Format

Send to

Choose Destination
Bioorg Med Chem Lett. 2004 May 3;14(9):2331-4.

Bioisosteric replacement of anilide with benzoxazole: potent and orally bioavailable antagonists of VLA-4.

Author information

1
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. linus_lin@merck.com

Abstract

We have designed and synthesized a series of heterocyclic bioisosteres for an anilide based on molecular modeling. Excellent potency was retained in the benzoxazole and the benzimidazole derivatives, where a hydrogen bond acceptor is appropriately positioned to mimic the amide bond oxygen. The deletion of the hydrogen bond donor (N-H) led to improved lipophilicity and bioavailability. In the process, 9a was identified as a potent, specific, and bioavailable VLA-4 antagonist, while 9c was found to be a potent and bioavailable dual antagonist of VLA-4 and alpha(4)beta(7).

PMID:
15081035
DOI:
10.1016/j.bmcl.2004.01.098
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center