Patent ID: 6214799
Filing Date: 2001-04-10
Classification: C07C,C07K

Abstract:
A compound of the formula (I): ##STR180##whereinR.sub.1, is H, F, an alkyl group, OH, SH, an O-alkyl group, or an S-alkyl group;R.sub.2 and R.sub.5 are independently selected from H, ##STR181##or an alkyl group, wherein said alkyl group is different from ##STR182##with the proviso that at least one of R.sub.2 or R.sub.5 must be ##STR183##and wherein, when R.sub.2 or R.sub.5 is ##STR184##X is .dbd.CH or .dbd.CF and Y.sub.1 is .dbd.CH or .dbd.CFor X and Y.sub.1 together with Q' form a three-membered ringin which Q' is --C(R.sub.10)(R.sub.11)-- or --O--, X is --CH-- or --CF--, and Y.sub.1 is --CH--, --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 --CH2--, --CF2--, --CHF--, or --S--, andY.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 atom to which they are bonded, form a cycloalkyl group or a heterocycloalkyl group;and 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.16wherein 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;and D.sub.1 is a moiety with a lone pair of electrons capable of forming a hydrogen bond;and B.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.18wherein 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, or, wherein any two of R.sub.17, R.sub.18, and R.sub.19, together with the atom(s) to which they are bonded, form a heterocycloalkyl group;and with the provisos that when D.sub.1 is the moiety .tbd.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 wherein, when R.sub.2 or R.sub.5 is ##STR185##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.2 is --CH--, --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--, andY.sub.2 is --O--, --S--, --N(R'.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, 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.13 and R'.sub.14, 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;and wherein any combination of Y.sub.2, A.sub.2, B.sub.2, and D.sub.2 forms a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group;and A.sub.2 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.16wherein 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;and D.sub.2 is a moiety with a lone pair of electrons capable of forming a hydrogen bond;and B.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.18wherein 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, or, wherein any two of R.sub.17 R.sub.18, and R.sub.19, together with the atom(s) to which they are bonded, form a heterocycloalkyl group;R.sub.3 and R.sub.6 are independently H, F, or an alkyl group;R.sub.4 is H, OH, or a suitable organic moiety;Z and Z.sub.1 are independently H, F, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, --C(O)R.sub.21, --CO.sub.2 R.sub.21 R.sub.22, --CN, --C(O)NR.sub.21,R.sub.22, --C(O)NR.sub.21 OR.sub.22, --C(S)R.sub.21, --C(S)NR.sub.21,R.sub.22, --NO.sub.2, --SOR.sub.21, --SO.sub.2 R.sub.21, --SO.sub.2 N.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, or 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;or Z.sub.1, as defined above, together with R.sub.1, as defined above, and the atoms to which Z.sub.1 and R.sub.1 are bonded, form a cycloalkyl or heterocycloalkyl group,or Z and Z.sub.1, both as defined above, together with the atoms to which they are bonded, form a cycloalkyl or heterocycloalkyl group;provided that no substituent is an oxazine or a pyridine and further provided that at least one of Z, Z.sub.1, R.sub.1, R.sub.2, R.sub.4, or R.sub.5 comprises a heteroaryl group having five ring atoms consisting of three carbon atoms, one oxygen heteroatom, and one nitrogen heteroatom: or a pharmaceutically acceptable prodrug, salt, or solvate thereof;and wherein said compound, pharmaceutically acceptable prodrug, salt, or solvate thereof, has antipicornaviral activity with an EC.sub.50 less than or equal to 100 .mu.M in the HI-HeLa cell culture assay.