title: Tetrahydroisoquinoline amide substituted phenyl pyrazoles as selective Bcl-2 inhibitors.
abstract: 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.
authors.affiliation: UCB Celltech, 216 Bath Road, Slough, United Kingdom. john.porter@ucb-group.com
authors.forename: John
authors.initials: J
authors.lastname: Porter
authors.forename: Andrew
authors.initials: A
authors.lastname: Payne
authors.forename: Ben
authors.initials: B
authors.lastname: de Candole
authors.forename: Daniel
authors.initials: D
authors.lastname: Ford
authors.forename: Brian
authors.initials: B
authors.lastname: Hutchinson
authors.forename: Graham
authors.initials: G
authors.lastname: Trevitt
authors.forename: James
authors.initials: J
authors.lastname: Turner
authors.forename: Chloe
authors.initials: C
authors.lastname: Edwards
authors.forename: Clare
authors.initials: C
authors.lastname: Watkins
authors.forename: Ian
authors.initials: I
authors.lastname: Whitcombe
authors.forename: Jeremy
authors.initials: J
authors.lastname: Davis
authors.forename: Colin
authors.initials: C
authors.lastname: Stubberfield
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D011720:Pyrazoles; D044005:Tetrahydroisoquinolines