Synthesis and antitumor activity of two ifosfamide analogs with a five-membered ring.
Two ifosfamide (CAS 3778-73-2) analogs with a five-membered ring, i.e. the oxazaphospholidine derivatives 6 and 7, were synthesized and their cytotoxic activity in vitro, acute toxicity and antitumor activity in vivo determined in comparison with the oxazaphorinane ifosfamide 1. The observed low biological activity gives evidence that both, the six-membered oxazaphosphorinane ring and the two N-2-chloroethyl-side chains are necessary for the generation of the ultimate alkylator, i.e. the ifosfamide mustard 5.
Kutscher
B
B
ASTA Medica AG, Frankfurt/Main, Fed. Rep. of Germany.
Niemeyer
U
U
Engel
J
J
Kleemann
A
A
Hilgard
P
P
Pohl
J
J
Scheffler
G
G
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007069:Ifosfamide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D007928:Lethal Dose 50; D007939:Leukemia L1210 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D051381:Rats; D012517:Sarcoma, Yoshida / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D007069:Ifosfamide