Expanding the scope of fused pyrimidines as kinase inhibitor scaffolds: synthesis and modification of pyrido[3, 4-d]pyrimidines. Issue 3 (19th November 2014)

• Record Type: Journal Article
• Authors: Innocenti, Paolo; Woodward, Hannah; O'Fee, Lisa; Hoelder, Swen
• Is Part Of: Organic & biomolecular chemistry. Volume 13:Issue 3(2015)
• Page Start: 893
• Page End: 904
• Publication Date: 2014-11-19
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c4ob02238f
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : A versatile and efficient entry into 2-amino-pyrido[3, 4- d ]pyrimidines was developed. Our strategy hinges on the concise preparation and derivatisation of 8-chloro-2-(methylthio)pyrido[3, 4- d ]pyrimidine intermediates to yield putative kinase inhibitors. Abstract : Fused pyrimidine cores are privileged kinase scaffolds, yet few examples of the 2-amino-pyrido[3, 4- d ]pyrimidine chemotype have been disclosed in the context of kinase inhibitor programs. Furthermore, no general synthetic route has been reported to access 2-amino-pyrido[3, 4- d ]pyrimidine derivatives. Here we report a versatile and efficient chemical approach to this class of molecules. Our strategy involves the concise preparation of 8-chloro-2-(methylthio)pyrido[3, 4- d ]pyrimidine intermediates and their efficient derivatisation to give novel compounds with potential as kinase inhibitors.