Patent ID: 6020371
Filing Date: 2000-02-01
Classification: A61K,C07C,C07D,Y02A

Abstract:
A compound of the formula (I): ##STR68## wherein: M is O or S;R.sub.1 is H, F, an alkyl group, OH, SH, or an O-alkyl group;R.sub.2 and R.sub.5 are independently selected from H, ##STR69## or an alkyl group, wherein said alkyl group is different from ##STR70## with the proviso that at least one of R.sub.2 or R.sub.5 must be ##STR71## and wherein, when R.sub.2 or R.sub.5 is ##STR72## X is .dbd.CH or .dbd.CF and Y.sub.1 is .dbd.CH or .dbd.CF, or X and Y.sub.1 together with Q' from a three-membered ring in which Q' is--C(R.sub.10)(R.sub.11)--or --O--, X is --CH--or --CF--, and Y.sub.1 is --CH--or --CF--, or --C(alkyl)--, where R.sub.10 and R.sub.11 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 --CH.sub.2 --, --CF.sub.2 --, --CHF--, or --S--, and Y.sub.1 is --O--, --S--, NR.sub.12 --,--C(R.sub.13)(R.sub.14)--, --C(O)--, --C(S)--, or --C(CR.sub.13 R.sub.14)--,wherein R.sub.12 is H or alkyl, and R.sub.13 and R.sub.14 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.A.sub.1 is C, CH, CF, S, P Se, N, NR.sub.15, S(O), Se(O), P--OR.sub.15, or P--NR.sub.15 R.sub.16,wherein R.sub.15 and R.sub.16 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;D.sub.1 is a moiety with a lone pair of electrons capable of forming a hydrogen bond; andB.sub.1 is H, F, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group --OR.sub.17, --SR.sub.17, --NR.sub.17 R.sub.18, --NR.sub.19 NR.sub.17 R.sub.18, or --NR.sub.17 OR.sub.18,wherein R.sub.17, R.sub.18, and R.sub.19 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 D.sub.1 is the moiety .ident.N with a lone pair of electrons capable of forming a hydrogen bond, B.sub.1 does not exist; and when A.sub.1 is an sp.sup.3 carbon, B.sub.1 is not --NR.sub.17 R.sub.18 when D.sub.1 is the moiety. --NR.sub.25 R.sub.26 with a lone pair of electrons capable of forming a hydrogen bond, wherein R.sub.25 and R.sub.26 are independently H, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group; and wherein D.sub.1 -A.sub.1 -B.sub.1 optionally forms a nitro group where A.sub.1 is N; and further wherein, when R.sub.2 or R.sub.5 is ##STR73## X is .dbd.CH or .dbd.CF and Y.sub.2 is .dbd.C, .dbd.CH, or .dbd.CF, or X and Y.sub.2 together with Q' form a three-membered ring in which Q' is--C(R.sub.10)(R.sub.11)--or --O--, X is --CH--or --CF--, and Y.sub.1 is --CH--or --CF--, or --C(alkyl)--, where R.sub.10 and R.sub.11 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 --CH.sub.2 --, --CF.sub.2 --, --CHF--, or --S--, and Y.sub.2 is --O--, --S--, N(R'.sub.12) --, --C(O)--, --C(R'.sub.13)(R'.sub.14)--, --C(S)--, or --C(CR'.sub.13 R'.sub.14)--,wherein R'.sub.12 is H, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, --OR'.sub.13 --NR'.sub.13 R'.sub.14, --C(O)--R'.sub.13 , --SO.sub.2 R'.sub.13, or --C(S)R'.sub.13 and R'.sub.14, independently are H, F, or an alkyl group, a cycloalkyl group, a heterocyclogroup, 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;A.sub.2 is C, CH, CH, S, P, Se, N, NR.sub.15, S(O), Se(O), P--NR.sub.15 R.sub.16, wherein R.sub.15 and R.sub.16 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;D.sub.2 is a moiety with a lone pair of electrons capable of forming a hydrogen bond; andB.sub.2 is H, F, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, --OR.sub.17, --SR.sub.17, --NR.sub.17 R.sub.18, --NR.sub.19 NR.sub.17 R.sub.18, or --NR.sub.17 OR.sub.18,wherein R.sub.17, R.sub.18, and R.sub.19 independently are H, an alkyl group, a cycloalkyl group,a heterocycloalkyl group, an aryl group, a heteroaryl group, a cycloalkyl group; and further wherein any combination of Y.sub.2, A.sub.2, B.sub.2, and D.sub.2 optionally can form a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group;R.sub.3 and R.sub.6 are independently H, F, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, --C(O)R.sub.17, --OR.sub.17, --SR.sub.17, --NR.sub.17 R.sub.18, --NR.sub.19 NR.sub.17 R.sub.18, or --NR.sub.17 OR.sub.18 provided that R.sub.3 and R.sub.6 cannot both be H,wherein R.sub.17, and R.sub.18, and R.sub.19 independently are H, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, or an acyl group; or, R.sub.3 and R.sub.6, together with the carbon atom to which they are attached, form a cycloalkyl group or a heterocycloalkyl group;R.sub.7 is H, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, as aryl group, a heteroaryl group, --OR.sub.17, --SR.sub.17, --NR.sub.17 R.sub.18, --NR.sub.19 NR.sub.17 R.sub.18, or --NR.sub.17 OR.sub.18,wherein R.sub.1, R.sub.18, and R.sub.19 independently are H, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, or an acyl group;or R.sub.7, together with R.sub.3 or R.sub.6 and the atoms to which they are attached, forms a heterocycloalkyl group;R.sub.20 is H, OH, or any suitable organic moiety; andZ is H, F, an alkyl, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, --C(O)R.sub.21, --CN, --C(O)NR.sub.21, R.sub.22, --C(O)NR.sub.21 OR.sub.22, --C(S)NR.sub.21, --C(S)NR.sub.21 R.sub.22, --NO.sub.2, --SOR.sub.2, --SO.sub.2 R.sub.2, --SO.sub.2 NR.sub.21 R.sub.22, --SO(NR.sub.21)(OR.sub.22), --SONR.sub.21, --SO.sub.3 R.sub.21, --PO(OR.sub.21).sub.2, --PO(R.sub.21)(R.sub.22), --PO(NR.sub.21 R.sub.22)(OR.sub.23), PO(NR.sub.21 R.sub.22)(NR.sub.23 R.sub.24), --C(O)NR.sub.21 NR.sub.22 R.sub.23, or --C(S)NR.sub.21 NR.sub.22 R.sub.23,wherein R.sub.21, R.sub.22, R.sub.23, and R.sub.24 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 R.sub.21, R.sub.22, R.sub.23, and R.sub.24, together with the atom(s) to which they are bonded, form a heterocycloalkyl group;Z.sub.1 is --CO.sub.2 R.sub.21, wherein R.sub.21 is an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, an acyl group, or a thioacyl 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 EC.sub.50 less than or equal to 10 .mu.M in the HI--HeLa cell culture assay.