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US 5,846,972 AGranted
Bicyclic pyrimidine derivatives and their use as anti-coagulants
AssigneeBerlex Laboratories, Inc.
InventorsBrad O. Buckman, Raju Mohan, Michael M. Morrissey
Life of this patent
Estimating the term…
Abstract
This invention is directed to bicyclic pyrimidine derivatives of the following formulae: ##STR1## where A is --O--and Z.sup.1,Z.sup.2,R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6,R.sup.7 are defined herein. These compounds are useful as anti-coagulants. This invention is also directed to pharmaceutical compositions containing these compounds and methods of using the compounds to treat disease-states characterized by thrombotic activity.
Claims8
A compound selected from the group consisting of the following formulae:
- ##STR8## wherein:
- A is --O--;
- Z.sup.1 and z.sup.2 are independently --O--, --N(R.sup.5)-- or --OCH.sub.2 --;
- R.sup.1 and R.sup.4 are each independently hydrogen, halo, alkyl, --OR.sup.8, --C(O)OR.sup.8, --C(O)N(R.sup.8)R.sup.9, --N(R.sup.8)R.sup.9, --N(R.sup.8)C(O)R.sup.9, or --N(H)S(O).sub.2 R.sup.11 ;
- R.sup.2 is --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.8, --C(NH)N(H)C(O)OR.sup.11, --C(NH)N(H)C(O)R.sup.8, --C(NH)N(H)S(O).sub.2 R.sup.11, or --C(NH)N(H)C(O)N(H)R.sup.8 ;
- R.sup.3 is halo, alkyl, haloalkyl, haloalkoxy, cyano, ureido, guanidino, --OR.sup.8, --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.8, --C(O)N(R.sup.8)R.sup.9, --R.sup.10 --C(O)N(R.sup.8)R.sup.9, --CH(OH)C(O)N(R.sup.8)R.sup.9, --N(R.sup.8)R.sup.9, --R.sup.10 --N(R.sup.8)R.sup.9, --C(O)OR.sup.8, --R.sup.10 --C(O)OR.sup.8, --N(R.sup.8)C(O)R.sup.8, (1,2)-tetrahydropyrimidinyl (optionally substituted by alkyl), (1,2)-imidazolyl (optionally substituted by alkyl), or (1,2)-imidazolinyl (optionally substituted by alkyl);
- each R.sup.5 is hydrogen, alkyl, aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl), or aralkyl (optionally substituted by halo, alkyl, aryl, hydroxy, alkoxy, aralkyl, amino, dialkylamino, monoalkylamino, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl);
- R.sup.6 is hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, --C(O)OR.sup.8, --R.sup.10 --C(O)OR.sup.8, --R.sup.10 --C(O)N(R.sup.8)R.sup.9, --C(O)--R.sup.10 --N(R.sup.8)R.sup.9, --R.sup.10 --C(O)R.sup.8, --R.sup.10 --C(O)N(R.sup.8)N(R.sup.8)R.sup.9, --R.sup.10 --C(R.sup.8)(OR.sup.9)--R.sup.10 --N(R.sup.8)(R.sup.9), --C(R.sup.8)(OR.sup.8)C(O)OR.sup.9, --R.sup.10 --C(R.sup.8)(C(O)OR.sup.9).sub.2, --C(R.sup.8)(N(R.sup.8)R.sup.9)C(O)OR.sup.8, --R.sup.10 --C(R.sup.8)(N(R.sup.8)R.sup.9)C(O)OR.sup.8, --C(R.sup.8)(OR.sup.8)R.sup.9, --R.sup.10 --N(R.sup.8)R.sup.9, --R.sup.10 --N(R.sup.8)C(O)OR.sup.11, --R.sup.10 --N(R.sup.8)C(O)R.sup.9, --R.sup.10 --N(R.sup.8)C(NR.sup.8)R.sup.11, --R.sup.10 --N(R.sup.8)S(O).sub.2 R.sup.11, --R.sup.10 --N(R.sup.8)C(O)N(R.sup.8)R.sup.9, --R.sup.10 --N(R.sup.8)C(NR.sup.8)N(R.sup.8)R.sup.9, --R.sup.10 --N(R.sup.8)C(NR.sup.8)N(R.sup.8)N(R.sup.8)R.sup.9, --R.sup.10 --N(R.sup.8)--R.sup.10 --C(R.sup.8)(N(R.sup.8)R.sup.9)C(O)OR.sup.8, --R.sup.10 --N(R.sup.8)S(O)R.sup.9 R.sup.10 OR.sup.8, --R.sup.10 --ON(R.sup.8)C(NR.sup.8)N(R.sup.8)R.sup.9, --R.sup.10 --OS(O).sub.2 OR.sup.8, --R.sup.10 --P(O)(OR.sup.8)R.sup.9, --R.sup.10 --OP(O)(OR.sup.8).sub.2, --R.sup.10 --P(O)(OR.sup.8).sub.2, --R.sup.10 --SR.sup.8, --R.sup.10 --S--R.sup.10 --C(O)OR.sup.8, R.sup.10 --S--R.sup.10 --N(R.sup.8)R.sup.9, --R.sup.10 --S--R.sup.10 --C(R.sup.8)(N(R.sup.8)R.sup.9)C(O)OR.sup.8, --R.sup.10 --S--R.sup.10 --N(R.sup.8)C(O)OR.sup.8, --R.sup.10 --S--R.sup.10 --N(R.sup.8)C(O)R.sup.8, --R.sup.10 --S--S--R.sup.10 --C(R.sup.8)(N(R.sup.8)R.sup.9)C(O)OR.sup.8, --R.sup.10 --SC(O)N(R.sup.8)R.sup.9, --R.sup.10 --SC(S)N(R.sup.8)R.sup.9, --R.sup.10 --S(O)R.sup.8, --R.sup.10 --S(O).sub.2 R.sup.11, --R.sup.10 --S(O)OR.sup.8, --R.sup.10 --S(O).sub.2 OR.sup.8, --R.sup.10 --S(O).sub.2 N(R.sup.8)R.sup.9, --R.sup.10 --S(O)(NR.sup.8)R.sup.9 ;
- or R.sup.6 is aryl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, haloalkoxy, --OR.sup.8, --SR.sup.8, --N(R.sup.8)R.sup.9, --C(O)OR.sup.8, --C(O)N(R.sup.8)R.sup.9, --S(O).sub.2 OR.sup.8 and --OP(O)(OR.sup.8).sub.2);
- or R.sup.6 is aralkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, haloalkoxy, --OR.sup.8, --SR.sup.8, --N(R.sup.8)R.sup.9, --C(O)OR.sup.8, --C(O)N(R.sup.8)R.sup.9, --S(O).sub.2 OR.sup.8 and --OP(O)(OR.sup.8).sub.2);
- or R.sup.6 is heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, haloalkoxy, aralkyl, --OR.sup.8, --C(O)OR.sup.8, --N(R.sup.8)R.sup.9, --C(O)N(R.sup.8)R.sup.9.sub.1 --S(O).sub.2 OR.sup.8 and --OP(O)(OR.sup.8).sub.2);
- or R.sup.6 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.8, --SR.sup.8, --C(O)OR.sup.8, --N(R.sup.8)R.sup.9, --C(O)N(R.sup.8)R.sup.9), --S(O).sub.2 OR.sup.8 and --OP(O)(OR.sup.8).sub.2);
- or R.sup.6 is adamantyl (optionally substituted by alkyl, halo, haloalkyl, haloalkoxy, --OR.sup.8, --SR.sup.8, --C(O)OR.sup.8, --N(R.sup.8)R.sup.9, --C(O)N(R.sup.8)R.sup.9, --S(O).sub.2 OR.sup.8 and --OP(O)(OR.sup.8).sub.2);
- or R.sup.6 is adamantylalkyl (where the adamantyl radical is optionally substituted by alkyl, halo, haloalkyl, haloalkoxy, --OR.sup.8, --SR.sup.8, --C(O)OR.sup.8, --N(R.sup.8)R.sup.9, --C(O)N(R.sup.8)R.sup.9, --S(O).sub.2 OR.sup.8 and --OP(O)(OR.sup.8).sub.2);
- R.sup.7 is hydrogen, alkyl, cycloalkyl, aralkyl or aryl;
- each RB and R.sup.9 is independently hydrogen, alkyl, aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl), or aralkyl (optionally substituted by halo, alkyl, aryl, hydroxy, alkoxy, aralkyl, amino, dialkylamino, monoalkylamino, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl);
- R.sup.10 is a straight or branched alkylene chain;
- and
- R.sup.11 is alkyl, aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl), or aralkyl (optionally substituted by halo, alkyl, aryl, hydroxy, alkoxy, aralkyl, amino, dialkylamino, monoalkylamino, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl);
- as a single stereoisomer or a mixture thereof;
- or a pharmaceutically acceptable salt thereof.
18 more elements
A pharmaceutical composition useful in treating a human having a disease-state characterized by thrombotic activity, which composition comprises a therapeutically effective amount of a compound selected from the group consisting of the following formulae:
- ##STR9## wherein:
- A is --O--;
- Z.sup.1 and Z.sup.2 are independently --O--, --N(R.sup.5)-- or --OCH.sub.2 --;
- R.sup.1 and R.sup.4 are each independently hydrogen, halo, alkyl, --OR.sup.8, --C(O)OR.sup.8, --C(O)N(R.sup.8)R.sup.9, --N(R.sup.8)R.sup.9, --N(R.sup.8)C(O)R.sup.9, or --N(H)S(O).sub.2 R.sup.11 ;
- R.sup.2 is --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.8, --C(NH)N(H)C(O)OR.sup.11, --C(NH)N(H)C(O)R.sup.8.sub.1 --C(NH)N(H)S(O).sub.2 R.sup.11, or --C(NH)N(H)C(O)N(H)R.sup.8 ;
- R.sup.3 is halo, alkyl, haloalkyl, haloalkoxy, cyano, ureido, guanidino, --OR.sup.8, --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.8, --C(O)N(R.sup.8)R.sup.9, --R.sup.10 --C(O)N(R.sup.8)R.sup.9, --CH(OH)C(O)N(R.sup.8)R.sup.9, --N(R.sup.8)R.sup.9, --R.sup.10 --N(R.sup.8) R.sup.9, --C(O)OR.sup.8, --R.sup.10 --C(O)OR.sup.8, --N(R.sup.8)C(O) R.sup.8, (1,2)-tetrahydropyrimidinyl (optionally substituted by alkyl), (1,2)-imidazolyl (optionally substituted by alkyl), or (1,2)-imidazolinyl (optionally substituted by alkyl);
- each R.sup.5 is hydrogen, alkyl, aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl), or aralkyl (optionally substituted by halo, alkyl, aryl, hydroxy, alkoxy, aralkyl, amino, dialkylamino, monoalkylamino, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl);
- R.sup.6 is hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, --C(O)OR.sup.8, --R.sup.10 --C(O)OR.sup.8, --R.sup.10 --C(O)N(R.sup.8)R.sup.9, --C(O)--R.sup.10 --N(R.sup.8)R.sup.9, --R.sup.10 --C(O)R.sup.8, --R.sup.10 --C(O)N(R.sup.8)N(R.sup.8)R.sup.9, --R.sup.10 --C(R.sup.8)(OR.sup.9)--R.sup.10 --N(R.sup.8)(R.sup.9), --C(R.sup.8)(OR.sup.8)C(O)OR.sup.9, --R.sup.10 --C(R.sup.8)(C(O)OR.sup.9).sub.2, --C(R.sup.8)(N(R.sup.8)R.sup.9)C(O)OR.sup.8, --R.sup.10 --C(R.sup.8)(N(R.sup.8)R.sup.9)C(O)OR.sup.8, --C(R.sup.8)(OR.sup.8)R.sup.9, --R.sup.10 --N(R.sup.8)R.sup.9, --R.sup.10 --N(R.sup.8)C(O)OR.sup.11, --R.sup.10 --N(R.sup.8)C(O)R.sup.9, --R.sup.10 --N(R.sup.8)C(NR.sup.8)R.sup.11, --R.sup.1 --N(R.sup.8)S(O).sub.2 R.sup.11, --R.sup.10 --N(R.sup.8)C(O)N(R.sup.8)R.sup.9, --R.sup.10 --N(R.sup.8)C(NR.sup.8)N(R.sup.8)R.sup.9, --R.sup.10 --N(R.sup.8)C(NR.sup.8)N(R.sup.8)N(R.sup.8)R.sup.9, --R.sup.10 --N(R.sup.8)--R.sup.10 --C(R.sup.8)(N(R.sup.8)R.sup.9)C(O)OR.sup.8, --R.sup.10 --N(R.sup.8)S(O)R.sup.9, --R.sup.10 OR.sup.8, --R.sup.10 --ON(R.sup.8)C(NR.sup.8)N(R.sup.8)R.sup.9, --R.sup.10 --OS(O).sub.2 OR.sup.8, R.sup.10 --P(O)(OR.sup.8)R.sup.9, --R.sup.1 0 --OP(O)(OR.sup.8).sub.2, --R.sup.10 --P(O)(OR.sup.8).sub.2, --R.sup.10 --SR.sup.8, --R.sup.10 --S--R.sup.10 --C(O)OR.sup.8, --R.sup.10 --S--R.sup.10 --N(R.sup.8)R.sup.9, --R.sup.10 --S--R.sup.10 --C(R.sup.8)(N(R.sup.8)R.sup.9)C(O)OR.sup.8, --R.sup.10 --S--R.sup.10 --N(R.sup.8)C(O)OR.sup.8, --R.sup.10 --S--R.sup.10 --N(R.sup.8)C(O)R.sup.8, --R.sup.10 --S--S--R.sup.10 --C(R.sup.8)(N(R.sup.8)R.sup.9)C(O)OR.sup.8, --R.sup.10 --SC(O)N(R.sup.8)R.sup.9, --R.sup.10 --SC(S)N(R.sup.8)R.sup.9, --R.sup.10 --S(O)R.sup.8, --R.sup.10 --S(O).sub.2 R.sup.11, --R.sup.10 --S(O)OR.sup.8, --R.sup.1 --S(O).sub.2 OR.sup.8, --R.sup.10 --S(O).sub.2 N(R.sup.8)R.sup.9, --R.sup.10 --S(O)(NR.sup.8)R.sup.9 ;
- or R.sup.6 is aryl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, haloalkoxy, --OR.sup.8, --SR.sup.8, --N(R.sup.8)R.sup.9, --C(O)OR.sup.8, --C(O)N(R.sup.8)R.sup.9, --S(O).sub.2 OR.sup.8 and --OP(O)(OR.sup.8).sub.2);
- or R.sup.6 is aralkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, haloalkoxy, --OR.sup.8, --SR.sup.8, --N(R.sup.8)R.sup.9, --C(O)OR.sup.8, --C(O)N(R.sup.8)R.sup.9, --S(O).sub.2 OR.sup.8 and --OP(O)(OR.sup.8).sub.2);
- or R.sup.6 is heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, haloalkoxy, aralkyl, --OR.sup.8, --C(O)OR.sup.8, --N(R.sup.8)R.sup.9, --C(O)N(R.sup.8)R.sup.9, --S(O).sub.2 OR.sup.8 and --OP(O)(OR.sup.8).sub.2);
- or R.sup.6 is heterocyclylalkyl (where the heterocyclyl radical is optionally substituted 25 by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, haloalkoxy, aralkyl, --OR.sup.8, --SR.sup.8, --C(O)OR.sup.8, --N(R.sup.8)R.sup.9, --C(O)N(R.sup.8)R.sup.9), --S(O).sub.2 OR.sup.8 and --OP(O)(OR.sup.8)2);
- or R.sup.6 is adamantyl (optionally substituted by alkyl, halo, haloalkyl, haloalkoxy, OR.sup.8.sub.1 --SR.sup.8, --C(O)OR.sup.8, --N(R.sup.8)R.sup.9, --C(O)N(R.sup.8)R.sup.9, --S(O).sub.2 OR.sup.8 and --OP(O)(OR.sup.8)2);
- or R.sup.6 is adamantylalkyl (where the adamantyl radical is optionally substituted by alkyl, halo, haloalkyl, haloalkoxy, --OR.sup.8, --SR.sup.8, --C(O)OR.sup.8, --N(R.sup.8)R.sup.9, --C(O)N(R.sup.8)R.sup.9, --S(O).sub.2 OR.sup.8 and --OP(O)(OR.sup.8)2);
- R.sup.7 is hydrogen, alkyl, cycloalkyl, aralkyl or aryl;
- each R.sup.8 and R.sup.9 is independently hydrogen, alkyl, aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl), or aralkyl (optionally substituted by halo, alkyl, aryl, hydroxy, alkoxy, aralkyl, amino, dialkylamino, monoalkylamino, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl);
- R.sup.10 is a straight or branched alkylene chain;
- and
- R.sup.11 is alkyl, aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl), or aralkyl (optionally substituted by halo, alkyl, aryl, hydroxy, alkoxy, aralkyl, amino, dialkylamino, monoalkylamino, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl);
- as a single stereoisomer or a mixture thereof;
- or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient thereof.
18 more elements
A method of treating a human having a disease-state characterized by thrombotic activity, which method comprises administering to a human in need thereof a therapeutically effective amount of a compound selected from the group consisting of the following formulae:
- ##STR10## wherein:
- A is --O--;
- Z.sup.1 and Z.sup.2 are independently --O--, --N(R.sup.5)-- or --OCH.sub.2 --;
- R.sup.1 and R.sup.4 are each independently hydrogen, halo, alkyl, --OR.sup.8, --C(O)OR.sup.8, --C(O)N(R.sup.8)R.sup.9, --N(R.sup.8)R.sup.9, --N(R.sup.8)C(O)R.sup.9, or --N(H)S(O).sub.2 R.sup.11 ;
- R.sup.2 is --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.8, --C(NH)N(H)C(O)OR.sup.11, --C(NH)N(H)C(O)R.sup.8, --C(NH)N(H)S(O).sub.2 R.sup.11, or --C(NH)N(H)C(O)N(H)R.sup.8 ;
- R.sup.3 is halo, alkyl, haloalkyl, haloalkoxy, cyano, ureido, guanidino, --OR.sup.8, --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.8, --C(O)N(R.sup.8)R.sup.9, --R.sup.10 --C(O)N(R.sup.8)R.sup.9, --CH(OH)C(O)N(R.sup.8)R.sup.9, --N(R.sup.8)R.sup.9, --R.sup.10 --N(R.sup.8)R.sup.9, --C(O)OR.sup.8, --R.sup.10 --C(O)OR.sup.8, --N(R.sup.8)C(O)R.sup.8.sub.1 (1,2)-tetrahydropyrimidinyl (optionally substituted by alkyl), (1,2)-imidazolyl (optionally substituted by alkyl), or (1,2)-imidazolinyl (optionally substituted by alkyl);
- each R.sup.5 is hydrogen, alkyl, aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl), or aralkyl (optionally substituted by halo, alkyl, aryl, hydroxy, alkoxy, aralkyl, amino, dialkylamino, monoalkylamino, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl);
- R.sup.6 is hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, --C(O)OR.sup.8, --R.sup.10 --C(O)OR.sup.8, --R.sup.10 --C(O)N(R.sup.8)R.sup.9, --C(O)--R.sup.10 --N(R.sup.8)R.sup.9, --R.sup.10 --C(O)R.sup.8, --R.sup.10 --C(O)N(R.sup.8)N(R.sup.8)R.sup.9, --R.sup.10 --C(R.sup.8)(OR.sup.9)--R.sup.10 --N(R.sup.8)(R.sup.9), --C(R.sup.8)(OR.sup.8)C(O)OR.sup.9, --R.sup.10 --C(R.sup.8)(C(O)OR.sup.9).sub.2, --C(R.sup.8)(N(R.sup.8)R.sup.9)C(O)OR.sup.8, --R.sup.10 --C(R.sup.8)(N(R.sup.8)R.sup.9)C(O)OR.sup.8, --C(R.sup.8)(OR.sup.8)R.sup.9, --R.sup.10 --N(R.sup.8)R.sup.9, --R.sup.10 --N(R.sup.8)C(O)OR.sup.11 --R.sup.10 --N(R.sup.8)C(O)R.sup.9, --R.sup.10 --N(R.sup.8)C(NR.sup.8)R.sup.11, --R.sup.10 --N(R.sup.8)S(O).sub.2 R.sup.1 --R.sup.10 --N(R.sup.8)C(O)N(R.sup.8)R.sup.9, --R.sup.10 --N(R.sup.8)C(NR.sup.8)N(R.sup.8)R.sup.9 --R.sup.10 N(R.sup.8)C(NR.sup.8)N(R.sup.8)N(R.sup.8)R.sup.9 --R.sup.10 --N(R.sup.8)--R.sup.10 --C(R.sup.8)(N(R.sup.8)R.sup.9)C(O)OR.sup.8, --R.sup.10 --N(R.sup.8)S(O)R.sup.9, --R.sup.10 OR.sup.8, --R.sup.10 --ON(R.sup.8)C(NR.sup.8)N(R.sup.8)R.sup.9, --R.sup.10 --OS(O).sub.2 OR.sup.8, --R.sup.10 --P(O)(OR.sup.8)R.sup.9, --R.sup.10 --OP(O)(OR.sup.8).sub.2, --R.sup.10 --P(O)(OR.sup.8).sub.2, --R.sup.10 --SR.sup.8 --R.sup.10 --S--R.sup.10 --C(O)OR.sup.8, --R.sup.10 --S--R.sup.10 --NR.sup.8) R.sup.9, --R.sup.10 --S--R.sup.10 --C(R.sup.8)(N(R.sup.8)R.sup.9)C(O)OR.sup.8, --R.sup.10 --S--R.sup.10 --N(R.sup.8)C(O)OR.sup.8, --R.sup.10 --S--R.sup.10 --N(R.sup.8)C(O)R.sup.8, --R.sup.10 --S--S--R.sup.10 --C(R.sup.8)(N(R.sup.8)R.sup.9)C(O)OR.sup.8, --R.sup.10 --SC(O)N(R.sup.8)R.sup.9, --R.sup.10 --SC(S)N(R.sup.8)R.sup.9, --R.sup.10 --S(O)R.sup.8, --R.sup.10 --S(O).sub.2 R.sup.11, --R.sup.10 --S(O)OR.sup.8, --R.sup.10 --S(O).sub.2 OR.sup.8, --R.sup.10 --S(O).sub.2 N(R.sup.8)R.sup.9, --R.sup.10 --S(O)(NR.sup.8)R.sup.9 ;
- or R.sup.6 is aryl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, haloalkoxy, --OR.sup.8, --SR.sup.8, --N(R.sup.8)R.sup.9, --C(O)OR.sup.8, --C(O)N(R.sup.8)R.sup.9, --S(O).sub.2 OR.sup.8 and --OP(O)(OR.sup.8).sub.2);
- or R.sup.6 is aralkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, haloalkoxy, --OR.sup.8, --SR.sup.8, --N(R.sup.8)R.sup.9, --C(O)OR.sup.8, --C(O)N(R.sup.8)R.sup.9, --S(O).sub.2 OR.sup.8 and OP(O)(OR.sup.8).sub.2);
- or R.sup.6 is heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, haloalkoxy, aralkyl, --OR.sup.8, --C(O)OR.sup.8, --N(R.sup.8)R.sup.9, --C(O)N(R.sup.8)R.sup.9, --S(O).sub.2 OR.sup.8 and --OP(O)(OR.sup.8).sub.2);
- or R.sup.6 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.8, --SR.sup.8, --C(O)OR.sup.8, --N(R.sup.8)R.sup.9, --C(O)N(R.sup.8)R.sup.9), --S(O).sub.2 OR.sup.8 and --OP(O)(OR.sup.8).sub.2);
- or R.sup.6 is adamantyl (optionally substituted by alkyl, halo, haloalkyl, haloalkoxy, --OR.sup.8, --SR.sup.8, --C(O)OR.sup.8, --N(R.sup.8)R.sup.9, --C(O)N(R.sup.8)R.sup.9, --S(O).sub.2 OR.sup.8 and --OP(O)(OR.sup.8).sub.2);
- or R.sup.6 is adamantylalkyl (where the adamantyl radical is optionally substituted by alkyl, halo, haloalkyl, haloalkoxy, --OR.sup.8, --SR.sup.8, --C(O)OR.sup.8, --N(R.sup.8)R.sup.9, --C(O)N(R.sup.8)R.sup.9, --S(O).sub.2 OR.sup.8 and --OP(O)(OR.sup.8).sub.2);
- R.sup.7 is hydrogen, alkyl, cycloalkyl, aralkyl or aryl;
- each R.sup.8 and R.sup.9 is independently hydrogen, alkyl, aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl), or aralkyl (optionally substituted by halo, alkyl, aryl, hydroxy, alkoxy, aralkyl, amino, dialkylamino, monoalkylamino, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl);
- R.sup.10 is a straight or branched alkylene chain;
- and
- R.sup.11 is alkyl, aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl), or aralkyl (optionally substituted by halo, alkyl, aryl, hydroxy, alkoxy, aralkyl, amino, dialkylamino, monoalkylamino, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl);
- as a single stereoisomer or a mixture thereof;
- or as a pharmaceutically acceptable salt thereof.
18 more elements
Dependencies are inferred from the claim text.