Synthesis and in vitro antiproliferative activity of C5-benzyl substituted 2-amino-pyrrolo[2, 3-d]pyrimidines as potent Hsp90 inhibitors. Issue 2 (15th January 2017)

• Record Type: Journal Article
• Authors: Lee, Ju-Hyeon; Shin, Sang Chul; Seo, Seon Hee; Seo, Young Ho; Jeong, Nakcheol; Kim, Chan-Wha; Kim, Eunice EunKyeong; Keum, Gyochang
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 2(2017)
• Page Start: 237
• Page End: 241
• Publication Date: 2017-01-15
• Subjects: Hsp90 -- Structure-based design -- Cancer -- Antiproliferative -- Pyrrolo[2, 3-d]pyrimidines; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.11.062
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: A novel series of heat shock protein 90 (Hsp90) inhibitors was identified by X-ray crystal analysis of complex structures at solvent-exposed exit pocket C. The 2-amino-pyrrolo[2, 3- d ]pyrimidine derivatives, 7-deazapurines substituted with a benzyl moiety at C5, showed potent Hsp90 inhibition and broad-spectrum antiproliferative activity against NCI-60 cancer cell lines. The most potent compound, 6a, inhibited Hsp90 with an IC50 of 36 nM and showed a submicromolar mean GI50 value against NCI-60 cell lines. The interaction of6a at the ATP-binding pocket of Hsp90 was confirmed by X-ray crystallography and Western blot analysis.