Tetrahydroisoquinoline amide substituted phenyl pyrazoles as selective Bcl-2 inhibitors.
Anti-apoptotic Bcl-2 protects cells from apoptosis by binding to pro-apoptotic members of the Bcl-2 family thereby playing a role in tumour survival in response to chemo- or radiation therapy. We describe a series of phenyl pyrazoles that have high affinity for Bcl-2 and rationalise the observed SAR by means of an X-ray crystal structure.
Porter
John
J
UCB Celltech, 216 Bath Road, Slough, United Kingdom. john.porter@ucb-group.com
Payne
Andrew
A
de Candole
Ben
B
Ford
Daniel
D
Hutchinson
Brian
B
Trevitt
Graham
G
Turner
James
J
Edwards
Chloe
C
Watkins
Clare
C
Whitcombe
Ian
I
Davis
Jeremy
J
Stubberfield
Colin
C
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D018360:Crystallography, X-Ray; D015394:Molecular Structure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000737:chemistry* / Q000494:pharmacology
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D011720:Pyrazoles; D044005:Tetrahydroisoquinolines