The rational design of inhibitors of nitric oxide formation by inducible nitric oxide synthase.

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Whitlow M, Adler M, Davey D, Huang Q, Koovakkat S, Parkinson JF, Pham E, Polokoff M, Xu W, Yuan S, Phillips G

The rational design of inhibitors of nitric oxide formation by inducible nitric oxide synthase.

Bioorg Med Chem Lett. 2007 May 1;17(9):2505-8. Epub 2007 Feb 9.

PubMed ID

17336523 [ View in PubMed

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Abstract

A series of compounds was rationally designed as inhibitors of dimer formation of the inducible isoform of nitric oxide synthase, and subsequent nitric oxide production. The conformation of two fragments obtained from a crystal structure was utilized to design a tether connecting those same two fragments. The resulting compounds were potent dimerization inhibitors that bound to the enzyme in a similar conformation as the fragments.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
4-(1,3-BENZODIOXOL-5-YLOXY)-2-[4-(1H-IMIDAZOL-1-YL)PHENOXY]-6-METHYLPYRIMIDINE	Nitric oxide synthase, inducible	IC 50 (nM)	90	N/A	N/A	Details
4-(1,3-BENZODIOXOL-5-YLOXY)-2-[4-(1H-IMIDAZOL-1-YL)PHENOXY]PYRIMIDINE	Nitric oxide synthase, inducible	IC 50 (nM)	55	N/A	N/A	Details