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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1987-4-15
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pubmed:abstractText |
The synthesis and characterization of DL-2-amino-7-bis[(2-chloroethyl)amino]-1,2,3,4-tetrahydro-2-naphthoic acid and DL-2-amino-5-bis[(2-chloroethyl)amino]-1,2,3,4-tetrahydro-2-napthoic+ ++ acid were accomplished. The correct assignment of the site of attachment of the bis(2-chloroethyl)amino side chain was ascertained by selective proton decoupling of the 13C NMR spectra performed on the corresponding nitrospirohydantoin precursors 2 and 3, which were obtained from the nitration of beta-tetralone hydantoin. The two target compounds 6 and 7 were designed as tumor-specific agents capable of being selectively transported into tumor cells by the leucine-preferring transport system (system L). Inhibition analysis of the initial rate of transport of the system L specific substrate 2-amino-bicyclo[2.2.1]heptane-2-carboxylic acid (BCH) by 6 and 7 indicated that the 7-substituted isomer 6 was an extremely potent competitive inhibitor of that transport system in murine L1210 leukemic cells (Ki = 0.2 microM). Evaluation of the selectivity of this compound indicated that it possessed enhanced in vitro antitumor activity and reduced myelosuppressive activity when compared to its prototype amino acid nitrogen mustard, L-phenylalanine mustard (L-PAM). In addition to being more selectively toxic to tumor cells, this compound differs from L-PAM in having a 2-3-fold shorter half-life (t1/2).
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-Naphthylamine,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Indicators and Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Naphthalenes,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrogen Mustard Compounds
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0022-2623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
30
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
542-7
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pubmed:dateRevised |
2003-11-14
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pubmed:meshHeading |
pubmed-meshheading:3820226-2-Naphthylamine,
pubmed-meshheading:3820226-Animals,
pubmed-meshheading:3820226-Antineoplastic Agents,
pubmed-meshheading:3820226-Biological Transport,
pubmed-meshheading:3820226-Bone Marrow,
pubmed-meshheading:3820226-Half-Life,
pubmed-meshheading:3820226-Indicators and Reagents,
pubmed-meshheading:3820226-Leukemia L1210,
pubmed-meshheading:3820226-Magnetic Resonance Spectroscopy,
pubmed-meshheading:3820226-Mice,
pubmed-meshheading:3820226-Naphthalenes,
pubmed-meshheading:3820226-Nitrogen Mustard Compounds,
pubmed-meshheading:3820226-Structure-Activity Relationship
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pubmed:year |
1987
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pubmed:articleTitle |
Selective cytotoxicity of a system L specific amino acid nitrogen mustard.
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pubmed:publicationType |
Journal Article
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