Synthesis and biological evaluation of cryptophycin analogs with substitution at C-6 (fragment C region).
Analogs of the antitumor agents cryptophycins 1 and 8 with dialkyl substitution at C-6 (fragment C) were synthesized and evaluated for in vitro cytotoxicity against human leukemia cells (CCRF-CEM). The activity of these analogs decreased as the size of the substituents at C-6 increased. The C-6 spirocylopropyl compound (2g) was highly potent in vitro and showed excellent antitumor activity in animal models.
Varie
D L
DL
Lilly Research Laboratories, A Division of Eli Lilly and Co., Indianapolis, IN 46285, USA.
Shih
C
C
Hay
D A
DA
Andis
S L
SL
Corbett
T H
TH
Gossett
L S
LS
Janisse
S K
SK
Martinelli
M J
MJ
Moher
E D
ED
Schultz
R M
RM
Toth
J E
JE
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D047630:Depsipeptides; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; C088419:cryptophycin