Back to Search Start Over

Identification of potent, highly constrained CGRP receptor antagonists.

Authors :
Stump CA
Bell IM
Bednar RA
Fay JF
Gallicchio SN
Hershey JC
Jelley R
Kreatsoulas C
Moore EL
Mosser SD
Quigley AG
Roller SA
Salvatore CA
Sharik SS
Theberge CR
Zartman CB
Kane SA
Graham SL
Selnick HG
Vacca JP
Williams TM
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2010 Apr 15; Vol. 20 (8), pp. 2572-6. Date of Electronic Publication: 2010 Feb 25.
Publication Year :
2010

Abstract

A novel series of potent CGRP receptor antagonists containing a central quinoline ring constraint was identified. The combination of the quinoline constraint with a tricyclic benzimidazolinone left hand fragment produced an analog with picomolar potency (14, CGRP K(i)=23 pM). Further optimization of the tricycle produced a CGRP receptor antagonist that exhibited subnanomolar potency (19, CGRP K(i)=0.52 nM) and displayed a good pharmacokinetic profile in three preclinical species.<br /> (Copyright 2010 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1464-3405
Volume :
20
Issue :
8
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
20299218
Full Text :
https://doi.org/10.1016/j.bmcl.2010.02.086