Compounds as modulators of RORC

Patent metadata

Field	Value
Publication number	US-9745267-B2
Application number	US-201414916576-A
Country	US
Kind code	B2
Filing date	Sep 4, 2014
Priority date	Sep 5, 2013
Publication date	Aug 29, 2017
Grant date	Aug 29, 2017

Abstract

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

First claim

The invention claimed is:

1. A compound of formula (I)

R 1 is:
—CN,
—S(O) m C 1-6 alkyl,
—S(O) m C 1-6 cyanoalkyl,
—S(O) m C 1-6 haloalkyl,
—S(O) m C 3-6 cycloalkyl,
—S(O) m C 1-6 hydroxyalkyl,
—S(O) m C 1-6 alkyloxy,
—SO 2 NR a R b ,
—NR a S(O) m C 1-6 alkyl,
—NR a S(O) m C 3-6 cycloalkyl,
—S(O)(NRc)C 1-6 alkyl,
—S(O)(NRc)C 3-6 cycloalkyl or
—S(O)(NRc)NR a R b
wherein R a and R b are each independently H, C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 haloalkyl, C 1-6 cyanoalkyl, or C 1-6 alkyloxy or;
R a and R b taken together with the nitrogen to which they are attached form a C 2-6 heterocyclic ring optionally containing 1-4 additional groups selected from NH, O and S;
and m is 0, 1 or 2; and
R c is each independently H, C 1-6 alkyl, C 3-6 cycloalkyl, or C 1-6 alkyloxy;
W is:
C 6-14 aryl,
a C 2-10 heteroaryl containing 1-4 groups selected from N, NH, O and S,
saturated and partially saturated C 2-10 heterocyclyl containing 1-4 groups selected from N, NH, O and S, or
saturated and partially saturated C 3-12 cycloalkyl ring,
wherein each W is optionally substituted with 0-4 substituents selected from the group consisting of cyano, halo, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkenyl, C 1-6 haloalkenyl, C 1-6 alkynyl, C 1-6 haloalkynyl, C 3-6 cycloalkyl, C 3-6 heterocycle containing 1-4 groups selected from NH, O and S, C 1-6 alkoxy, C 3-6 cycloalkyl-oxy, —S(O) m C 1-6 alkyl, —S(O) m C 3-6 cycloalkyl, CN, —C(O)—NR c R d —C(O)—OR c , —NR c R d , NR c R d —C 1-6 alkyl-, and R c O—C 1-6 alkoxy NR c R d —C 1-6 alkoxy-,
wherein R c and R d is each independently H, C 1-6 alkyl, C 1-6 alkenyl, C 1-6 alkynyl, C 3-12 cycloalkyl, C 6-14 aryl, C 2-6 heterocycle containing 1-4 groups selected from NH, O and S, or a C 2-10 heteroaryl containing 1-4 groups selected from N, NH, O and S,
or Rc and R d taken together with the nitrogen to which they are attached form a C 2-6 heterocyclic ring optionally containing 1-4 additional groups selected from NH, O and S;
R 2 is:
—C 1-6 alkyl,
—C 3-6 cycloalkyl,
—C 1-6 alkyloxy,
—C 1-6 hydroxyalkyl,
—C 1-6 haloalkyl,
—H,
—C(O)OR e , or —C(O)NR e R f , wherein R e and R f is each independently H or C 1-6 alkyl;
R 3 is:
—C 1-6 alkyl,
—C 3-6 cycloalkyl,
—C 1-6 alkyloxy;
—H,
—C(O)OR e , or C(O)NR e R f , wherein R e and R f is each independently H or C 1-6 alkyl;
or R 2 and R 3 taken together with the carbon to which they are attached form a C 3-12 carbocyclic ring or a C 2-10 heterocyclic containing 1-4 groups selected from NH, O and S;
R 4 is:
—H,
—C 1-6 alkyl,
—C 1-6 alkyloxy, or
—C 3-6 cycloalkyl;
X, Y and Z are chosen independently from CR e
wherein R e is:
—H,
-halo,
—C 1-6 alkyl,
—C 1-6 haloalkyl,
—C 1-6 haloalkenyl,
—C 1-6 haloalkynyl,
—C 3-6 cycloalkyl,
—C 1-6 alkoxy,
—C 3-6 cycloalkyloxy,
—OC 1-6 alkyl,
—OC 3-6 cycloalkyl,
—S(O) m C 1-6 alkyl,
—S(O) m C 3-6 cycloalkyl,
CN,
—C(O)—NR f R g , —C(O)—OR f , or —NR f R g , wherein R f and R g is each independently H or —C 1-6 alkyl;
C 1-6 alkenyl,
C 1-6 alkynyl,
C 3-12 cycloalkyl, C 6-14 aryl, C 3-6 heterocycle containing 1-4 groups selected from N, NH, O and S, or a C 2-10 heteroaryl containing 1-4 groups selected from N, NH, O and S;
R 5 is:
—H
-halo,
—C 1-6 alkyl, C 1-6 alkenyl,
—C 1-6 alkoxy,
—S(O) m C 1-6 alkyl,
—C 6-14 aryl,
—C 2-10 heterocyclyl containing 1-4 groups selected from N, NH, O and S,
—C 2-10 heteroaryl containing 1-4 groups selected from N, NH, O and S,
—CN,
—C 3 -C 6 cycloalkyl, or-
—C 1-6 haloalkyl,
wherein R 5 may be optionally substituted with 0-5 halo, C 1-6 alkyl, C 1-6 alkoxy, —S(O) m C 1-6 alkyl, C 6-14 aryl, C 2-10 heterocyclyl containing 1-4 groups selected from N, NH, O and S, or a C 2-10 heteroaryl containing 1-4 groups selected from N, NH, O and S, CN, C 3 -C 6 cycloalkyl, OH or —C(O)—NR a R b ,
R 6 is:
-halo,
—C 1-6 alkyl
—C 1-6 alkenyl,
—C 1-6 alkoxy,
—S(O) m C 1-6 alkyl,
—C 6-14 aryl,
—C 2-10 heterocyclyl containing 1-4 groups selected from N, NH, O and S,
—C 2-10 heteroaryl containing 1-4 groups selected from N, NH, O and S,
—H,
—CN,
—C 3 -C 6 cycloalkyl, or-
—C 1-6 haloalkyl,
wherein R 6 may be optionally substituted with 0-5 halo, C 1-6 alkyl, C 1-6 alkoxy, —S(O) m C 1-6 alkyl, C 6-14 aryl, C 2-10 heterocyclyl containing 1-4 groups selected from N, NH, O and S, or a C 2-10 heteroaryl containing 1-4 groups selected from N, NH, O and S, CN, C 3 -C 6 cycloalkyl, OH or —C(O)—NR a R b ,
or R 5 and R 6 taken together with the carbon to which they attached form a C 3-12 carbocyclic ring or a C 2-10 heterocyclic containing 1-4 groups selected from N, NH, O and S;
L is:
a direct bond,
—C═C—

—S(O) m —,
—NR a S(O) m ,
—S(O) m NR a —
—O—,
—C(O)—,
—(CH 2 ) n —,
—O—(CH 2 ) n —,
—N(R a )—,
—N(R a )—(CH 2 ) n —,
—(CH 2 ) n —N(R a )—,
—C(O)—N(Ra)—,
—C(O)—N(R a )—(CH 2 ) n — or
—N(R a )—C(O)—N(R b )—;
wherein R a and R b is each independently H or C 1-3 alkyl;
R 7 is:
halo,
cycloalkyl, cycloalkenyl,

—C 6-14 aryl,
—C 2-10 heterocyclyl containing 1-4 groups selected from N, NH, O and S,
C 2-10 heteroaryl containing 1-4 groups selected from N, NH, O and S,
wherein R 7 may be optionally substituted with 0-5 substituents selected from the group consisting of halogen, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 haloalkenyl, C 1-6 haloalkynyl, C 3-6 cycloalkyl, C 3-7 heterocycle containing 1-4 groups selected from N, NH, O and S, C 6-14 aryl, C 2-10 heteroaryl containing 1-4 groups selected from N, NH, O and S, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyloxy, —S(O) m C 1-6 alkyl, —S(O) m C 3-6 cycloalkyl, CN, —C(O)—NR c R d , —C(O)—OR c , NR c R d and NR c R d C 1-6 alkyl-, wherein R c and R d is each independently H, C 1-6 alkyl, C 1-6 alkenyl, C 1-6 alkynyl, cycloalkyl, —C 6-14 aryl, C 2-10 heterocyclyl containing 1-4 groups selected from N, NH, O and S, or a C 2-10 heteroaryl containing 1-4 groups selected from N, NH, O and S, wherein each heterocyclyl, aryl or heteroaryl is optionally substituted by C 1-6 alkyl, C 1-6 alkoxy; or Rc and Rd—together with the nitrogen to which they are attached form a C 2-6 heterocyclic ring optionally containing 1-4 additional groups selected from N, NH, O and S;
each n is independently 1-4; each m is independently 0-2;
or a pharmaceutically acceptable salt thereof.

2. A compound of formula (I) according to claim 1 , wherein:
R 1 is:

Assignees

• Cook Brian Nicholas
• Huber John D
• Hughes Robert Owen
• Kirrane Jr Thomas Martin
• Lasota Celina
• Li Xiang
• Liang Shuang
• Mugge Ingo Andreas
• Zhang Qiang
• Boehringer Ingelheim Int

Inventors

• Cook Brian Nicholas
• Huber John D
• Hughes Robert Owen
• Kirrane Jr Thomas Martin
• Lasota Celina
• Li Xiang
• Liang Shuang
• Mugge Ingo Andreas
• Zhang Qiang

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

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P37/02

  Immunomodulators · CPC title