Heterocyclic compound

Patent metadata

Field	Value
Publication number	US-9637483-B2
Application number	US-201414779347-A
Country	US
Kind code	B2
Filing date	Mar 27, 2014
Priority date	Mar 28, 2013
Publication date	May 2, 2017
Grant date	May 2, 2017

Abstract

Provided is a compound or a salt thereof, which has an excellent JAK inhibitory action, and is useful as a prophylactic or therapeutic agent for autoimmune diseases (rheumatoid arthritis, psoriasis, inflammatory bowel disease, Sjogren's syndrome, Behcet's syndrome, multiple sclerosis, systemic lupus erythematosus, etc.), cancer (leukemia, uterine leiomyosarcoma, prostate cancer, multiple myeloma, cachexia, myelofibrosis, etc.) and the like. The present invention relates to a compound represented by the formula (I)

wherein each symbol is as defined in the present specification, or a salt thereof.

First claim

The invention claimed is:

1. A compound of formula (I):

wherein
R 1 is an optionally substituted C 1-6 alkyl group, or an optionally substituted cyclic group;
R 2 is a hydrogen atom or a cyano group;
R 3 is an optionally substituted C 1-3 alkyl group;
R 4 is a halogen atom, a cyano group, an optionally substituted hydroxyl group, an optionally substituted amino group, an acyl group, an optionally substituted hydrocarbon group, or an optionally substituted heterocyclic group; and
R 5 is a hydrogen atom, a halogen atom, a cyano group, an optionally substituted C 1-6 alkyl group, an optionally substituted C 1-6 alkoxy group, or an acyl group,
or a salt thereof.

2. The compound according to claim 1 , wherein
R 1 is
(1) a C 1-6 alkyl group optionally substituted by 1 to 5 substituents selected from the group consisting of:
(a) a halogen atom,
(b) a C 3-8 cycloalkyl group optionally substituted by 1 to 3 C 1-6 alkyl groups,
(c) a C 1-6 alkoxy-carbonyl group, and
(d) a carbamoyl group,

(2) a C 3-10 cycloalkyl group optionally substituted by 1 to 3 C 1-6 alkyl groups, or
(3) a C 6-14 aryl group optionally substituted by 1 to 3 substituents selected from the group consisting of:
(a) a halogen atom,
(b) a C 1-6 alkyl group optionally substituted by 1 to 3 halogen atoms, and
(c) a cyano group;

R 2 is a hydrogen atom or a cyano group;
R 3 is a C 1-3 alkyl group optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and a C 1-6 alkoxy group;
R 4 is
(1) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the group consisting of:
(a) a halogen atom,
(b) a cyano group,
(c) a hydroxy group,
(d) an amino group optionally mono- or di-substituted by C 1-6 alkyl-carbonyl group(s), and
(e) a carbamoyl group optionally mono- or di-substituted by C 1-6 alkyl group(s),

(2) a C 3-10 cycloalkyl group,
(3) a C 6-14 aryl group optionally substituted by 1 to 3
carbamoyl groups optionally mono-or di-substituted by C 1-6 alkyl group(s),

(4) a 5-or 6-membered non-aromatic heterocyclic group having one oxygen atom, or
(5) a group represented by the formula:

wherein
R 6 and R 7 are each independently a C 1-6 alkyl group; or
R 6 and R 7 form, together with the adjacent carbon atom, cyclobutane, cyclohexane, tetrahydropyran or tetrahydrothiopyran, each of which is optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom
and an oxo group;
R 8 and R 9 are each independently
(i) a hydrogen atom,
(ii) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, a C 3-8 cycloalkyl group and a C 1-6 alkoxy group,
(iii) a C 3-10 cycloalkyl group optionally substituted by 1 to 3 halogen atoms,
(iv) a C 6-14 aryl group optionally substituted by 1 to 3 halogen atoms,
(v) a C 1-6 alkoxy group optionally substituted by 1 to 3 halogen atoms,
(vi) a C 6-14 aryloxy group optionally substituted by 1 to 3 halogen atoms,
(vii) a C 1-6 alkyl-carbonyl group optionally substituted by 1 to 3 halogen atoms,
(viii) a C 1-6 alkoxy-carbonyl group optionally substituted by 1 to 3 halogen atoms,
(ix) a C 1-6 alkylsulfonyl group optionally substituted by 1 to 3 halogen atoms,
(x) a carbamoyl group optionally mono- or di-substituted by C 1-6 alkyl group(s) optionally substituted by 1 to 3 halogen atoms,
(xi) an aromatic heterocyclic group, or
(xii) a 5- or 6-membered non-aromatic heterocyclic group having one oxygen atom; or
R 8 and R 9 form, together with the adjacent nitrogen atom,
(i) an aromatic nitrogen-containing heterocycle optionally substituted by 1 to 3 substituents selected from the group consisting of:
(a) a C 1-6 alkyl group optionally substituted by 1 to 3 halogen atoms,
(b) a hydroxy group,
(c) a C 1-6 alkoxy group optionally substituted by 1 to 3 halogen atoms, and
(d) a halogen atom, or

(ii) a non-aromatic nitrogen-containing heterocycle optionally forming a fused ring or a spiro ring, and optionally substituted by 1 to 3 substituents selected from the group consisting of:
(a) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, a hydroxyl group and a C 1-6 alkoxy group,
(b) a hydroxy group,
(c) a C 1-6 alkoxy group optionally substituted by 1 to 3 halogen atoms,
(d) a halogen atom,
(e) a C 1-6 alkyl-carbonyl group,
(f) a C 1-6 alkoxy-C 1-6 alkyl-carbonyl group, and
(g) an oxo group

R 10 and R 11 are each independently
(i) a hydrogen atom,
(ii) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, a C 3-8 cycloalkyl group and a C 1-6 alkoxy group,
(iii) a C 3-10 cycloalkyl group optionally substituted by 1 to 3 halogen atoms,
(iv) a C 6-14 aryl group optionally substituted by 1 to 3 halogen atoms,
(v) a C 1-6 alkoxy group optionally substituted by 1 to 3 halogen atoms,
(vi) a C 6-14 aryloxy group optionally substituted by 1 to 3 halogen atoms,
(vii) a C 1-6 alkyl-carbonyl group optionally substituted by 1 to 3 halogen atoms,
(viii) a C 1-6 alkoxy-carbonyl group optionally substituted by 1 to 3 halogen atoms,
(ix) a C 1-6 alkylsulfonyl group optionally substituted by 1 to 3 halogen atoms,
(x) a carbamoyl group optionally mono- or di-substituted by C 1-6 alkyl group(s) optionally substituted by 1 to 3 halogen atoms,
(xi) an aromatic heterocyclic group, or
(xii) a 5- or 6-membered non-aromatic heterocyclic group having one oxygen atom; or
R 10 and R 11 form, together with the adjacent nitrogen atom,
(i) an aromatic nitrogen-containing heterocycle optionally substituted by 1 to 3 substituents selected from the group consisting of:
(a) a C 1-6 alkyl group optionally substituted by 1 to 3 halogen atoms,
(b) a hydroxy group,
(c) a C 1-6 alkoxy group optionally substituted by 1 to 3 halogen atoms, and
(d) a halogen atom, or

(ii) a non-aromatic nitrogen-containing heterocycle optionally forming a fused ring or a spiro ring, which is optionally substituted by 1 to 3 substituents selected from the group consisting of:
(a) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, a hydroxy group and a C 1-6 alkoxy group,
(b) a hydroxy group,
(c) a C 1-6 alkoxy group optionally substituted by 1 to 3 halogen atoms,
(d) a halogen atom,
(e) a C 1-6 alkyl-carbonyl group,
(f) a C 1-6 alkoxy-C 1-6 alkyl-carbonyl group, and
(g) an oxo group; and

R 5 is a hydrogen atom,
or a salt thereof.

3. 3-Amino-7-(5-(2-hydroxypropan-2-yl)-1-methyl-1H-pyrazol-3-yl)-5-((2S)-3-methylbutan-2-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one or a salt thereof.

4. 3-Amino-5-(dicyclopropylmethyl)-7-(1-methyl-5-(morpholin-4-yl)-1H-pyrazol-3-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one or a salt thereof.

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

6. The pharmaceutical composition according to claim 5 , which is a Janus kinase inhibitor.

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Yoshida Masato
• Nagamiya Hiroyuki
• Ohba Yusuke
• Seto Masaki
• Yogo Takatoshi
• Sasaki Satoshi
• Tokunaga Norihito
• Aso Kazuyoshi

Classifications

• A61P43/00

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

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title