[Synthesis and biological properties of 3,5-cyclophosphates- and -amidophosphates of 1,2-O-alkylydene-6-deoxy-6-halogeno-alpha -D-glucofuranoses].
3,5-Cyclic phosphates and phosphoramides of 6-halogenated glucofuranoses were synthesized via interaction of 3,5,6-bicyclophosphites of 1,2-O-alkylidene-alpha-D-glucofuranoses with halogens (followed by treatment with nucleophilic reagents) and N-chloroamines. 3,5-Cyclic trans-dibutylphosphoramides of 6-chloro-6-deoxy-1,2-O-isopropylidene- and 6-chloro-6-deoxy-(R)-(2,2,2)-trichloroethylidene)-alpha-D-glucofuranoses were shown to possess antiproliferative activity against CaOv human ovarian carcinoma cells in vitro (CE50 of approximately 10(-5) M). Cyclic trans-dibutylphosphoramide of 6-chloro-6-deoxy-1,2,-O-isopropylidene-alpha-D-glucofuranose also displayed marked antitumor effect on P-388 transplantable murine leukemia in vivo (the maximum increase in life span of 100% was reached at the quintuple injection of 100 mg/kg daily).
Koroteev
M P
MP
Moscow State Pedagogical University, Chemical Faculty, Russia.
Pugashova
N M
NM
Khrebtova
S B
SB
Nifant'ev
E E
EE
Zhukova
O S
OS
Ivanova
T P
TP
Peretolchina
N M
NM
Gerasimova
G K
GK
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D005958:Glucosephosphates / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D007941:Leukemia P388 / Q000188:drug therapy* / Q000401:mortality; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005958:Glucosephosphates