Patent ID: 6221886
Filing Date: 2001-04-24
Classification: A61P,C07D

Abstract:
A compound selected from the group consisting of the following formulae: ##STR6##wherein:Z.sup.1 is --O--, --N(R.sup.12)--, --CH.sub.2 O-- or --S(O).sub.n (where n is 0 to 2);Z.sup.2 is --O--, -N(R.sup.12)--, --OCH.sub.2 --or -S(O), (where n is 0 to 2);R.sup.1 and R.sup.4 are each independently hydrogen, halo, alkyl, nitro, --OR.sup.12, --C(O)OR.sup.12, --C(O)N(R.sup.12)R.sup.13, --N(R.sup.12)R.sup.13, --N(R.sup.12)C(O)R.sup.12, or --N(H)S(O).sub.2 R.sup.15 ;R.sup.2 is --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.12, --C(NH)N(H)C(O)OR.sup.15, --C(NH)N(H)C(O)R.sup.12, --C(NH)N(H)S(O).sub.2 R.sup.15, or --C(NH)N(H)C(O)N(H)R.sup.12 ;R.sup.3 is hydrogen, halo, alkyl, haloalkyl, nitro, ureido, guanidino, --OR.sup.12, --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.2, --C(O)N(R.sup.12)R.sup.13, --R.sup.14 --C(O)N(R.sup.12)R.sup.13, --CH(OH)C(O)N(R.sup.12)R.sup.13, --N(R.sup.12)R.sup.13, --R.sup.14 --N(R.sup.12)R.sup.13, --C(O)OR.sup.12, --R.sup.14 --C(O)OR.sup.2, --N(R.sup.12)C(O)R.sup.12, (1,2)-tetrahydropyrimidinyl (optionally substituted by alkyl), (1,2)-imidazolyl (optionally substituted by alkyl), or (1,2)-imidazolinyl (optionally substituted by alkyl);R.sup.5 and R.sup.6 are independently hydrogen, halo, alkyl, haloalkyl, nitro, --N(R.sup.12)R.sup.13, --C(O)OR.sup.12, --C(O)N(R.sup.12)R.sup.13, --C(O)N(R.sup.12)CH.sub.2 C(O)N(R.sup.12)R.sup.13, --N(R.sup.12)C(O)N(R.sup.12)R.sup.13, --N(R.sup.12)C(O)R.sup.13, --N(R.sup.12)S(O).sub.2 R.sup.15, or --N(R.sup.12)C(O)N(R.sup.12)--CH.sub.2 C(O)N(R.sup.12)R.sup.13 ;R.sup.7 is S(O).sub.n --(C(R.sup.9)(R.sup.10).sub.m --R.sup.11 (where n is 0 to 2 and m is 1 to 4) or --S(O).sub.n --(C(R.sup.12)(R.sup.13)).sub.p --R.sup.16 (where n is 0 to 2 and p is 0 to 4), with the proviso that the carbon atom bonded to the sulfur atom in either of these radicals can not be bonded to another hetero atom;each R.sup.9 is independently hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, --C(O)OR.sup.2, --R.sup.14 --C(O)OR.sup.12 --C(O)N(R.sup.12)R.sup.3 --R.sup.14 --C(O)N(R.sup.12)R.sup.13 --C(O)--R.sup.14 --N(R.sup.12)R.sup.13, --R.sup.14 C(O)--R.sup.14 --N(R.sup.12)R.sup.13, --C(O)R.sup.12, --R.sup.14 --C(O)R.sup.12, --C(O)N(R.sup.12)N(R.sup.12)R.sup.13, --R.sup.14 --C(O)N(R.sup.12)N(R.sup.12)R.sup.13, --C(R.sup.12)(OR.sup.12)--R.sup.14 --N(R.sup.12)(R.sup.13), --R.sup.14 --C(R.sup.12)(OR.sup.12)--R.sup.14 --N(R.sup.12)(R.sup.13), --C(R.sup.12)(OR.sup.12)C(O)OR.sup.12, --R.sup.14 C(R.sup.12)(OR.sup.12)C(O)OR.sup.12, --C(R.sup.12)(C(O)NR.sup.12).sub.2, --R.sup.14 --C(R.sup.12)(C(O)OR.sup.12).sub.2, --C(R.sup.12)(N(R.sup.12)R.sup.13)C(O)OR.sup.12, --R.sup.14 --C(R.sup.12)(N(R.sup.12)R.sup.13)C(O)OR.sup.12, --C(R.sup.12)(OR.sup.12)R.sup.13, --R.sup.14 --C(R.sup.12)(OR.sup.12)R.sup.13, --N(R.sup.12)R.sup.13, --R.sup.14 --N(R.sup.12)R.sup.13, --N(R.sup.12)C(O)OR.sup.15, --R.sup.14 --N(R.sup.12)C(O)OR.sup.15, --N(R.sup.12)C(O)R.sup.13, --R.sup.14 N(R.sup.12)C(O)R.sup.13, --N(R.sup.12)C(NR.sup.12)R.sup.15, --R.sup.14 --N(R.sup.13 C(NR.sup.12)R.sup.15, --N(R.sup.12)S(O).sub.2 R.sup.15, --R.sup.14 --N(R.sup.12)S(O).sub.2 R.sup.15, --N(R.sup.12)C(O)N(R.sup.12)R.sup.13, --R.sup.14 N(R.sup.12)C(O)N(R.sup.12)R.sup.13, --N(R.sup.12)C(NR.sup.12)N(R.sup.12)R.sup.13, --R.sup.14 --N(R.sup.12)C(NR.sup.12)N(R.sup.12)R.sup.13, --N(R.sup.12)C(NR.sup.12)N(R.sup.12)N(R.sup.12)R.sup.13, --R.sup.14 --N(R.sup.12)C(NR.sup.12)N(R.sup.12)N(R.sup.12)R.sup.13, --N(R.sup.12)--R.sup.14 --C(R.sup.12)(N(R.sup.12)R.sup.13)C(O)OR.sup.12, --R.sup.14 --N(R.sup.12)--R.sup.14 --C(R.sup.12)(N(R.sup.12)R.sup.13)C(O)OR.sup.12, --N(R.sup.12)S(O)R.sup.13, --R.sup.14 --N(R.sup.12)S(O)R.sup.13, --OR.sup.12, --R.sup.14 --OR.sup.12, --O--N(R.sup.12)C(NR.sup.12)N(R.sup.12)R.sup.13, --R.sup.14 --O--N(R.sup.12)C(NR.sup.12)N(R.sup.12)R.sup.13, --OS(O).sub.2 OR.sup.12, --R.sup.14 --OS(O).sub.2 OR.sup.12, --P(O)(OR.sup.12)R.sup.13, --R.sup.14 --P(O)(OR.sup.12)R.sup.13, --OP(O)(OR.sup.12).sub.2, --R.sup.14 --OP(O)(OR.sup.12).sub.2, --P(O)(OR.sup.12).sub.2, --R.sup.14 --P(O)(OR.sup.12).sub.2, --SR.sup.12, --R.sup.14 --SR.sup.12, --C(SR.sup.12)(R.sup.12)C(O)OR.sup.12, --R.sup.14 --C(SR.sup.12)(R.sup.12)C(O)OR.sup.12, --S(O).sub.n --R.sup.14 --C(O)OR.sup.12 (where n is 0 to 2), --R.sup.14 --S(O).sub.n --R.sup.14 --C(O)OR.sup.12 (where n is 0 to 2), --S(O).sub.n --R.sup.14 --N(R.sup.12)R.sup.13 (where n is 0 to 2), --R.sup.14 --S(O).sub.n --R.sup.14 --N(R.sup.12)R.sup.13 (where n is 0 to 2), --S(O).sub.n --R.sup.14 --C(R.sup.12)(N(R.sup.12)R.sup.13)C(O)OR.sup.12 (where n is 0 to 2), --R.sup.14 --S(O).sub.n --R.sup.14 --C(R.sup.12)(N(R.sup.12)R.sup.13)C(O)OR.sup.12 (where n is 0 to 2), --S(O).sub.n --R.sup.14 --N(R.sup.12)C(O)OR.sup.12 (where n is 0 to 2), --R.sup.14 --S(O).sub.n --R.sup.14 --N(R.sup.12)C(O)OR.sup.12 (where n is 0 to 2), --S(O).sub.n --R.sup.14 --N(R.sup.12)C(O)R.sup.12 (where n is 0 to 2), --R.sup.14 --S(O).sub.n --R.sup.14 --N(R.sup.12)C(O)R.sup.12 (where n is 0 to 2), --S--SR.sup.14 --C(R.sup.12)(N(R.sup.12)R.sup.13)C(O)OR.sup.12, --R.sup.14 --S--S--R.sup.14 --C(R.sup.12)(N(R.sup.12)R.sup.13)C(O)OR.sup.12, --SC(O)N(R.sup.12)R.sup.13, --R.sup.14 --SC(O)N(R.sup.12)R.sup.13, --SC(S)N(R.sup.12)R.sup.13, --R.sup.14 --SC(S)N(R.sup.12)R.sup.13, --S(O).sub.q R.sup.15 (where q is 1 or 2), --R.sup.14 --S(O).sub.q R.sup.15, (where q is 1 or 2), --R.sup.14 --S(O)OR.sup.12, --R.sup.14 --S(O).sub.2 OR.sup.12, --R.sup.14 --S(O).sub.2 N(R.sup.12)R.sup.13, or --R.sup.14 --S(O)(NR.sup.12)R.sup.13 ;or each R.sup.9 is aryl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, haloalkoxy, nitro, --OR.sup.12, CR.sup.12, --S(O).sub.q R.sup.15 (where q is 1 or 2), --N(R.sup.12)R.sup.13, --C(O)OR.sup.12, --C(O)N(R.sup.12)R.sup.13, --S(O).sub.2 OR.sup.12 and --OP(O)(OR.sup.12).sub.2);or each R.sup.9 is aralkyl (where the aryl radical is optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, haloalkoxy, nitro, --OR.sup.12, --SR.sup.12, --S(O).sub.q R.sup.15 (where q is 1 or 2), --N(R.sup.12)R.sup.13, --C(O)OR.sup.12, --C(O)N(R.sup.12)R.sup.13, --S(O).sub.2 OR.sup.12 and --OP(O)(OR.sup.12).sub.2);or each R.sup.9 is aralkenyl (where the aryl radical is optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, haloalkoxy, nitro, --OR.sup.12, --SR.sup.12, --S(O).sub.q R.sup.15 (where q is 1 or 2), --N(R.sup.12)R.sup.13, --C(O)OR.sup.12, --C(O)N(R.sup.12)R.sup.13, --S(O).sub.2 OR.sup.12 and --OP(O)(OR.sup.12).sub.2);or each R.sup.9 is heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, haloalkoxy, nitro, aralkyl, --OR.sup.12, CR.sup.12, --S(O).sub.q R.sup.15 (where q is 1 or 2), --C(O)OR.sup.12, --N(R.sup.12)R.sup.13, --C(O)N(R.sup.12)R.sup.13, --S(O).sub.2 OR.sup.12 and --OP(O)(OR.sup.12).sub.2);or each R.sup.9 is heterocyclylalkyl (where the heterocyclyl radical is optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, haloalkoxy, aralkyl, --OR.sup.12, --SR.sup.12, --S(O).sub.q R.sup.15 (where q is 1 or 2), --C(O)OR.sup.12, --N(R.sup.12)R.sup.13, --C(O)N(R.sup.12)R.sup.13), --S(O).sub.2 OR.sup.12 and --OP(O)(OR.sup.12).sub.2);or each R.sup.9 is heterocyclylalkenyl (where the heterocyclyl radical is optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, haloalkoxy, aralkyl, --OR.sup.12, --SR.sup.12, --S(O).sub.q R.sup.15 (where q is 1 or 2), --C(O)OR.sup.12, --N(R.sup.12)R.sup.13, --C(O)N(R.sup.12)R.sup.13), --S(O).sub.2 OR.sup.12 and --OP(O)(OR.sup.12).sub.2);or each R.sup.9 is adamantyl (optionally substituted by alkyl, halo, haloalkyl, haloalkoxy, --OR.sup.2, --SR.sup.12, --S(O).sub.q R.sup.15 (where q is 1 or 2), --C(O)OR.sup.12, --N(R.sup.12)R.sup.13, --C(O)N(R.sup.12)R.sup.13, --S(O).sub.2 OR.sup.12 and --OP(O)(OR.sup.12).sub.2);or each R.sup.9 is adamantylalkyl (where the adamantyl radical is optionally substituted by alkyl, halo, haloalkyl, haloalkoxy, --OR.sup.12, --CR.sup.12, --S(O).sub.q R.sup.15 (where q is 1 or 2), --C(O)OR.sup.12, --N(R.sup.12)R.sup.13, --C(O)N(R.sup.12)R.sup.13, --S(O).sub.2 OR.sup.12 and --OP(O)(OR.sup.12).sub.2);each R.sup.10 is independently hydrogen, alkyl, cycloalkyl, aryl or aralkyl;or R.sup.9 and R.sup.10 together form a mono-, bi- or tricylic carbocyclic ring system containing from 3 to 15 carbon atoms which may be partially or fully saturated or aromatic, wherein the carbon atoms may be optionally oxidized and wherein the carbocyclic ring system is optionally substituted by alkyl, aryl, aralkyl, alkoxy, aryloxy, aralkoxy, halo, haloalkyl, haloalkoxy, hydroxy, --N(R.sup.12)R.sup.13, --C(O)OR.sup.12, or --C(O)N(R.sup.12)R.sup.13 ;R.sup.11 is --C(O)OR.sup.12 or --C(O)N(R.sup.12)R.sup.13 ;each R.sup.12 and R.sup.13 is independently hydrogen, alkyl, aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl), or aralkyl (optionally substituted by halo, alkyl, aryl, hydroxy, alkoxy, aralkyl, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl);R.sup.14 is an alkylene or alkylidene chain;R.sup.15 is alkyl, aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl), or aralkyl (optionally substituted by halo, alkyl, aryl, hydroxy, alkoxy, aralkyl, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl); andR.sup.16 is a mono-, bi- or tricyclic heterocyclic ring system containing from 3 to 15 ring members including carbon and 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur atoms, wherein the carbon, nitrogen and sulfur atoms may be optionally oxidized and the nitrogen atoms may be optionally quarternized, and wherein the heterocyclic ring system may be partially or fully saturated or aromatic and is substituted by --(C(R.sup.12)(R.sup.13)).sub.p --R.sup.11 (where p is 0 to 4 and R.sup.11 is defined above), and is optionally substituted by alkyl, aryl, aralkyl, alkoxy, aryloxy, aralkoxy, halo, haloalkyl, haloalkoxy, hydroxy, --N(R.sup.12)R.sup.13, --C(O)OR.sup.12, or --C(O)N(R.sup.12)R.sup.13 ;as a single stereoisomer or a mixture thereof; or a pharmaceutically acceptable salt thereof.