Substituted benzocyloheptenes as potent and selective alpha(v) integrin antagonists

Françoise Perron-Sierra; Dominique Saint Dizier; Marc Bertrand; Annie Genton; Gordon C Tucker; Patrick Casara

doi:10.1016/s0960-894x(02)00696-0

Substituted benzocyloheptenes as potent and selective alpha(v) integrin antagonists

Bioorg Med Chem Lett. 2002 Nov 18;12(22):3291-6. doi: 10.1016/s0960-894x(02)00696-0.

Authors

Françoise Perron-Sierra¹, Dominique Saint Dizier, Marc Bertrand, Annie Genton, Gordon C Tucker, Patrick Casara

Affiliation

¹ Institut de Recherches Servier, 125 chemin de Ronde, 78290 Croissy sur Seine, France.

PMID: 12392735
DOI: 10.1016/s0960-894x(02)00696-0

Abstract

A novel series of potent and specific alpha(v) integrin antagonists has been obtained by aminoalkyl substitutions on benzocyloheptene acetic acids as a rigid GD bioisostere. The preferred compounds 1-2, 1-3 and 1-8, showed nano- to subnanomolar IC(50) values on alpha(v)beta(3) and alpha(v)beta(5) integrins, with favorable pharmacokinetics.

MeSH terms

Animals
Benzocycloheptenes / chemical synthesis*
Benzocycloheptenes / pharmacology*
Biological Availability
Cell Adhesion / drug effects
Cell Membrane Permeability
Humans
Inhibitory Concentration 50
Integrin alphaV / drug effects*
Integrin alphaVbeta3 / antagonists & inhibitors
Integrins / antagonists & inhibitors
Microsomes, Liver / metabolism
Molecular Conformation
Oligopeptides
Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors
Rats
Receptors, Vitronectin / antagonists & inhibitors
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

Benzocycloheptenes
Integrin alphaV
Integrin alphaVbeta3
Integrins
Oligopeptides
Platelet Glycoprotein GPIIb-IIIa Complex
Receptors, Vitronectin
integrin alphaVbeta5
arginyl-glycyl-aspartic acid