title: Synthesis and SAR of vinca alkaloid analogues.
abstract: Versatile intermediates 12'-iodovinblastine, 12'-iodovincristine and 11'-iodovinorelbine were utilized as substrates for transition metal based chemistry which led to the preparation of novel analogues of the vinca alkaloids. The synthesis of key iodo intermediates, their transformation into final products, and the SAR based upon HeLa and MCF-7 cell toxicity assays is presented. Selected analogues 27 and 36 show promising anticancer activity in the P388 murine leukemia model.
authors.affiliation: Albany Molecular Research, Inc., 26 Corporate Circle, PO Box 15098, Albany, NY 12212-5098, USA. matthew.voss@amriglobal.com
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Voss
authors.forename: Jeffery M
authors.initials: JM
authors.lastname: Ralph
authors.forename: Dejian
authors.initials: D
authors.lastname: Xie
authors.forename: David D
authors.initials: DD
authors.lastname: Manning
authors.forename: Xinchao
authors.initials: X
authors.lastname: Chen
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Frank
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Leyhane
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Jason M
authors.initials: JM
authors.lastname: Stevens
authors.forename: Cheryl
authors.initials: C
authors.lastname: Budde
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Surman
authors.forename: Thomas
authors.initials: T
authors.lastname: Friedrich
authors.forename: Denise
authors.initials: D
authors.lastname: Peace
authors.forename: Ian L
authors.initials: IL
authors.lastname: Scott
authors.forename: Mark
authors.initials: M
authors.lastname: Wolf
authors.forename: Randall
authors.initials: R
authors.lastname: Johnson
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D007941:Leukemia P388; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014748:Vinca Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014750:Vincristine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: C538873:11'-iodovinorelbine; C538874:12'-iodovinblastine; C538872:12'-iodovincristine; D000972:Antineoplastic Agents, Phytogenic; D014748:Vinca Alkaloids; D014750:Vincristine; D014747:Vinblastine