, s), 7.37 (2H, m), 8.71 (2H, s), 9.08 (1H, s), MS(APCI+) M+1=611, C33H47FN6O2S requires 610 (gum).

Example 317-1- (3- (3-Ethoxyprop-lylaminocarbonyl) prop-1-yl)-2- (3,4- difluorobenzyl) thio-5-(pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 282 by general method E. 'H-NMR (CDC13) 6 1.14-1.35 (5H, m), 1.70-1.88 (2H, m), 2.11-2.23 (2H, t), 3.70-3.43 (2H, q), 3.435-3.60 (4H, m), 3.70 (2H, s), 3.87-4.01 (2H, t), 4.44 (2H, s), 6.23-6.38 (1H, br. t), 7.01-7.33 (4H, m), 8.71 (2H, s), 9.09 (1H, s) ; MS (APCI+) found (M+1) =518; C25H29F2N5O3S requires 517.

Example 318-1- (3- (5- (Methoxycarbonyl)-5- (benzykloxycarbonylamino) pent- lylaminocarbonyl) prop-1-yl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from Example 279 by general method E. 1H-NMR (CDC13) 8 1.2-2.2 (10H, m), 3.19 (2H, m), 3.67 (2H, s), 3.74 (3H, s), 3.85 (2H, t), 4.35 (1H, m), 4.45 (2H, s), 5.09 (2H, s), 5.55 (2H, m), 6.99 (2H, m), 7.22-7.37 (8H, m), 8.71 (2H, s), 9.08 (1H, s), MS (APCI+) M+1=691, C35H39FN606S requires 690 (colourless foam).

Example 319-1- (3- (5- (Methoxycarbonyl) pent-lylaminocarbonyl) prop-1-yl)-2- (4- fluorobenzyl) thio-5-(pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 279 by general method E. 'H-NMR (CDC) § 1.2-1.7 (6H, m), 1.98-2.21 (4H, m), 2.31 (2H, t), 3.22 (2H, m), 3.66 (3H, s), 3.70 (2H, s), 3.92 (2H, t), 4.45 (2H, s), 5.57 (1H, bm), 6.99 (2H, m), 7.26 (1H, s), 7.36 (2H, m), 8.71 (2H, s), 9.08 (1H, s); MS(APCI+) M+1=542. C27H32FN5O4S requires 541. (oil).

Example 320-1- (3- (Hex-lylaminocarbonyl) prop-1-yl)-2- (3, 4-difluorobenzyl) thio- 5- (pyrimid-5-ylmethyl)(pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 279 by general method E as a solid. lH-NMR (CDCI3) â 0.83- 0.98 (3H, t), 1. 20-1.59 (8H, m), 1.97-2.28 (4H, m), 3.15-3.29 (2H, q), 3.69 (2H, s), 3.87- 4.01 (2H, t), 4.43 (2H, s), 5.49-5.64 (1H, br. t), 6.99-7.32 (4H, m), 8.71 (2H, s), 9.08 (1H, s); MS (APCI+) found (M+1) = 516: C26H30F2N5O2 S requires 515.

Example 321-1- (3- (5- (t-Butoxycarbonylamino) pent-lylaminocarbonyl) prop-1-yl)- 2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 279 by general method E. 1H-NMR (CDCl3) # 1.18-1.5 (15H, m), 2.05 (2H, m), 2.19 (2H, m), 3.16 (4H, m), 3.70 (2H, s), 3.92 (2H, t), 4.52 (2H, s), 4.64 (lH, bm), 5.71 (1H, bm), 6.99 (2H, m), 7.28 (1H, s), 7.37 (2H, m), 8.72 (2H, s), 9.08 (1H, s); MS (APCI+) M+1=599, C3oH39FN604S requires 598. (colourless foam).

Example 322-1- (3- (6- (t-Butoxycarbonylamino) hex-lylaminocarbonyl) prop-1-yl)- 2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 279 by general method E 1H-NMR (CDCl3) # 1.18-1.5 (17H, m), 2.04 (2H, m), 2.20 (2H, m), 3.15 (4H, m), 3.69 (2H, s), 3.92 (2H, t), 4.45 (2H, s), 4.59 (1H, bm), 5.80 (1H, bm), 6.96 (2H, s), 7.28 (1H, s), 7.36 (2H, m), 8.71 (2H, s), 9.08 (1H, s); MS(APCI+) M+1=613, C31H41FN6O4S requires 612. MPt 90-98°C (colourless foam).

Example 323-1-(3-(Dec-lylaminocarbonyl) prop-1-yl)-2-(4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 279 by general method E. 'H-NMR (CDCy 5 0.88 (3H, t), 1.26 (14H, m), 1.47 (2H, m), 1.98-2.20 (4H, m), 3.20 (2H, m), 3.69 (2H, s), 3.92 (2H, t), 4.46 (2H, s), 5.39 (1H, bm), 6.98 (2H, m), 7.24 (1H, s), 7.37 (2H, m), 8.70 (2H, s), 9.08 (1H, s); s); MS(APCI+) M+1=554, C30H40FN5O2S requires 553. MPt 90-98°C (colourless solid).

Example 324-1- (3- (Dec-lylaminocarbonyl) prop-1-yl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 279 by general method E. lH-NMR (d6-DMSO) o 0.85 (3H, m), 1.22 (14H, m), 1.31 (2H, m), 1.87 (2H, m), 2.12 (2H, m), 2.98 (2H, m), 3.35 (3H, s), 3.37 (2H, s), 3.84 (2H, m), 4.41 (2H, s), 6.13 (2H, m), 7.13 (2H, m), 7.51 (3H, m), 7.77 (2H, m); MS (APCI+) M+1=583, C32H43FN403S requires 582. MPt 133.3°C (colourless solid).

Example 325-1-(3-(Hept-lylaminocarbonyl) prop-1-yl)-2-(4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 279 by general method E. 'H-NMR (CDC13) 6 0.88 (3H, t), 1.27 (8H, m), 1.47 (2H, m), 1.98-2.25 (4H, m), 3.20 (2H, m), 3.69 (2H, s), 3.92 (2H, t), 4.52 (2H, s), 5.42 (1H, bm), 6.98 (2H, m), 7.25 (1H, s), 7.37 (2H, m), 8.68 (2H, s), 9.08 (1H, s); MS (APCI+) M+l=512, C27H34FN502S requires 511. MPt 84-89°C (colourless solid). MPt. 84-89 Example 326-1-(3-(Hex-lylaminocarbonyl) prop-1-yl)-2. (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 279 by general method E. 1H-NMR (CDCl3) # 0.89 (3H, m), (8H, m), 1.98-2.20 (4H, m), 3.19 (2H, m), 3.69 (2H, s), 3.92 (2H, t), 4.45 (2H, s), 5.44 (1H, bm), 6.96 (2H, m), 7.25 ((1H, s), 7.37 (2H, m), 8.68 (2H, s), 9.08 (1H, s); MS (APCI=) M+1=498, C26H32FN5O2S requires 497. MPt 106-109°C (colourless solid).

Example 327-1- (3- (Non-lylaminocarbonyl) prop-1-yl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 279 by general method E. 'H-NMR (CDC) 5 0.87 (3H, t), 1.26 (12H, m), 1.47 (2H, m), 1.98-2.25 (4H, m), 3.20 (2H, m), 3.69 (2H, s), 3.91 (2H, t), 4.46 (2H, s), 5.39 (1H, bm), 6.98 (2H, m), 7.24 (1H, s), 7.37 (2H, m), 8.70 (2H, s), 9.08 (1H, s); MS (APCI+) M+1=540, C29H38FN502S requires 539. MPt 92-97°C (colourless solid).

Example 328-1- (3- (Oct-lylaminocarbonyl) prop-1-yl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 279 by general method E. 1H-NMR (CDCl3) # 0.88 (3H, t), 1.27 (10H, m), 1.47 (2H, m), 1.98-2.20 (4H, m), 3.22 (2H, m), 3.69 (2H, s), 3.92 (2H, t), 4.45 (2H, s), 5.43 (1H, bm), 6.98 (2H, m), 7.25 (1H, s), 7.37 (2H, m), 8.70 (2H, s), 9.08 (1H, s); MS(APCI+) M+1=526, C28H36FN5O2S requires 525. MPt 72-83°C (colourless solid).

Example 329-1- (3- (Pent-lylaminocarbonyl) prop-1-yl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 279 by general method E. 'H-NMR (CDC13) a 0.90 (3H, m), 1.17-1.61 (6H, m), 1.98-2. 26 (4H, m), 3. 20 (2H, m), 3.69 (2H, s), 3.92 (2H, t), 4.45 (2H, s), 5.44 (1H, bm), 6.97 (2H, m), 7. 25 (1H, s), 7.38 (2H, m), 8.68 (2H, s), 9.08 (1H, s); MS (APCI+) M+1=484, C25H30FN502S requires 483. MPt 64-69°C (colourless solid).

Example 330-1- (3- (N-Hex-lyl-N-methylaminocarbonyl) prop-1-yl)-2- (3,4- difluorobenzyl)thio-5-(pyrimid-5-ylmethyl)pyrimidin-4-one

Prepared from Example 282 by general method E. lH-NMR (CDCl3) õ 0.78-0.99 (3H, m), 1.19-1.77 (8H, m), 1.95-2.14 (2H, m), 2.25-2.44 (2H, q), 2.92 (3H, d), 3.12-3.27 (1H, t), 3.29-3.42 (1H, t), 3.70 (2H, s), 3.84-4.00 (2H, t), 4.44 (2H, t), 7.01-7.31 (4H, m), 8.71 (2H, s), 9.10 (1H, s); MS (APCI+) found (M+1) = 530; C27H33F2N502S requires 529.

Example 331-1- (5- (2-mEthoxyethylaminocarbonyl) pent-1-yl)-2- (3,4- difluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 283 by general method E. 1H-NMR (CDCl3) # 1.22-1.85 (6H, m), 2.13-2.25 (2H, t), 3.29-3.38 (3H, s), 3.39-3.53 (4H, s), 3.68-3.85 (4H, m), 4.44 (2H, s), 5.90-6.04 (1H, br. s), 7.01-7.29 (4H, m), 8.72 (2H, s), 9.09 (1H, s); MS (APCI+) found (M+1) = 518; C25H29F2N503S requires 517.

Example 332-1- (5- (2-Phenylethylaminocarbonyl) pent-1-yl)-2- (3,4- difluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 283 by general method E as a foam. 1H-NMR (CDCl3) # 1.17- 1.38 (2H, m), 1.56-1.84 (4H, m), 2.04-2.19 (2H, t), 2.77-2.89 (2H, t), 3.41-3.60 (2H, m), 3.64-3.86 (4H, m), 4.43 (2H, s), 5.68-5.85 (1H, m), 7.00-7.38 (9H, m), 8.67 (2H, s), 9.06 (1H, s); MS (APCI+) found (M+l) = 564; C30H31F2N502S requires 563.

Example 333-1- (5- (But-1-ylaminocarbonyl) pent-1-yl)-2- (3,4-difluorobenzyl) thio- 5- (pyrimid-5-ylmethyl) pyrimidin-4-one

Prepared from Example 283 by general method E. IH-NMR (CDC13) 6 (3H, t), 1.17-1.76 (10H, m), 2.11-2.22 (2H, t), 3.18-3.30 (2H, q), 3.67-3.88 (4H, m), 4.43 (2H, s), 5.52-5.70 (1H, br. t), 7.00-7.30 (4H, m), 8.71 (2H, s), 9.09 (1H, s); MS (APCI+) found (M+1) = 516; C26H31F2N5OS2S requres 515.

Example 334-1- (5- (N- (2-Phenylethyl)-N-methylaminocarbonyl) pent-1-yl)-2- (3,4- difluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 283 by general method E. 1H-NMR (CDC13) b 1.01-1.86 (6H, m), 1.98-2.09 (1H, t), 2.21-2.35 (1H, t), 2.76-2.99 (5H, m), 3.44-3.87 (6H, m), 4.44 (2H, s), 7.00-7.35 (9H, m), 8.71 (2H, d), 9.09 (1H, s); MS (APCI+) found (M+1) = 578; C31H33F2N502S requires 577.

Example 335-1- (5- (N-But-1-yl-N-methylaminocarbonyl) pent-1-yl)-2- (3,4- difluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 283 by general method E. 1H-NMR (CDCl3) # 1.20-1.87 (13H, m), 2.24-2.39 (2H, q), 2.88-2.99 (3H, d), 3.18-3.42 (2H, m), 3.68-3.88 (4H, m), 4.44 (2H, s), 7.00-7.29 (4H, m), 8.72 (2H, s), 9.09 (1H, s); MS (APCI+) found (M+1) = 530; sNsOSrequires 529.

Example 336-1-((R)-1-(Hex-1-ylaminocarbonyl) ethylaminocarbonylmethyl)-2-(4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. IH-NMR (d6 DMSO) 8 (3H, m), 1.15-1.5 (1 lH, m), 2.95-3.2 (2H, m), 3.64 (2H, s), 4.3-4.5 (3H, m), 4.64 (2H, s), 6.95-7.1 (2H, m), 7.3-7.5 (2H, m), 7.71 (1H. d), 8.47 (lH, bd), 8.7 (2H, s), 8.97 (lH, s); MS (APCI+) found (M+l) = 541; C, 7H33FN603S requires 540.

Example 337-1-((S)-1-(Hex-1-ylaminocarbonyl) ethylaminocarbonylmethyl) 2 (4 fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. IH-NMR (d6 DMSO) 8 (3H, m), (llH, m), 3.0-3.25 (2H, m), 3.64 (2H, s), 4.35-4.5 (3H, m), 4.60 (2H, s), 6.90- 7.05 (2H, m), 7.25-7.45 (4H, m), 8.3 (lH, bd), 8.71 (2H, s), 9.01 (lH, s); MS (APCI+) found (M+1) = 541; C27H33FN603S requires 540.

Example 1-((S)-2-(Hex-1-ylaminocarbonyl)pyrrolidin-1-ylcarbonylmethy l)-2-- (4-fluorobenzyl)thio-5-(pyrimid-5-ylmethyl)pyrimidin-4-one Prepared from Example 280 by general method E. 1H-NMR (CDCl3) # (3H, m), 1.15-1.55 (8H, m), 1.75-2.45 (4H, m), 3.0-3.8 (6H, m), 3.72 (2H, bd), 4.35-4.60 (5H, m), 6.43 (lH, m), 6.90-7.05 (2H, m), 7.26 (lH, s), 7.27-7.45 (2H, m), 8.71 (2H, s), 9.09 (lH, s); MS (APCI+) found (M+l) = 567 ; C, 9H3sFN603S requires 566.

Example 339-1-(1-Pyrrolidinocarbonylmethyl)-2-(4-fluorobenzyl) thio-5-(pyrimid- 5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. 1H-NMR (CDCl3) # 1.87-2.08 (4H, m), 3.44-3.52 (4H, m), 3.72 (2H, s), 4.46 (2H, s), 4.49 (2H, s), 6.95 (3H, m), 7.34 (2H, m), 8.73 (2H, s), 9.10 (1H, s); MS (APCI+) found (M+1) = 440; C2 H22FN502S requires 439.

Example 340-1- (3-Butoxyprop-1-ylaminocarbonylmethyl)-2- (4-fluorobenzyl) thio- 5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. IH-NMR (CDC13) # 0.89 (3H, t), 1.32 (2H, m), 1.47 (2H, m), 1.75 (2H, m), 3.32-3.44 (4H, m), 3.51 (2H, t), 3.71 (2H, s), 4.31 (2H, s), 4.47 (2H, s), 6.73 (1H, br. t), 6.98 (3H, m), 7,32 (2H, m), 8.71 (2H, s), 9.11 (1H, s); MS (APCI+) found (M+1) = 500; C25H30FN5O3S requires 499.

Example 341-1- (6-Hydroxyhex-1-ylaminocarbonylmethyl)-2- (4-fluorobenzyl) thio- 5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. 'H-NMR (CDCl3/d6 DMSO) 8 1.2-1.6 (8H, m), 3.14 (2H, q), 3.5 (2H, q), 3.67 (2H, s), 3.95 (lH, t) 4.44 (2H, s), 4.52 (2H, s), 6.9-7.1 (2H, m), 7.3-7.5 (2H, m), 7.51 (1H, s), 8.04 (lH, bt), 8.73 (2H, s), 9.01 (lH, s); MS (APCI+) found (M+1) = 486; C24H28FN503S requires 485.

Example 342-1- (6- (4-Fluorophenyl) hex-1-ylaminocarbonylmethyl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. lH-NMR (d6-DMSO) 6 1.20-1.55 (8H, m), 2.51 (2H, m), 3.05 (2H, m), 3.59 (2H, s), 4.38 (2H, s), 4.53 (2H, s), 7.03-7.22 (6H, m), 7.43 (2H, m), 7.69 (1H, s), 8.21 (1H, m), 8.71 (2H, s), 9.02 (1H, s); MS (APCI+) M+1=564, C30H31F2N5O2S requires 563. MPt 170.8°C (cream solid). MPt.

170.8 Example 343-1- (Tridec-1-ylaminocarbonylmethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one

Prepared from Example 280 by general method E. IH-NMR (d6-DMSO) 8 0.85 (3H, m), 1.20 (20H, m), 1.37 (2H, m), 3.06 (2H, m), 3.59 (2H, s), 4.39 (2H, s), 4.53 (2H, s), 7.12 (2H, m), 7.44 (2H, m), 7.69 (1H, s), 8.21 (1H, m), 8.70 (2H, s), 9.05 (1H, s); MS (APCI+) M+1=568, C31H42FN5O2S requires 567. MPt 191.5°C (colourless solid).

Example 344-1-(Tetradec-1-ylaminocarbonylmethyl)-2-(4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. IH-NMR (d6-DMSO) 5 0.85 (3H, m), 1.23 (22H, m), 1.36 (2H, m), 3.05 (2H, m), 3.59 (2H, s), 4.38 (2H, s), 4.53 (2H, s), 7.12 (2H, m), 7.44 (2H, m), 7.69 (1H, s), 8.25 (1H, m), 8.70 (2H, s), 9.02 (1H, s); MS (APCI+) M+1=582, C32H44FN502S requires 581. MPt 191.7°C (colourless solid).

Example 345-1-(Octadec-1-ylaminocarbonylmethyl)-2-(4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. 'H-NMR (CDC'3) 8 0.87 (3H, m), 1.25 (30H, m), 1.47 (2H, m), 3.26 (2H, m), 3.70 (2H, s), 4.37 (2H, s), 4.45 (2H, s), 5.95 (1H, m), 6.99 (3H, m), 7.32 (2H. m), 8.70 (2H, s), 9.09 (1H, s), MS (APCI+) M+1=638, C36HS2FNSO, S requires 637. MPt 189.8°C (pale yellow solid).

Example 346-1- (Octadec-9- (Z)-en-lylaminocarbonylmethyl)-2- (4- fluorobenzyl)thio-5-(pyrimid-5-ylmethyl)pyrimidin-4-one Prepared from Example 280 by general method E. 'H-NMR (CDC) 5 0.88 (3H, s), 1.26 (22H, m), 1.47 (2H, m), 2.01 (4H, m), 3. 26 (2H, m), 3.71 (2H, s), 4.35 (2H, s), 4.46 (2H, s), 5.33 (2H, m), 5.73 (1H, m), 6.98 (3H, m), 7.34 (2H, m), 8.70 (2H, s), 9.09 (1H, s), MS(APCI+) M+1=636, C36H50FN5O2S requires 635. MPt 179.7°C (cream solid).

Example 347-1- (Octadec-9- (E)-en-lylaminocarbonylmethyl)-2- (4- fluorobenzyl) thio-5-(pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. 1H-NMR (CDCl3) 8 0.88 (3H, s), 1.26 (22H, m), 1.47 (2H, m), 1.95 (4H, m), 3.26 (2H, m), 3.70 (2H, s), 4.36 (2H, s), 4.45 (2H, s), 5.38 (2H, m), 5.87 (1H, m), 6.98 (3H, m), 7.32 (2H, m), 8.70 (2H, s), 9.08 (1H, s), MS (APCI+) M+1=636, C36H50FN5O2S requires 635. MPt 184.6°C (yellow solid). MPt.

184.6 Example 348-1- (Dec-l-ylaminocarbonylmethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. IH-NMR (d6-DMSO) 6 0.85 (3H, m), 1.21 (14H, m), 1.37 (2H, m), 3.06 (2H, m), 3.59 (2H, s), 4.39 (2H, s), 4.53 (2H, s), 7.12 (2H, m), 7.42 (2H, m), 7.69 (1H, s), 8.26 (1H, m), 8.70 (2H, s), 9.03 (1H, s); MS (APCI+) M+1=526, C2gH36FN50S requires 525. MPt 187.7°C (colourless solid). MPt.

187.7 Example 349-1-(Dodec-l-ylaminocarbonylmethyl)-2-(4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. lH-NMR (d6-DMSO) õ 0.85 (3H, m), 1.23 (18H, m), 1.35 (2H, m), 3.05 (2H, m), 3.59 (2H, s), 4.39 (2H, s), 4.53 (2H, s), 7.12 (2H, m), 7.43 (2H, m), 7.69 (1H, s), 8.20 (1H, m), 8.71 (2H, s), 9.03 (1H, s); MS (APCI+) M+1=554, C30H40FN50, requires 553. MPt 191.1°C (colourless solid).

Example 350-1- (Hept-1-ylaminocarbonylmethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one

Prepared from Example 280 by general method E. 1H-NMR (d6-DMSO) 5 0.84 (3H, m), 1.20 (8H, m), 1.37 (2H, m), 3.06 (2H, m), 3.59 (2H, s), 4.38 (2H, s), 4.54 (2H, s), 7.13 (2H, m), 7.42 (2H, m), 7.70 (1H, s), 8.26 (1H, m), 8.70 (2H, s), 9.03 (1H, s); MS (APCI+) M+1=484, C25H30FN502, requires 483. MPt 189.1°C (colourless solid). MPt.

189.1 Example 351-1- (Oct-1-ylaminocarbonylmethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. 1H-NMR (CDC13) 8 0.88 (3H, t), 1.25 (10H. m), 1.48 (2H, m), 3.26 (2H, m), 3.70 (2H, s), 4.35 (2H, s), 4.46 (2H, s), 5.81 (1H, m), 6.93-7.03 (3H, m), 7.34 (2H. m), 8.71 (2H, s), 9.08 (1H, s); MS (APCI+) M+1=498, C26H32FN5OWS requires 497. MPt 191-192°C (colourless solid). MPt. 190-192 Example 352-1- (Undec-1-ylaminocarbonylmethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. IH-NMR (d6-DMSO) 8 0.85 (3H, m), 1.20 (16H, m), 1.37 (2H, m), 3.06 (2H, m), 3.59 (2H, s), 4.39 (2H, s), 4.53 (2H, s), 7.12 (2H, m), 7.42 (2H, m), 7.69 (1 H, s), 8.26 (1H, m), 8.70 (2H, s), 9.03 (1H, s); MS (APCI+) M+1=540. C29H38FN502S requires 539. MPt 190.1°C (colourless solid).

MPt. 190.1 Example 353-1-(2-Hydroxyethylaminocarbonylmethyl)-2-(4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E as a white solid'H-NMR (d6 DMSO) 8 3.15 (2H, q), 3.4 (2H, q), 3.58 (2H, s), 4.37 (2H, s), 4.57 (2H, s), 4.68 (lH, t), 7.05-7.2 (2H, m), 7.4-7.55 (2H, m), 7.70 (1H,s), 8.33 (lH, bt), 8.70 (2H, s), 9.03 (lH, s); MS (APCI+) found (M+1) = 430; C,, OHOFN503S requires 429.

Example 354-1- (2-Methoxyethylaminocarbonylmethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E as a white solid IH-NMR (CDCl3/d6 DMSO) 8 3.2-3.45 (7H, m), 3.63 (2H, s), 4.41 (2H, s), 4.59 (2H, s), 6.95-7.1 (2H, m), 7.35- 7.5 (2H, m), 7.69 (1H, s), 8.37 (1H, bt), 8.70 (2H, s), 9.06 (1H, s); MS (APCI+) found (M+1) = 444; C2lH22FN503S requires 443.

Example 355-1- (2-Phenylethylaminocarbonylmethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. IH-NMR (CDC13) õ 2.80 (2H, t), 3.55 (2H, q), 3.66 (2H, s), 4.32 (2H, s), 4.41 (2H, s), 6.08 (lH, bt), 6.9-7.4 (10H, m), 8.66 (2H, s), 9.05 (IH. s); MS (APCI+) found (M+1) = 490; C26H24FN502S requires 489.

Example 356-1- (2- (4-Pent-1-ylphenyl) ethylaminocarbonylmethyl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. 'H-NMR (dg-DMSO) 5 0.86 (3H, m), 1.25 (4H, m), 1.51 (2H, m), 2.46 (2H, m), 2.66 (2H, m), 3.24 (2H, m), 3.59 (2H, s), 4.39 (2H, s), 4.53 (2H, s), 7.0-7.17 (6H, m), 7.46 (2H, m), 7.69 (1H, s), 8.32 (1H, m), 8.71 (2H, s), 9.02 (1H, s); MS (APCI+) M+1=560, C31H34FNsO2S requires 559. MPt 170.6°C (colourless solid).

Example 357-1- (Hex-1-ylaminocarbonylmethylaminocarbonylmethyl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one

Prepared from Example 280 by general method E. white solid IH-NMR (d6 DMSO) 8 0.8-0.95 (3H, m), 1.2-1.45 (8H, m), 2.95-3.10 (2H m), 3.58 (2H, s), 3.72 (2H, bd), 4.38 (2H, m), 4.64 (2H, s), 7.05-7.2 (2H, m), 7.40-7.55 (2H, m), 7.70 (lH, s), 7.75-7.9 (lH, m), 8.5-8.6 (lH, m), 8.70 (2H, s), 9.01 (lH, s); MS (APCI+) found (M+1) = 527; C26H3lFN603S requires 526.

Example 358-1- (N- (Dodec-1-yl)-N-methylaminocarbonylmethyl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. 'H-NMR (CDCy § 0.88 (3H, m), 1.25 (18H, m), 1.50 (2H, m), 2.98 (3H, d), 3.21,3.37 each 1H, m), 3.73 (2H, s), 4.52 (4H, m), 6.88 (1H, s), 6.99 (2H, m), 7.33 (2H, m), 8.71 (2H, s), 9.10 (1H, s), MS (APCI+) M+1=568, C3lH42FN5., S requires 567. MPt 145.3°C (cream solid).

Example 359-1- (N- (2-Phenylethyl)-N-methylaminocarbonylmethyl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E as a solid. 'H-NMR (CDC'3) 8 2.78- 2.97 (3H, m), 3.05 (2H, s), 3.42-3.57 (1H, m), 3.58-3.69 (2H, m), 3.73 (2H, s), 4.35-4.53 (3H, m), 6.12 (1H, s), 6.90-7.43 (9H, m), 8.62-8.75 (2H, d), 9.06-9.18 (1H, d); MS (APCI+) found (M+1) = 504; C'-7H26FN50-, S requires 503.

Example 360-1- (4- (But-1-ylaminocarbonyl) cyclohex-1-yl)-2- (4-fluorobenzyl) thio- 5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 285 by general method E as a solid. 'H-NMR (CDC'3) 8 0.85- 1.04 (3H, t), 1.20-2.50 (13H, m), 3.18-3.33 (2H. q), 3.70 (2H, s), 4.01-4.20 (1H, m), 4.44 (2H, s), 5.47-5.63 (1H, br. t), 6.93-7.07 (2H, t), 7.32-7.43 (2H, m), 7.44 (1H, s), 8.72 (2H, s), 9.08 (1H, s); MS (APCI+) found (M+l) = 510; C27H3, FN502S requires 509.

Example 361-1- (4- (Hex-1-ylaminocarbonyl) cyclohex-1-yl)-2- (4-fluorobenzyl) thio- 5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 285 by general method E as a solid. 'H-NMR (CDCy 5 0.78- 0.97 (3H, t), 1.20-2.50 (17H, m), 3.17-3.32 (2H, q), 3.70 (2H, s), 4.03-4.20 (1H, m), 4.44 (2H, s), 5.47-5.60 (1H, br. t), 6.92-7.06 (2H, t), (2H, m), 7.44 (1H, s), 8.71 (2H, s), 9.09 (1H, s); MS (APCI+) found (M+1) = 538; C29H36FN502S requires 537.

Example 362-1- (4- (2-Methoxyethylaminocarbonyl) cyclohex-1-yl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 285 by general method E as a solid. 1H-NMR (CDCl3) # 1.58- 1.90 (4H, m), 2.02-2.30 (4H, m), 2.48 (1H, br. s), 3.36 (3H, s), 3.47 (4H, s), 3.64 (2H, s), @ 4.03-4.20 (1H, m), 4.44 (2H, s), 5.91 (1H, br. s), 6.92-7.06 (2H, t), 7.31-7.45 (3H, m), 8.72 (2H, s), 9.06 (1H, s); MS (APCI+) found (M+1) = 512; C26H30FN5O3S requires 511.

Example 363-1- (1- (6- (4-Fluorophenyl) hex-1-yl) aminocarbonyl) cycloprop-1-yl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 269, analogously to Example 315. 1H-NMR (CDCl3) õ 1.15-1.71 (1OH, m), 1.73-1.89 (1H, m), 1.94-2.01 (1H, m), 2.47-2.52 (2H, t), 2.98-3.18 (1H, m), 3. 20-3.39 (1H, m), 3.60-3.69 (2H, d), 4.38 (2H, s), 5.64-5.78 (1H, br. t), 6.88-7.01 (4H, m), 7.03-7.20 (3H, m), 7.28-7.40 (2H, m), 8.68 (2H, s), 9.07 (1H, s); MS (APCI+) found (M+1) = 590; C32H33F2N50, S requires 589.

Example 364-1- (1- (Non-1-ylaminocarbonyl) cycloprop-1-yl)-2- (4- fluorobenzyl)thio-5-(pyrimid-5-ylmethyl)pyrimidin-4-one

Prepared from Example 269, analogously to Example 315. 'H-NMR (CDC13) 6 0.78-0.98 (3H, t), 1.11-1.69 (16H, m), 1.73-1.89 (1H, m), 1.95-2.11 (1H, m), 3.00-3.19 (1H, m), 3.22-3.41 (1H, m), 3.55-3.78 (2H, br. q), 4.40 (2H, s), 5.52-5.65 (1H, br. t), 6.92-7.07 (2H, t), 7.26 (1H, s), 7.29-7.40 (2H, m), 8.69 (2H, s), 9.09 (1H, s); MS (APCI+) found (M+1) = 538; C29H36FN502S requires 537.

Example 365-1-((R)-1-(Non-1-ylaminocarbonyl) ethyl)-2-(4-fluorobenzyl) thio-S- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 272, analogously to Example 315. 1H-NMR (CDCl3)# 0.80-0.94 (3H, t), 1.15-1.37 (12H, m), 1.38-1.54 (2H, m), 1.55-1.66 (3H, d), 3.10-3.36 (2H, m), 3.58-3.80 (2H, br. q), 4.32-4.55 (2H, br. q), 4.72-4.88 (1H, q), 6.08-6.20 (1H, br. t), 6.41- 7.06 (2H, t), 7.29-7.39 (2H, m), 7.50 (1H, s), 8.70 (2H, s), 9.07 (1H, s); MS (APCI+) found (M+1) = 526; C28H36FNs02S requires 525.

Example 366-1- (11- (Dimethylamino) undec-1-ylaminocarbonylmethyl)-2- (4- fluorobenzyl)thio-5-(pyrimid-5-ylmethyl)pyrimidin-4-one Prepared from Example 280 by general method E. I H-NMR (d6-DMSO) 8 1.20 (16H, m), 1.37 (2H, m), 2.15 (6H, s), 2.22 (2H, m), 3.07 (2H, m), 3.59 (2H, s), 4.38 (2H, s), 4.54 (2H, s), 7.13 (2H, m), 7.43 (2H, m), 7.70 (1H, s), 8.26 (1H, m), 8.70 (2H, s), 9.03 (1H, s); MS (APCI+) M+1=583, C3iH43FN602S requires 582. MPt 152-155°C (colourless solid). MPt. 152-155

Example 367-1- (2- (6- (4-Fluorophenyl) hex-1-yloxy) ethylaminocabonylmethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. IH-NMR (d6-DMSO) 8 1.26 (4H, m), 1.47 (4H, m), 2.56 (2H, m), 3.23 (2H, m), 3.40 (4H, m), 3.59 (2H, s), 4.38 (2H, s), 4.56 (2H, s), 7.03-7.21 (6H, m), 7.43 (2H, m), 7.69 (1H, s), 8.26 (1H, m), 8.70 (2H, s), 9.03 (1H, s); MS (APCI+) M+1=608, C32H35F2N503S requires 607. MPt 155-159°C (colourless solid). MPt. 155-159 Example 368-1- (5- (Methoxycarbonyl)-5- (benzyloxycarbonylamino) pent-1- ylaminocarbonylmethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4- one Prepared from Example 280 by general method E. IH-NMR (d6-DMSO) 8 1.35 (4H, m), 1.61 (2H, m), 3.05 (2H, m), 3.61 (5H, m), 3.99 (1H, m), 4.38 (2H, s), 4.52 (2H, s), 5.03 (2H, s), 7.11 (2H, m), 7.34 (5H, m), 7.44 (2H, m), 7.69 (2H, m), 8.24 (1 H, m), 8.71 (2H, s), 9.02 (1H, s); MS (APCI+) M+1=663, C33H35FN606S requires 662. (colourless solid).

Example 369-1- (5- (Methoxycarbonyl) pent-1-ylaminocarbonylmethyl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. lH-NMR (d6-DMSO) õ 1.19-1.55 (6H, m), 2.24 (2H, m), 3.06 (2H, m), 3.58 (3H, s), 3.60 (2H, s), 4.39 (2H, s), 4.53 (2H, s), 7.12 (2H, m), 7.44 (2H, m), 7.69 (1H, s), 8.26 (1H, m), 8.70 (2H, s), 9.03 (1H, s); MS (APCI+) M+l=514, C5H28FN504S requires 513. MPt 166.8°C (colourless solid). MPt.

166-172

Example 370-1- (Non-1-ylaminocarbonylmethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E, 1H-NMR (d6-DMSO) # 0.85 (3H, m), 1. 21 (12H, bs), 1.35 (2H, m), 3.07 (2H, m), 3.60 (2H, s), 4.39 (2H, s), 4.53 (2H, s), 7.14 (2H, m), 7.45 (2H, m), 7.69 (1H, s), 8.22 (1H, m), 8.68 (2H, s), 9.06 (1H, s); MS (APCI+) M+1=512, C27H34FN5O2S requires 511. MPt 200-202°C (colourless solid).

Example 371-1-Dimethylaminocarbonylmethyl-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E as a solid. lH-NMR (DMSO) 8 2.86 (3H, s), 2.97 (3H, s), 3.59 (2H, s), 4.39 (2H, s), 4.86 (2H, s), 7.06-7.20 (2H, t), 7.49-7.52 (2H, m), 7.59 (1H, s), 8.70 (2H, s), 9.04 (1H, s); MS (APCI+) found (M+1) = 414; C2oH20FN502, requires 413.

Example 372-1- (N- (2-Hydroxyethyl)-N-methylaminocabonylmethyl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. pale yellow solid 1H-NMR (d6 DMSO) 5 2.86 + 3.02 (2H, 2 x s), 3.2-3. 65 (6H, m), 4.39 (2H, s), 4.6-5.05 (3H, m), 7.05- 7.2 (2H, m), 7.35-7.55 (2H, m), 8.70 (2H, s), 9.03 (lH, s); MS (APCI+) found (M+1) = 444; C,, H,,, FN503S requires 443.

Example 373-1- (trans-4- (4-Fluorobenzylaminocarbonyl) cyclohex-1-ylmethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one

Prepared from Example 273, analogously to Example 315. IH-NMR (CDC13) õ 0.80- 2.15 (10H, m), 3.51-3.65 (2H, d), 3.71 (2H, s), 4.33-4.43 (2H, d), 4.47 (2H, s), 5.64-5.78 (1H. br. t), 6.89 (1H, s), 6.92-7.08 (4H, t), 7.15-7.44 (4H, m), 8.69 (2H, s), 9.10 (1H, s); MS (APCI+ found (M+I) = 576; C3lH3lF2N502S requires 575.

Example 374-1- (trans-4- (Pent-1-ylaminocarbonyl) cyclohex-1-ylmethyl)-2- (4- fluorobenzyl)thio-5-(pyrimid-5-ylmethyl)pyrimidin-4-one Prepared from Example 273, analogously to Example 315. 1H-NMR (CDC13) 80.81-2.09 (19H, m), 3.16-3.40 (2H, q), 3.52-3.65 (2H, d), 3.71 (2H, s), 4.46 (2H, s), 5.32-5.45 (1H, br. t), 6.89 (1H, s), 6.95-7.08 (2H, t, 7.30-7.45 (2H, m), 8.70 (2H, s), 9.11 (1H, s); MS (APCI+) found (M+1) = 538; CelS requires 537.

Example 375-1- (3- (Hex-lylaminocarbonyl) prop-1-yl)-2- (4-fluorobenzyl) thio-5- ( (l-methyl-2-oxo-pyrid-4-yl) methyl) pyrimidin-4-one Prepared from Example 281 by general method E. IH-NMR (CDC13) õ 0.88 (3H, t), 1.28 (6H, m). 1.45 (2H, m), 2.04 (2H, m), 2.20 (2H, m), 3.19 (2H, m), 3.50 (3H, s), 3.54 (2H, s), 3.86 (2H, t), 4.47 (2H, s), 5.69 (1h, bm), 6.21 (1H, m), 6.34 (1H, s), 7.01 (2H, m), 7.09 (1H, s), 7.19 (1H, d), 7.39 (2H, m) : MS (APCI+) M+1=527, C28H35FN4O3S requires 526.

MPt 134-136°C (colourless solid). MPt. 134-136 Example 1-(N-(N'-Hex-1-yl-N'-methylaminocarbonylmethyl)-N-methyl-- aminocarbonylmethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4- one Prepared from Example 280 by general method E. lH-NMR (CDCI3) 6 0.88 (3H, m), 1.28 (6H, m), 1.4-1.65 (2H, m), 2.92-3.09 (6H, m), 3.17-3.36 (2H, m), 3.70 (2H, s), 4.05-

4.19 (2H, m), 4.48-4.67 (4H, m), 6.97 (2H, m) 7.07 (1H, s), 7.35 (2H, m), 8.71 (2H, s), 9.08 (1H, s); MS (APCI+) found (M+1) = 555; C28H35FN603S requires 554.

Example 1-(N-(N'-Hex-1-ylaminocarbonylmethyl)-N-methylaminocarbonyl- - methyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. IH-NMR (CDC13) õ 0.87 (3H, m), 1.26 (6H, m), 1.44 (2H, m), 2.98 and 3.14 (3H, 2Xs), 3.19 (2H, m), 3.70 (2H, s), 3.87 and 3.97 (2H, 2Xs), 4.46 (2H, m), 4.64 (2H, m), 5.98 and 6.16 (1H, 2Xt), 6.98 (3H, m), 7.33 (2H, m), 8.70 (2H, s), 9.08 (1H, s); MS (APCI+) found (M+1) = 541; C27H33FN603S requires 540.

Example 378-1- (N- (N'-Hex-1-yl-N'-methylaminocarbonylmethyl) aminocarbonyl- methyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. 1H-NMR (CDC13) b 0.88 (3H, m), 1.28 (6H. m), 1.52 (2H, m), 2.94 (3H, m), 3.18 and 3.38 (2H, 2Xt), 3.72 (2H, s), 4.03 (2H, m), 4.47 (4H, m), 6.98 (3H, m), 7.34 (2H, m), 8.71 (2H, s), 9.09 (1H, s); MS (APCI+) found (M+l) = 541: 7H33FN603S requires 540.

Example 379-1-Phenylaminocarbonylmethyl-2-(4-fluorobenzyl) thio-5-(pyrimid-5- ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. 'H-NMR (d6-DMSO) 8 3.62 (2H, s), 4.41 (2H, s), 4.79 (2H, s), 7.0-7.2 (3H. m), 7.25-7.4 (2H, m), 7.4-7.6 (4H,m), 7.76 (lH, bs), 8.72 (2H, s), 9.04 (lH, s); MS (APCI+) found (M+1)=462; C24H20FN5O2S requires 461.

Example 380-1- (4-Methoxycarbonylbenzylaminocarbonylmethyl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. IH-NMR (d6-DMSO) 8 3.60 (2H, s), 3.86 (3H, s), 4.38 (2H, s), 4.40 (2H, s), 4.67 (2H, s), 7.05-7.25 (2H, m), 7.3-7.55 (4H, m), 7.74 (lH, s), 7.84 (2H, d), 8.70 (2H, s), 8.93 (lH, t), 9.03 (lH, s); MS (APCI+) found (M+1) = 532; C27H24FN504S requires 533.

Example 381-1- (N-Benzylaminocarbonylmethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. IH-NMR (CDC13) õ 3.66 (2H, s), 4.41 (4H, s), 4.45 (2H, d.j=5. 7Hz), 6.40 (1H, brs), 6.94 (lH, t, j=8.6Hz), 7.03 (lH, s), 7.23 (8H. m), 8.66 (2H, s), 9.06 (1H, s): MS (APCI) found (M+H)=4.76; C25H22FN5O2S requires 475.

Example 382-1- (N, N-Di- (but-1-yl) aminocarbonylmethyl)-2- (4-fluorobenzyl) thio- 5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 280 by general method E. 'H-NMR (CDC13) 8 0.8-1.05 (6H, m), 1.1-1.75 (8H, m), 3.19 (2H, t), 3.33 (2H, t), 3.72 (2H, s), 4.49 (2H, s), 4.52 (2H, s), 6.85-7.1 (3H, m), 7.3-7.45 (2H, m), 8.70 (1H, s), 9.09 (lH, s); MS (APCI+) found (M+1)-498 ; C28H32FN50, S requires 497 Example 383-1- (N-Methyl-N- (dodec-1-yl) aminocarbonylmethyl)-2- (4- fluorobenzyl) thio-5- (2-methoxypyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 108 by general method C2. 'H-NMR (CDC'3) 8 0.85 (3H, t), 1.2 (18H, m), 1.5 (2H, m,), 2.92 and 2.95 (3H, 2xs), 3.17 and 3.33 (2H, 2xm), 3.63 (2H, s), 3.96

(3H, s), 4.45 (2H, s), 4.49 and 4.52 (2H, 2xs), 6.79 (lH, s), 6.95 (2H, m), 7.30 (2H, m), 8.42 (2H, s); MS (APCI+) found (M+1) = 598, C32H44FN503S requires 597.

Example 384-1- (N-Methyl-N- (oct-1-yl) aminocarbonylmethyl)-2- (4- fluorobenzyl) thio-5- (2-methoxypyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 108 by general method C2. IH-NMR (CDC'3) 6 0-8-0.95 (3H, m), 1. 1-1.7 (12H, m), 2.95 and 2.99 (3H, 2xs), 3.21 and 3.36 (2H, 2xt), 3.66 (2H, s), 3.99 (3H, s), 4.48 (2H, s), 4.51 and 4.55 (2H, d), 6.80 (lH, s), 6.9-7.1 (2H, m), 7.3-7.45 (2H, m), 8.45 (2H, s); MS (APCI+) found (M+1) = 542; C28H36FN5O3S requires 541.

Example 385-1- (N-Methyl-N- (oct-1-yl) aminocarbonylmethyl)-2- (4- fluorobenzyl) thio-5- (2-ethoxypyrimid-5-ylmethyl) pyrimidin-4-one Isolated as an impurity from one of the batches of Example 384, which had in turn been made from an impure batch of Example 108. 1H-NMR (CDCl3) # 0.8-0.95 (3H, t), 1.1-1.7 (12H, m), 1.42 (3H, t), 2.95 and 2.99 (3H, 2xs), 3. 23 and 3.36 (2H, 2xt), 3.65 (2H, s), 4.39 (2H. q), 4.49 (2H, s), 4.50 and 4.54 (2H, d), 6.77 (lH, s), 6.9-7.1 (2H, m), 7.3-7.4 (2H, m), 8.43 (2H, s) ; MS (APCI+) found (M+1) = 556; C29H38FN503S requires 555.

Example 386-1- (N-Methyl-N- (oct-1-yl) aminocarbonylmethyl)-2- (4- fluorobenzyl) thio-5- (2-benzyloxypyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 109 by general method C2. IH-NMR (CDCl3) õ 0.75-1.0 (3H, t), 1.05-1.75 (12H. m), 2.95 and 2.98 (3H, 2xs), 3.20 and 3.36 (2H, 2xs), 3.65 (2H, s), 4.4-4.6 (4H, m), 5.42 (2H, s), 6.80 (1H. s), 6.9-7.1 (2H, m), 7.05-7.2 (2H, m), 7.15-7.55 (7H, m), 8.45 (2H, s); MS (APCI-) found (M+1)=618; C34H40FN5O3S requies 617.

Example 387-1- (N-Methyl-N- (dodec-1-yl) aminocarbonylmethyl)-2- (4- fluorobenzyl) thio-5- (2-oxopyrimid-5-ylmethyl) pyrimidin-4-one To a stirring solution of Example 383 (7.05 g) in dichloromethane (200 ml) was added in one portion B-bromocatecholborane (10 g). After stirring for 16 h at room temperature, the mixture was poured into water with stirring, diluted with more dichloromethane, shaken, and the phases allowed to separate slowly. The organic layer was purified by flash chromatography (silica, methanol-dichloromethane) and trituration with pet. ether.

'H-NMR (CDC 8 0.87 (3H, m), 1.2-1.4 (20, m), 2.88 and 2.96 (3H, 2xs), 3.15-3.4 (4H, m), 3.43 (2H, s), 4.41 (2H, m), 4.88 (2H, m), 6.9-7.0 (2H, m), 7.25-7.4 (2H, m), 7.50 (lH, m), 8.15 (2H, b); MS (APCI+) found (M+1) = 584; C31H42FN503S requires 583.

Example 388-1- (N-Methyl-N- (oct-1-yl) aminocarbonylmethyl)-2- (4- fluorobenzyl) thio-5- (2-oxopyrimid-5-ylmethyl) pyrimidin-4-one Prepared analogously to Example 387, from Example 384. IH-NMR (d6 DMSO) 8 0.8- 0.95 (3H, m), 1.05-1.65 (12, m), 2.81 and 2.94 (3H, 2xs), 3.15-3.4 (4H, m), 4.39 (2H, s), 4.83 and 4.85 (2H, 2xd), 7.05-7.2 (2H. m), 7.35-7.55 (3H, m), 7.95-8.35 (2H, b); MS (APCI+) found (M+l) = 526 ; C7H35FN503S requires 525.

Example 389-1- (3- (N- (Hept-1-yl)-N-methylaminocarbonyl) phenyl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 288 by general method E. lH NMR (DMSO-d6) 8: 0.7-1.05 (m, 6H), 1.3 (m, 5H), 1.41 (m, 1H), 1.56 (br s, 1H), 2.9 (d, 3H), 3.15 (m, 1H), 3.4 (m, 1H), 3.63 (s, 2H), 4.30 (s, 2H), 7.10 (t, 2H), 7.41 (m, 2H), 7.55 (m, 1H), 7.60-7.85 (m, 3H), 7.95 (m, 1H), 8.78 (s, 2H), 9.02 (s, 1H). MS (APCI+) Found (M+l) = 560; C31H34FN50nS requires 559.

Example 390-1- (3- (N-Ethyl-N-methylaminocarbonyl) phenyl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one

Prepared from Example 288 by general method E. IH NMR (DMSO-d6) 8: 1.0-1.2 (m, 3H), 2.9 (d, 3H), 3.18 (m, 1H), 3.45 (m, 1H), 3.62 (s, 2H), 4.31 (s, 2H), 7.10 (t, 2H), 7.40 (m, 2H), 7.60-7.85 (m, 4H), 7.96 (s, 1H), 8.78 (s, 2H), 9.01 (s, 1H). MS (APCI+) Found (M+1) = 490; C26H24FN502S requires 489.

Example 391-1-(4-(Prop-1-ylaminocarbonyl) phenyl)-2-(4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 292 by general method E. IH NMR (CDC13) 8: 1.00 (t, 3H), 1.65 (m, 2H), 3.44 (q, 2H), 3.81 (s, 2H), 4.35 (s, 2H), 6.15 (t, 1H), 6.95 (t, 2H), 7.20 (s, 1H), 7.25 (m, 2H), 7.41 (d, 2H), 7.89 (d, 2H), 8.95 (s, 2H), 9.20 (s, 1H). MS (APCI+) Found (M+1) = 490; C26H24FN5O2S requires 489.

Examplc 392-1- (4- (But-1-ylaminocarbonyl) phenyl)-2- (8- (4-chlorophenyl)-8- oxooct-1-yl) thio-5-(pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 293 by general method E. IH NMR (CDC13) 5: 1.01 (t, 3H), 1.21 (m, 2H), 1.3 (m, 6H), 1.7 (m, 4H), 2.91 (t, 2H), 3.15 (t, 2H), 3.46 (m, 2H), 3.73 (s, 2H), 6.29 (t, 1H), 7.03 (s, 1H), 7.4 (m, 4H), 7.95 (m, 4H), 8.71 (s, 2H), 9.08 (s, 1H). MS (APCI+) Found (M+1) = 618/620; C33H36CIN5O3S requires 618.

Example 393-1- (4- (Hex-1-yloxycarbonyl) phenyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one

Prepared from Example 292 by general method E as a white solid, m. p. 121-123°.'H NMR (CDC13) b: 0.89 (t, 3H), 1.35 (m, 4H), 1.65 (m, 4H), 3.46 (q, 2H), 3.74 (s, 2H), 4.36 (s, 2H), 6.11 (t, 1H), 6.95 (t, 2H), 7.04 (s, 1H), 7.30 (m, 2H), 7.39 (d, 2H), 7.90 (d, 2H), 8.72 (s, 2H), 9.10 (s, 1H). MS (APCI+) Found (M+1) = 532; C29H30FNsO2S requires 531.

Example 394-1- (4-Methylaminocarbonylbenzyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one

Carbonyl diimidazole (105mg. 0.65mmol) was added to a suspension of Example 284 (150mg, 0.32mmol) in dichloromethane (10ml) under an atmosphere of argon and the reaction stirred for lh. Methylamine (1.62ml, 2M solution in THF) was added and stirring continued for 2h. The solvent was removed under reduced pressure and the residue partitioned between ethyl acetate and water. The aqueous phase was extracted with ethyl acetate and the combined organic phase dried (MgS04) and the the solvent removed under reduced pressure. The residue was purified by flash chromatography (10% methanol/ethyl acetate) to afford the desired compound as an off white solid (77mg, 50%).

H-NMR (CDCl3) 8. 90 (s, 1H), 8.47 (s, 2H), 7.60 (m, 2H), 7.25-6.65 (m, 6H), 6.28 (s, 1H), 4.85 (s, 2H), 4.27 (s, 2H), 3.51 (s, 2H), 2.85 (s, 3H). MS (AP+) 476 (M+H+, 100%).

Example 395-1- (3-Methylaminocarbonyl-4- (hept-1-yloxy) benzyl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared analogously to Example 394, from Example 298, as an off white solid. 1H- NMR (CDC13) 8. 98 (s, 1H), 8.67 (s. 2H), 8.58 (s, 1H), 8.06 (m, 1H), 7.28 (m, 2H), 7.06

(m, 2H), 6.89 (m, 2H), 4.87 (s, 2H), 4.38 (s, 2H), 4.05 (t, 2H), 3.58 (s, 2H), 2.93 (s, 3H), 1.81 (m, 2H), (m, 8H). 0.82 (m, 3H). MS (AP+) 590 (M+H+, 100%).

Example 396-1- (2- (t-Butoxycarbonylamino) ethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B 138 by general method A2. 1H-NMR (CDC13) 8 1.41 (9H, s), 3.43 (2H, q, J 6.0Hz), 3.67 (2H, s), 3.97 (2H, s), 4.46 (2H, s), 4.88 (1H, s), 6.99 (2H, m), 7.07 (1H. s), 7.36 (2H, m), 8.70 (2H, s) and 9.09 (1H, s). (APCI+) Found (M+1) = 472. C23H26FN5O3S requires 471..

Example 397-1- (2- (Trifluoroacetylamino) ethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one

The compound of Example 396 (200mg) was dissolved in neat TFA (lml) at room temperature. After 5min. the solution was concentrated to a brown gum and re-evaporated from ethyl acetate. The crude amine salt in ethyl acetate (5ml) was treated with diisopropylethylamine (81mg) and acetyl chloride (50mg) for 24h. The crude reaction mixture was purified by silica gel chromatography to give the title compound as a colourless solid, (72mg, 37%), IH-NMR (CDCl3) 6 3.58 (2H, s), 3.77 (2H, m), 4.11 (2H, t, J 4.7Hz), 4.37 (2H, s), 6.92-7.02 (3H, m), 7.24-7.31 (2H, m), 8.63 (2H, s), 9.04 (1H, s) and 9.13 (1H, t, J 5. 5Hz). (APCI-) Found (M-1) = 466. C20HI7F4NsO, S requires 467.

Example 398-1- (2- (Benzoylamino) ethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5- ylmethyl) pyrimidin-4-one

The compound of Example 396 was treated with trifluoroacetic acid as described in the previous example. A solution of the salt in ethyl acetate was treated with excess 1M hydrochloric acid in ether. The corresponding dihydrochloride salt was precipitated, filtered, washed with ether and dried in vacuo to give the crude salt as a white solid. 1- (3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (72mg), 1-hydroxy-

benzotriazole hydrate (52mg) and benzoic acid (42mg) in dichloromethane (5ml) at room temperature was treated with the above dihydrochloride (150mg). Diisopropylethylamine (88mg) in DMF (lml) was added and the solution stirred for 48h. The reaction mixture was diluted with dichloromethane washed with water, brine, dried over anhydrous magnesium sulfate and concentrated. The crude product was purified by silica gel chromatography to give the title compound as a white solid, (84mg, 52%), 1H-NMR (CDCl3) 3.52 (2H, s), 3.60 (2H, m), 4.04 (2H, t, J 5.5Hz), 4.36 (2H, s), 7.09 (2H, m), 7.35-7.53 (5H. m), 7.71-7.75 (3H, m), 8.63 (3H, m and s) and 9.02 (1H, s). (APCI+) Found (M+1) = 476. C2sH2, FNsO, S requires 475.

Example 399 1- (2- (Hex-1-ylcarbonylamino) ethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one

Prepared analogously to Example 398, using heptanoic acid. 1H-NMR (CDC13) 8 0.87 (3H, t, J 6.8Hz), 1.26 (6H, br. s), 1.56 (2H, m), 2.14 (2H, t, J 7.9Hz), 3.54 (2H, dd, J 5.8,5.9Hz), 3.66 (2H, s), 4.00 (2H, t, J 5.9Hz), 4.43 (2H, s), 6.19 (1H, t, J 5.8Hz) 7.02 (2H, m), 7.06 (1H, s), 8.70 (2H, s) and 9.08 (1H, s). (APCI+) Found (M+1) = 484.

483.C25H30FN5O2Srequires Example 400-1- (2- (5-Phenylpent-1-ylcarbonylamino) ethyl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one

a) Prepared analogously to Example 398, using 6-phenylhexanoic acid. 1H-NMR (CDC13) 8 1.33 (2H, m), 1.61 (4H, m), 2.13 (2H, t, J 7.7Hz), 2.59 (2H, t, J 7.7Hz), 3.52 (2H, m), 3.60 (2H, s), 3.97 (2H, t, J 5.8Hz), 4.40 (2H, s), 6.44 (1H, t, J 5.2Hz), 6.99 (2H, t, J 8.6Hz), 7.04 (1H, s), 7.12-8.57 (7H, m), 8.67 (2H, s) and 9.05 (1H, s). (APCI+) Found (M+1) = 546. C3oH32FN502S requires 545. b) Also prepared by reaction of the amine dihydrochloride with 6-phenylhexanoyl chloride in the presence of diisopropylamine. After work up and purification by silica gel chromatography, the title compound was obtained as a colourless solid in 49% yield.

Example 401-1- (2- (Hept-1-ylcarbonylamino) ethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared analogously to Example 398, using octanoic acid. 1H-NMR (CDC13) 8 0.86 (3H, t, J 6.8Hz), 1.25 (8H, br. s), 1.58 (2H, m), 2.16 (2H, t, J 7.8Hz), 3.55 (2H, m), 3.63 (2H, s), 4.01 (2H, t, J 5.7Hz), 4.40 (2H, s), 6.69 (1H, br. t, J 5.4Hz), 6.98 (2H, t, J 8.5Hz), 7.09 (1H, s), 7.31 (2H, m), 8.69 (2H, s) and 9.07 (1H, s). (CPCI+) Found (M+1) = 498.

C6H32FNsO, S requires 497. <BR> <BR> <P>Example 402-1- (2-Acetylaminoethyl)-2- (8- (4-chlorophenyl)-8-oxooct-1-yl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B76 by general method A4. 1H-NMR (CDCI3) # 1.2- 1.9 (10H. m), 2.02 (3H, s), 2.92 (2H, t), 3.20 (2H, t), 3.5-3.8 (4H, m), 4.04 (2H, m), 7.04 (1H, s), 7.43 (2H, m), 7.88 (2H, m), 8.71 (2H. s) and 9.06 (lH, s); MS (APCI+) found (M+1) =542; C, 7H3ClN503S requires 541.

Example 403-1- (4- (tert-Butoxycarbonylamino) but-1-yl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B 122 by general method A2. IH NMR (CDCL3) 8: 1.43 (s, 9H), 1.5 (m, 2H), 1.75 (m, 2H), 3.15 (m, 2H), 3.70 (s, 2H), 3.83 (t, 2H), 4.46 (s, 2H), 4.65 (br s, 1H), 7.00 (t, 2H), 7.20 (s, 1H), 7.37 (m, 2H), 8.70 (s, 2H), 9.08 (s, 1H). MS (APCI+) Found (M+1) = 500; C25H30FN5O3S requires 499.

Example 404-1- (3- (Ethoxycarbonylamino) prop-1-yl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from intermediate B 123 by general method A2. IH NMR (CDC13) 8: 1.23 (t, 3H), 1.93 (m, 2H), 3.20 (q, 2H), 3.71 (s, 2H), 3.86 (t, 2H), 4.10 (m, 2H), 4.46 (s, 2H), 5.25 (br s, 1H), 7.00 (t, 2H), 7.30 (s, 1H), 7.40 (m, 2H), 8.72 (s, 2H), 9.06 (s, 1H). MS (APCI+) Found (M+1) = 458; C,,, H24FN503S requires 457.

Example 405-1-(2-(Benzylaminocarbonylamino) ethyl)-2-(4-fluorobenzyl) thio-5- (pyrimid-5-vlmethyl) pyrimidin-4-one Prepared from Example 396 by general method F. 1H-NMR (CDC13) 8 3.39 (2H, s), 3.58 (2H, m), 4.03 (2H, t, J 5.7Hz), 4.31 (2H, s), 4.30 (2H, d, J 5. OHz), 5.97 (1H, t, J 5.9Hz), 6.26 (1H, t, J 5.6Hz), 6.91-6.99 (3H, m), 7.20-8.58 (7H, m), 8.58 (2H, s) and 9.05 (1H, s).

(APCI+) Found (M+1) = 505. C, 6H, 5FN602S requires 504.

Example 406-1- (2- (Dodec-1-ylaminocarbonylamino) ethyl)-2- (4-fluorobenzyl) thio- 5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 396 by general method F. 1H-NMR (CDC13) 8 0.87 (3H, t, J 6.8Hz), 1.27 (18H, v. br s), 1.48 (2H, m), 3.17 (2H, dd, J 6.5,13. 0Hz), 3.52 (2H, m), 3.58 (2H, s), 4.03 (2H, t, J 5. OHz), 4.40 (2H, s), 5.21 (1H, m), 5.70 (1H, m), 6.95 (2H, m), 7.10 (1H, s), 7.30 (2H, m), 8.66 (2H, s) and 9.08 (1H, s). (APCI+) Found (M+1) = 583.

C3lH43FN602S requires 582.

Example 407-1- (2- (Hept-1-ylaminocarbonylamino) ethyl)-2- (4-fluorobenzyl) thio- 5-(pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 396 by general method F. 1H-NMR (CDCl3) 8 0.85 (3H, m), 1.26 (8H, m), 1.49 (2H, m), 3.16 (2H, m), 3.51-3.60 (4H, s and m), 4.04 (2H, t, J5.8Hz), 4.39 (2H, s), 5.30 (1H, m), 5.83 (1H, m), 6.94-7.02 (2H, m), 7.07 (1H, s), 7. 28-8.60 (2H, m), 8.67 (2H, s) and 9.08 (1H, s). (APCI+) Found (M+1) = 513. C26H33FN602S requires 512.

Example 408-1- (2- (Oct-1-ylaminocarbonylamino) ethyl)-2- (4-fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 396 by general method F. 1H-NMR (CDCl3) # 0.86 (3H, m), 1.24 (10H, m), 1.50 (2H, m), 3.17 (2H, dd, J 6.8,13. 0Hz), 3.52 (2H, m), 3.57 (2H, s), 4.04 (2H, t, JS. 5Hz), 4.39 (2H, s), 5.31 (1H, m), 5.85 (1H, m), 7.01 (2H, m), 7.07 (1H, s), 7.30 (2H, m), 7.68 (2H, s) and 9.08 (1H, s). (APCI+) Found (M+1) = 527. C27H35FN602S requires 526.

Example 409-1- (2- (2-Thien-2-ylethylaminocarbonylamino) ethyl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one

Prepared from Example 396 by general method F. 1H-NMR (CDCL3) # 3.06 (2H, t, J 6.8Hz), 3.52 (6H, m), 4.01 (2H, t, J 5.6Hz), 4.37 (2H, s), 5.47 (1H, t, J 5.7Hz), 5.97 (1H, t, J 5.3Hz), 6.85-7.31 (8H, m), 8.65 (2H, s) and 9.07 (1H, s). (APCI+) Found (M+1) = 525. C, 5H25FN602S2 requires 524.

Example 410-1- (2- (1, 1,3,3-Tetramethylbut-1-ylaminocarbonylamino) ethyl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 396 by general method F. 1H-NMR (CDCl3) # 1.01 (9H, s), 1.39 (6H, s), 1.75 (2H, s), 3.51 (2H. m), 3.59 (2H, s), 4.02 (2H, t, J 5.5Hz), 4.39 (2H, s), 5.25 (1H, s), 5.78 (1H, t, J 5.6Hz), 6.98 (2H, m), 7.13 (1H, s), 7.31 (2H, m), 8.67 (2H, s) and 9.08 (1H, s). (APCI+) Found (M+l) = 527. C27H35FN602S requires 526.

Example 411-1- (2- (4- (Butoxvcarbonyl) phenylaminocarbonylamino) ethyl)-2- (4- fluorobenzyl) thio-5-(pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 396 by general method F. 1H-NMR (CDCl3) # 0.97 (3H, t, J 7.4Hz), 1.44 (2H, m), 1.73 (2H, m), 3.54 (2H, s), 3.67 (2H, m), 4.13 (2H, m), 4.28 (4H, m), 6.92 (3H, m), 7.18 (2H, m), 7.55 (2H, d, J 8.8Hz), 7.93 (2H, d, J 8.8Hz), 8.62 (2H, s), 8.82 (1H, s) and 9.10 (1H, s). (APCI+) Found (M+1) = 591. C30H3lFN604S requires 590.

Example 412-1- (2- (4- (1-Methylethyl) phenylaminocarbonylamino) ethyl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one

Prepared from Example 396 by general method F. 1H-NMR (CDCl3) # 1.20 (6H, d, J 6.9Hz), 2.84 (1H, m), 3.55 (2H, s), 3.60 (2H, m), 4.12 (2H, t, J 4.8Hz), 4.33 (2H, s), 6.48 (1H, m), 6.92 (2H, m), 7.11-7.34 (7H, m), 8.00 (1H, s), 8.63 (2H, s) and 9.10 (1H, s).

(APCI+) Found (M+1) = 533. C28H29FN602S requires 532.

Example 413-1- (2- (4-Methylphenylaminocarbonylamino) ethyl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 396 by general method F. 1H-NMR (CDC13) 5 2.29 (3H, s), 3.54 (2H, s), 3.60 (2H, m), 4.11 (2H, t J 5. 5Hz), 4.32 (2H, s), 6.50 (1H, m), 6.90-7.08 (4H, m), 7.18-7.30 (5H, m), 8.03 (1H, br. s), 8.64 (2H, s) and 9.09 (1H, s). (APCI+) Found (M+1) = 505. C26H25FN602S requires 504.

Example 414-1- (2- (4-Ethoxyphenylaminocarbonylamino) ethyl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one Prepared from Example 396 by general method F. 1H-NMR (CDCl3) # 1.40 (3H, t, J 4.2Hz), 3.57 (4H, v. br. s), 3.97 (2H, q, J 4.2Hz), 4.08 (2H, t, J 5.4Hz), 4.34 (2H, s), 6.13 (1H, br. s), 6.79-6.98 (4H, m), 7.17 (1H, s), 7.23 (4H, m), 7.63 (1H, br. s), 8.66 (2H, s) and 9.09 (1H, s). (APCI+) Found (M+1) = 535. C27H27FN6O3S requires 534.

Example 415-1- (2- (4-Phenoxyphenylaminocarbonylamino) ethyl)-2- (4- fluorobenzyl) thio-5- (pyrimid-5-ylmethyl) pyrimidin-4-one

Prepared from Example 396 by general method F. 1H-NMR (CDC13) 5 3.56 (2H, s), 3.63 (2H, m), 4.13 (2H, m), 6.57 (1H, m), 6.57-8. 22 (14H, m), 8.23 (1 H, s), 8.65 (2H, s) and 9.05 (1H, s). (APCI+) Found (M+1) = 583. C3lH27FN603S requires 582.

References 1. EP 645370 (1995) 2. Eur J Med Chem 1989,24 (1), 65 3. Eur J Med Chem 1990,25 (3), 217 4. Eur J Med Chem 1993,28 (7-8), 601 5. J Labelled Comp Radiopharm 1987,24 (4), 431 6. J Med Chem 1995,38,3850 7. EP 117345 (1984) 8. EP 68833 (1982) 9. Liebigs Ann Chem 1994,1849 10. J Amer Chem Soc 1950,72,3539 11. GB 1 582 527 12. Bull. Soc. Chi. Fr. 1263 (1956); ibid. 1466 (1957) 13. DE 84-3414752 A1 1984 14. Tet Lett 1983,24 (48), 5309-5312 15. J. Chem. Soc. 1957,3314.

Biological Data 1. Screen for Lp-PLA2 inhibition.

Enzyme activity was determined by measuring the rate of turnover of the artificial substrate (A) at 37 C in 50mM HEPES (N-2-hydroxyethylpiperazine-N'-2- ethanesulphonic acid) buffer containing 150mM NaCl. pH 7.4.

Assays were performed in 96 well titre plates.

Recombinant LpPLA2 was purified to homogeneity from baculovirus infected Sf9 cells, using a zinc chelating column, blue sepharose affinity chromatography and an anion exchange column. Following purification and ultrafiltration, the enzyme was stored at 6mg/ml at 4°C. Assay plates of compound or vehicle plus buffer were set up using automated robotics to a volume of 170p1. The reaction was initiated by the addition of 20|lu of lOx substrate (A) to give a final substrate concentration of 20WM and lO Fl of diluted enzyme to a final 0.2nM LpPLA2.

The reaction was followed at 405 nm and 37 °C for 20 minutes using a plate reader with automatic mixing. The rate of reaction was measured as the rate of change of absorbance.

Results The compounds described in the above Examples were tested as hereinbefore described and were found to have IC5o values in the range 0.0001 to 60 uM.