6533b827fe1ef96bd1285cf2
RESEARCH PRODUCT
Quinazoline antifolate thymidylate synthase inhibitors: replacement of glutamic acid by aminophosphonic acids
Barbara GołosKrzysztof PawelczakMaciej MakowskiMałgorzata BalińskaPaweł KafarskiJolanta M. DzikWojciech Rodesubject
biologyStereochemistryOrganic ChemistryGlutamic acidBiochemistryThymidylate synthaseInorganic Chemistrychemistry.chemical_compoundResidue (chemistry)chemistryBiochemistryAntifolateantifolatesQuinazolinebiology.proteinSolubilitythymidylate synthase inhibitorsaminophosphonic acid analogues of antifolatesdescription
The synthesis of six analogues of the potent thymidylate synthase (TS) inhibitor N -[4-[ N -[(3,4-dihydro-2-methyl-4-oxo-6-quinazolinoyl)-methyl]- N -prop-2-ynylamino]benzoyl]- L -glutamic acid 2 is described in which the glutamic acid residue has been replaced by DL -aminophosphonic acids. New antifolates were tested as inhibitors of TS isolated from mouse L1210 leukemic cells as well as inhibitors of growth mouse leukemic L5178Y cells. In general these modifications result in compounds that are considerably less potent than 2 as TS inhibitors with K i 's 0.17-1.10 w M. Very poor solubility in water limited their proper assay of growth cells inhibition.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2003-08-01 | Phosphorus Sulfur and Silicon and the Related Elements |