The discovery and synthesis of JNJ 31020028, a small molecule antagonist of the Neuropeptide Y Y₂ receptor

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• 作者：Devin M. Swanson ; ^a ; ^{dswanso1@its.jnj.com"" rel=""nofollow} ; Victoria D. Wong^a ; Jill A. Jablonowski^a ; Chandra Shah^a ; Dale A. Rudolph^a ; Curt A. Dvorak^a ; Mark Seierstad^a ; Lisa K. Dvorak^a ; Kirsten Morton^a ; Diane Nepomuceno^a ; John R. Atack^a ; Pascal Bonaventure^a ; Timothy W. Lovenberg^a ; Nicholas I. Carruthers^a
• 关键词：Neuropeptide Y Y₂ antagonist ; Neuropeptide Y Y₂ receptor ; Neuropeptide Y
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2011
• 出版时间：15 September 2011
• 年：2011
• 卷：21
• 期：18
• 页码：5552-5556
• 全文大小：1776 K

文摘

A series of small molecules based on a chemotype identified from our compound collection were synthesized and tested for binding affinity (IC₅₀) at the human Neuropeptide Y Y₂ receptor (NPY Y₂). Six of the 23 analogs tested possessed an NPY Y₂ IC₅₀  15 nM. One member of this series, JNJ 31020028, is a selective, high affinity, receptor antagonist existing as a racemic mixture. As such a synthetic route to the desired enantiomer was designed starting from commercially available (S)-(+)-mandelic acid.