Inhibitors of TRIM33 and methods of use

Patent metadata

Field	Value
Publication number	US-11731967-B2
Application number	US-201816604030-A
Country	US
Kind code	B2
Filing date	Apr 27, 2018
Priority date	Apr 28, 2017
Publication date	Aug 22, 2023
Grant date	Aug 22, 2023

Abstract

The application relates to a compound of Formula (I):which modulates the activity of TRIM33, a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease in which TRIM33 plays a role.

First claim

The invention claimed is:

1. A compound of Formula Ic:

or a pharmaceutically acceptable salt or ester thereof, wherein:
R 7 and R 7 ′ are each independently H, (C 1 -C 4 ) alkyl, (C 1 -C 4 ) haloalkyl, or (CHR 5 ) n2 -R 7 a , or R 7 and R 7 ′, together with the carbon atom to which they are attached, form a C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkenyl, or a heterocyclyl having one, two, or three 4- to 7-membered rings and 1-4 heteroatoms selected from N, O, and S, wherein the two or three 4- to 7-membered rings are fused, and wherein the cycloalkyl, cycloalkenyl, or heterocyclyl is optionally substituted with one or more R sb2 ;
R 7a is OH, SH, S(C 1 -C 4 ) alkyl, (C 1 -C 4 ) alkoxy, (C 1 -C 4 ) haloalkoxy, O—C 6 -C 10 aryl, NH 2 , NH(C 1 -C 4 ) alkyl, N((C 1 -C 4 ) alkyl) 2 , C(O)OH, C(O)(C 1 -C 4 ) alkyl, C(O)O(C 1 -C 4 ) alkyl, C(O)NH(C 1 -C 4 ) alkyl, NHC(O)(C 1 -C 4 ) alkyl, NHC(O)O(C 1 -C 4 ) alkyl, NHC(O)NH(C 1 -C 4 ) alkyl, (C 2 -C 8 ) alkenyl, (C 2 -C 8 ) alkynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 a cycloalkenyl, or a heterocyclyl having one, two, or three 4- to 7-membered rings and 1-4 heteroatoms selected from N, O, and S, wherein the two or three 4- to 7-membered rings are fused, or heteroaryl having one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O, and S, wherein the two 5- or 6-membered rings are fused, and wherein the alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more R sb2 ;
n2 is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
each R sb2 is independently (C 1 -C 6 ) alkyl, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkoxy, (C 2 -C 6 ) alkenyl, (C 2 -C 6 ) alkynyl, halogen, nitro, CN, oxo, B(OH) 2 , OH, SH, S(C 1 -C 6 ) alkyl, NH 2 , NH(C 1 -C 4 ) alkyl, N((C 1 -C 4 ) alkyl) 2 , NH(C 6 -C 10 ) aryl, N((C 6 -C 10 ) aryl) 2 , C(O)OH, C(O)(C 1 -C 4 ) alkyl, C(O)O(C 1 -C 4 ) alkyl, C(O)NH(C 1 -C 4 ) alkyl, NHC(O)(C 1 -C 4 ) alkyl, NHC(O)O(C 1 -C 4 ) alkyl, NHC(O)NH(C 1 -C 4 ) alkyl, S(O) o R 6 , S(O) 2 NH 2 , O—C 3 -C 8 cycloalkyl, O—C 3 -C 8 cycloalkenyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkenyl, heterocyclyl having one or two 4- to 7-membered rings and 1-4 heteroatoms selected from N, O, and S, C 6 -C 10 aryl, or heteroaryl having one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O, and S, wherein the cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted, and the two 4- to 7-membered rings and the two 5- or 6-membered rings are fused, and wherein the (C 1 -C 6 ) alkyl or (C 1 -C 6 ) alkoxy is optionally substituted with CN, OH, NH 2 , NH(C 1 -C 4 ) alkyl, or N((C 1 -C 4 ) alkyl) 2 ;
each R 5 is independently H or (C 1 -C 4 ) alkyl;
o is 0, 1, or 2; and
R 6 is OH, (C 1 -C 4 ) alkyl, or C 6 -C 10 aryl, wherein the aryl is optionally substituted.

2. A method of inhibiting TRIM33 or treating a disease or disorder in which TRIM33 plays a role in a subject in need thereof, comprising administering to the subject an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt or ester thereof.

3. A compound, which is:

or a pharmaceutically acceptable salt or ester thereof, wherein R is selected from:

4. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt or ester thereof, and a pharmaceutically acceptable carrier.

5. A pharmaceutical composition comprising the compound of claim 3 , or a pharmaceutically acceptable salt or ester thereof, and a pharmaceutically acceptable carrier.

Assignees

• Dana Farber Cancer Inst Inc

Inventors

• Qi Jun
• Pei Cheng-Kui

Classifications

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title