Spirocyclic compounds
The present invention provides compounds and intermediates. The present invention also provides compounds which bind to the ubiquitously expressed E3 ligase protein cereblon (CRBN) and their use for the treatment of abnormal cellular proliferation. The present invention also provides compounds that may be used as synthetic intermediates in the synthesis of bifunctional compounds used for targeted protein degradation.
1 . A method of treating cancer in a subject in need thereof comprising administering an effective amount of a compound of formula:
or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutical composition,
wherein:
Y is NH or CH 2 ;
n is 0 or 1;
A is selected from the group consisting of
i.) aryl;
ii.) aryl substituted by R 1 ;
iii.) heteroaryl; and
iv.) heteroaryl substituted by R 2 ;
R 1 is selected from the group consisting of
i.) —C(═O)—O—C 1-6 -alkyl;
ii.) —COOH;
iii.) —NH—C(═O)—C 1-6 -alkyl;
iv.) —NH 2 ; and
v.) —NO 2 ;
R 2 is selected from the group consisting of
i.) —COOH;
ii.) —C(═O)—O—C 1-6 -alkyl;
iii.) —NH 2 ; and
iv.) —NO 2 .
2 . The method of claim 1 , wherein the subject is a human.
3 . The method of claim 2 , wherein A is aryl.
4 . The method of claim 2 , wherein A is heteroaryl.
5 . The method of claim 3 , wherein Y is NH and n is 0.
6 . The method of claim 3 , wherein Y is NH and n is 1.
7 . The method of claim 3 , wherein Y is CH 2 and n is 0.
8 . The method of claim 3 , wherein Y is CH 2 and n is 1.
9 . The method of claim 4 , wherein Y is NH and n is 0.
10 . The method of claim 4 , wherein Y is NH and n is 1.
11 . The method of claim 4 , wherein Y is CH 2 and n is 0.
12 . The method of claim 4 , wherein Y is CH 2 and n is 1.