6-[4-(1H-Imidazol-1-yl)phenoxy]-N,N-dimethyl-1-hexanamine, dihydrochloride

20-HETE is an important metabolite of arachidonic acid in the vasculature, especially in the kidney, where it is synthesized by cytochrome P450 (CYP450) enzymes of the 4A family.^1,2 Alkylaryl imidazoles have been shown to inhibit certain CYP450 enzymes, including the CYP4A enzymes associated with 20-HETE synthesis.³ CAY10462 is the hydrochloride salt of CAY10434 and selective inhibitor of the 20-HETE synthase CYP4A11 exhibiting an IC₅₀ of 8.8 nM when tested in human renal microsomes.⁴ CAY10434 is nearly 200 times less potent as an inhibitor of 1A, 1C, and 3A CYP450 enzymes.

CAY 10434 dihydrochloride is a potent CYP4A hydroxylase inhibitor. CAY 10434 dihydrochloride improves contractile response to angiotensin II with the maximal contractile response (Emax) 6764 mg[1].

1. Harder, D.R., Lange, A.R., Gebremedhin, D., et al. Cytochrome P450 metabolites of arachidonic acid as intracellular signaling molecules in vascular tissue J. Vasc. Res. 34,237-243(1997).
2. Imig, J.D., Zou, A.P., Stec, D.E., et al. Formation and actions of 20-hydroxyeicosatetraenoic acid in rat renal arterioles Am. J. Physiol. 270,R217-R227(1996).
3. Nakamura, T., Kakinuma, H., Umemiya, H., et al. Imidazole derivatives as new potent and selective 20-HETE synthase inhibitor Bioorg. Med. Chem. Lett. 14,333-336(2004).