Structure-activity relationship of a series of diaminoalkyl substituted benzimidazole as neuropeptide Y Y1 receptor antagonists

H Zarrinmayeh; D M Zimmerman; B E Cantrell; D A Schober; R F Bruns; S L Gackenheimer; P L Ornstein; P A Hipskind; T C Britton; D R Gehlert

doi:10.1016/s0960-894x(99)00082-7

Structure-activity relationship of a series of diaminoalkyl substituted benzimidazole as neuropeptide Y Y1 receptor antagonists

Bioorg Med Chem Lett. 1999 Mar 8;9(5):647-52. doi: 10.1016/s0960-894x(99)00082-7.

Authors

H Zarrinmayeh¹, D M Zimmerman, B E Cantrell, D A Schober, R F Bruns, S L Gackenheimer, P L Ornstein, P A Hipskind, T C Britton, D R Gehlert

Affiliation

¹ Eli Lilly and Company, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA.

PMID: 10201822
DOI: 10.1016/s0960-894x(99)00082-7

Abstract

A series of benzimidazoles (4) was synthesized and evaluated in vitro as potent and selective NPY Y1 receptor antagonists. Substitution of the piperidine nitrogen of 4 with appropriate R groups resulted in compounds with more than 80-fold higher affinity at the Y receptor compared to the parent compound 5 (R = H). The most potent benzimidazole in this series was 21 (Ki = 0.052 nM).

MeSH terms

Adenylyl Cyclases / metabolism
Animals
Benzimidazoles / chemical synthesis*
Benzimidazoles / chemistry
Benzimidazoles / pharmacology
CHO Cells
Cricetinae
Humans
Neuropeptides / drug effects
Neuropeptides / genetics
Receptors, Neuropeptide Y / antagonists & inhibitors*
Structure-Activity Relationship
Transfection

Substances

Benzimidazoles
Neuropeptides
Receptors, Neuropeptide Y
neuropeptide Y-Y1 receptor
benzimidazole
Adenylyl Cyclases