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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
1984-1-7
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pubmed:abstractText |
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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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0022-2623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
26
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1788-90
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:6644750-Animals,
pubmed-meshheading:6644750-Antineoplastic Agents,
pubmed-meshheading:6644750-Colorimetry,
pubmed-meshheading:6644750-Female,
pubmed-meshheading:6644750-Leukemia L1210,
pubmed-meshheading:6644750-Liver,
pubmed-meshheading:6644750-Magnetic Resonance Spectroscopy,
pubmed-meshheading:6644750-Male,
pubmed-meshheading:6644750-Mice,
pubmed-meshheading:6644750-Oximes,
pubmed-meshheading:6644750-Phosphoramide Mustards,
pubmed-meshheading:6644750-X-Ray Diffraction
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pubmed:year |
1983
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pubmed:articleTitle |
O-imino esters of N,N-bis(2-chloroethyl)phosphorodiamidic acid. Synthesis, X-ray structure determination, and anticancer evaluation.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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