L-N6-(1-Iminoethyl)lysine: A Selective Inhibitor of Inducible Nitric Oxide Synthase

• Published in: Journal of medicinal chemistry 1994-11, Vol.37 (23), p.3886-3888
• Main Authors: Moore, William M., Webber, R. Keith, Jerome, Gina M., Tjoeng, Foe S., Misko, Thomas P., Currie, Mark G.
• Format: Article
• Language: English
• Subjects: Aliphatic compounds; Amino Acid Oxidoreductases - antagonists & inhibitors; Animals; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Brain - enzymology; Chemistry; Exact sciences and technology; Lysine - analogs & derivatives; Lysine - pharmacology; Medical sciences; Mice; Nitric Oxide Synthase; Organic chemistry; Pharmacology. Drug treatments; Preparations and properties; Rats
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00049a007

L-N6-(1-Iminoethyl)lysine (L-NIL) has been synthesized and is shown to be both a potent and selective inhibitor of mouse inducible nitric oxide synthase (miNOS). L-NIL has an IC50 of 3.3 microM for miNOS compared to an IC50 of 92 microM for rat brain constitutive NOS indicating that L-NIL is 28-fold more selective for inducible NOS. L-N5-(1-Iminoethyl)ornithine (L-NIO), which differs from L-NIL by having one less methylene group, has very similar potency for inducible NOS, but lacks selectivity. DL-N7-(1-Iminoethyl)homolysine was also synthesized and found to be substantially less potent than L-NIL or L-NIO, with intermediate selectivity for inducible NOS. These data suggest that L-NIL may be useful as a selective inhibitor of inducible NOS for determining the role of this enzyme in disease models.