327618-19-9Relevant academic research and scientific papers
Bioisosteric replacement of anilide with benzoxazole: Potent and orally bioavailable antagonists of VLA-4
Lin, Linus S.,Lanza Jr., Thomas J.,Castonguay, Laurie A.,Kamenecka, Theodore,McCauley, Ermenegilda,Van Riper, Gail,Egger, Linda A.,Mumford, Richard A.,Tong, Xinchun,MacCoss, Malcolm,Schmidt, John A.,Hagmann, William K.
, p. 2331 - 2334 (2007/10/03)
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 α4β7.
