Highly Potent, Water Soluble Benzimidazole Antagonist for Activated 41 Integrin

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• 作者：Richard D. Carpenter ; Mirela Andrei ; Edmond Y. Lau ; Felice C. Lightstone ; Ruiwu Liu ; Kit S. Lam ; Mark J. Kurth
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：November 15, 2007
• 年：2007
• 卷：50
• 期：23
• 页码：5863 - 5867
• 全文大小：256K
• 年卷期：v.50,no.23(November 15, 2007)
• ISSN：1520-4804

文摘

The cell surface receptor ₄₁ integrin, activated constitutively in lymphoma, can be targeted with the bisarylurea peptidomimetic antagonist 1 (LLP2A). However, concerns on its preliminary pharmacokinetic (PK)profile provided an impetus to change the pharmacophore from a bisaryl urea to a 2-arylaminobenzimidazolemoiety, resulting in improved solubility while maintaining picomolar potency [5 (KLCA4); IC₅₀ = 305pM]. With exceptional solubility, this finding has the potential for improving PK to help diagnose and treatlymphomas.