Patent CA-2315262-C (CA)
Title: Substituted cyclopentane and cyclopentene compounds useful as neuraminidase inhibitors
Inventor: BABU YARLAGADDA S
IPC: C07D/
Filed: 1998-12-17
Granted: 2009-11-10
Abstract: Compounds represented by the formulae: (see formula I), (see formula II), or (see formula III) wherein U is CH, O, or S; Z is -C(R2)(R3), -CH-N(R2)(R3), C(R3)[(CH2)n R2], CH-C(R3)(R8)(CH2)n R2, C[(CH2)n R2]-[CH(R3)(R8)], C[(R3)][CH[(CH2)n R2](R8)]; R1 is H, (CH2)n OH, (CH2)n NH2, (CH2)n NR10R11, (CH2)n OR11, (CH2)n SR11, o r (CH2)n halogen R9 is (CH2)n CO2H, (CH2)n SO3H, (CH2)n PO3H2, (CH2)n NO2, CH(SCH3)3, esters thereof, or salts thereof; or R1 R9 together represent = O, or (see formula IV) R2 is H, NHC(O)R5, NHC(S)R5, NHSO2R5, C(O)NHR5, SO2NHR5, CH2S(O)R5, or CH2SO2R5 R3 and R8 individually is H, (CH2)n C(O)R10, (CH2)n CO2R10, (CH2)m OR10, CH(OR10)CH(R10)m, C(O)N(R10)m, C(O)N(OR10)R10, (CH2)n N(R10)m, CH(R10)m, (CH2)n(R10)m, , CH2CH(OR10)CH2OR10, CH(OR10)CH(OR10)CH2OR10, CH2OR10, CH(OR10)CH2NHR10, CH2CH(OR10)CH2NHR10, CH(OR10)CH(OR10)CH2NHR10, C(=NR10)N(R10)m, NHR10, NHC(=NR10)N(R10)m, (CH2)m-X-W-Y, CH2CH(X-W- Y)CH2OR10, CH(X-W-Y)CH(OR10)CH2OR10, CH(X-W-Y)CH2(OR10), CH(OR10)CH(X-W-Y)CH2OR10, CH(OR10)CH2(X-W-Y), CH2CH(X-W- Y)CH2NHR10, CH(X-W-Y)CH(OR10)CH2NHR10, CH(X-W-Y)CH2(NHR10), CH(OR10)CH(X-W-Y)CH2NHR10, or CH(NHR10)CH2(X-W-Y); provided that at least one of R2, R3, and R8 is other than H; R4 is H, (CH2)n OH, (CH2)n OR11, (CH2)n OC(O)R11, (CH2)n NHC(NR11)NHR11, (CH2)n NR10R11, (CH2)n NH2, (CH2)n C(=NH)(NH2), (CH2)n NHC(=NR11)NH2, (CH2)n NHC(=NR7)NH2, (CH2)n CN, (CH2)n N3, C(=NH)NH2, C(NR7)NH2, or C(NR11)NH2; R5 is H, lower alkyl, cyclo alkyl, halogen substituted alkyl, aryl, substituted aryl, or CF3; R7 is H, (CH2)n OH, (CH2)n CN, (CH2)n NH2, or (CH2)n NO2; R10 is H, lower alkyl, lower alkylene, branched alkyl, cyclic alkyl, (CH2)n aromatic, (CH2)n substituted aromatic, or when m is 2 both R10 groups can also be interconnected to form an N substituted heterocyclic ring, or other 5 or 6 membered heterocyclic ring; R11 is lower alkyl, branched alkyl, (CH2)m aromatic, SO2R10, C(O)R10, or C(O)OR10; R12 and R13 is H, (CH2)n OH, (CH2)n NH2, (CH2)n NR10R11, (CH2)n OR11, (CH2)n F, (CH2)n OC(O)R11, (CH2)n NHC(O)R11, or X-W-Y; m is 1 or 2; n is 0-4; p is 0 or 1; X is O, S, CH2, or NH; W is a spacer group made up of a chain of 1 to 100 atoms, and optionally als o comprising of substituted carbon and/ or nitrogen atoms and optionally including oxygen or sulphur atoms; and Y is H, OH, SH, NH2, CH=O, CH=CH2, CO2H, CONHNH2, or a protected form of one of these end functionalities; and pharmaceutically aceptable salts thereof and their method of preparation are provided. Compounds of the above formula are influenza virus nueraminidase inhibitors and can be used in treating patients infected with influenza viru s. Also provided are intermediates represented by the formulae:. Another aspect of the present invention relates to intermediates represented by the following formulae: (see formula V) Wherein R4 and R9 are the same as defined above; and (see formula VI) Wherein each R14 individually is H, O, (CH2)n CO2H, (CH2)n SO3H, (CH2)n PO3H , (CH2)n NO2, CH(SCH3)3, (see formula IV) esters thereof or salts thereof, and provided at least one of R14 is H, and R3 and R4 are as defined above.