Thromboxane receptor antagonists

Patent metadata

Field	Value
Publication number	US-9932304-B2
Application number	US-201615180805-A
Country	US
Kind code	B2
Filing date	Jun 13, 2016
Priority date	Jun 16, 2015
Publication date	Apr 3, 2018
Grant date	Apr 3, 2018

Abstract

The invention relates to novel chemical entities that act as thromboxane (TX) A 2 receptor, or T prostanoid receptor (TP), antagonists and to their use in the treatment of human diseases in which thromboxane (TX) A and of all other agents that act as incidental ligands of TP, including the endoperoxide prostaglandin (PG)G 2 /PGH 2 , 20-hydroxyeicosatetraenoic acid (20-HETE) and the free-radical derived isoprostanes (e.g., 8-iso-prostaglandin (PG)F 2α ), play a role. Compounds of the invention preferably include a benzenesulfonyl urea in which the benzene is substituted by a substituted biphenylyloxy group (e.g., at the 2 position) and by a nitrile group (e.g., at the 5 position), which compounds show promising results as TP-isoform selective TP antagonists.

First claim

What is claimed is:

1. A compound represented by formula (I):

wherein
R 1 is selected from the group consisting of: a difluoromethyl group, a halogenated methoxy group, a primary amide, a secondary amide, a tertiary amide, and a nitrile group; and
R 2 is selected from the group consisting of an alkyl group of 3 to 6 carbons, and a halogenated alkyl group of 3 to 6 carbons,
or a pharmaceutically acceptable salt thereof.

2. A compound represented by formula (I):

wherein
R 1 is selected from the group consisting of: a difluoromethyl group, a difluoromethoxy group, a trifluoromethoxy group, a primary amide, a secondary amide, a tertiary amide, and a nitrile group; and
R 2 is selected from the group consisting of an alkyl group of 6 or fewer carbons and a halogenated alkyl group of 6 or fewer carbons,
or a pharmaceutically acceptable salt thereof.

3. A compound represented by formula (II):

wherein
R 1 is selected from the group consisting of: a halogenated methoxy group and a tertiary amide; and
R 2 is an alkyl group of 3 to 5 carbons,
or a pharmaceutically acceptable salt thereof.

4. A compound represented by formula (II):

wherein
R 1 is selected from the group consisting of: a difluoromethyl group, a difluoromethoxy group, a trifluoromethoxy group, a primary amide, a secondary amide, a tertiary amide, and a nitrile group; and
R 2 is selected from the group consisting of an alkyl group of 3 to 5 carbons and a halogenated alkyl group of 3 to 5 carbons,
or a pharmaceutically acceptable salt thereof.

5. A compound represented by formula (III):

wherein R 1 is selected from the group consisting of a difluoromethyl group, a difluoromethoxy group, a trifluoromethoxy group, a primary amide, a secondary amide, a tertiary amide, and a nitrile group, or a pharmaceutically acceptable salt thereof.

6. A compound represented by a formula selected from the group consisting of (IV), (V), (VI), (VIII), (IX), (X), and (XI):

or a pharmaceutically acceptable salt thereof.

7. A compound represented by a formula selected from the group consisting of (IV), (V), and (X):

or a pharmaceutically acceptable salt thereof.

8. A compound represented by formula (IV):

or a pharmaceutically acceptable salt thereof.

9. A compound represented by formula (V):

or a pharmaceutically acceptable salt thereof.

10. A compound represented by formula (X):

or a pharmaceutically acceptable salt thereof.

Assignees

• Univ College Dublin Nat Univ Ireland Dublin

Inventors

• Kinsella B Therese
• Reid Helen

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title