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US 5,334,596 AGranted
Fibrinogen receptor antagonists
AssigneeMerck & Co., Inc.
InventorsGeorge D. Hartman, Wasyl Halczenko, John D. Prugh
Life of this patent
Estimating the term…
Abstract
Fibrinogen receptor antagonists having the formula ##STR1## for example ##STR2##
Claims18
A compound having the formula ##STR123## and pharmaceutically acceptable salts, wherein X is a 6-membered non-aromatic ring with 0 to 1 N atoms;
- Y is (CH.sub.2).sub.m, where m is an integer from 0-6;
- Z is (CH.sub.2).sub.2 ;
- D is O or S;
- E is C;
- A is ##STR124## wherein n is 1 or 2;
- B is chosen from ##STR125## where R.sup.3 is H, C.sub.1-10 alkyl or aryl C.sub.0-8 alkyl;
- R.sup.5 is H;
- R.sup.6 is independently chosen from substituted or unsubstituted:
- hydrogen, fluorine,
- C.sub.1-8 alkyl, hydroxyl, hydroxy C.sub.1-6 alkyl, carboxy C.sub.0-6 alkyl,
- C.sub.1-6 alkyloxy, C.sub.1-6 alkylcarbonyl, aryl C.sub.0-6 alkylcarbonyl,
- C.sub.1-6 alkylcarbonyloxy, aryl C.sub.0-6 alkylcarbonyloxy, C.sub.1-6 alkylaminocarbonyloxy, arylC.sub.0-6 alkylaminocarbonyloxy,
- C.sub.3-8 cycloalkyl,
- aryl C.sub.0-6 alkyl,
- C.sub.0-6 alkylamino C.sub.0-6 alkyl,
- C.sub.0-6 dialkylamino C.sub.0-6 alkyl,
- C.sub.1-8 alkylsulfonylamino C.sub.0-6 alkyl,
- aryl C.sub.0-6 alkylsulfonylamino C.sub.0-6 alkyl,
- C.sub.1-8 alkyloxycarbonylamino C.sub.0-8 alkyl,
- aryl C.sub.0-8 alkyloxycarbonylamino C.sub.0-8 alkyl,
- C.sub.1-8 alkylcarbonylamino C.sub.0-6 alkyl,
- aryl C.sub.0-6 alkylcarbonylamino C.sub.0-6 alkyl,
- C.sub.0-8 alkylaminocarbonylamino C.sub.0-6 alkyl,
- aryl C.sub.0-8 alkylaminocarbonylamino C.sub.0-6 alkyl,
- C.sub.0-8 alkylaminosulfonylamino C.sub.0-6 alkyl,
- aryl C.sub.0-8 alkylaminosulfonylamino C.sub.0-6 alkyl,
- C.sub.1-6 alkylsulfonyl C.sub.0-6 alkyl,
- aryl C.sub.0-6 alkylsulfonyl C.sub.0-6 alkyl,
- C.sub.1-6 alkylcarbonyl C.sub.0-6 alkyl,
- aryl C.sub.0-6 alkylcarbonyl C.sub.0-6 alkyl,
- C.sub.1-6 alkylthiocarbonylamino C.sub.0-6 alkyl, and
- aryl C.sub.0-6 alkylthiocarbonylamino C.sub.0-6 alkyl,
- wherein groups may be unsubstituted or substituted with one or more substituents selected from hydrogen,
- C.sub.1-10 alkyl,
- aryl C.sub.0-8 alkyl,
- oxo,
- thio,
- amino C.sub.0-8 alkyl, C.sub.1-3 acylamino C.sub.0-8 alkyl,
- C.sub.0-6 alkylamino C.sub.0-8 alkyl,
- C.sub.1-6 dialkylamino C.sub.0-8 alkyl,
- C.sub.1-4 alkoxy C.sub.0-6 alkyl,
- carboxy C.sub.0-6 alkyl, C.sub.1-3 alkoxycarbonyl C.sub.0-6 alkyl,
- carboxy C.sub.0-6 alkyloxy, and
- hydroxy C.sub.0-6 alkyl,
- and ##STR126## where G is an L- or D-amino acid, or its corresponding ester, connected through an amide linkage;
- R.sup.7 is H or CH.sub.3 ;
- R.sup.8 is H or CH.sub.3 ;
- R.sup.9 is H;
- R.sup.10 is independently chosen from substituted or unsubstituted:
- hydrogen, fluorine,
- C.sub.1-8 alkyl, hydroxyl, hydroxy C.sub.1-6 alkyl, carboxy C.sub.0-6 alkyl,
- C.sub.1-6 alkyloxy, C.sub.1-6 alkylcarbonyl, aryl C.sub.0-6 alkylcarbonyl,
- C.sub.1-6 alkylcarbonyloxy, aryl C.sub.0-6 alkylcarbonyloxy, C.sub.1-6 alkylaminocarbonyloxy, arylC.sub.0-6 alkylaminocarbonyloxy,
- C.sub.3-8 cycloalkyl,
- aryl C.sub.0-6 alkyl,
- C.sub.0-6 alkylamino C.sub.0-6 alkyl,
- C.sub.0-6 dialkylamino C.sub.0-6 alkyl,
- C.sub.1-8 alkylsulfonylamino C.sub.0-6 alkyl,
- aryl C.sub.0-6 alkylsulfonylamino C.sub.0-6 alkyl,
- C.sub.1-8 alkyloxycarbonylamino C.sub.0-8 alkyl,
- aryl C.sub.0-8 alkyloxycarbonylamino C.sub.0-8 alkyl,
- C.sub.1-8 alkylcarbonylamino C.sub.0-6 alkyl,
- aryl C.sub.0-6 alkylcarbonylamino C.sub.0-6 alkyl,
- C.sub.0-8 alkylaminocarbonylamino C.sub.0-6 alkyl,
- aryl C.sub.0-8 alkylaminocarbonylamino C.sub.0-6 alkyl,
- C.sub.0-8 alkylaminosulfonylamino C.sub.0-6 alkyl,
- aryl C.sub.0-8 alkylaminosulfonylamino C.sub.0-6 alkyl,
- C.sub.1-6 alkylsulfonyl C.sub.0-6 alkyl,
- aryl C.sub.0-6 alkylsulfonyl C.sub.0-6 alkyl,
- C.sub.1-6 alkylcarbonyl C.sub.0-6 alkyl,
- aryl C.sub.0-6 alkylcarbonyl C.sub.0-6 alkyl,
- C.sub.1-6 alkylthiocarbonylamino C.sub.0-6 alkyl, and
- aryl C.sub.0-6 alkylthiocarbonylamino C.sub.0-6 alkyl,
- wherein groups may be unsubstituted or substituted with one or more substituents selected from hydrogen,
- C.sub.1-10 alkyl,
- aryl C.sub.0-8 alkyl,
- oxo,
- thio,
- amino C.sub.0-8 alkyl, C.sub.1-3 acylamino C.sub.0-8 alkyl,
- C.sub.0-6 alkylamino C.sub.0-8 alkyl,
- C.sub.1-6 dialkylamino C.sub.0-8 alkyl,
- C.sub.1-4 alkoxy C.sub.0-6 alkyl,
- carboxy C.sub.0-6 alkyl, C.sub.1-3 alkoxycarbonyl C.sub.0-6 alkyl,
- carboxy C.sub.0-6 alkyloxy, and
- hydroxy C.sub.0-6 alkyl,
- and ##STR127## where G is an L- or D-amino acid, or its corresponding ester, connected through an amide linkage;
- and
- R.sup.11 is chosen from
- hydroxy,
- C.sub.1-8 alkyloxy,
- aryl C.sub.0-6 alkyloxy,
- C.sub.1-8 alkylcarbonyloxy C.sub.1-4 alkyloxy, and
- aryl C.sub.1-8 alkylcarbonyloxy C.sub.1-4 alkyloxy, or
- an L- or D-amino acid joined by an amide linkage and wherein the carboxylic acid moiety of said amino acid is as the free acid or is esterified by C.sub.1-6 alkyl.
91 more elements
Dependencies are inferred from the claim text.