Patent ID: 6649639
Filing Date: 2003-11-18
Classification: A61K,C07C,C07D

Abstract:
A compound of the formula (I): wherein:M is O or S; R1 is H, F, an alkyl group, OH, SH, or an O-alkyl group; R2 and R5 are independently selected from H, or an allyl group, wherein said alkyl group is different from with the proviso that at least one of R2 or R5 must be and wherein, when R2 or R5 is X is &boxH;CH or &boxH;CF and Y1 is &boxH;CH or &boxH;CF, or X and Y1 together with Qâ€² form a three-membered ring in which Qâ€² is â€”C(R10)(R11)â€” or â€”Oâ€”, X is â€”CHâ€” or â€”CFâ€”, and Y1 is â€”CHâ€”, â€”CFâ€”, or â€”C(alkyl)-, where R10 and R11 independently are H, a halogen, or an alkyl group, or, together with the carbon atom to which they are attached, form a cycloalkyl group or a heterocycloalkyl group, or X is â€”CH2â€”, â€”CF2â€”, â€”CHFâ€”, or â€”Sâ€”, and Y1 is â€”Oâ€”, â€”Sâ€”, â€”NR12â€”, â€”C(R13)(R14)â€”, â€”C(O)â€”, â€”C(S)â€”, or â€”C(CR13R14)â€”, wherein R12 is H or alkyl, and R13 and R14 independently are H, F, or an alkyl group, or, together with the atoms to which they are bonded, form a cycloalkyl group or a heterocycloalkyl group; A1 is C, CH, CF, S, P, Se, N, NR15, S(O), Se(O), Pâ€”OR15, or Pâ€”NR15R16, wherein R15 and R16 independently are an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group, or, together with the atom to which they are bonded, form a heterocycloalkyl group; D1 is a moiety with a lone pair of electrons capable of forming a hydrogen bond; and B1 is H, F, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, â€”OR17, â€”SR17, â€”NR17R18, â€”NR19NR17R18, or â€”NR17OR18, wherein R17, R18, and R19 independently are H, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, or an acyl group; and with the provisos that when D1 is the moiety &square;N with a lone pair of electrons capable of forming a hydrogen bond, B1 does not exist; and when A1 is an sp3 carbon, B1 is not â€”NR17R18 when D1 is the moiety â€”NR25R26 with a lone pair of electrons capable of forming a hydrogen bond, wherein R25 and R26 are independently H, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group; and wherein D1-A1-B1 optionally forms a nitro group where A1 is N; and further wherein, when R2 or R5 is X is &boxH;CH or &boxH;CF and Y2 is =C, &boxH;CH, or &boxH;CF, or X and Y2 together with Qâ€² form a three-membered ring in which Qâ€² is â€”C(R10)(R11)â€” or â€”Oâ€”, X is â€”CHâ€” or â€”CFâ€”, and Y2 is â€”CHâ€”, â€”CFâ€”, or â€”C(alkyl)-, where R10 and R11 independently are H, a halogen, or an alkyl group, or, together with the carbon atom to which they are attached, form a cycloalkyl group or a heterocycloalkyl group, or X is â€”CH2â€”, â€”CF2â€”, â€”CHFâ€”, or â€”Sâ€”, and Y2 is â€”Oâ€”, â€”Sâ€”, â€”N(Râ€²12)â€”, â€”C(O)â€”, â€”C(Râ€²13)(R14)â€”, â€”C(S)â€”, or â€”C(CRâ€²13Râ€²14)â€”, wherein Râ€²12 is H, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, â€”ORâ€²13, â€”NRâ€²13Râ€²14, â€”C(O)â€”Râ€²13, â€”SO2Râ€²13, or â€”C(S)Râ€²13, and Râ€²13 and Râ€²14, independently are H, F, or an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group, or, together with the atom to which they are attached, form a cycloalkyl group or a heterocycloalkyl group; A2 is C, CH, CF, S, P, Se, N, NR15, S(O), Se(O), Pâ€”OR15, or Pâ€”NR15R16, wherein R15 and R16 independently are an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group, or, together with the atom to which they are bonded, form a heterocycloalkyl group; D2 is a moiety with a lone pair of electrons capable of forming a hydrogen bond; and B2 is H, F, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, â€”OR17, â€”SR17, â€”NR17R18, â€”NR19NR17R18, or â€”NR17OR18, wherein R17, R18, and R19 independently are H, an alkyl group, a cycloalkyl group, a heterocycloakyl group, an aryl group, a heteroaryl group, or an acyl group; and further wherein any combination of Y2, A2, B2, and D2 optionally can form a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group; R3 and R6 are independently H, F, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, â€”C(O)R17, â€”OR17, â€”SR17, â€”NR17R18, â€”NR19NR17R18, or â€”NR17OR18, wherein R17, R18, and R19 independently are H, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, or an acyl group; or, R3 and R6, together with the carbon atom to which they are attached, form a cycloalkyl group or a heterocycloalkyl group; R7 is H, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, â€”OR17, â€”SR17, â€”NR17R18, â€”NR19NR17R18, or â€”NR17OR18, wherein R17, R18, and R19 independently are H, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, or an acyl group; or R7, together with R3 or R6 and the atoms to which they are attached, forms a heterocycloalkyl group; R20 is H, OH, or any suitable organic moiety; and Z and Z1 are independently H, F, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, â€”C(O)R21, â€”CO2R21, â€”CN, â€”C(O)NR21R22, â€”C(O)NR21OR22, â€”C(S)R21, â€”C(S)NR21R22, â€”NO2, â€”SOR21, â€”SO2R21, â€”SO2NR21R22, â€”SO(NR21)(OR22), â€”SONR21, â€”SO3R21, â€”PO(OR21)2, â€”PO(R21)(R22), â€”PO(NR21R22)(OR23), PO(NR21R22)(NR23R24), â€”C(O)NR21NR22R23, or â€”C(S)NR21NR22R23, wherein R21, R22, R23, and R24 are independently H, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, an acyl group, or a thioacyl group, or wherein any two of R21, R22, R23, and R24, together with the atom(s) to which they are bonded, form a heterocycloalkyl group; or Z1, as defined above, together with R1, as defined above, and the atoms to which Z1 and R1 are bonded, form a cycloalkyl or heterocycloalkyl group, or Z and Z1, both as defined above, together with the atoms to which they are bonded, form a cycloalkyl or heterocycloalkyl group; or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof; and wherein said compound, or pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof, has antipicornaviral activity with an EC50 less than or equal to 10 &mgr;M in the HI-HeLa cell culture assay.