Patent AU-2003212040-C1 (AU)
Title: Substituted Cyclopentane And Cyclopentene Compounds Useful As Neuraminidase Inhibitors
Inventor: BABU YARLAGADDA S
IPC: C07D341/00
Filed: 2003-07-10
Granted: 2019-02-28
Abstract: -192 SUBSTITUTED CYCLOPENTANE AND CYCLOPENTENE COMPOUNDS USEFUL AS NEURAMINIDASE INHIBITORS Abstract of Disclosure Compounds represented by the formulae: (R 12 )p R12 R12 z z R , or z R R 4 R 13 R 4 R13 R 4 R 13 wherein U is CH, 0, or S; Z is -C(R 2)(R3 ), -CH-N(R2)(R3), C(R 3)[(CH 2)nR 2], CH-C(R3)(R8 )(CH2)nR 2, C[(CH2)nR 2]-[CH(R3)(Rs)], C[(R 3)][CH[(CH 2)nR2](Rs)]; R1 is H, (CH 2)nOH, (CH 2)nNH 2, (CH2)nNRio RI1 , (CH 2)nORI, (CH 2)nSR 1 , or (CH 2)n halogen R9 is (CH2)nCO 2H, (CH 2)nSO 3H, (CH2)nPO 3H2, (CH2)nNO 2, CH(SCH 3)3, esters thereof, or salts thereof; or R, R9 together represent =0, or =( - 193 R 2 is H, NHC(O)R 5, NHC(S)R 5 , NHSO 2R5, C(O)NHR5 , SO 2NHR5 , CH 2S(O)R5 , or R3 and R8 individually is H, (CH2)nC(O)RIo, (CH 2)nCO 2Rio, (CH2)mORio, CH(0Rjo)CH(Rio)m, C(O)N(Rio)m, C(O)N(0Rio)RIo, (CH 2)nN(Rio)m, CH(RIO)m, (CH2)n(Rio)m, , CH2CH(ORio)CH 2ORio, CH(ORio)CH(ORio)CH 2ORio, CH20RIo, CH(ORIo)CH 2NHRio, CH 2CH(ORio)CH 2NHRio, CH(0RIo)CH(ORio)CH 2NHRio, C(=NRio)N(Rio)m, NHRio, NHC(=NRio)N(Rio)m, (CH 2)m-X-W-Y, CH2CH(X-W Y)CH2 ORio, CH(X-W-Y)CH(ORO)CH20Rio, CH(X-W-Y)CH 2(ORio), CH(ORio)CH(X-W-Y)CH2ORIo, CH(0RIo)CH 2(X-W-Y), CH2CH(X-W Y)CH 2NHRIo, CH(X-W-Y)CH(ORio)CH 2NHRo, CH(X-W-Y)CH 2(NHR 10), CH(ORio)CH(X-W-Y)CH 2NHRio, or CH(NHRio)CH 2(X-W-Y); provided that at least one of R2, R3, and R8 is other than H; R4 is H, (CH 2)nOH, (CH 2)nORii, (CH2)nOC(O)Rii, (CH2)nNHC(NRii)NHRii, (CH 2)nNRjoRii, (CH2)nNH 2, (CH 2)nC(=NH)(NH 2), (CH2)nNHC(=NRii)NH 2, (CH 2)nNHC(=NR7 )NH2, (CH2)nCN, (CH 2)nN 3, C(=NH)NH 2, C(NRy)NH 2, or C(NRii)NH 2; R5 is H, lower alkyl, cyclo alkyl, halogen substituted alkyl, aryl, substituted aryl, or CF3; R7 is H, (CH2 )nOH, (CH 2)nCN, (CH2)nNH 2, or (CH2)nNO 2; RIo is H, lower alkyl, lower alkylene, branched alkyl, cyclic alkyl, (CH 2)n aromatic, (CH2)n substituted aromatic, or when m is 2 both RIO groups can also be interconnected to form an N substituted heterocyclic ring, or other 5 or 6 membered heterocyclic ring; -194 R I is lower alkyl, branched alkyl, (CH2)m aromatic, S0 2Rio, C(O)Rjo, or C(O)ORio; R12 and R13 is H, (CH 2)nOH, (CH 2)nNH 2, (CH2)nNRioRii, (CH2)nORI1, (CH 2)nF, (CH 2)nOC(O)RI1, (CH2)nNHC(O)RI1, or X-W-Y; m is 1 or 2; n is 0- 4 ; p is 0 or 1; X is 0, S, CH2, or NH; W is a spacer group made up of a chain of 1 to 100 atoms, and optionally also 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, CONHNH 2, 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 virus. Also provided are intermediates represented by the formulae:. Another aspect of the present invention relates to intermediates represented by the following formulae: - 195 Wherein R4 and R9 are the same as defined above; and R NN'O N Wherein each R 14 individually is H, 0, (CH2)nCO2H, (CH2)nSO 3H, (CH2)nPO 3H, (CH 2)nNO 2 , CH(SCH3)3, esters thereof or salts thereof, and provided at least one of R14 is H, and R3 and R4 are as defined above.