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Updated: Aug 16, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Aza-bicyclic amino acid carboxamides as alpha4beta1/alpha4beta7 integrin receptor antagonists
Alexey B Dyatkin1, Yong Gong, Tamara A Miskowski
1Drug Discovery, Johnson & Johnson Pharmaceutical Research & Development, LLC., Spring House, PA 19477-0776, USA. adyatkin@prdus.jnj.com
Abstract:
A series of N-carboxy, N-alkyl, and N-carboxamido azabicyclo[2.2.2]octane carboxamides were prepared and assayed for inhibition of alpha4beta1-VCAM-1 and alpha4beta7-MAdCAM-1 interactions. Potency and alpha4beta1/alpha4beta7 selectivity were sensitive to the substituent R1-R3 in the structures 6, 7, and 8. Several compounds demonstrated low nanomolar balanced alpha4beta1/alpha4beta7 in vitro activity. Two compounds were selected for in vivo leukocytosis studies and demonstrated increases in circulating lymphocytes up to 250% over control.
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