Design, synthesis, and biological activity of bicyclic radester analogues as Hsp90 inhibitors.
Bicyclic radester analogues have been synthesized and evaluated for Hsp90 inhibitory activity. These analogues induce concentration-dependent degradation of Hsp90-dependent client proteins with the six-membered bicyclic analogues manifesting increased activity versus the five-membered counterparts.
Jadhav
Vinod D
VD
Department of Medicinal Chemistry, The University of Kansas, 1251 Wescoe Hall Drive, Malott 4070, Lawrence, KS 66045-7562, USA.
Duerfeldt
Adam S
AS
Blagg
Brian S J
BS
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001555:Benzene Derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016227:Benzoquinones / Q000737:chemistry; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D047029:Lactams, Macrocyclic / Q000737:chemistry; D018942:Macrolides / Q000737:chemistry; D011487:Protein Conformation
D000970:Antineoplastic Agents; D001555:Benzene Derivatives; D016227:Benzoquinones; D001643:Bridged Bicyclo Compounds; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D018942:Macrolides; C507937:radester; C035359:monorden; C001277:geldanamycin