Aminopyrimidinyl compounds

Patent metadata

Field	Value
Publication number	US-11197867-B2
Application number	US-202016920027-A
Country	US
Kind code	B2
Filing date	Jul 2, 2020
Priority date	Aug 21, 2014
Publication date	Dec 14, 2021
Grant date	Dec 14, 2021

Abstract

A compound compound having the structure:

or a pharmaceutically acceptable salt thereof, wherein X is N or CR, where R is hydrogen, deuterium, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 3 -C 6 cycloalkyl, aryl, heteroaryl, aryl(C 1 -C 6 alkyl), CN, amino, alkylamino, dialkylamino, CF 3 , or hydroxyl; A is selected from the group consisting of a bond, C═O, —SO 2 —, —(C═O)NR 0 —, and —(CR a R b ) q —, where R 0 is H or C 1 -C 4 alkyl, and R a and R b are independently hydrogen, deuterium, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, aryl, aryl(C 1 -C 6 alkyl), heteroaryl, (C 1 -C 6 alkyl)heteroaryl, etc.; A′ is selected from the group consisting of a bond, C═O, —SO 2 —, —(C═O)NR 0 ′, —NR 0 ′(C═O)—, and —(CR a ′R b ′) q —, where R 0 ′ is H or C 1 -C 4 alkyl, and R a ′ and R b ′ are independently hydrogen, deuterium, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, aryl, aryl(C 1 -C 6 alkyl), heteroaryl, (C 1 -C 6 alkyl)heteroaryl, heteroaryl(C 1 -C 6 alkyl), and heterocyclic(C 1 -C 6 alkyl); Z is —(CH 2 ) h — or a bond, where one or more methylene units are optionally substituted by one or more C 1 -C 3 alkyl, CN, OH, methoxy, or halo, and where said alkyl may be substituted by one or more fluorine atoms; R 1 and R 1 ′ are independently selected from the group consisting of hydrogen, deuterium, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, aryl, heteroaryl, aryl(C 1 -C 6 alkyl), CN, etc., wherein said alkyl, aryl, cycloalkyl, heterocyclic, or heteroaryl is further optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, halo, CN, C 1 -C 4 alkylamino, C 3 -C 6 cycloalkyl, etc.; R 2 is selected from the group consisting of hydrogen, deuterium, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, halo, and cyano, where said alkyl may be substituted by one or more fluorine atoms; R 3 is selected from the group consisting of hydrogen, deuterium, and amino; R 4 is monocyclic or bicyclic aryl or monocyclic or bicyclic heteroaryl wherein said aryl or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, heterocycloalkyl, halo, C 3 -C 6 cycloalkyl, etc., where said alkyl, cycloalkyl, alkoxy, or heterocycloalkyl may be substituted by one or more C 1 -C 6 alkyl, halo, CN, OH, alkoxy, amino, —CO 2 H, —(CO)NH 2 , —(CO)NH(C 1 -C 6 alkyl), or —(CO)N(C 1 -C 6 alkyl) 2 , and where said alkyl may be further substituted by one or more fluorine atoms; R 5 is independently selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, and hydroxyl; h is 1, 2 or 3; j and k are independently 0, 1, 2, or 3; m and n are independently 0, 1 or 2; and, q is 0, 1 or 2. Also provided are methods of treatment as Janus Kinase inhibitors and pharmaceutical compositions containing the compounds of the invention and combinations with other therapeutic agents.

First claim

What is claimed is:

1. A compound having the structure:

or a pharmaceutically acceptable salt thereof, wherein
X is N;
A is selected from the group consisting of a bond and C═O;
R 1 is C 3 -C 6 cycloalkyl, wherein said cycloalkyl is further optionally substituted with one or more halo;
R 2 is hydrogen;
R 3 is hydrogen;
R 4 is monocyclic heteroaryl wherein said heteroaryl is optionally substituted with one or more C 1 -C 6 alkyl; and,
R 5 is hydrogen; and, j is 0 or1.

2. The compound of claim 1 , wherein A is C═O, or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 , wherein j is 0, or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 , wherein R 4 is monocyclic heteroaryl and said monocyclic heteroaryl is pyrazole, or a pharmaceutically acceptable salt thereof.

5. The compound of claim 4 , wherein said monocyclic heteroaryl is pyrazole substituted by C 1 -C 6 alkyl, or a pharmaceutically acceptable salt thereof.

6. A compound having the structure:

or a pharmaceutically acceptable salt thereof, wherein R 1 is C 3 -C 6 cycloalkyl, further optionally substituted with one or more halo and wherein R′ is C 1 -C 6 alkyl.

7. The compound of claim 6 having the structure:

wherein R′ is C 1 -C 6 alkyl.

8. The compound of claim 6 having the structure:

wherein R′ is C 1 -C 6 alkyl.

9. A pharmaceutical composition comprising a compound of any of claims 1 to 8 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

Assignees

• Pfizer

Inventors

• Fensome Andrew
• Gopalsamy Ariamala
• Gerstenberger Brian S
• Efremov Ivan Viktorovich
• Wan Zhao-Kui
• PIERCE Betsy
• Telliez Jean-Baptiste
• Trujillo John I
• Zhang Liying
• Xing Li
• Saiah Eddine

Classifications

• C07D487/08 Primary

  Bridged systems · CPC title

• A61P17/14

  for baldness or alopecia · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61K31/55 Primary

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title

• C07D403/14

  containing three or more hetero rings · CPC title