Synthesis and SAR of vinca alkaloid analogues.
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.
Voss
Matthew E
ME
Albany Molecular Research, Inc., 26 Corporate Circle, PO Box 15098, Albany, NY 12212-5098, USA. matthew.voss@amriglobal.com
Ralph
Jeffery M
JM
Xie
Dejian
D
Manning
David D
DD
Chen
Xinchao
X
Frank
Anthony J
AJ
Leyhane
Andrew J
AJ
Liu
Lei
L
Stevens
Jason M
JM
Budde
Cheryl
C
Surman
Matthew D
MD
Friedrich
Thomas
T
Peace
Denise
D
Scott
Ian L
IL
Wolf
Mark
M
Johnson
Randall
R
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
C538873:11'-iodovinorelbine; C538874:12'-iodovinblastine; C538872:12'-iodovincristine; D000972:Antineoplastic Agents, Phytogenic; D014748:Vinca Alkaloids; D014750:Vincristine; D014747:Vinblastine