4-Fluorinated L-lysine analogs as selective i-NOS inhibitors: methodology for introducing fluorine into the lysine side chain

• Published in: Organic & biomolecular chemistry Vol. 1; no. 20; p. 3527
• Main Authors: Hallinan, E Ann, Kramer, Steven W, Houdek, Stephen C, Moore, William M, Jerome, Gina M, Spangler, Dale P, Stevens, Anna M, Shieh, Huey S, Manning, Pamela T, Pitzele, Barnett S
• Format: Journal Article
• Language: English
• Published: England 21-10-2003
• Subjects: Animals; Crystallography, X-Ray; Enzyme Inhibitors - chemistry; Fluorine - chemistry; Humans; Lysine - analogs & derivatives; Lysine - chemistry; Mice; Models, Biological; Models, Chemical; Molecular Structure; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase Type II
• ISSN: 1477-0520
• DOI: 10.1039/b307563j

In the literature, the introduction of fluorine into bioactive molecules has been known to enhance the biological activity relative to the parent molecule. Described in this article is the synthesis of 4R-fluoro-L-NIL (12) and 4,4-difluoro-L-NIL (23) as part of our iNOS program. Both 12 and 23 were found to be selective iNOS inhibitors as shown in Table 2 below. Secondarily, methodology to synthesize orthogonally protected 4-fluoro-L-lysine and 4,4-difluoro-L-lysine has been developed.