Compositions and methods for preparing and using azetidines

Patent metadata

Field	Value
Publication number	US-11512072-B2
Application number	US-201917048500-A
Country	US
Kind code	B2
Filing date	Apr 19, 2019
Priority date	Apr 19, 2018
Publication date	Nov 29, 2022
Grant date	Nov 29, 2022

Abstract

The present disclosure provides azetidine compounds of Formula I and their pharmaceutically acceptable salts, their compositions, and methods for their use in determining azetidine compound binding to proteins. The azetidine compounds are useful as probes, for monitoring diacylglycerol kinase activity, and for identifying druggable targets.

First claim

We claim:

1. An azetidine compound of Formula I or a pharmaceutically acceptable salt thereof:

wherein
A is —NH;
X is NR 4 and Y is CH;

B is a bond, C 1 -C 6 -alkylene, or —(C 1 -C 6 -alkylene)(C 6 -C 12 -arylene);
R 1 is selected from the group consisting of H and C 6 -C 12 -aryl;
R 4 is selected from the group consisting of C 6 -C 12 -aryl, 5- to 12-membered heteroaryl (wherein one or more members is selected from N, O, and S), 5- to 12-membered —O-(heteroaryl) (wherein one or more members is selected from N, O, and S), and 4- to 12-membered heterocycle (wherein one or more members is selected from N, O, and S);
m is 0, 1, 2, 3, or 4; and
any aryl, heterocycle, or heteroaryl is optionally substituted with one to four substituents selected from the group consisting of halogen, hydroxy, cyano, acyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, alkoxy, amino, amide, thiol, oxo, nitro, and carboxy.

2. The compound or pharmaceutically acceptable salt according to claim 1 , wherein R 4 is C 6 -C 12 -aryl or 5- to 12-membered heteroaryl (wherein one or more members is selected from N, O, and S).

3. An azetidine compound of Formula I or a pharmaceutically acceptable salt thereof,

wherein
A is —CH 2 —;
X is CR 2 R 3 ;
Y is N;
B is —CH 2 CH 2 —;
R 1 is selected from the group consisting of H and C 6 -C 12 -aryl;
R 2 is H;
R 3 is selected from the group consisting of —(C 1 -C 6 -alkyl)(C 6 -C 12 -aryl), C 6 -C 12 -aryl, —O—(C 6 -C 12 -aryl); 5- to 12-membered heteroaryl except triazole and diazole (wherein one or more members is selected from N, O, and S), and 5-to 12-membered —O-(heteroaryl) (wherein one or more members is selected from N, O, and S);
m is 0, 1, 2, 3, or 4; and
any aryl, or heteroaryl is optionally substituted with one to four substituents selected from the group consisting of halogen, hydroxy, cyano, acyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, alkoxy, amino, amide, thiol, nitro, and carboxy.

4. A compound or pharmaceutically acceptable salt thereof, wherein the compound is selected from the following table:

Example
Structure

TH055

TH056

TH057

RLM-1451

RLM-1452

RLM-1453

RLM-207

RLM-266

RLM-275

RLM-277

TH058

TH059

TH060

TH061

TH062

TH064

TH065

TH066

Assignees

• Univ Virginia Patent Foundation

Inventors

• Hsu Ku-Lung
• Mccloud Rebecca L

Classifications

• C07D205/04 Primary

  having no double bonds between ring members or between ring members and non-ring members · CPC title

• C07D401/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D205/12

  condensed with carbocyclic rings or ring systems · CPC title

• C07D403/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D417/12

  linked by a chain containing hetero atoms as chain links · CPC title