US 2018/0022749 A1Published application

Compounds as modulators of ror gamma

AssigneeBoehringer Ingelheim International GmbH

InventorsJohanna BAKONYI, Steven Richard BRUNETTE, Delphine COLLIN, Robert Owen HUGHES, Xiang LI, Shuang LIANG, Robert SIBLEY, Michael Robert TURNER, Lifen WU, Qiang ZHANG

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Abstract

The present invention encompasses compounds of the formula (I) wherein the variables are defined herein which are suitable for the modulation of RORγ and the treatment of diseases related to the modulation of RORγ. The present invention also encompasses processes of making compounds of formula (I) and pharmaceutical preparations containing them.

Claims23

Dependent claims

A compound of formula (I)

wherein:
R1 is:
—CN;
—S(O)nR6;
—S(O)nNR7R8;
—S(O)(NR9)R6;
—N(R9)C(O)R6;
—N(R9)C(O)OR6;
—N(R9)S(O)nR6;
—C(O)OR9;
—C(O)NR7R8;
or
—C(O)R9;
or
R6, R7, R8 or R9 of R1 may be cyclized onto W to form a ring;
and
R2 and R3 are each independently:
(A) —H;
(B) C1-3 alkyl optionally substituted with one, two or three groups selected from:
a) C3-6 cycloalkyl;
b) —OR9;
c) —CN;
d) —CF3;
e) -halo;
f) —C(O)OR9;
g) —C(O)N(R9)2;
h) —S(O)nR9;
and
i) —S(O)nNR7R8;
or
(C) C3-6 cycloalkyl;
(D) C3-6 heterocyclyl;
or
R2 and R3 are taken together with the carbon to which they are attached to form a C3-6 carbocyclic ring;
or
R2 and R3 are taken together with the carbon to which they are attached to form a C3-6 heterocyclic ring;
or
R2 or R3 may be cyclized onto W to form a ring;
R4 is:
(A) C1-6 alkyl optionally substituted with one, two or three groups selected from:
a) C3-6 cycloalkyl;
b) C3-6 heterocyclyl;
c) —OR9;
d) —CN;
e) —S(O)nR9;
f) -halo;
and
g) —CF3;
or
(B) C3-12 cycloalkyl optionally substituted with one, two or three groups selected from:
a) C1-6 alkyl;
b) —OR9;
c) —CN;
d) —S(O)nR9;
e) -halo;
and
f) —CF3;
or
(C) aryl, heteroaryl or heterocyclyl each optionally substituted with one, two or three groups selected from:
a) C1-6 alkyl;
b) C3-6cycloalkyl;
c) —OR9;
d) —CN;
e) —S(O)nR9;
f) -halo;
and
g) —CF3;
R5 is aryl, heteroaryl, heterocyclyl or C3-12 cycloalkyl each optionally substituted with one, two or three groups selected from:
(A) C1-6 alkyl, C3-6 cycloalkyl or C3-6 heterocyclyl each optionally substituted with one, two or three groups selected from:
a) C3-6 cycloalkyl;
b) C3-6 heterocyclyl;
c) —OR9;
d) —CN;
e) —S(O)nNR7R8
f) —S(O)nR9;
g) -halo;
and
h) —CF3;
or
(B) —OR9;
(C) —CN;
(D) —CF3;
(E) -halo;
(F) —S(O)nNR7R8;
(G) —S(O)nR9;
and
(H) —NR7R8;
W is aryl, heteroaryl, heterocyclyl, C3-12 cycloalkyl, or alkynyl each optionally substituted with one or two groups selected from:
a) C1-6 alkyl;
b) C3-6 cycloalkyl;
c) —OR9;
d) —CN;
e) —CF3;
f) -halo;
g) —NR7R8;
h) —C(O)OR9;
and
i) —C(O)N(R9)2;
R6 is selected from:
(A) —OH;
(B) C1-6 alkyl optionally substituted with one or two groups selected from:
a) C3-6cycloalkyl;
b) —OR9;
c) —CN;
d) —CF3;
and
e) -halo;
(C) C3-6 cycloalkyl;
and
(D) —CF3;
R7 and R8 are independently selected from:
(A) —H;
(B) C1-3 alkyl optionally substituted with one or two groups selected from:
a) C3-6cycloalkyl;
b) —OR9;
c) —CN;
and
d) -halo;
and
(C) C3-6cycloalkyl;
or
R7 and R8, together with the nitrogen to which they are bonded, form a saturated ring with 3-6 carbon atoms wherein one carbon atom in said saturated ring may be optionally replaced by —O—, —NR9— or —S(O)n—;
R9 is selected from;
(A) —H;
(B) C1-3 alkyl optionally substituted with one or two groups selected from:
a) C3-6cycloalkyl;
b) —OR9;
c) —CN;
d) —CF3
e) -halo;
or
(C) C3-6cycloalkyl;
and
n is 0, 1 or 2;
or a pharmaceutically acceptable salt thereof.

132 more elements

Dependencies are inferred from the claim text.

Facts

Application: 15/426,208Filed 7 Feb 2017
Priority: 14 Apr 2014
Published: 25 Jan 2018
Term ends: Not estimatedThe source records don’t support an estimate.

Classification26 codes

C07D 475/00
Heterocyclic compounds containing pteridine ring systems
A61K 31/33
Medicinal preparations containing organic active ingredients: heterocyclic compounds
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…

Family

Application61/979,231Us provisional application · filed 14 Apr 2014
Application14/683,682Continuation · filed 10 Apr 2015
Application14/946,873Continuation · filed 20 Nov 2015
Application15/270,029Continuation · filed 20 Sep 2016
Application15/426,208Continuation
US 2015/0291607 A1Published application
US 2016/0075706 A1Published application
US 2017/0008894 A1Published application
US 9,242,989 B2Related patent
US 9,598,415 B2Related patent
US 2018/0022749 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of formula (I)

wherein:
R1 is:
—CN;
—S(O)nR6;
—S(O)nNR7R8;
—S(O)(NR9)R6;
—N(R9)C(O)R6;
—N(R9)C(O)OR6;
—N(R9)S(O)nR6;
—C(O)OR9;
—C(O)NR7R8;
or
—C(O)R9;
or
R6, R7, R8 or R9 of R1 may be cyclized onto W to form a ring;
and
R2 and R3 are each independently:
(A) —H;
(B) C1-3 alkyl optionally substituted with one, two or three groups selected from:
a) C3-6 cycloalkyl;
b) —OR9;
c) —CN;
d) —CF3;
e) -halo;
f) —C(O)OR9;
g) —C(O)N(R9)2;
h) —S(O)nR9;
and
i) —S(O)nNR7R8;
or
(C) C3-6 cycloalkyl;
(D) C3-6 heterocyclyl;
or
R2 and R3 are taken together with the carbon to which they are attached to form a C3-6 carbocyclic ring;
or
R2 and R3 are taken together with the carbon to which they are attached to form a C3-6 heterocyclic ring;
or
R2 or R3 may be cyclized onto W to form a ring;
R4 is:
(A) C1-6 alkyl optionally substituted with one, two or three groups selected from:
a) C3-6 cycloalkyl;
b) C3-6 heterocyclyl;
c) —OR9;
d) —CN;
e) —S(O)nR9;
f) -halo;
and
g) —CF3;
or
(B) C3-12 cycloalkyl optionally substituted with one, two or three groups selected from:
a) C1-6 alkyl;
b) —OR9;
c) —CN;
d) —S(O)nR9;
e) -halo;
and
f) —CF3;
or
(C) aryl, heteroaryl or heterocyclyl each optionally substituted with one, two or three groups selected from:
a) C1-6 alkyl;
b) C3-6cycloalkyl;
c) —OR9;
d) —CN;
e) —S(O)nR9;
f) -halo;
and
g) —CF3;
R5 is aryl, heteroaryl, heterocyclyl or C3-12 cycloalkyl each optionally substituted with one, two or three groups selected from:
(A) C1-6 alkyl, C3-6 cycloalkyl or C3-6 heterocyclyl each optionally substituted with one, two or three groups selected from:
a) C3-6 cycloalkyl;
b) C3-6 heterocyclyl;
c) —OR9;
d) —CN;
e) —S(O)nNR7R8
f) —S(O)nR9;
g) -halo;
and
h) —CF3;
or
(B) —OR9;
(C) —CN;
(D) —CF3;
(E) -halo;
(F) —S(O)nNR7R8;
(G) —S(O)nR9;
and
(H) —NR7R8;
W is aryl, heteroaryl, heterocyclyl, C3-12 cycloalkyl, or alkynyl each optionally substituted with one or two groups selected from:
a) C1-6 alkyl;
b) C3-6 cycloalkyl;
c) —OR9;
d) —CN;
e) —CF3;
f) -halo;
g) —NR7R8;
h) —C(O)OR9;
and
i) —C(O)N(R9)2;
R6 is selected from:
(A) —OH;
(B) C1-6 alkyl optionally substituted with one or two groups selected from:
a) C3-6cycloalkyl;
b) —OR9;
c) —CN;
d) —CF3;
and
e) -halo;
(C) C3-6 cycloalkyl;
and
(D) —CF3;
R7 and R8 are independently selected from:
(A) —H;
(B) C1-3 alkyl optionally substituted with one or two groups selected from:
a) C3-6cycloalkyl;
b) —OR9;
c) —CN;
and
d) -halo;
and
(C) C3-6cycloalkyl;
or
R7 and R8, together with the nitrogen to which they are bonded, form a saturated ring with 3-6 carbon atoms wherein one carbon atom in said saturated ring may be optionally replaced by —O—, —NR9— or —S(O)n—;
R9 is selected from;
(A) —H;
(B) C1-3 alkyl optionally substituted with one or two groups selected from:
a) C3-6cycloalkyl;
b) —OR9;
c) —CN;
d) —CF3
e) -halo;
or
(C) C3-6cycloalkyl;
and
n is 0, 1 or 2;
or a pharmaceutically acceptable salt thereof.

132 more elements

Facts

Application

15/426,208Filed 7 Feb 2017

Priority

14 Apr 2014

Published

25 Jan 2018

Term ends

Not estimatedThe source records don’t support an estimate.

Classification26 codes

C07D 475/00
Heterocyclic compounds containing pteridine ring systems
A61K 31/33
Medicinal preparations containing organic active ingredients: heterocyclic compounds
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…

Family

Application61/979,231Us provisional application · filed 14 Apr 2014

Application14/683,682Continuation · filed 10 Apr 2015

Application14/946,873Continuation · filed 20 Nov 2015

Application15/270,029Continuation · filed 20 Sep 2016

Application15/426,208Continuation

US 2015/0291607 A1Published application

US 2016/0075706 A1Published application

US 2017/0008894 A1Published application

US 9,242,989 B2Related patent

US 9,598,415 B2Related patent

US 2018/0022749 A1This patent

From the US filing history. Foreign family members aren’t listed.