Amide compound

Patent metadata

Field	Value
Publication number	US-10472376-B2
Application number	US-201414902388-A
Country	US
Kind code	B2
Filing date	Jul 2, 2014
Priority date	Jul 3, 2013
Publication date	Nov 12, 2019
Grant date	Nov 12, 2019

Abstract

The present invention relates to compound (I) or a salt thereof which has a RORγt inhibitory action. In the formula (I), each symbol is as defined in the specification.

First claim

The invention claimed is:

1. A compound represented by the following formula (I):

wherein
Ring A is a 6-membered aromatic ring optionally further substituted by 1 to 3 substituents selected from
(1) a halogen atom, and
(2) a cyano group;

R 1 is
(1) a group represented by the formula: -Q(R 1a )(R 1b )(R 1c )
wherein
Q is a carbon atom, a silicon atom or a germanium atom, and
R 1a , R 1b and R 1c are each independently
(a) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from
(i) a halogen atom, and
(ii) a C 1-6 alkoxy group,

(b) a hydroxy group,
(c) a C 6-14 aryl group,
(d) a C 3-10 cycloalkyl group,
(e) a cyano group,
(f) a carbamoyl group optionally mono- or di-substituted by C 3-10 cycloalkyl group(s), or
(g) a 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl group, or
R 1a and R 1b in combination form, together with the adjacent Q, a C3-10 cycloalkane ring,

(2) a neopentyl group, or
(3) a trimethylsilylmethyl group;
R 2 is
(1) a group represented by the formula:

wherein
R 5 is
(A) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from
(a) a C 1-6 alkoxy group optionally substituted by 1 to 3 substituents selected from
(i) a halogen atom, and
(ii) a C 1-6 alkoxy group, and

(b) a hydroxy group, or

(B) a C 1-6 alkoxy group optionally substituted by 1 to 3 C 1-6 alkoxy groups, and
the benzene ring in the formula optionally has, besides R 5 , additional 1 to 3 substituents selected from
(A) a C 1-6 alkyl group, and
(B) a C 1-6 alkoxy group,

(2) a bicyclic fused heterocyclic group optionally substituted by 1 to 3 C1-6 alkyl groups, or
(3) a group represented by the formula -L-Z 1 :
wherein
L is a bond; and
Z 1 is
(A) a C 3-10 cycloalkyl group optionally substituted by 1 to 3 substituents selected from
(a) a halogen atom, and
(b) a hydroxy group, or

(B) a 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted by C 1-6 alkyl group(s) optionally substituted by 1 to 3 halogen atoms;

R 3 is
(1) a hydrogen atom, or
(2) a C 1-6 alkyl group optionally substituted by 1 to 3 cyano groups; and
R 4 is
(1) a C 1-6 alkyl group optionally substituted by 1 to 7 substituents selected from
(a) a 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted by 1 to 3 substituents selected from
(i) an oxo group,
(ii) a C 1-6 alkyl group,
(iii) a hydroxy group, and
(iv) a cyano group,

(b) a 5- or 6-membered monocyclic aromatic heterocyclic group optionally substituted by 1 to 3 substituents selected from
(i) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from a halogen atom and a C 6-14 aryl group,
(ii) a hydroxy group, and
(iii) a C 1-6 alkoxy group optionally substituted by 1 to 3 C 6-14 aryl groups,

(c) a 8- to 14-membered fused polycyclic aromatic heterocyclic group,
(d) a 9- to 14-membered fused polycyclic non-aromatic heterocyclic group optionally substituted by 1 to 3 oxo groups,
(e) a halogen atom,
(f) a hydroxy group,
(g) a cyano group,
(h) a carboxy group,
(i) a carbamoyl group,
(j) a C 1-6 alkylsulfonyl group,
(k) a C 3-10 cycloalkyl group optionally substituted by 1 to 3 substituents selected from
(i) a hydroxy group, and
(ii) a cyano group,

(l) an amino group optionally mono- or di-substituted by substituent(s) selected from
(i) a C 1-6 alkyl group,
(ii) a C 1-6 alkyl-carbonyl group, and
(iii) a C 1-6 alkoxy-carbonyl group,

(m) an imino group optionally substituted by a hydroxy group, and
(n) a 5- or 6-membered monocyclic aromatic heterocyclyloxy group optionally substituted by 1 to 3 C 1-6 alkyl groups,

(2) a 3- to 8-membered monocyclic non-aromatic heterocyclic group selected from the group consisting of pyrrolidinyl, oxazolidinyl, azetidinyl, piperidyl, tetrahydropyranyl, tetrahydrothiopyranyl, 1,1-dioxidotetrahydrothiopyranyl, 1-oxidotetrahydrothiopyranyl, imidazolidinyl, tetrahydrofuryl, 1,1-dioxidotetrahydrothienyl, morpholinyl, dihydrooxazolyl, dihydrothiazolyl, piperazinyl and dihydrooxadiazolyl, each optionally substituted by 1 to 3 substituents selected from
(a) an oxo group,
(b) a hydroxy group,
(c) a cyano group,
(d) a halogen atom,
(e) a C 1-6 alkyl group optionally substituted by 1 to 3 hydroxy groups,
(f) a C 1-6 alkoxy group optionally substituted by 1 to 3 C 6-14 aryl groups,
(g) a C 1-6 alkyl-carbonyl group, and
(h) a C 1-6 alkylidene group optionally substituted by 5- or 6-membered monocyclic aromatic heterocyclic group(s) optionally substituted by 1 to 3 substituents selected from
(i) a C 1-6 alkyl group, and
(ii) a halogenated boryl group,

(3) a 5-membered monocyclic aromatic heterocyclic group optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group,
(b) a cyano group,
(c) a carboxy group,
(d) a halogen atom,
(e) a C 1-6 alkyl group optionally substituted by 1 to 3 hydroxy groups,
(f) a C 1-6 alkoxy group,
(g) a C 1-6 alkoxy-carbonyl group, and
(h) an amino group optionally mono- or di-substituted by C 1-6 alkyl-carbonyl group(s),

(4) a C 3-10 cycloalkyl group optionally substituted by 1 to 3 substituents selected from
(a) a halogen atom,
(b) a hydroxy group,
(c) an oxo group,
(d) a cyano group,
(e) a carboxy group, and
(f) a C 1-6 alkyl group optionally substituted by 1 to 3 hydroxy groups,

(5) a C 2-6 alkenyl group optionally substituted by 1 to 3 substituents selected from
(a) a carbamoyl group, and
(b) a hydroxy group,

(6) a C 6-14 aryl group optionally substituted by 1 to 3 hydroxy groups,
(7) a 9- to 14-membered fused polycyclic non-aromatic heterocyclic group optionally substituted by 1 to 3 oxo groups,
(8) a 8- to 14-membered fused polycyclic aromatic heterocyclic group,
(9) a C 1-6 alkoxy-carbonyl group,
(10) a 5- to 14-membered spiro heterocyclic group,
(11) a 3- to 8-membered monocyclic non-aromatic heterocyclyloxy group, or
(12) an amino group optionally mono- or di-substituted by substituent(s) selected from
(a) a C 1-6 alkyl group optionally substituted by 1 to 3 hydroxy groups, and
(b) a 5- or 6-membered monocyclic aromatic heterocyclic group; or

when R 3 is a substituent, R 3 and R 4 in combination form, together with the nitrogen atom adjacent to R 3 and the carbon atom adjacent to R 4 , a 3- to 14-membered non-aromatic heterocycle selected from the group consisting of pyrrolidine and 2,7-diazaspiro[4.4]nonane, each substituted by one oxo group and each optionally further substituted by 1 to 3 oxo groups,
provided that
α-(acetylamino)-N-[4-(1,1-dimethylettyl)phenyl]-cyclopentaneacetamide
is excluded,
or a salt thereof.

2. The compound or salt of claim 1 , wherein the substituent that Ring A optionally further has is a fluorine atom or a chlorine atom.

3. The compound or salt of claim 1 , wherein R 1 is a tert-butyl group, a neopentyl group or a trimethylsilyl group.

4. The compound or salt of claim 1 , wherein R 2 is
(1) a group represented by the formula:

wherein R 5 is an alkoxy group or an alkoxyalkyl group,

(2) a tetr

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Yamamoto Satoshi
• Shirai Junya
• Kono Mitsunori
• Tomata Yoshihide
• Sato Ayumu
• Ochida Atsuko
• Fukase Yoshiyuki
• Fukumoto Shoji
• Oda Tsuneo
• Tokuhara Hidekazu
• Ishii Naoki
• Sasaki Yusuke

Classifications

• A61P43/00

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

• A61P19/02

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

• A61P17/06

  Antipsoriatics · CPC title