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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
11
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pubmed:dateCreated |
1989-11-28
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pubmed:abstractText |
A series of 2,4-diamino-5-aryl-6-ethylpyrimidines embracing basic substituents in the 5-aryl ring was synthesized and evaluated for inhibitory activity against rat liver dihydrofolate reductase (DHFR). Maximal enzyme inhibition was observed for compounds bearing a benzylamino (19) or N-alkylbenzylamino substituent (29 and 30) in the 4-position of the phenyl ring and a nitro group in the 3-position, the corresponding 3-amino, 3-azido, or unsubstituted analogues proving only weakly active or inactive as DHFR inhibitors. Selected compounds were also screened in vivo against a methotrexate-resistant tumor, the M5076 murine reticulosarcoma, and antitumor activity in general paralleled activity against DHFR, the (3,4-dichlorobenzyl)amino analogue 26 proving the least toxic compound to exhibit significant antitumor activity. The X-ray crystal structure of the ethanesulfonic acid salt of the N-methylbenzylamino compound 29 has been determined to facilitate future molecular modeling studies in this new series of DHFR inhibitors.
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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 |
Nov
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pubmed:issn |
0022-2623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
32
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2468-74
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:2810335-Animals,
pubmed-meshheading:2810335-Antineoplastic Agents,
pubmed-meshheading:2810335-Chemical Phenomena,
pubmed-meshheading:2810335-Chemistry,
pubmed-meshheading:2810335-Crystallization,
pubmed-meshheading:2810335-Folic Acid Antagonists,
pubmed-meshheading:2810335-Leukemia, Experimental,
pubmed-meshheading:2810335-Liver,
pubmed-meshheading:2810335-Methotrexate,
pubmed-meshheading:2810335-Mice,
pubmed-meshheading:2810335-Molecular Structure,
pubmed-meshheading:2810335-Pyrimidines,
pubmed-meshheading:2810335-Rats,
pubmed-meshheading:2810335-Structure-Activity Relationship,
pubmed-meshheading:2810335-Tumor Cells, Cultured
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pubmed:year |
1989
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pubmed:articleTitle |
Structural studies on bioactive compounds. 8. Synthesis, crystal structure, and biological properties of a new series of 2,4-diamino-5-aryl-6-ethylpyrimidine dihydrofolate reductase inhibitors with in vivo activity against a methotrexate-resistant tumor cell line.
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pubmed:affiliation |
Department of Pharmaceutical Sciences, Aston University, Birmingham, U.K.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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