In:
ChemMedChem, Wiley, Vol. 3, No. 12 ( 2008-12-15), p. 1893-1904
Abstract:
Rho kinase plays a pivotal role in several cellular processes such as vasoregulation, making it a suitable target for the treatment of hypertension and related disorders. We discovered a new compound class of Rho kinase (ROCK) inhibitors containing a 7‐azaindole hinge‐binding scaffold tethered to an aminopyrimidine core. Herein we describe the structure–activity relationships elucidated through biochemical and functional assays. The introduction of suitable substituents at the 3‐position of the bicyclic moiety led to an increase in activity, which was required to design compounds with favorable pharmacokinetic profile. Azaindole 32 was identified as a highly selective and orally available ROCK inhibitor able to cause a sustained blood pressure reduction in vivo.
Type of Medium:
Online Resource
ISSN:
1860-7179
,
1860-7187
DOI:
10.1002/cmdc.200800211
Language:
English
Publisher:
Wiley
Publication Date:
2008
detail.hit.zdb_id:
2209649-8
SSG:
15,3