O-imino esters of N,N-bis(2-chloroethyl)phosphorodiamidic acid. Synthesis, X-ray structure determination, and anticancer evaluation.
J Med Chem
; 26(12): 1788-90, 1983 Dec.
Article
en En
| MEDLINE
| ID: mdl-6644750
ABSTRACT
Nine representatives of the title series of compounds [(ClCH2CH2)2NP(O)(NH2)ON = CRR'] were synthesized as potential anticancer prodrugs, based on the possibility of enzymatic reduction of the N-O bond to release the known cytotoxic agent phosphoramide mustard [1, (ClCH2CH2)2NP(O)(NH2)OH]. The dimethyl derivative (2, R = R' = CH3) exhibited a statistically significant, albeit low, level of anti-L1210 activity in mice. Derivative 2, which was shown by 31P NMR measurements to be very stable toward hydrolysis at 37 degrees C over a pH range of 5.7-7.4 (T1/2 congruent to 7-8 weeks), gave colorimetrically detectable amounts of alkylating material upon incubation with mouse liver slices approximately 3-5% conversion after 20 min at 37 degrees C. A single-crystal X-ray study of 2 revealed an unusual hydrogen-bonded "ladder" and a very similar steric relationship for the NCH2CH2Cl and ON = CCH3 moieties.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Oximas
/
Mostazas de Fosforamida
/
Antineoplásicos
Límite:
Animals
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
1983
Tipo del documento:
Article