Studies on the Synthesis of 5-(Substituted Phenyl) Thio-2,4- Diaminopyrimidines and Their QSAR of the Inhibition to E. coli DHFR

Abstract

Abstract: Eight dihydrofolate reductase inhibitors, 5-(X-phenyl) thio-2,4-diamino-pyrimidines (X = 4′-NH₂ and its hydrochloride; 4′-Ihydrochloride;4′-NHCOCH₃; 4′-OH, 4′,-NNSCH₃; 3′,5′- (Br)₂,4′ -NH₂ hydrochloride, 4′-OCH₂CH₃; 4′-OCH₂CH₂CH₃), have been synthesized from 5-(4′-nitrophenyl) thio-2,4-diamino pyrimidine. Their inhibitory activities to E.coli MB 1428 DHFRhave been tested. All sixteen thiophenyl pyrimidines (eight of them were reported previously) have been correlated with Hansch analyses. The correlation equation shows that their inhibitory activities are linearly correlated with MR_3,4,5 and bilinearly correlated with π_3,4,5. MR′is, defined with a maximum value cf 0.79 which means the MRvalues of substitvents have to te trurcaled at the value of 0.79 when the substituent is larger than methoxy group, similar to the definition in the correlation of benzylpyrimidines.

Key words: Pyrimidine derivatives, QSAR, Dihydrofolate reductase inhibitor

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Zhang Wensheng, Li Renli, Zhang Jundong, Martin Poe. Studies on the Synthesis of 5-(Substituted Phenyl) Thio-2,4- Diaminopyrimidines and Their QSAR of the Inhibition to E. coli DHFR[J]. Chem. J. Chinese Universities, 1988, 9(10): 1029.

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Studies on the Synthesis of 5-(Substituted Phenyl) Thio-2,4- Diaminopyrimidines and Their QSAR of the Inhibition to E. coli DHFR

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