US 4,908,380 AGranted

Pharmaceutical compositions

AssigneeImperial Chemical Industries PLC

InventorsAndrew G. Brewster, George R. Brown, Michael J. Smithers

Life of this patent

Estimating the term…

Abstract

The invention concerns novel pharmaceutical compositions containing a 4(Z)-6-(2,4-diphenyl-1,3-dioxan-5-yl)-alkenoic acid which antagonizes one or more of the actions of thromboxane A.sub.2, together with a compound which inhibits the synthesis of thromboxane A.sub.2. The compositios are useful as medicines in treating a variety of diseases or medical conditions in which thromboxane A.sub.2 and/or other prostanoid contractile substances are involved.

Claims14

Dependent claims

A pharmaceutical composition for use in a disease or medical condition in which thromboxane A.sub.2 and/or a related prostanoid constrictor substance is involved which comprises as active ingredients:

(i) an effective amount of 1,3-dioxane ether of the formula I:
##STR2## wherein X is selected from fluoro, chloro, bromo, trifluoromethyl, cyano, methoxy and nitro;
and one of Y and Z is hydrogen or fluoro, and the other is hydrogen;
and wherein the groups at positions 2, 4 and 5 of the dioxane ring have cis-relative stereochemistry;
or a pharmaceutically acceptable salt thereof;
and
(ii) an effective amount of inhibitor of the synthesis of thromboxane A.sub.2 selected from the group consisting of:
(1) 4-[2-(1H-imidazol-1-yl)ethoxy]benzoic acid (dazoxiben),
(2) sodium 5-(3-pyridylmethyl)benzofuran-2-carboxylic acid (furegrelate),
(3) 3-[3-(1H-imidazol-1-ylmethyl)-2-methyl-1H-indol-1-yl]propanoic acid (UK38485),
(4) 8-[3-methyl-2-(3-pyridyl)-1H-indol-1-yl]octanoic acid (CGS12970),
(5) 5-(5-carboxypentyl)imidazo[1,5-a]pyridine (CGS13080),
(6) 6-[5-chloro-3-methyl-2-(3-pyridyl)-1H-indol-1-yl]hexanoic acid (CGS14854),
(7) (E)-4-(1-imidazolylmethyl)cinnamic acid (OKY046),
(8) sodium (E)-3-[4-(3-pyridylmethyl)phenyl]methacrylate (OKY1580),
(9) (E)-3-[4-(3-pyridylmethyl)phenyl]methacrylic acid hydrochloride (OKY1581),
(10) (E)-7-phenyl-7-(3-pyridyl)-6-heptenoic acid (CV4151),
(11) N-[(1H)-imidazol-1-yl)octyl]-4-chlorobenzamide,
(12) 1-(3-benzloxy-1(E)-octenyl)imidazole (CBS645),
(13) 2,2-dimethyl-6-[2-(1H-imidazol-1-yl)-1-([4-methoxyphenyl]methoxymethyl)-et hoxy]hexanoic acid (SC41156),
(14) sodium 4-[alpha-hydroxy-5-(1H-imidazol-1-yl)-2-methylbenzyl]-3,5-dimethyl-benzoat e (Y20811);
having the formulae set out hereinbefore;
and the pharmaceutically acceptable salts thereof or, in the case of inhibitor (2), (8), (9) and (14), the salt free form thereof;
together with a pharmaceutically acceptable diluent or carrier.

21 more elements

Dependencies are inferred from the claim text.

Facts

Application: 07/118,226Filed 3 Nov 1987
Priority: GB 86262974 Nov 1986
Granted: 13 Mar 1990
Term ends: Not estimatedThe source records don’t support an estimate.

Classification9 codes

A61K 31/335
Heterocyclic compounds: having oxygen as the only ring hetero atom, e.g. fungichromin
A61K 31/415
Having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole: 1,2-Diazoles
A61K 31/44
Having six-membered rings with one nitrogen as the only ring hetero atom: non condensed pyridines; Hydrogenated derivatives thereof
A61P 7/02
Drugs for disorders of the blood or the extracellular fluid: antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Family

No related US applications are recorded in the indexed filing history.

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Abstract

(i) an effective amount of 1,3-dioxane ether of the formula I:
##STR2## wherein X is selected from fluoro, chloro, bromo, trifluoromethyl, cyano, methoxy and nitro;
and one of Y and Z is hydrogen or fluoro, and the other is hydrogen;
and wherein the groups at positions 2, 4 and 5 of the dioxane ring have cis-relative stereochemistry;
or a pharmaceutically acceptable salt thereof;
and
(ii) an effective amount of inhibitor of the synthesis of thromboxane A.sub.2 selected from the group consisting of:
(1) 4-[2-(1H-imidazol-1-yl)ethoxy]benzoic acid (dazoxiben),
(2) sodium 5-(3-pyridylmethyl)benzofuran-2-carboxylic acid (furegrelate),
(3) 3-[3-(1H-imidazol-1-ylmethyl)-2-methyl-1H-indol-1-yl]propanoic acid (UK38485),
(4) 8-[3-methyl-2-(3-pyridyl)-1H-indol-1-yl]octanoic acid (CGS12970),
(5) 5-(5-carboxypentyl)imidazo[1,5-a]pyridine (CGS13080),
(6) 6-[5-chloro-3-methyl-2-(3-pyridyl)-1H-indol-1-yl]hexanoic acid (CGS14854),
(7) (E)-4-(1-imidazolylmethyl)cinnamic acid (OKY046),
(8) sodium (E)-3-[4-(3-pyridylmethyl)phenyl]methacrylate (OKY1580),
(9) (E)-3-[4-(3-pyridylmethyl)phenyl]methacrylic acid hydrochloride (OKY1581),
(10) (E)-7-phenyl-7-(3-pyridyl)-6-heptenoic acid (CV4151),
(11) N-[(1H)-imidazol-1-yl)octyl]-4-chlorobenzamide,
(12) 1-(3-benzloxy-1(E)-octenyl)imidazole (CBS645),
(13) 2,2-dimethyl-6-[2-(1H-imidazol-1-yl)-1-([4-methoxyphenyl]methoxymethyl)-et hoxy]hexanoic acid (SC41156),
(14) sodium 4-[alpha-hydroxy-5-(1H-imidazol-1-yl)-2-methylbenzyl]-3,5-dimethyl-benzoat e (Y20811);
having the formulae set out hereinbefore;
and the pharmaceutically acceptable salts thereof or, in the case of inhibitor (2), (8), (9) and (14), the salt free form thereof;
together with a pharmaceutically acceptable diluent or carrier.

21 more elements

Facts

Application

07/118,226Filed 3 Nov 1987

Priority

GB 86262974 Nov 1986

Granted

13 Mar 1990

Term ends

Not estimatedThe source records don’t support an estimate.

Classification9 codes

A61K 31/335
Heterocyclic compounds: having oxygen as the only ring hetero atom, e.g. fungichromin
A61K 31/415
Having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole: 1,2-Diazoles
A61K 31/44
Having six-membered rings with one nitrogen as the only ring hetero atom: non condensed pyridines; Hydrogenated derivatives thereof
A61P 7/02
Drugs for disorders of the blood or the extracellular fluid: antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors