US 11,578,069 B2Granted

Compounds for inhibition of α4 β7 integrin

AssigneeGilead Sciences, Inc.

InventorsPeter A. Blomgren, Taryn L. Campbell, Jayaraman Chandrasekhar, Christopher T. Clark, Kevin S. Currie, Jeffrey E. Kropf, Yasamin Moazami, Nicole A. Nava, Leena Patel, Jason K. Perry, Natalie Seeger, Kirk L. Stevens, Zhongdong Zhao

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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), therapeutic methods for treating inflammatory disease.

Claims11

Dependent claims

A compound of formula (IIc):

or a pharmaceutically acceptable salt thereof, wherein;
Rb is C1-4alkyl, or C1-6haloalkyl;
Rd is selected from the group consisting of H, C1-4alkyl, and C1-4haloalkyl;
each R2 and R6 is independently selected from the group consisting of H, halo, cyano, hydroxyl, —NRa1Ra2, C1-4alkyl, C1-4alkoxyl, C1-4haloalkyl, and C1-4haloalkoxyl;
R7 is selected from the group consisting of H, C1-10alkyl, C1-10haloalkyl, C3-10cycloalkyl, 3-14 membered heterocyclyl, C6-10aryl, 5-10 membered heteroaryl, —C1-4alkylene-NRa1Ra2, —C1-4alkylene-C(O)NRa1Ra2, C1-4alkylene-C3-10cycloalkyl, —C1-4alkylene-3-14 membered heterocyclyl, —C1-4alkylene-C6-10aryl, —C1-4alkylene-5-10 membered heteroaryl, and -L1-R9;
wherein L1 is selected from the group consisting of —C1-4alkylene-O—, —C1-4alkylene-C(O)—, —C1-4alkylene-O—C(O)—, —C1-4alkylene-O—C(O)—C1-4alkylene-, —C1-4alkylene-C(O)—O—, —C1-4alkylene-C(O)—O—C1-4alkylene-, —C1-4alkylene-O—C(O)—O—, —C1-4alkylene-O—C(O)—O—C1-4alkylene-, —C1-4alkylene-NRa1C(O)—O—, and —C1-4alkylene-O—C(O)—NRa1—;
R9 is selected from the group consisting of C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, 3-14 membered heterocyclyl, C6-10aryl, and 5-10 membered heteroaryl,
wherein each C3-10cycloalkyl, 3-14 membered heterocyclyl, C6-10aryl, and 5-10 membered heteroaryl of R7 and R9 is optionally substituted with one to four members independently selected from the group consisting of halo, hydroxyl, C1-4 alkyl, C1-4alkoxyl, C1-4haloalkyl, C1-4haloalkoxyl, —NRa1Ra2, and —C1-4alkylene-NRa1Ra2;
and
each Ra1 and Ra2 is independently selected from the group consisting of H, C1-6alkyl, C1-6haloalkyl, and C3-10cycloalkyl.

7 more elements

A compound of formula (TIN:

or a pharmaceutically acceptable salt thereof, wherein;
R1 is 5-10 membered heteroaryl or 6-10 membered heterocyclyl;
wherein each 5-10 membered heteroaryl and 6-10 membered heterocyclyl of R′ contains one to four N and optionally one to three C(O) as a ring member(s);
and
wherein each 5-10 membered heteroaryl and 6-10 membered heterocyclyl of R′ is optionally substituted with one to four Ra;
and wherein each Ra is independently selected from the group consisting of halo, cyano, hydroxyl, —NRa1Ra2, C1-4alkyl, C1-4alkoxyl, C1-4haloalkyl, C1-4haloalkoxyl, —C1-4alkylene-O—C1-4alkyl, and C3-10cycloalkyl;
each R2, and R6 is independently selected from the group consisting of H, halo, cyano, hydroxyl, —NRa1Ra2, C1-4alkyl, C1-4alkoxyl, C1-4haloalkyl, and C1-4haloalkoxyl;
Rb is C1-4alkyl, or C1-6haloalky;
Rc is H, halo, cyano, hydroxyl, —NRa1Ra2, C1-4alkyl, C1-4alkoxyl, C1-4haloalkyl, and C1-4haloalkoxyl;
and
R7 is selected from the group consisting of H, C1-10alkyl, C1-10haloalkyl, C3-10cycloalkyl, 3-14 membered heterocyclyl, C6-10aryl, 5-10 membered heteroaryl, —C1-4alkylene-NRa1Ra2, —C1-4alkylene-C(O)NRa1Ra2, C1-4alkylene-C3-10cycloalkyl, —C1-4alkylene-3-14 membered heterocyclyl, —C1-4alkylene-C6-10aryl, —C1-4alkylene-5-10 membered heteroaryl, and -L2-R9;
wherein L1 is selected from the group consisting of —C1-4alkylene-O—, —C1-4alkylene-C(O)—, —C1-4alkylene-O—C(O)—, —C1-4alkylene-O—C(O)—C1-4alkylene-, —C1-4alkylene-C(O)—O—, —C1-4alkylene-C(O)—O—C1-4alkylene-, —C1-4alkylene-O—C(O)—O—, —C1-4alkylene-O—C(O)—O—C1-4alkylene-, —C1-4alkylene-NRa1C(O)—O—, and —C1-4alkylene-O—C(O)—NRa1—;
R9 is selected from the group consisting of C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, 3-14 membered heterocyclyl, C6-10aryl, and 5-10 membered heteroaryl,
wherein each C3-10cycloalkyl, 3-14 membered heterocyclyl, C6-10aryl, and 5-10 membered heteroaryl of R7 and R9 is optionally substituted with one to four groups independently selected from group consisting of halo, hydroxyl, C1-4alkyl, C1-4alkoxyl, C1-4haloalkyl, C1-4haloalkoxyl, —NRa1Ra2, and —C1-4alkylene-NRa1Ra2;
and
each Ra1 and Ra2 is independently selected from the group consisting of H, C1-6alkyl, C1-6haloalkyl, and C3-10cycloalkyl.

13 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/991,708Filed 12 Aug 2020 · us provisional application
Priority: 14 Aug 2019
Published: US 2021/0053967 A125 Feb 2021
Granted: 14 Feb 2023
Term ends: Not estimatedThe source records don’t support an estimate.

Classification15 codes

C07D 471/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 29/00
Non-central analgesic, antipyretic or antiinflammatory agents
C07C 233/87
With the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom: of a carbon skeleton…
C07D 213/64
One oxygen atom: attached in position 2 or 6