Quinoline derivatives

Patent metadata

Field	Value
Publication number	US-11116760-B2
Application number	US-201916667306-A
Country	US
Kind code	B2
Filing date	Oct 29, 2019
Priority date	Oct 30, 2018
Publication date	Sep 14, 2021
Grant date	Sep 14, 2021

Abstract

The present disclosure provides a compound of Formula (I):

or a pharmaceutically acceptable salt thereof as described herein. The present disclosure also provides pharmaceutical compositions comprising a compound of Formula (I), processes for preparing compounds of Formula (I), and therapeutic methods for treating inflammatory disease.

First claim

What is claimed is:

1. A compound of formula (II):

or a pharmaceutically acceptable salt thereof, wherein:
L is selected from a bond, —O—, —O—C(O)—*, —NH—, —C(O)—N(H)—*, and —N(H)—C(O)—*; wherein * indicates the point of attachment of L to R 1 ;
R 1 is selected from A 1 , A 2 , and A 3 ;
A 1 is 5-10 membered heteroaryl containing one to five heteroatoms independently selected from S, N, and O; wherein A 1 optionally comprises one to three C(O); and wherein A 1 is optionally substituted with one to six R a ;
A 2 is C 6-10 aryl, optionally substituted with one to six R a ; and
A 3 is C 5-10 cycloalkyl or 5-14 membered heterocyclyl; wherein A 3 is optionally substituted with one to four groups independently selected from oxo and R a ;

wherein each R a is independently selected from halo, cyano, hydroxyl, —NR a1 R a2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxyl, C 1-6 haloalkyl, C 1-6 haloalkoxyl, —S(O) m —C 1-6 alkyl, C 3-8 cycloalkyl, 3-6 membered heterocyclyl, C 6-10 aryl, 5-6 membered heteroaryl, —O—C 3-8 cycloalkyl, —O-(3-6 membered heterocyclyl), —O—C 1-4 alkylene-C 3-8 cycloalkyl, and —O-phenyl;
wherein each C 3-8 cycloalkyl, 3-6 membered heterocyclyl, C 6-10 aryl, 5-6 membered heteroaryl, —O—C 3-8 cycloalkyl, —O-(3-6 membered heterocyclyl), —O—C 1-4 alkylene-C 3-8 cycloalkyl, and —O-phenyl of R a is independently optionally substituted with one to three groups independently selected from halo, cyano, hydroxyl, —NR a1 R a2 , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxyl, and C 1-6 haloalkoxyl; and
wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxyl, C 1-6 haloalkyl, C 1-6 haloalkoxyl, and —S(O) m —C 1-6 alkyl of R a is optionally substituted with one to three R a3 , wherein each R a3 is independently selected from halo, cyano, hydroxyl, —NR a1 R a2 , C 1-6 alkoxyl, C 3-8 cycloalkyl, and 3-6 membered heterocyclyl;
wherein each C 3-8 cycloalkyl and 3-6 membered heterocyclyl of R a3 is optionally substituted with one to three R a4 ; and each R a4 is independently selected from halo, cyano, hydroxyl, —NR a1 R a2 , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxyl, C 1-6 haloalkoxyl, C 3-8 cycloalkyl, and 3-6 membered heterocyclyl;

each R 2 , R 3 , R 4 , R 5 , and R 6 is independently selected from H, halo, cyano, hydroxyl, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxyl, C 1-8 haloalkyl, C 1-8 haloalkoxyl, —NR b1 R b2 , —R b3 S(O) m R b4 , —S(O) m R b4 , —NR b1 S(O) n R b4 , —COOR b1 , —CONR b1 R b2 , —NR b1 COOR b2 , —NR b1 COR b4 , —R b3 NR b1 R b2 , —S(O) n NR b1 R b2 , C 3-12 cycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, and 3-12 membered heterocyclyl;
wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxyl, C 1-8 haloalkyl, and C 1-8 haloalkoxyl of R 2 , R 3 , R 4 , R 5 , and R 6 is optionally substituted with one to two R c ; wherein each R c is independently selected from azido, oxo, cyano, halo, hydroxyl, —NR a1 R a2 , C 1-4 alkoxyl, C 3-8 cycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, and 4-6 membered heterocyclyl; wherein each C 3-8 cycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, and 4-6 membered heterocyclyl of R c is optionally substituted with one to three groups independently selected from halo, cyano, hydroxyl, —NR a1 R a2 , C 1-4 alkyl, C 1-6 haloalkyl, C 1-6 alkoxyl, and C 3-6 cycloalkyl;
wherein each C 6-10 aryl, and 5-6 membered heteroaryl of R 2 , R 3 , R 4 , R 5 , and R 6 is independently optionally substituted with one to five R b ; and
wherein each C 3-12 cycloalkyl, and 3-12 membered heterocyclyl of R 2 , R 3 , R 4 , R 5 , and R 6 is independently optionally substituted one to six groups independently selected from ═CR b1 R b2 and R b ;
wherein each R b is independently selected from azido, cyano, halo, hydroxyl, —NR a1 R a2 , C 1-6 alkyl, C 1-8 haloalkyl, C 1-6 alkoxyl, C 3-6 cycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, and 4-6 membered heterocyclyl; wherein each C 3-6 cycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, and 4-6 membered heterocyclyl of R b is independently optionally substituted with one to three groups independently selected from halo, cyano, hydroxyl, —NR a1 R a2 , C 1-4 alkyl, C 1-4 haloalkyl, and C 1-4 alkoxyl;
wherein each R b1 and R b2 is independently selected from H, C 1-8 alkyl, C 1-8 haloalkyl, C 3-8 cycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, and 3-8 membered heterocyclyl;
wherein each C 3-8 cycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, and 4-6 membered heterocyclyl of R b1 and R b2 is independently optionally substituted with one to three groups independently selected from halo, cyano, hydroxyl, —NR a1 R a2 , C 1-8 alkyl, C 1-8 haloalkyl, C 1-6 alkoxyl, C 3-6 cycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, and 4-6 membered heterocyclyl; and
 wherein each C 1-8 alkyl and C 1-8 haloalkyl of R b1 and R b2 is optionally substituted with one to two R b5 ;
 wherein R b3 is C 1-4 alkylene;

wherein R b4 is selected from C 1-4 alkyl, C 1-4 haloalkyl, C 3-6 cycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, and 4-6 membered heterocyclyl; wherein each C 1-4 alkyl, C 1-4 haloalkyl, C 3-8 cycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, and the 4-6 membered heterocyclyl of R b4 is optionally substituted with one to three R b6 ;
wherein each R b5 is independently selected from cyano, hydroxyl, C 1-4 alkoxyl, C 3-8 cycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, and 4-6 membered heterocyclyl; and each C 1-4 alkoxyl, C 3-8 cycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, and 4-6 membered heterocyclyl of R b5 is optionally substituted with one to three groups independently selected from halo, cyano, hydroxyl, —NR a1 R a2 , C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxyl, and phenyl; and
wherein each R b6 is independently selected from halo, cyano, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxyl, C 3-6 cycloalkyl, phenyl, 4-6 membered heterocyclyl, and 5-6 membered heteroaryl; wherein each C 3-6 cycloalkyl, 4-6 membered heterocyclyl, and 5-6 membered heteroaryl of R b6 is independently optionally substituted with one to three groups independently selected from halo, cyano, —NR a1 R a2 , C 1-4 alkyl, C 1-4 haloalkyl, and C 1-4 alkoxyl; or

R 2 and R 3 , R 3 and R 4 , or R 5 and R 6 together with the atoms to which they are attached form a C 6-10 aryl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, or 5-6 membered heterocyclyl; wherein each C 6-10 aryl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, and 5-6 membered heterocyclyl is independently optionally substituted with one to three groups independently selected from halo, cyano, —NR a1 R a2 , C 1-6 alkyl, C 1-6 alkoxyl, C 1-6 haloalkyl, C 3-8 cycloalkyl, 3-6 membered heterocyclyl, C 6-10 aryl, 5-6 membered heteroaryl, C 1-4 alkylene-C 3-8 cycloalkyl, C 1-4 alkylene-C 6-10 aryl, and C 1-4 alkylene-(5-6 membered heteroaryl);

each R 7 , R 8 , R 9 , R 19 , and R 11 is independently selected from H, halo, hydroxyl, cyano, C 1-6 alkyl, C 1-6 alkoxyl, C 1-6 haloalkyl, C 1-6 haloalkoxyl, and —NR a1 R a2 ;
R 13 is selected from H, C 1-4 alkyl, and C 1-4 haloalkyl; and
R 14 is selected from H, C 1-6 alkyl, —C 1-4 alkylene-NR a1 R a2 , —C 1-4 alkylene-C(O)NR a1 R a2 , —C 1-4 alkylene-O—C(O)—C 1-4 alkyl, —C 1-4 alkylene-O—C(O)—O—C 1-4 alkyl, —C 1-4 alkylene—O—C(O)—C 1-4 alkylene-NR a1 R a2 , —C 1-4 alkylene-O—C 1-4 alkyl, C 3-8 cycloalkyl, —C 1-4 alkylene-C 3-8 cycloalkyl, 4-6 membered heterocyclyl, and —C 1-4 alkylene-(4-6 membered heterocyclyl);
wherein each C 3-8 cycloalkyl, —C 1-4 alkylene-C 3-8 cycloalkyl, 4-6 membered heterocyclyl, and —C 1-4 alkylene-(4-6 membered heterocyclyl) of R 14 is optionally substituted with one to three groups independently selected from halo, C 1-4 alkyl, C 1-4 alkoxyl, and C 1-4 haloalkyl; or
R 14 together with the N that attaches to R 13 forms a 5 membered

Assignees

• Gilead Sciences Inc

Inventors

• Blomgren Peter A
• Campbell Taryn
• Chandrasekhar Jayaraman
• Clark Christopher T
• Codelli Julian A
• Currie Kevin S
• Kropf Jeffrey E
• Moazami Yasamin
• Nava Nicole
• Patel Leena
• Perreault Stephane
• Perry Jason K
• Sedillo Kassandra F
• Seeger Natalie
• Stevens Kirk L
• Treiberg Jennifer Anne
• Yeung Suet C
• Zhao Zhongdong

Classifications

• A61P31/18

  for HIV · CPC title

• A61P13/12

  of the kidneys · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title

• A61P29/00

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