Hydroxytriazine compounds and pharmaceutical use thereof

Patent metadata

Field	Value
Publication number	US-12492182-B2
Application number	US-202318114043-A
Country	US
Kind code	B2
Filing date	Feb 24, 2023
Priority date	Aug 17, 2015
Publication date	Dec 9, 2025
Grant date	Dec 9, 2025

Abstract

The present invention provides a compound having an mPGES-1 inhibitory activity and useful for the prophylaxis or treatment of pain, rheumatism, osteoarthritis, fever, Alzheimer's disease, multiple sclerosis, arteriosclerosis, glaucoma, ocular hypertension, ischemic retinal disease, systemic scleroderma and/or cancer including colorectal cancer.
The present invention relates to a compound of formula [I-a], [I-b] or [I-c] or a pharmaceutically acceptable salt thereof:

wherein each symbol is as defined in the specification.

First claim

The invention claimed is:

1 . A compound of the formula [I-c], or a pharmaceutically acceptable salt thereof:

wherein
R is
(1) the formula:

wherein
R 1a is C 1-4 alkyl,
R 1b is C 1-4 alkyl or trifluoromethyl, and
R 1c is
(a) C 1-4 alkyl,
(b) C 1-4 fluoroalkyl,
(c) C 1-4 alkoxy, or
(d) C 1-4 alkoxy C 1-4 alkyl, or
(2) the formula:

wherein
n is 1,2, 3, 4 or 5, and
R 1d is
(a) fluoro,
(b) C 1-4 alkyl,
(c) C 1-4 fluoroalkyl,
(d) C 1-4 alkoxy, or
(e) C 1-4 alkoxy C 1-4 alkyl,
R 2 is hydrogen, and
R 6 is 1-methylbutyl or n-hexyl.

2 . The compound or pharmaceutically acceptable salt according to claim 1 , wherein R 1 is the formula:

wherein
R 1a is C 1-4 alkyl,
R 1b is C 1-4 alkyl or trifluoromethyl, and
R 1c is
(b) difluoromethyl or trifluoromethyl, or
(c) methoxy.

3 . The compound or pharmaceutically acceptable salt according to claim 1 , wherein R 1 is the formula:

wherein
n is 3, 4 or 5, and
R 1d is
(a) fluoro,
(c) C 1-4 fluoroalkyl,
(d) methoxy, or
(e) methoxymethyl.

4 . The compound or pharmaceutically acceptable salt according to claim 3 , wherein
n is 3 or 4, and R 1d is monofluoromethyl, difluoromethyl or trifluoromethyl.

5 . A compound selected from the following formulas:

or a pharmaceutically acceptable salt thereof.

6 . A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt according to claim 1 , and a pharmaceutically acceptable carrier.

7 . A method of treating pain, rheumatism, fever, osteoarthritis, glaucoma, or ocular hypertension, which comprises administering a therapeutically effective amount of the compound or pharmaceutically acceptable salt according to claim 1 to a human in need thereof.

8 . A compound of the following formula or a pharmaceutically acceptable salt thereof:

9 . A compound of the following formula:

Assignees

• Japan Tobacco Inc

Inventors

• Mitani Ikuo
• Hirono Yutaro
• Yamashita Masaki

Classifications

• A61K31/53 Primary

  having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495}) · CPC title

• A61P19/02

  for joint disorders, e.g. arthritis, arthrosis · CPC title

• A61P27/06

  Antiglaucoma agents or miotics · CPC title

• C07D251/22 Primary

  to two ring carbon atoms · CPC title

• C07D401/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title