Prostaglandin derivative

Patent metadata

Field	Value
Publication number	US-10494338-B2
Application number	US-201716099929-A
Country	US
Kind code	B2
Filing date	May 9, 2017
Priority date	May 9, 2016
Publication date	Dec 3, 2019
Grant date	Dec 3, 2019

Abstract

The present invention relates to a novel prostaglandin derivative having an alkynyl group on ω-chain, particularly, a novel prostaglandin derivative having a double bond at the 2-position and an alkynyl group on the ω-chain and a medicament containing the compound as an active ingredient.
According to the present invention, a compound represented by the formula (1) or a pharmaceutically acceptable salt thereof;

wherein each symbol is as defined in the present specification, or a cyclodextrin clathrate compound thereof, and a medicament containing the compound as an active ingredient, particularly, a medicament for the prophylaxis or treatment of a blood flow disorder associated with spinal canal stenosis or chronic arterial occlusion, can be provided.

First claim

The invention claimed is:

1. A compound, represented by formula (1) or a pharmaceutically acceptable salt thereof;

wherein
R A is —CH 2 —CZ 1 Z 2 (COX) or —CH═CZ 1 (COX),
Z 1 and Z 2 are each independently a hydrogen atom or a fluorine atom,
X is OR 4 or NR 5 R 6 ,
R 4 is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms or a substituted alkyl group having 1 to 6 carbon atoms,
R 5 is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms or a substituted alkyl group having 1 to 6 carbon atoms,
R 6 is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, a substituted alkyl group having 1 to 6 carbon atoms, an alkylsulfonyl group having 1 to 6 carbon atoms, a substituted alkylsulfonyl group having 1 to 6 carbon atoms, an arylsulfonyl group having 6 to 10 carbon atoms or a substituted arylsulfonyl group having 6 to 10 carbon atoms;
Y is CH 2 , S or O;
A-B is a carbon-carbon single bond or a carbon-carbon double bond;
a hydroxy group bonded by a wavy line is a hydroxy group having α-configuration, β-configuration or a mixed configuration of α-configuration and β-configuration;
R 1 and R 2 are each independently a hydrogen atom, an alkyl group having 1 to 3 carbon atoms or a substituted alkyl group having 1 to 3 carbon atoms;
n is an integer of 0 to 2; and
R 3 is an alkyl group having 2 to 3 carbon atoms or a cycloalkyl group having 3 to 5 carbon atoms.

2. The compound or pharmaceutically acceptable salt of claim 1 , wherein Y is CH 2 .

3. The compound or pharmaceutically acceptable salt of claim 1 , wherein R A is —CH═CZ 1 (COX).

4. The compound or pharmaceutically acceptable salt of claim 1 , wherein R A is —CH 2 —CZ 1 Z 2 (COX).

5. The compound or pharmaceutically acceptable salt of claim 1 , wherein n is 1.

6. The compound or pharmaceutically acceptable salt of claim 1 , wherein A-B is a carbon-carbon double bond.

7. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 1 is a hydrogen atom and R 2 is an alkyl group having 1 to 3 carbon atoms.

8. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 3 is a cycloalkyl group having 3 to 5 carbon atoms.

9. The compound or pharmaceutically acceptable salt of claim 1 , wherein X is OR 4 .

10. A cyclodextrin clathrate compound, comprising the compound or pharmaceutically acceptable salt of claim 1 .

11. A medicament, comprising the compound or pharmaceutically acceptable salt of claim 1 .

12. A method of treating a blood flow disorder, the method comprising administering the medicament of claim 11 , as a prophylactic or therapeutic agent, to a subject in need thereof.

13. The method of claim 12 , wherein the blood flow disorder is a blood flow disorder of a nerve.

14. The method of claim 13 , wherein the blood flow disorder of the nerve is a blood flow disorder associated with spinal canal stenosis.

15. The method of claim 12 , wherein the blood flow disorder is a blood flow disorder of a peripheral artery, skin or brain.

16. The method of claim 15 , wherein the blood flow disorder is a blood flow disorder of a peripheral artery that is a blood flow disorder associated with chronic arterial occlusion or pulmonary hypertension.

17. The method of claim 15 , wherein the blood flow disorder is a blood flow disorder of skin that is a blood flow disorder associated with a pressure ulcer.

18. The method of claim 15 , wherein the blood flow disorder is a blood flow disorder of brain that is a blood flow disorder associated with a suppression of recurrence after a cerebral infarction.

19. A medicament, comprising the cyclodextrin clathrate compound of claim 10 .

20. A method of treating a blood flow disorder, the method comprising administering the medicament of claim 19 , as a prophylactic or therapeutic agent, to a subject in need thereof.

Assignees

• Agc Inc
• Nippon Zoki Pharmaceutical Co

Inventors

• Yasuda Arata
• Matsumura Yasushi
• Sawada Kazuyoshi
• Nanba Hiroyoshi
• Taguchi Kazuki

Classifications

• C07C405/00 Primary

  Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins {; Analogues or derivatives thereof} · CPC title

• A61K31/5575

  having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha · CPC title

• A61K47/40

  Cyclodextrins; Derivatives thereof · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61K47/6951

  using cyclodextrin (cyclodextrins used as simple excipients A61K47/40) · CPC title