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Your search keyword '"Pitzele, Barnett S."' showing total 13 results
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13 results on '"Pitzele, Barnett S."'

11. 5-Fluorinated L-lysine analogues as selective induced nitric oxide synthase inhibitors.

Author

Hallinan EA, Hagen TJ, Bergmanis A, Moore WM, Jerome GM, Spangler DP, Stevens AM, Shieh HS, Manning PT, and Pitzele BS

Subjects
Crystallography, X-Ray, Isoenzymes antagonists & inhibitors, Isoenzymes chemistry, Lysine analogs & derivatives, Lysine chemistry, Models, Molecular, Nitric Oxide Synthase chemistry, Nitric Oxide Synthase Type II, Lysine chemical synthesis, Nitric Oxide Synthase antagonists & inhibitors
Abstract

5(S)-Fluoro-N6-(iminoethyl)-l-lysine (14), an analogue of the potent, selective induced nitric oxide synthase (iNOS) inhibitor iminoethyl-l-lysine (1), was synthesized and found to be a selective iNOS inhibitor.

Published
2004
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12. 4-Fluorinated L-lysine analogs as selective i-NOS inhibitors: methodology for introducing fluorine into the lysine side chain.

Author

Hallinan EA, Kramer SW, Houdek SC, Moore WM, Jerome GM, Spangler DP, Stevens AM, Shieh HS, Manning PT, and Pitzele BS

Subjects
Animals, Crystallography, X-Ray, Humans, Lysine chemistry, Mice, Models, Biological, Models, Chemical, Molecular Structure, Nitric Oxide Synthase Type II, Enzyme Inhibitors chemistry, Fluorine chemistry, Lysine analogs & derivatives, Nitric Oxide Synthase antagonists & inhibitors
Abstract

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.

Published
2003
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13. Synthesis and biological characterization of L-N(6)-(1-iminoethyl)lysine 5-tetrazole-amide, a prodrug of a selective iNOS inhibitor.

Author

Hallinan EA, Tsymbalov S, Dorn CR, Pitzele BS, Hansen DW Jr, Moore WM, Jerome GM, Connor JR, Branson LF, Widomski DL, Zhang Y, Currie MG, and Manning PT

Subjects
Acute Disease, Administration, Oral, Animals, Arthritis, Experimental pathology, Carrageenan, Chronic Disease, Crystallization, Edema chemically induced, Edema enzymology, Edema pathology, Enzyme Inhibitors chemistry, Enzyme Inhibitors metabolism, Homoarginine analogs & derivatives, Homoarginine chemistry, Homoarginine metabolism, Humans, Isoenzymes antagonists & inhibitors, Nitric Oxide Synthase Type I, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III, Prodrugs chemistry, Prodrugs metabolism, Rats, Recombinant Proteins antagonists & inhibitors, Enzyme Inhibitors chemical synthesis, Homoarginine chemical synthesis, Lysine analogs & derivatives, Lysine chemistry, Nitric Oxide Synthase antagonists & inhibitors, Prodrugs chemical synthesis
Abstract

The 5-tetrazole amide of L-N(6)-(1-iminoethyl)lysine (L-NIL), L-N(6)-(1-iminoethyl)lysine 5-tetrazole amide (1), has been prepared and evaluated. In contrast to L-NIL, 1 is a stable, nonhygroscopic, crystalline solid. Unlike L-NIL, 1 has minimal inhibitory activity in vitro on human inducible nitric oxide synthase (iNOS). However, it is rapidly converted in vivo to L-NIL and produces dose-dependent inhibition of iNOS in acute and chronic models of inflammation in the rodent with efficacy comparable to L-NIL. In addition, both 1 and L-NIL exhibit significant and comparable in vivo selectivity for the inhibition of iNOS vs endothelial NOS. Doses approximately 80-fold greater than those that inhibited inflammation do not elevate systemic blood pressure. In summary, both the physical properties and the pharmacological profile of 1 make it an ideal molecule for preclinical and clinical studies on the role of selective iNOS inhibitors in mediating inflammatory disease processes.

Published
2002
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