Antimalarial hexahydropyrimidine analogues
The application relates to a series of 2-imino-6-methylhexahydropyrimidin-4-one derivatives and 3-imino-5-methyl-1,2,4-thiadiazinane 1,1-dioxide derivatives of formula (I), substituted by an arylaminophenyl or heteroarylaminophenyl moiety. The compounds are potent inhibitors of the growth and propagation of the Plasmodium falciparum parasite in human blood and thus useful as pharmaceutical agents for the treatment of malaria.
1. A compound of formula (I) or a pharmaceutically acceptable salt thereof:
wherein
W represents C(O) or S(O) 2 ;
Z represents aryl or heteroaryl, either of which groups may be optionally substituted by one or more substituents;
R 1 represents C 2-6 alkyl, optionally substituted by hydroxy; or R 1 represents C 3-7 cycloalkyl, C 3-7 cycloalkyl(C 1-6 )alkyl, aryl(C 1-6 )alkyl, C 3-7 heterocycloalkyl, C 3-7 heterocycloalkyl(C 1-6 )alkyl, C 4-9 heterobicycloalkyl, C 4-9 spiroheterocycloalkyl or heteroaryl(C 1-6 )alkyl, any of which groups may be optionally substituted by one or more substituents; and
R 2 , R 3 and R 4 independently represent hydrogen, halogen or trifluoromethyl.
2. A compound as claimed in claim 1 wherein Z represents phenyl, naphthyl, 2,3-dihydroindolyl, 2,3-dihydrobenzoxazinyl, pyrazolyl, pyrazolo[1,5-a]pyridinyl, pyrazolo-[3,4-b]pyridinyl, indazolyl, imidazo[1,2-a]pyridinyl, imidazo[1,5-a]pyridinyl, imidazo-[4,5-b]pyridinyl, [1,2,4]triazolo[1,5-a]pyridinyl, pyridinyl, quinolinyl, isoquinolinyl, pyridazinyl, pyrimidinyl or pyrazinyl, any of which groups may be optionally substituted by one, two or three substituents independently selected from halogen, cyano, C 1-6 alkyl, difluoromethyl, trifluoromethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyanocyclobutyl, phenyl, azetidinyl, oxopyrrolidinyl, morpholinyl, oxazolyl, methyloxadiazolyl, triazolyl, methyltetrazolyl, oxo, C 1-6 alkoxy, difluoromethoxy, trifluoromethoxy, difluoroethoxy, trifluoroethoxy, phenoxy, methylenedioxy, difluoromethylenedioxy, C 1-6 alkylsulfonyl, di(C 1-6 )alkylamino, C 2-6 alkylcarbonyl, C 2-6 alkoxycarbonyl and di(C 1-6 )alkylsulfoximino.
3. A compound as claimed in claim 1 represented by formula (IIA), or a pharmaceutically acceptable salt thereof:
wherein
R 15 and R 16 independently represent hydrogen, halogen, cyano, nitro, C 1-6 alkyl, difluoromethyl, trifluoromethyl, phenyl, oxopyrrolidinyl, oxazolyl, methyloxadiazolyl, hydroxy, hydroxy(C 1-6 )alkyl, C 1-6 alkoxy, difluoromethoxy, trifluoromethoxy, phenoxy, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, amino, C 1-6 alkylamino, amino, amino(C 1-6 )alkyl, di(C 1-6 )alkylamino(C 1-6 )alkyl, C 2-6 alkylcarbonylamino, C 2-6 alkoxycarbonylamino, C 1-6 alkylsulfonylamino, formyl, C 2-6 alkylcarbonyl, carboxy, C 2-6 alkoxycarbonyl, am inocarbonyl, C 1-6 alkylaminocarbonyl, di(C 1-6 )alkylaminocarbonyl, aminosulfonyl, C 1-6 alkylaminosulfonyl, di(C 1-6 )alkylaminosulfonyl or di(C 1-6 )alkylsulfoximino; and
R 1 , R 2 and R 3 are as defined in claim 1 .
4. A compound as claimed in claim 3 wherein R 15 represents hydrogen, halogen, cyano, C 1-6 alkyl, trifluoromethyl, phenyl, oxopyrrolidinyl, oxazolyl, methyloxadiazolyl, C 1-6 alkoxy, difluoromethoxy, trifluoromethoxy, phenoxy, C 1-6 alkylsulfonyl, C 2-6 alkoxycarbonyl or di(C 1-6 )alkylsulfoximino.
5. A compound as claimed in claim 3 wherein R 16 represents hydrogen, halogen, cyano, C 1-6 alkyl, trifluoromethyl or C 1-6 alkoxy.
6. A compound as claimed in claim 1 represented by formula (IIB), or a pharmaceutically acceptable salt thereof:
wherein
V represents N or CH;
R 25 represents methyl, cyclopropyl, difluoromethoxy or difluoroethoxy; and
R 1 , R 2 and R 3 are as defined in claim 1 .
7. A compound as claimed in claim 1 wherein R 1 represents C 3-7 cycloalkyl, C 3-7 cycloalkyl(C 1-6 )alkyl, C 3-7 heterocycloalkyl, C 3-7 heterocycloalkyl(C 1-6 )alkyl, C 4-9 heterobicycloalkyl or C 4-9 spiroheterocycloalkyl, any of which groups may be optionally substituted by one, two or three substituents independently selected from halogen, cyano, C 1-6 alkyl, trifluoromethyl and hydroxy.
8. A compound as claimed in claim 1 represented by formula (IIC), or a pharmaceutically acceptable salt thereof:
wherein
R 11 represents hydrogen or methyl;
R 12 represents hydrogen or methyl; and
Z, R 2 and R 3 are as defined in claim 1 .
9. A compound as claimed in claim 1 wherein R 2 represents chloro.
10. A compound as claimed in claim 1 which is
(6S)-6-(3-Anilino-2-chloro-phenyl)-3-[(1-hydroxy-cyclopropyl)methyl]-2-imino-6-methylhexahydropyrimidin-4-one;
(6S)-6-(3-Anilino-2-chloro-phenyl)-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
(6S)-6-(3-Anilino-2-chloro-phenyl)-2-imino-6-methyl-3-(tetrahydropyran-4-ylmethyl)-hexahydropyrimidin-4-one;
(6S)-6-(3-Anilino-2-chloro-phenyl)-3-cyclohexyl-2-imino-6-methylhexahydropyrimidin-4-one;
(6S)-6-(3-Anilino-2-chloro-phenyl)-2-imino-6-methyl-3-[(3S or 3R*)-tetrahydrofuran-3-yl]hexahydropyrimidin-4-one;
(6S)-6-(3-Anilino-2-chloro-phenyl)-2-imino-6-methyl-3-[(3S or 3R*)-tetrahydrofuran-3-yl]hexahydropyrimidin-4-one;
(6S)-6[2-Chloro-3-(3-chloro-anilino)phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6[2-Chloro-3-(3-methyl-anilino)phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
3-{2-Chloro-3-[(4S)-2-imino-4-methyl-6-oxo-1-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-yl]anilino}benzonitrile;
(6S)-6[2-Chloro-3-(4-fluoro-3-methylanilino)phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[4-(tri-fluoromethyl)anilino]phenyl}-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(4-fluoro-anilino)phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-(3-Anilino-2-chloro-phenyl)-3-(3-hydroxy-3-methyl-cyclobutyl)-2-imino-6-methyl-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(6-methyl-pyridin-3-yl)amino]phenyl}-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(2-chloro-anilino)phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[2-(trifluoromethyl)anilino]-phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
2-{2-Chloro-3-[(4S)-2-imino-4-methyl-6-oxo-1-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-yl]anilino}benzonitrile;
4-{2-Chloro-3-[(4S)-2-imino-4-methyl-6-oxo-1-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-yl]anilino}benzonitrile;
(6S)-6-{2-Chloro-3-[(2-methyl-pyrimidin-5-yl)amino]phenyl}-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(pyridin-3-ylamino)phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(quinolin-5-ylamino)phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[2-fluoro-5-(trifluoromethoxy)anilino]-phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(3-fluoro-5-methoxyanilino)phenyl]-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
2-Chloro-4-{2-chloro-3-[(4S)-2-imino-4-methyl-6-oxo-1-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-yl]-anilino}benzonitrile;
(6S)-6-(2-Chloro-3-{[6-(morpholin-4-yl)pyridin-3-yl]amino}phenyl)-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[2-(trifluoromethyl)pyridin-3-yl]amino}phenyl)-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(5-fluoro-2-methoxyanilino)phenyl]-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(2-methyl-pyridin-3-yl)amino]phenyl}-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(2-fluoro-pyridin-4-yl)amino]phenyl}-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(quinolin-3-ylamino)phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[6-(trifluoromethyl)pyridin-3-yl]amino}phenyl)-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[2-chloro-5-(trifluoromethyl)pyridin-3-yl]amino}phenyl)-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(4-chloro-3-fluoroanilino)phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
3-Chloro-5-{2-chloro-3-[(4S)-2-imino-4-methyl-6-oxo-1-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-yl]-anilino}benzonitrile;
(6S)-6-[2-Chloro-3-(imidazo-[1,2-a]pyridin-2-ylamino)-phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(2-fluoro-anilino)phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[4-(difluoro-methoxy)anilino]phenyl}-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(2,4,5-trifluoroanilino)phenyl]-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(4-methyl-sulfonylanilino)phenyl]-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
5-{2-Chloro-3-[(4S)-2-imino-4-methyl-6-oxo-1-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-yl]anilino}pyridine-2-carbonitrile;
(6S)-6-[2-Chloro-3-(3-methyl-sulfonylanilino)phenyl]-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[6-(difluoromethoxy)pyridin-3-yl]-amino}phenyl)-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(2-methyl-sulfonylanilino)phenyl]-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(5-methyl-pyrazin-2-yl)amino]phenyl}-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[6-(trifluoromethoxy)pyridin-3-yl]-amino}phenyl)-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(isoquinolin-4-ylamino)phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
4-{2-Chloro-3-[(4S)-2-imino-4-methyl-6-oxo-1-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-yl]anilino}-3-methoxy-benzonitrile;
3-{2-Chloro-3-[(4S)-2-imino-4-methyl-6-oxo-1-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-yl]anilino}pyridine-4-carbonitrile;
(6S)-6-{2-Chloro-3-[(5-fluoro-6-methoxypyridin-3-yl)amino]-phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(2-methoxypyridin-3-yl)amino]-phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
3-{2-Chloro-3-[(4S)-2-imino-4-methyl-6-oxo-1-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-yl]anilino}pyridine-2-carbo-nitrile;
(6S)-6-(2-Chloro-3-{[2-(trifluoromethyl)pyrimidin-5-yl]amino}phenyl)-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[2-(trifluoromethoxy)anilino]-phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(4-methoxypyridin-3-yl)amino]-phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(2-methoxy-6-methylpyridin-3-yl)-amino]phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[4-(trifluoromethyl)pyridin-3-yl]-amino}phenyl)-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(1-naphthyl-amino)phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(3-phenyl-anilino)phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[3-(1,3-Benzodioxol-5-ylamino)-2-chlorophenyl]-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(6-chloro-pyridin-3-yl)amino]phenyl}-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[3-(isoxazol-5-yl)anilino]phenyl}-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{3-[(2-tert-Butyl-pyrimidin-5-yl)amino]-2-chloro-phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[3-(difluoro-methoxy)anilino]phenyl}-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[4-(trifluoromethoxy)anilino]-phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
(6S)-6-{3-[(1-Acetylindolin-5-yl)amino]-2-chlorophenyl}-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[2-(difluoro-methoxy)anilino]phenyl}-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[3-(4-tert-Butylanilino)-2-chlorophenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[3-(4-tert-Butylanilino)-2-chlorophenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(2,2-difluoro-1,3-benzodioxol-4-yl)amino]phenyl}-2-imino-6-methyl-3-tetrahydropyran-4-yl-hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(2,6-dimethylanilino)phenyl]-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(4-fluoro-pyrazolo[1,5-a]pyridin-6-yl)-amino]phenyl}2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(4-phenyl-anilino]phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[6-(dimethylamino)pyridin-3-yl]-amino}phenyl)-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(1-methyl-2-oxopyridin-4-yl)amino]-phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(2-isopropoxyanilino)phenyl]-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(3-phenoxy-anilino)phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(2-isopropoxyanilino)phenyl]-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(2-methyl-indazol-4-yl)amino]phenyl}-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(2-methyl-indazol-5-yl)amino]phenyl}-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[3-(2-oxo-pyrrolidin-1-yl)anilino]phenyl}-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[4-(5-methyl-1,3,4-oxadiazol-2-yl)-anilino]phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[6-(difluoromethyl)pyridin-3-yl]-amino}phenyl)-2-imino-6-methyl-3-tetrahydropyran-4-yl-hexahydropyrimidin-4-one;
2-{2-Chloro-3-[(4S)-2-imino-4-methyl-6-oxo-1-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-yl]anilino}-5-fluorobenzo-nitrile;
2-{2-Chloro-3-[(4S)-2-imino-4-methyl-6-oxo-1-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-yl]anilino}-5-(trifluoro-methy)benzonitrile;
(6S)-6-{2-Chloro-3-[(6-methyl-pyridazin-3-yl)amino]phenyl}-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-([1,2,4]-triazolo[1,5-a]pyridin-6-yl-amino)phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(4-methyl-2,3-dihydro-1,4-benzoxazin-7-yl)amino]phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(2-methoxypyridin-4-yl)amino]-phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
3-{2-Chloro-3-[(4S)-2-imino-4-methyl-6-oxo-1-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-yl]anilino}-6-methylpyridine-2-carbonitrile;
3-{2-Chloro-3-[(4S)-2-imino-4-methyl-6-oxo-1-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-yl]anilino}quinoline-4-carbonitrile;
(6S)-6-{2-Chloro-3-[(1-methyl-isoquinolin-4-yl)amino]phenyl}-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(pyrazolo-[1,5-a]pyridin-5-ylamino)-phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[2-(difluoro-methoxy)-4-fluoro-anilino]-phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[6-methyl-5-(trifluoromethyl)pyridin-3-yl]-amino}phenyl)-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[2-(difluoromethoxy)-6-methyl-pyridin-3-yl]amino}phenyl)-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[1-(difluoromethoxy)isoquinolin-4-yl]amino}phenyl)-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
4-{2-Chloro-3-[(4S)-2-imino-4-methyl-6-oxo-1-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-yl]anilino}-3-(difluoro-methoxy)benzonitrile;
(6S)-6-(2-Chloro-3-{[2-(difluoromethoxy)pyridin-3-yl]-amino}phenyl)-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[2-(difluoromethoxy)quinolin-3-yl]amino}phenyl)-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(6-cyclo-propylpyridin-3-yl)amino]-phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
3-{2-Chloro-3-[(4S)-2-imino-4-methyl-6-oxo-1-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-yl]anilino}-6-(difluoro-methyl)pyridine-2-carbonitrile;
(6S)-6-(2-Chloro-3-{[3-(difluoromethoxy)pyrazin-2-yl]-amino}phenyl)-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[3-(difluoromethoxy)pyridin-2-yl]-amino}phenyl)-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
1-(5-{2-Chloro-3-[(4S)-2-imino-4-methyl-6-oxo-1-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-yl]anilino}pyridin-2-yl)-cyclobutanecarbonitrile;
(6S)-6-{2-Chloro-3-[4-fluoro-2-(methylsulfonyl)anilino]-phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
(6S)-6-{3-[(6-tert-Butylpyridin-3-yl)amino]-2-chlorophenyl}-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(6-cyclo-butylpyridin-3-yl)amino]-phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
(6S)-6-{3-[(5-tert-Butylpyrazin-2-yl)amino]-2-chlorophenyl}-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(imidazo-[1,2-a]pyridin-7-ylamino)-phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(2-{[dimethyl(oxo)-λ6-sulfanylidene]amino}anilino)-phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(4-chloro-6-methylpyridin-3-yl)amino]-phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(6-ethyl-pyridin-3-yl)amino]phenyl}-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]-amino}phenyl)-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-(3-{[6-(Azetidin-1-yl)-pyridin-3-yl]amino}-2-chloro-phenyl)-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[6-(1,2,4-triazol-1-yl)pyridin-3-yl]-amino}phenyl)-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(1-methyl-pyrazolo[3,4-b]pyridin-5-yl)-amino]phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(3-methyl-imidazo[4,5-b]pyridin-6-yl)-amino]phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[6-(2-methyltetrazol-5-yl)pyridin-3-yl]amino}phenyl)-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[4-chloro-2-(methylsulfonyl)anilino]-phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[6-(2,2,2-trifluoroethyl)pyridin-3-yl]-amino}phenyl)-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(2,4-difluoroanilino)phenyl]-3-(3-hydroxy-3-methylcyclobutyl)-2-imino-6-methylhexahydro-pyrimidin-4-one;
4-{2-Chloro-3-[(4S)-1-(3-hydroxy-3-methylcyclobutyl)-2-imino-4-methyl-6-oxo-hexahydropyrimidin-4-yl]-anilino}-2-fluorobenzonitrile;
5-{2-Chloro-3-[(4S)-1-(3-hydroxy-3-methylcyclobutyl)-2-imino-4-methyl-6-oxo-hexahydropyrimidin-4-yl]-anilino}pyridine-2-carbonitrile;
4-{2-Chloro-3-[(4S)-1-(3-hydroxy-3-methylcyclobutyl)-2-imino-4-methyl-6-oxo-hexahydropyrimidin-4-yl]-anilino}benzonitrile;
(6S)-6-(2-Chloro-3-{[6-(trifluoromethyl)pyridin-3-yl]-amino}phenyl)-3-(3-hydroxy-3-methylcyclobutyl)-2-imino-6-methylhexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(6-methyl-pyridin-3-yl)amino]phenyl}-3-(3-hydroxy-3-methylcyclo-butyl)-2-imino-6-methyl-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(5-fluoro-pyridin-2-yl)amino]phenyl}-3-(3-hydroxy-3-methylcyclo-butyl)-2-imino-6-methyl-hexahydropyrimidin-4-one;
2-{2-Chloro-3-[(4S)-1-(3-hydroxy-3-methylcyclobutyl)-2-imino-4-methyl-6-oxo-hexahydropyrimidin-4-yl]-anilino}-5-fluorobenzonitrile;
(6S)-6-(2-Chloro-3-{[6-(difluoromethoxy)pyridin-3-yl]-amino}phenyl)-3-(3-hydroxy-3-methylcyclobutyl)-2-imino-6-methylhexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(5-methyl-pyrazin-2-yl)amino]phenyl}-3-(3-hydroxy-3-methylcyclo-butyl)-2-imino-6-methyl-hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[6-(trifluoromethoxy)pyridin-3-yl]-amino}phenyl)-3-(3-hydroxy-3-methylcyclobutyl)-2-imino-6-methylhexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[2-(trifluoromethyl)pyridin-4-yl]amino}phenyl)-3-(3-hydroxy-3-methylcyclobutyl)-2-imino-6-methylhexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(pyrazolo-[1,5-a]pyridin-5-ylamino)-phenyl]-3-(3-hydroxy-3-methyl-cyclobutyl)-2-imino-6-methyl-hexahydropyrimidin-4-one;
4-{2-Chloro-3-[(4S)-1-(3-hydroxy-3-methylcyclobutyl)-2-imino-4-methyl-6-oxo-hexahydropyrimidin-4-yl]-anilino}-3-(difluoromethoxy)-benzonitrile;
(6S)-6-{2-Chloro-3-[(6-methyl-pyridin-3-yl)amino]phenyl}-3-(3-hydroxy-3-isopropylcyclo-butyl)-2-imino-6-methyl-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(6-methyl-pyridin-3-yl)amino]phenyl}-2-imino-6-methyl-3-[(cis)-2-methyltetrahydropyran-4-yl]-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(6-methyl-pyridin-3-yl)amino]phenyl}-2-imino-6-methyl-3-[(cis)-2-methyltetrahydropyran-4-yl]-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(4-fluoro-pyrazolo[1,5-a]pyridin-6-yl)-amino]phenyl}-2-imino-6-methyl-3-[(cis)-2-methyl-tetrahydropyran-4-yl]-hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[6-(difluoromethoxy)pyridin-3-yl]-amino}phenyl)-2-imino-6-methyl-3-[(cis)-2-methyl-tetrahydropyran-4-yl]-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(6-methyl-pyridin-3-yl)amino]phenyl}-3-(4,4-difluorocyclohexyl)-2-imino-6-methylhexahydro-pyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[6-(difluoromethoxy)pyridin-3-yl]-amino}phenyl)-3-(4,4-difluoro-cyclohexyl)-2-imino-6-methyl-hexahydropyrimidin-4-one;
(6S)-6-{3-[(2-tert-Butyl-pyrimidin-5-yl)amino]-2-chloro-phenyl}-3-(4,4-difluoro-cyclohexyl)-2-imino-6-methyl-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(6-cyclo-propylpyridin-3-yl)amino]-phenyl}-3-(4,4-difluoro-cyclohexyl)-2-imino-6-methyl-hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[6-(difluoromethoxy)pyridin-3-yl]-amino}phenyl)-3-[(4R*)-2,2-dimethyltetrahydropyran-4-yl]-2-imino-6-methylhexahydro-pyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[6-(difluoromethoxy)pyridin-3-yl]-amino}phenyl)-3-[(4S*)-2,2-dimethyltetrahydropyran-4-yl]-2-imino-6-methylhexahydro-pyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(6-methyl-pyridin-3-yl)amino]phenyl}-3-[(4R*)-2,2-dimethyltetrahydro-pyran-4-yl]-2-imino-6-methyl-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(6-methyl-pyridin-3-yl)amino]phenyl}-3-[(4S*)-2,2-dimethyltetrahydro-pyran-4-yl]-2-imino-6-methyl-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(6-cyclo-propylpyridin-3-yl)amino]-phenyl}-3-[(4S*)-2,2-dimethyl-tetrahydropyran-4-yl]-2-imino-6-methylhexahydropyrimidin-4-one;
(6S)-6-{3-[(6-tert-Butylpyridin-3-yl)amino]-2-chlorophenyl}-3-[(4S*)-2,2-dimethyltetrahydro-pyran-4-yl]-2-imino-6-methyl-hexahydropyrimidin-4-one;
(6S)-6-{3-[(5-tert-Butylpyrazin-2-yl)amino]-2-chlorophenyl}-3-[(4S*)-2,2-dimethyltetrahydro-pyran-4-yl]-2-imino-6-methyl-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(6-cyclo-propylpyridazin-3-yl)amino]-phenyl}-3-[(4S*)-2,2-dimethyl-tetrahydropyran-4-yl]-2-imino-6-methylhexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(5-cyclo-propylpyrazin-2-yl)amino]-phenyl}-3-[(4S*)-2,2-dimethyl-tetrahydropyran-4-yl]-2-imino-6-methylhexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(6-methyl-pyridin-3-yl)amino]phenyl}-3-[3-hydroxy-3-(trifluoromethyl)-cyclobutyl]-2-imino-6-methyl-hexahydropyrimidin-4-one (cis isomer;
(6S)-6-{2-Chloro-3-[(6-methyl-pyridin-3-yl)amino]phenyl}-3-[3-hydroxy-3-(trifluoromethyl)-cyclobutyl]-2-imino-6-methyl-hexahydropyrimidin-4-one (trans isomer);
(6S)-6-{2-Chloro-3-[(6-cyclo-propylpyridin-3-yl)amino]-phenyl}-3-[3-hydroxy-3-(trifluoromethyl)cyclobutyl]-2-imino-6-methylhexahydro-pyrimidin-4-one (cis isomer);
(6S)-6-{2-Chloro-3-[(4-chloro-anilino]phenyl}-2-imino-6-methyl-3-[(2R*,4R*)-2-methyl-tetrahydropyran-4-yl]-hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[6-(difluoromethoxy)pyridin-3-yl]-amino}phenyl)-2-imino-6-methyl-3-[(1SR,5RS)-8-oxa-bicyclo[3.2.1]octan-3-yl]-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(6-methyl-pyridin-3-yl)amino]phenyl}-2-imino-6-methyl-3-[(1SR,5RS)-8-oxabicyclo[3.2.1]octan-3-yl]-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(6-cyclo-propylpyridin-3-yl)amino]-phenyl}-3-[(4S*)-2,2-dimethyl-tetrahydropyran-4-yl]-2-imino-6-methylhexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(4-methoxy-anilino)phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(4-methyl-anilino)phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(3,5-dimethoxyanilino)phenyl]-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(4-chloro-anilino)phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[3-(trifluoromethyl)anilino]-phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(3,4-dimethoxyanilino)phenyl]-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(2-methyl-anilino)phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
Methyl 3-{2-chloro-3-[(4S)-2-imino-4-methyl-6-oxo-1-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-yl]-anilino}benzoate;
(6S)-6-[2-Chloro-3-(3-chloro-4-fluoroanilino)phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(3-fluoro-anilino)phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(4-fluoro-anilino)phenyl]-2-imino-6-methyl-3-[(3R*)-tetrahydro-furan-3-yl]hexahydropyrimidin-4-one;
(6S*)-6-[2-Chloro-3-(4-fluoro-anilino)phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-ylmethyl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(4-fluoro-anilino)phenyl]-2-imino-6-methyl-3-(2-oxaspiro[3.3]-heptan-6-yl)hexahydro-pyrimidin-4-one;
(6S)-6-[2-Chloro-3-(4-fluoro-anilino)phenyl]-3-(3-hydroxy-3-methylcyclobutyl)-2-imino-6-methylhexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[4-(trifluoromethyl)anilino]-phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-ylmethyl)-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[4-(trifluoromethyl)anilino]-phenyl}-3-(3-hydroxy-3-methyl-cyclobutyl)-2-imino-6-methyl-hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(4-fluoro-anilino)phenyl]-2-imino-6-methyl-3-[(3-methyloxetan-3-yl)methyl]hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(4-chloro-anilino)phenyl]-3-(3-hydroxy-3-methylcyclobutyl)-2-imino-6-methylhexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(4-fluoro-anilino)phenyl]-3-(3-ethyl-3-hydroxycyclobutyl)-2-imino-6-methylhexahydropyrimidin-4-one (trans isomer);
(6S)-6-[2-Chloro-3-(4-fluoro-anilino)phenyl]-3-(3-ethyl-3-hydroxycyclobutyl)-2-imino-6-methylhexahydropyrimidin-4-one (cis isomer);
(6S)-6-[2-Chloro-3-(4-fluoro-anilino)phenyl]-3-[3-hydroxy-3-(trifluoromethyl)cyclobutyl]-2-imino-6-methyl-hexahydro-pyrimidin-4-one (cis isomer);
3-{(4S)-4-[2-Chloro-3-(4-fluoroanilino)phenyl]-2-imino-4-methyl-6-oxohexahydro-pyrimidin-1-yl}-1-methyl-cyclobutanecarbonitrile (trans isomer);
3-{(4S)-4-[2-Chloro-3-(4-fluoroanilino)phenyl]-2-imino-4-methyl-6-oxohexahydro-pyrimidin-1-yl}-1-methyl-cyclobutanecarbonitrile (cis isomer);
(6S)-6-{2-Chloro-3-[(5-chloro-pyridin-2-yl)amino]phenyl}-2-imino-6-methyl-3-(tetrahydro-yran-4-yl)-hexahydropyrimidin-4-one;
6-{2-Chloro-3-[(4S)-2-imino-4-methyl-6-oxo-1-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-yl]anilino}pyridine-3-carbonitrile;
2-{2-Chloro-3-[(4S)-2-imino-4-methyl-6-oxo-1-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-yl]anilino}pyridine-3-carbonitrile;
(6S)-6-[2-Chloro-3-(imidazo-[1,2-a]pyridin-3-ylamino)-phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(3,5-dimethyl-1-phenylpyrazol-4-yl)-amino]phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(imidazo-[1,5-a]pyridin-3-ylamino)-phenyl]-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(4-fluoro-anilino)phenyl]-2-imino-6-methyl-3-[(1RS,2SR,4SR)-7-oxabicyclo[2.2.1]heptan-3-yl]-hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(4-fluoro-anilino)phenyl]-2-imino-6-methyl-3-[(3S*)-tetrahydro-pyran-3-yl]hexahydropyrimidin-4-one;
(6S)-6-[2-Chloro-3-(4-fluoro-anilino)phenyl]-2-imino-6-methyl-3-[(3R* or 3S)-tetrahydropyran-3-yl]-hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[6-(difluoromethoxy)pyridin-3-yl]-amino}phenyl)-2-imino-6-methyl-3-[(2R*,4S*)-2-methyl-tetrahydropyran-4-yl]-hexahydropyrimidin-4-one (Peak 1);
(6S)-6-(2-Chloro-3-{[6-(difluoromethoxy)pyridin-3-yl]-amino}phenyl)-2-imino-6-methyl-3-[(2S*,4R*)-2-methyl-tetrahydropyran-4-yl]-hexahydropyrimidin-4-one (Peak 2);
(6S)-6-{2-Chloro-3-[(6-cyclo-propylpyridin-3-yl)amino]-phenyl}-2-imino-6-methyl-3-[(2R*,4S*)-2-methyltetrahydro-pyran-4-yl]hexahydropyrimidin-4-one (Peak 1);
(6S)-6-{2-Chloro-3-[(6-cyclo-propylpyridin-3-yl)amino]-phenyl}-2-imino-6-methyl-3-[(2S*,4R*)-2-methyltetrahydro-pyran-4-yl]hexahydropyrimidin-4-one (Peak 2);
(6S)-6-{2-Chloro-3-[(6-methyl-pyridin-3-yl)amino]phenyl}-2-imino-6-methyl-3-[(2R*,4S*)-2-methyltetrahydropyran-4-yl]-hexahydropyrimidin-4-one (Peak 1);
(6S)-6-{2-Chloro-3-[(6-methyl-pyridin-3-yl)amino]phenyl}-2-imino-6-methyl-3-[(2S*,4R*)-2-methyltetrahydropyran-4-yl]-hexahydropyrimidin-4-one (Peak 2);
(6S)-6-{2-Chloro-3-[(6-cyclo-propylpyridazin-3-yl)amino]phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(6-cyclo-propylpyridin-3-yl)amino]-phenyl}-2-imino-6-methyl-3-[(2R*,4R*)-2-methyltetrahydro-pyran-4-yl]hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(6-cyclo-propylpyridin-3-yl)amino]phenyl}-2-imino-6-methyl-3-[(2S*,4S*)-2-methyltetrahydro-pyran-4-yl]hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(6-cyclo-propylpyridazin-3-yl)amino]-phenyl}-2-imino-6-methyl-3-[(2R*,4R*)-2-methyltetrahydro-pyran-4-yl]hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]-amino}phenyl)-2-imino-6-methyl-3-[(2R*,4R*)-2-methyl-tetrahydropyran-4-yl]-hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[6-(2,2,2-trifluoroethoxy)pyridazin-3-yl]-amino}phenyl)-2-imino-6-methyl-3-[(2R*,4R*)-2-methyl-tetrahydropyran-4-yl]-hexahydropyrimidin-4-one;
(6S)-6-(2-Chloro-3-{[6-(2,2-difluoroethoxy)pyridin-3-yl]-amino}phenyl)-2-imino-6-methyl-3-[(2R*,4R*)-2-methyl-tetrahydropyran-4-yl]-hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(2-cyclo-propylpyrimidin-5-yl)amino]-phenyl}-2-imino-6-methyl-3-[(2R*,4R*)-2-methyltetrahydro-pyran-4-yl]hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-3-[(1-cyclo-propyl-2-oxopyridin-4-yl)-amino]phenyl}-3-[(4R*)-2,2-dimethyltetrahydropyran-4-yl]-2-imino-6-methylhexahydro-pyrimidin-4-one;
(6S)-6-[2-Chloro-4-fluoro-3-(4-fluoroanilino)phenyl]-2-imino-6-methyl-3-(tetrahydro-pyran-4-yl)hexahydropyrimidin-4-one;
(6S)-6-{2-Chloro-4-fluoro-3-[(6-methylpyridin-3-yl)amino]phenyl}-2-imino-6-methyl-3-(tetrahydropyran-4-yl)hexahydropyrimidin-4-one; or
a pharmaceutically acceptable salt thereof.
11. A pharmaceutical composition comprising a compound of formula (I) as defined in claim 1 or a pharmaceutically acceptable salt thereof in association with a pharmaceutically acceptable carrier.
12. A method for the treatment and/or prevention of malaria, which comprises administering to a patient in need of such treatment an effective amount of a compound of formula (I) as defined in claim 1 or a pharmaceutically acceptable salt thereof.
13. A compound as claimed in claim 4 wherein R 16 represents hydrogen, halogen, cyano, C 1-6 alkyl, trifluoromethyl or C 1-6 alkoxy.
14. A compound as claimed in claim 3 wherein R 2 represents chloro.
15. A compound as claimed in claim 6 wherein R 2 represents chloro.
16. A compound as claimed in claim 8 wherein R 2 represents chloro.
17. A compound as claimed in claim 3 wherein R 1 represents C 3-7 cycloalkyl, C 3-7 cycloalkyl(C 1-6 )alkyl, C 3-7 heterocycloalkyl, C 3-7 heterocycloalkyl(C 1-6 )alkyl, C 4-9 heterobicycloalkyl or C 4-9 spiroheterocycloalkyl, any of which groups may be optionally substituted by one, two or three substituents independently selected from halogen, cyano, C 1-6 alkyl, trifluoromethyl and hydroxy.
18. A compound as claimed in claim 6 wherein R 1 represents C 3-7 cycloalkyl, C 3-7 cycloalkyl(C 1-6 )alkyl, C 3-7 heterocycloalkyl, C 3-7 heterocycloalkyl(C 1-6 )alkyl, C 4-9 heterobicycloalkyl or C 4-9 spiroheterocycloalkyl, any of which groups may be optionally substituted by one, two or three substituents independently selected from halogen, cyano, C 1-6 alkyl, trifluoromethyl and hydroxy.