Warning: Undefined array key "mm" in /www/wwwroot/www.ai-bt.com/si.php on line 10 Deprecated: trim(): Passing null to parameter #1 ($string) of type string is deprecated in /www/wwwroot/www.ai-bt.com/si.php on line 10 Discovery and development of neuronal nitric oxide synthase inhibitors.

Literature DB >> 10927171

Discovery and development of neuronal nitric oxide synthase inhibitors.

D W Reif¹, D J McCarthy, E Cregan, J E Macdonald.

Abstract

The role of neuronally derived nitric oxide (NO) in neurotransmission and neural injury remains an area of active investigation. NO generation has been postulated to be involved in the deleterious events surrounding ischemia/reperfusion injury either directly or via the production of more reactive oxidants such as peroxynitrite. In our search for novel therapeutics for the treatment of a variety of neurological diseases including stroke, we have discovered novel, potent, and selective inhibitors of the neuronal nitric oxide synthase (nNOS) isoform. These compounds have proven to be effective in models of ischemia/reperfusion supporting the role of nNOS in these processes. The effects of these compounds as well as additional aspects critical to their development will be presented.

Entities: Chemical Disease Gene

Mesh：

Substances：

Year: 2000 PMID： 10927171 DOI： 10.1016/s0891-5849(00)00250-1

Source DB: PubMed Journal: Free Radic Biol Med ISSN： 0891-5849 Impact factor: 7.376

Keyword Cloud
Cited

11 in total

1. Structures of nitric oxide synthase isoforms complexed with the inhibitor AR-R17477 suggest a rational basis for specificity and inhibitor design.

Authors: Roman Fedorov; Ryan Vasan; Dipak K Ghosh; Ilme Schlichting
Journal: Proc Natl Acad Sci U S A Date: 2004-04-07 Impact factor: 11.205

2. Selective monocationic inhibitors of neuronal nitric oxide synthase. Binding mode insights from molecular dynamics simulations.

Authors: He Huang; Haitao Ji; Huiying Li; Qing Jing; Kristin Jansen Labby; Pavel Martásek; Linda J Roman; Thomas L Poulos; Richard B Silverman
Journal: J Am Chem Soc Date: 2012-07-10 Impact factor: 15.419

10. Minimal pharmacophoric elements and fragment hopping, an approach directed at molecular diversity and isozyme selectivity. Design of selective neuronal nitric oxide synthase inhibitors.

Authors: Haitao Ji; Benjamin Z Stanton; Jotaro Igarashi; Huiying Li; Pavel Martásek; Linda J Roman; Thomas L Poulos; Richard B Silverman
Journal: J Am Chem Soc Date: 2008-03-06 Impact factor: 15.419

Discovery and development of neuronal nitric oxide synthase inhibitors.

1. Structures of nitric oxide synthase isoforms complexed with the inhibitor AR-R17477 suggest a rational basis for specificity and inhibitor design.

2. Selective monocationic inhibitors of neuronal nitric oxide synthase. Binding mode insights from molecular dynamics simulations.

Review 3. Nitric oxide synthase and structure-based inhibitor design.

4. Structure-guided design of selective inhibitors of neuronal nitric oxide synthase.

Review 5. Target- and mechanism-based therapeutics for neurodegenerative diseases: strength in numbers.

Review 6. Development of nitric oxide synthase inhibitors for neurodegeneration and neuropathic pain.

7. A cellular model for screening neuronal nitric oxide synthase inhibitors.

8. Structural Basis for Isoform Selective Nitric Oxide Synthase Inhibition by Thiophene-2-carboximidamides.

Review 9. Recent advances toward improving the bioavailability of neuronal nitric oxide synthase inhibitors.

10. Minimal pharmacophoric elements and fragment hopping, an approach directed at molecular diversity and isozyme selectivity. Design of selective neuronal nitric oxide synthase inhibitors.