Novel pyrazolo[1,5-a]pyridines with improved aqueous solubility as p110α-selective PI3 kinase inhibitors

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• 作者：Jackie D. Kendall^a ; ^b ; ^{j.kendall@auckland.ac.nz} ; Anna C. Giddens^a ; Kit Yee Tsang^a ; Elaine S. Marshall^a ; Claire L. Lill^c ; Woo-Jeong Lee^c ; Sharada Kolekar^c ; Mindy Chao^c ; Alisha Malik^c ; Shuqiao Yu^c ; Claire Chaussade^b ; ^c ; ^d ; Christina Buchanan^b ; ^c ; Stephen M.F. Jamieson^a ; ^b ; Gordon W. Rewcastle^a ; ^b ; Bruce C. Baguley^a ; ^b ; William A. Denny^a ; ^b ; Peter R. Shepherd^b ; ^c
• 关键词：NKJYYWGDGSKPEW-LPYMAVHISA-N ; AOXAAEQFLNMCLC-BUVRLJJBSA-N ; WBWLQGYBHWVMKE-DHRITJCHSA-N ; MXOGXVOOBVIVJW-YDZHTSKRSA-N ; AZJHDRSPNKBZGF-MFKUBSTISA-N ; QIGFDKVDGDNYSS-LGJNPRDNSA-N ; QPTBMDPOZNSWEZ-WSDLNYQXSA-N ; OCKIBXWFWFCVNS-YDZHTSKRSA-N ; UZWYFVJGBGJHHK-OEAKJJBVSA-N ; IHHGTHQQCPWJCF-BUVRLJJBSA-N ; LAWUZULWVPIZEA-PCLIKHOPSA-N ; KJKKEUXQKMRBSJ-YZSQISJMSA-N ; PJBLMNWKWHJQJT-PCLIKHOPSA-N ; FCUSNDJMENFTMM-YZSQISJMSA-N ; JXBONZLAZJXGLS-VULFUBBASA-N ; VZUIUZAIADXPHJ-VULFUBBASA-N ; VSPKBGAMPVYLDO-VULFUBBASA-N ; VWPPTJM
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：27
• 期：2
• 页码：187-190
• 全文大小：697 K
• 卷排序：27

文摘

As part of our investigation into pyrazolo[1,5-a]pyridines as novel p110α selective PI3 kinase inhibitors, we report a range of analogues with improved aqueous solubility by the addition of a basic amine. The compounds demonstrated comparable p110α potency and selectivity to earlier compounds but with up to 1000× greater aqueous solubility, as the hydrochloride salts. The compounds also displayed good activity in a cellular assay of PI3 kinase activity.