Potent and selective small-molecule human urotensin-II antagonists with improved pharmacokinetic profiles.
Bioorg Med Chem Lett
; 18(13): 3716-9, 2008 Jul 01.
Article
in En
| MEDLINE
| ID: mdl-18524591
ABSTRACT
Lead compound 1 was successfully redesigned to provide compounds with improved pharmacokinetic profiles for this series of human urotensin-II antagonists. Replacement of the 2-pyrrolidinylmethyl-3-phenyl-piperidine core of 1 with a substituted N-methyl-2-(1-pyrrolidinyl)ethanamine core as in compound 7 resulted in compounds with improved oral bioavailability in rats. The relationship between stereochemistry and selectivity for hUT over the kappa-opioid receptor was also explored.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Urotensins
/
Chemistry, Pharmaceutical
Limits:
Animals
/
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2008
Document type:
Article
Affiliation country: