Novel pyrazolo[1, 5-a]pyridines with improved aqueous solubility as p110α-selective PI3 kinase inhibitors. Issue 2 (15th January 2017)

• Record Type: Journal Article
• Authors: Kendall, Jackie D.; Giddens, Anna C.; Tsang, Kit Yee; Marshall, Elaine S.; Lill, Claire L.; Lee, Woo-Jeong; Kolekar, Sharada; Chao, Mindy; Malik, Alisha; Yu, Shuqiao; Chaussade, Claire; Buchanan, Christina; Jamieson, Stephen M.F.; Rewcastle, Gordon W.; Baguley, Bruce C.; Denny, William A.; Shepherd, Peter R.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 2(2017)
• Page Start: 187
• Page End: 190
• Publication Date: 2017-01-15
• Subjects: 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 -- VWPPTJMNNYKWGI-JVWAILMASA-N -- WDTIVBPVYKJXBJ-JVWAILMASA-N -- MKHGTPPDGWFEBX-JVWAILMASA-N -- QXDGRWHIMSRKBI-AFUMVMLFSA-N -- JQUYMGRFGDKEMR-RPPGKUMJSA-N -- GZMXSTUKASDCMA-WGOQTCKBSA-N -- BRCHSRCZNYQTCR-MFKUBSTISA-N -- OINXPJSUSPOFIX-MTDXEUNCSA-N -- JICCUMKRLUNNGM-RWPZCVJISA-N -- VYKHDQIDNBEKFU-OEAKJJBVSA-N -- PSQDXBFKNOHNNI-LPYMAVHISA-N -- FKPZCDCUJSGHSJ-PCLIKHOPSA-N -- UNSNQEWWNXCKRM-DHRITJCHSA-N -- RVUSWRURQZHIRT-ZVHZXABRSA-N -- LXOUGCJVTMGECM-CVKSISIWSA-N -- JXAABJVXMHQJPG-BUVRLJJBSA-N -- RDHWTWLEHDOGEE-OVVQPSECSA-N -- UFGITOOKANCZLC-JVWAILMASA-N -- OSSKMBRJARMVDN-OEAKJJBVSA-N -- XOOMWMDSYAMLRI-YZSQISJMSA-N -- ATMXKSOXUDBGFO-CVKSISIWSA-N -- SJIXEBMUNVXCHL-PCLIKHOPSA-N -- SIGWZMGBQQIEFC-TURZUDJPSA-N -- QUOIBHFHLNBGGV-OGLMXYFKSA-N -- WPMMFMIFCVOFKG-BUVRLJJBSA-N -- RFSBFVKQGVFNAT-OVVQPSECSA-N -- UBENTQBOORQDPV-JVWAILMASA-N; PI3 kinase -- PI3K -- P110α -- Pyrazolo[1, 5-a]pyridine -- Sulfonohydrazide -- Aqueous solubility; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.11.078
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: 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.