2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents. 11. Quinolylmethyl analogues with basic substituents conveying specificity.

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Davis SE, Rauckman BS, Chan JH, Roth B

2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents. 11. Quinolylmethyl analogues with basic substituents conveying specificity.

J Med Chem. 1989 Aug;32(8):1936-42.

PubMed ID

2502633 [ View in PubMed

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Abstract

A series of nine 2,4-diamino-5-[6-( or 7-)quinolylmethyl]pyrimidines has been prepared by condensations of quinolinecarboxaldehydes with beta-anilinopropionitriles, followed by treatment with guanidine. All compounds has basic or methoxy substituents at the 2- or 4-positions of the quinoline ring. All of the 6-quinolylmethyl derivatives were highly inhibitory against Escherichia coli dihydrofolate reductase (DHFR), provided that an 8-substituent was present in the quinoline ring. Those compounds that had basic substituents in the 2-position of the quinoline ring were also highly specific for bacterial dihydrofolate DHFR, relative to a vertebrate counterpart. Protonation on the quinoline ring nitrogen is a possible cause of specificity.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Trimethoprim	Dihydrofolate reductase	IC 50 (nM)	5	N/A	N/A	Details
Trimethoprim	Dihydrofolate reductase	IC 50 (nM)	400	N/A	N/A	Details