Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Editor

Personal info

View

About

Terms

Javascript disabled

Please enable Javascript support in your browser to use this application.

Instructions on how to enable JavaScript on different browsers can be found here: http://www.google.com/support/bin/answer.py?answer=23852.

[edit this page]

Ulhaq, S. et al.

Heterocyclic analogues of L-citrulline as inhibitors of the isoforms of nitric oxide synthase (NOS) and identification of N(delta)-(4,5-dihydrothiazol-2-yl)ornithine as a potent inhibitor.

L-Thiocitrulline is a known potent inhibitor of several isoforms of nitric oxide synthase (NOS). To explore the structure-activity relationships (SARs) for this molecule in more depth than has previously been reported, three analogues substituted at the sulphur of the isothioureas have been synthesised. In two of these, the S-substituent was 'tied back' sterically by cyclisation to the nitrogen remote from the amino-acid unit. N(delta)-(4,5-Dihydrothiazol-2-yl)ornithine was identified as an inhibitor of rat inducible and constitutive isoforms of NOS and of a constitutive NOS derived from a human tumour xenograft. Analogous N(delta)-(thiazol-2-yl)ornithines were less active, whereas the corresponding N(delta)-(oxazol-2-yl)ornithine and N(delta)-(pyrimidin-2-yl)ornithine failed completely to inhibit NOS. A new efficient preparation of the critical synthetic intermediate, N(alpha)-Boc-thiocitrulline t-butyl ester, has been developed. Further exploration of the SAR with 2-amino-5-(heterocyclylthio)pentanoic acids (synthesised from 2-(Boc-amino)-5-bromopentanoic acid t-butyl ester), with N-(4-aminobutyl)thiourea and with 2-(4-aminobutylamino)-4,5-dihydrothiazole enabled refinement of our previous model for binding of the substrate, L-arginine, and the inhibitors to NOS.[1]

References

Heterocyclic analogues of L-citrulline as inhibitors of the isoforms of nitric oxide synthase (NOS) and identification of N(delta)-(4,5-dihydrothiazol-2-yl)ornithine as a potent inhibitor. Ulhaq, S., Chinje, E.C., Naylor, M.A., Jaffar, M., Stratford, I.J., Threadgill, M.D. Bioorg. Med. Chem. (1999) [Pubmed]

Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenes Open Access Licence Privacy Policy Terms of Use apsburg

The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.