Patent ID: 6545018
Filing Date: 2003-04-08
Classification: A61P,C07C,C07D

Abstract:
A compound of the Formula a prodrug thereof, a geometric or optical isomer thereof, or a pharmaceutically acceptable salt of said compound, said prodrug, or said isomer, wherein:R1, R2 and R3 are each independently hydrogen, halogen, C1-6 alkyl, trifluoromethyl, â€”CN, â€”OCF3 or â€”OC1-6 alkyl; R4 is hydrogen, C1-12 alkyl optionally substituted with one to three substitutents independently selected from Group Z, C2-12 alkenyl, halogen, â€”CN, aryl, heteroaryl, C3-10 cycloalkyl, heterocycloalkyl, â€”S(O)2NR9R10, â€”C(O)NR9R10, â€”(C1-6 alkyl)-NR9R10, â€”NR9C(O)R10, â€”NR9C(O)NR9R10, â€”NR9S(O)2R10, â€”(C1-6 alkyl)-OR11, â€”OR11 or â€”S(O)aR12, provided that, where R5 is not fluoro, R4 is â€”S(O)2NR9R10, â€”C(O)NR9R10, â€”(C1-6 alkyl)-NR9R10, â€”NR9C(O)R10, â€”NR9C(O)NR9R10, â€”NR9S(O)2R10, â€”(C1-6 alkyl)-OR11, â€”OR11 or â€”S(O)aR12; R5 is fluoro, hydroxy, C1-4 alkoxy or OC(O)R9; or R4 and R5 may be taken together to form a heterocyclic ring B selected from the group consisting of â€”CR9&boxH;CR10â€”NHâ€”, â€”N&boxH;CR9â€”NHâ€”, â€”CR9&boxH;CHâ€”Oâ€” and â€”CR9&boxH;CHâ€”Sâ€”; R6 is hydrogen, halogen, C1-4 alkyl or trifluoromethyl; R7 is hydrogen or C1-6 alkyl; R8 is â€”OR9 or â€”NR19R20; R9 and R10 for each occurrence are independently (A) hydrogen, (B) C1-12 alkyl optionally substituted with one or more substituents independently selected from Group V, (C) C2-12 alkenyl, (D) C3-10 cycloalkyl optionally substituted with one or more substituents independently selected from C1-6 alkyl, C2-5 alkynyl, C3-10 cycloalkyl, â€”CN, â€”NR13R14, oxo, â€”OR18, â€”COOR18 or aryl optionally substituted with X and Y, (E) aryl optionally substituted with X and Y, or (F) het optionally substituted with X and Y; or R9 and R10 for any occurrence may be taken together to form a heterocyclic ring C optionally further containing a second heterogroup selected from the group consisting of â€”Oâ€”, â€”NR13â€” and â€”Sâ€”, and optionally further substituted with one or more substituents independently selected from C1-5 alkyl, oxo, â€”NR13R14, â€”OR18, â€”C(O)2R18, â€”CN, â€”C(O)R9, aryl optionally substituted with X and Y, het optionally substituted with X and Y, C5-6 spirocycloalkyl, and a carbocyclic ring B selected from the group consisting of 5-, 6-, 7- and 8-membered partially and fully saturated, and unsaturated carbocyclic rings, and including any bicyclic group in which said carbocyclic ring B is fused to a carbocyclic ring C selected from the group consisting of 5-, 6-, 7- and 8-membered partially and fully saturated, and unsaturated carbocyclic rings; R11 is C1-12 alkyl optionally substituted with one or more substituents independently selected from Group V, C2-12 alkenyl, C3-10 cycloalkyl, trifluoromethyl, difluoromethyl, monofluoromethyl, aryl optionally substituted with X and Y, het optionally substituted with X and Y, â€”C(O)NR9R10 or â€”C(O)R9; R12 is C1-12 alkyl optionally substituted with one or more substituents independently selected from Group V, C2-12 alkenyl, C3-10 cycloalkyl, aryl optionally substituted with X and Y, or het optionally substituted with X and Y; R13 and R14 for each occurrence are independently hydrogen, C1-6 alkyl, C2-6 alkenyl, â€”(C1-6 alkyl)-C1-6 alkoxy, aryl optionally substituted with X and Y, het optionally substituted with X and Y, â€”(C1-4 alkyl)-aryl optionally substituted with X and Y, â€”(C1-4 alkyl)-heterocycle optionally substituted with X and Y, â€”(C1-4 alkyl)-hydroxy, â€”(C1-4 alkyl)-halo, â€”(C1-4 alkyl)-poly-halo, â€”(C1-4 alkyl)-CONR15R16 or C3-10 cycloalkyl; R15 and R16 for each occurrence are independently hydrogen, C1-6 alkyl, C3-10 cycloalkyl or aryl optionally substituted with X and Y; R18 is hydrogen, C1-6 alkyl, C2-6 alkenyl, â€”(C1-6 alkyl)-C1-6 alkoxy, aryl optionally substituted with X and Y, het optionally substituted with X and Y, â€”(C1-4 alkyl)-aryl optionally substituted with X and Y, â€”(C1-4 alkyl)-heterocycle optionally substituted with X and Y, â€”(C1-4 alkyl)-hydroxy, â€”(C1-4 alkyl)-halo, â€”(C1-4 alkyl)-poly-halo, â€”(C1-4 alkyl)-CONR15R16, â€”(C1-4 alkyl)-(C1-4 alkoxy) or C3-10 cycloalkyl; R19 is hydrogen or C1-6 alkyl; R20 is hydrogen or C1-6 alkyl; W is O, S(O)d, CH2 or NR9; Group Z is C2-6 alkenyl, C2-6 alkynyl, halogen, â€”CF3, â€”OCF3, hydroxy, oxo, â€”CN, aryl, heteroaryl, C3-10 cycloalkyl, hetercycloalkyl, â€”S(O)aR12, â€”S(O)2NR9R10, â€”C(O)R9R10, and â€”NR9R10; Group V is halogen , â€”NR13R14, â€”OCF3, â€”OR9, oxo, trifluoromethyl , â€”CN , C3-10 cycloalkyl, aryl optionally substituted with X and Y, and het optionally substituted with X and Y; het for each occurrence is a heterocyclic ring D selected from the group consisting of 4-, 5-, 6-, 7- and 8-membered partially and fully saturated, and unsaturated, heterocyclic rings containing from one to four heteroatoms independently selected from the group consisting of N, O and S, and including any bicyclic group in which said heterocyclic ring D is fused to a benzene ring or a heterocyclic ring E selected from the group consisting of 4-, 5-, 6-, 7- and 8-membered partially and fully saturated, and unsaturated, heterocyclic rings containing from one to four heteroatoms independently selected from the group consisting of N, O and S; X and Y for each occurrence are independently (A) hydrogen, (B) halogen, (C) trifluoromethyl, (D) â€”OCF3, (E) â€”CN, (F) C1-6 alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, â€”OCF3, â€”CF3 and phenyl, (G) C1-6 alkoxy, (H) aryl optionally substituted with one or more substituents independently selected from the group consisting of halogen, â€”OCF3, â€”CF3, C1-4 alkyl and C1-4 alkoxy, (I) â€”C(O)2R13, (J) â€”C(O)NR13R14, (K) â€”C(O)R13, (L) â€”NR13C(O)NR13R14 and (M) â€”NR13C(O)R14; or X and Y for any occurrence in the same variable may be taken together to form (a) a carbocyclic ring D of the formula â€”(CH2)eâ€” or (b) a heterocyclic ring F selected from the group consisting of â€”O(CH2)fOâ€”, (CH2)gNHâ€” and â€”CH&boxH;CHNHâ€”; a and d are each independently 0, 1 or 2; f and g are each independently 2, 3, 4, 5 or 6; and e is 3, 4, 5, 6 or 7.