PD 176252--the first high affinity non-peptide gastrin-releasing peptide (BB2) receptor antagonist

V Ashwood; V Brownhill; M Higginbottom; D C Horwell; J Hughes; R A Lewthwaite; A T McKnight; R D Pinnock; M C Pritchard; N Suman-Chauhan; C Webb; S C Williams

doi:10.1016/s0960-894x(98)00462-4

PD 176252--the first high affinity non-peptide gastrin-releasing peptide (BB2) receptor antagonist

Bioorg Med Chem Lett. 1998 Sep 22;8(18):2589-94. doi: 10.1016/s0960-894x(98)00462-4.

Authors

V Ashwood¹, V Brownhill, M Higginbottom, D C Horwell, J Hughes, R A Lewthwaite, A T McKnight, R D Pinnock, M C Pritchard, N Suman-Chauhan, C Webb, S C Williams

Affiliation

¹ Parke-Davis Neuroscience Research Centre, Cambridge University Forvie Site, UK.

PMID: 9873586
DOI: 10.1016/s0960-894x(98)00462-4

Abstract

In this paper we describe the development of a novel series of non-peptide, "balanced" neuromedin-B preferring (BB1)/gastrin-releasing peptide preferring (BB2) receptor ligands as exemplified by PD 176252. PD 176252, which exhibits nanomolar affinity for both the BB1 (Ki = 0.15 nM) and BB2 (Ki = 1.0 nM) receptors, has been demonstrated to be a competitive antagonist at these bombesin receptor subtypes.

MeSH terms

Animals
Gastrin-Releasing Peptide / metabolism
Humans
Indoles / chemistry
Indoles / metabolism*
Kinetics
Ligands
Models, Chemical
Neurokinin B / analogs & derivatives
Neurokinin B / metabolism
Rats
Receptors, Bombesin / antagonists & inhibitors*
Species Specificity
Structure-Activity Relationship

Substances

Indoles
Ligands
PD 165929
Receptors, Bombesin
Gastrin-Releasing Peptide
Neurokinin B
neuromedin B
PD 176252