Discovery of potent, selective and orally bioavailable imidazo[1,5-a]pyrazine derived ACK1 inhibitors

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• 作者：Meizhong Jin ; ^{Meizhong.jin@astellas.com} ; Jing Wang ; Andrew Kleinberg ; Mridula Kadalbajoo ; Kam W. Siu ; Andrew Cooke ; Mark A. Bittner ; Yan Yao ; April Thelemann ; Qunsheng Ji ; Shripad Bhagwat ; Kristen M. Mulvihill ; Josef A. Rechka ; Jonathan A. Pachter ; Andrew P. Crew ; David Epstein ; Mark J. Mulvihill
• 关键词：Activated Cdc42-associated kinase (ACK1) ; Inhibitors ; Structure&ndash ; activity relationships (SAR) ; Imidazo[1 ; 5-a]pyrazine ; Cancer
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：15 February, 2013
• 年：2013
• 卷：23
• 期：4
• 页码：979-984
• 全文大小：1193 K

文摘

This Letter describes the medicinal chemistry effort towards a series of novel imidazo[1,5-a]pyrazine derived inhibitors of ACK1. Virtual screening led to the discovery of the initial hit, and subsequent exploration of structure-activity relationships and optimization of drug metabolism and pharmacokinetic properties led to the identification of potent, selective and orally bioavailable ACK1 inhibitors.