Claims
- 1. A compound having the formula
- X--Y--Z--A--B
- or a pharmaceutically acceptable salt thereof, wherein
- X is piperazine, piperidine, pyridine or phenyl;
- Y is piperazine, piperidine, pyridine or phenyl; ##STR88## Z represents a bond; R.sup.4 is selected from the group consisting of
- hydrogen,
- halogen,
- C.sub.1-10 alkyl,
- C.sub.3-8 cycloalkyl,
- aryl,
- aryl C.sub.1-8 alkyl,
- amino,
- amino C.sub.1-8 alkyl,
- C.sub.1-3 acylamino,
- C.sub.1-3 acylamino C.sub.1-8 alkyl,
- C.sub.1-6 alkylamino,
- C.sub.1-6 alkylamino C.sub.1-8 alkyl,
- C.sub.1-6 dialkylamino,
- C.sub.1-6 dialkylamino C.sub.1-8 alkyl,
- C.sub.1-4 alkoxy,
- C.sub.1-4 alkoxy C.sub.1-6 alkyl,
- carboxy,
- carboxy .sub.1-6 alkyl,
- C.sub.1-3 alkoxycarbonyl,
- C.sub.1-3 alkoxycarbonyl C.sub.1-6 alkyl,
- carboxy C.sub.1-6 alkyloxy,
- hydroxy, and
- hydroxy C.sub.1-6 alkyl;
- A is
- a 5 or 6 membered aromatic ring, having 0, 1, 2 or 3 heteroatoms selected from N, O, and S, and either unsubstituted or monosubstituted on carbon and nitrogen atoms with R.sup.5, disubstituted on carbon and nitrogen atoms with R.sup.5 and R.sup.6, or trisubstituted on carbon and nitrogen with R.sup.5, R.sup.6, and R.sup.9, where R.sup.5, R.sup.6, and R.sup.9 are independently selected from the group consisting of
- hydrogen,
- halogen,
- C.sub.1-10 alkyl,
- C.sub.3-8 cycloalkyl,
- aryl,
- aryl C.sub.1-8 alkyl,
- amino,
- amino C.sub.1-8 alkyl,
- C.sub.1-3 acylamino,
- C.sub.1-3 acylamino C.sub.1-8 alkyl,
- C.sub.1-6 alkylamino,
- C.sub.1-6 alkylamino C.sub.1-8 alkyl,
- C.sub.1-6 dialkylamino,
- C.sub.1-6 dialkylamino C.sub.1-8 alkyl,
- C.sub.1-6 alkoxy,
- C.sub.1-6 alkoxy C.sub.1-6 alkyl,
- aryl C.sub.1-6 alkyloxy,
- aryl C.sub.1-6 alkyloxy C.sub.1-6 alkyl,
- carboxy C.sub.1-6 alkyl,
- C.sub.1-3 alkoxycarbonyl,
- C.sub.1-3 alkoxycarbonyl C.sub.1-6 alkyl,
- carboxy,
- carboxy C.sub.1-6 alkyloxy,
- hydroxy, and
- hydroxy C.sub.1-6 alkyl, or
- a 9 or 10 membered fused aromatic ring, having 0, 1, 2 or 3 heteroatoms selected from N, O, and S, and either unsubstituted or monosubstituted on carbon and nitrogen atoms with R.sup.5, disubstituted on carbon and nitrogen atoms with R.sup.5 and R.sup.6, or trisubstituted on carbon and nitrogen with R.sup.5, R.sup.6, and R.sup.9, where R.sup.5, R.sup.6, and R.sup.9 are independently selected from the group consisting of
- hydrogen,
- halogen,
- C.sub.1-10 alkyl,
- C.sub.3-8 cycloalkyl,
- aryl,
- aryl C.sub.1-8 alkyl,
- amino,
- amino C.sub.1-8 alkyl,
- C.sub.1-3 acylamino,
- C.sub.1-3 acylamino C.sub.1-8 alkyl,
- C.sub.1-6 alkylamino,
- C.sub.1-6 alkylamino C.sub.1-8 alkyl,
- C.sub.1-6 dialkylamino,
- C.sub.1-6 dialkylamino C.sub.1-8 alkyl,
- C.sub.1-6 alkoxy,
- C.sub.1-6 alkoxy C.sub.1-6 alkyl,
- aryl C.sub.1-6 alkyloxy,
- aryl C.sub.1-6 alkyloxy C.sub.1-6 alkyl,
- carboxy C.sub.1-6 alkyl,
- C.sub.1-3 alkoxycarbonyl,
- C.sub.1-3 alkoxycarbonyl C.sub.1-6 alkyl,
- carboxy,
- carboxy C.sub.1-6 alkyloxy,
- hydroxy, and
- hydroxy C.sub.1-6 alkyl;
- B is ##STR89## wherein n is 1 or 2, and m is 0, 1, or 2; R.sup.7 is selected from the group consisting of
- hydrogen,
- halogen,
- C.sub.1-10 alkyl,
- C.sub.3-8 cycloalkyl,
- aryl,
- aryl C.sub.1-8 alkyl,
- amino,
- amino C.sub.1-8 alkyl,
- C.sub.1-3 acylamino,
- C.sub.1-3 acylamino C.sub.1-8 alkyl,
- C.sub.1-6 alkylamino,
- C.sub.1-6 alkylamino C.sub.1-8 alkyl,
- C.sub.1-6 dialkylamino,
- C.sub.1-6 dialkylamino C.sub.1-8 alkyl,
- C.sub.1-6 alkoxy,
- C.sub.1-6 alkoxy C.sub.1-6 alkyl,
- aryl C.sub.1-6 alkyloxy,
- aryl C.sub.1-6 alkyloxy C.sub.1-6 alkyl,
- carboxy,
- carboxy C.sub.1-6 alkyl,
- C.sub.1-3 alkoxycarbonyl,
- C.sub.1-3 alkoxycarbonyl C.sub.1-6 alkyl,
- carboxy,
- carboxy C.sub.1-6 alkyloxy,
- hydroxy, and
- hydroxy C.sub.1-6 alkyl;
- R.sup.8 is selected from the group consisting of
- hydrogen,
- --C(O)--C.sub.1-8 alkyl,
- --C(O)--C.sub.3-8 cycloalkyl,
- --C(O)-aryl, and
- --C(O)--C.sub.1-3 alkylaryl.
- 2. A compound of claim 1 having the formula ##STR90## or a pharmaceutically acceptable salt thereof, wherein A is a 6-membered aromatic ring unsubstituted, mono-substituted with a moiety selected from the group consisting of halogen, C.sub.1-3 alkyl, and C.sub.1-3 alkylsulfonylamino, disubstituted with one or more moieties, same or different, selected from the group consisting of halogen, C.sub.1-3 alkyl, and C.sub.1-3 alkylsulfonylamino or trisubstituted with one or more moieties, same or different, selected from the group consisting of halogen, C.sub.1-3 alkyl, and C.sub.1-3 alkylsulfonylamino.
- 3. A compound of claim 2 having the formula ##STR91## or a pharmaceutically acceptable salt thereof, wherein A is a 6-membered aromatic ring unsubstituted, mono-substituted with a moiety selected from the group consisting of Br, CH.sub.3, and NHSO.sub.2 CH.sub.3, disubstituted with one or more moieties, same or different, selected from the group consisting of Br, CH.sub.3, and NHSO.sub.2 CH.sub.3, or trisubstituted with one or more moieties, same or different, selected from the group consisting of Br, CH.sub.3, and NHSO.sub.2 CH.sub.3.
- 4. A compound of claim, 3 having the formula ##STR92## and pharmaceutically acceptable salts, wherein ##STR93##
- 5. A compound of claim 4 selected from the group consisting of 2-(4-(4-(1-Piperazinyl)phenylcarbonylamino)phenoxy)ethanol,
- 2-(3-Methyl-4-(4-(1-piperazinyl)phenylcarbonylamino )phenoxy)-ethanol,
- 2-(4-(4-(4-piperazin-1-yl)phenylcarbonylamino)-2-methanesulfonyl-aminophenoxy)ethanol,
- 2-(3-methyl-4-1,2,3,4-tetrahydro-9H-pyrido[3,4-B]indol-7-yl-carboxamido)phenoxy)ethanol,
- 2-(2,6-Dibromo-3-methyl-4-(4-(piperizin-4-yl)phenylcarbox-amide)phenoxy) ethanol, and
- N-(4-Pyridyl)piperidin-4-carbonylamino-3-methylphenoxyethanol,
- and pharmaceutically acceptable salts thereof.
- 6. A composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
- 7. A method for inhibiting the binding of fibrinogen to blood platelets in a mammal, comprising treating the mammal with a composition of claim 6.
- 8. A method for inhibiting the aggregation of blood platelets in a mammal, by blocking fibrinogen from acting at its receptor site, comprising treating the mammal with a composition of claim 6.
- 9. A composition for inhibiting the aggregation of blood platelets in a mammal, comprising an efficacious amount of a compound of claim 1 in combination with one or more agents selected from a thrombolytic agent, an anticoagulant agent, and an antiplatelet agent and a pharmaceutically acceptable carrier.
- 10. A method for inhibiting the aggregation of blood platelets in a mammal, by blocking fibrinogen from acting at its receptor site, comprising treating the mammal with a composition of claim 9.
- 11. A method for inhibiting osteoclast mediated bone resorption, comprising treating the mammal with a composition of claim 6.
Parent Case Info
This application claims the benefit of U.S. Provisional Application No. 60/020,976, filed Jun. 28, 1996.
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