Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 하정미 | - |
dc.date.accessioned | 2021-02-16T00:47:13Z | - |
dc.date.available | 2021-02-16T00:47:13Z | - |
dc.date.issued | 2001-06 | - |
dc.identifier.citation | Journal of Medicinal Chemistry, v. 44, no. 16, page. 2667-2670 | en_US |
dc.identifier.issn | 0022-2623 | - |
dc.identifier.issn | 1520-4804 | - |
dc.identifier.uri | https://pubs.acs.org/doi/10.1021/jm0101491 | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/158261 | - |
dc.description.abstract | Selective inhibition of the isoforms of nitric oxide synthase (NOS) could be therapeutically useful in the treatment of certain disease states arising from the overproduction of nitric oxide. Recently, we reported nitroarginine-containing dipeptide amides (Huang, H; Martasek, P.; Roman, L. J.; Masters, B. S. S.; Silverman, R. B. J. Med. Chem.1999, 42, 3147.) and some peptidomimetic analogues (Huang, H; Martasek, P.; Roman, L. J.; Silverman, R.B. J. Med Chem.2000, 43, 2938.) as potent and selective inhibitors of neuronal NOS (nNOS). Here, reduced amide bond pseudodipeptide analogues are synthesized and evaluated for their activity. The deletion of the carbonyl group from the amide bond either preserves or improves the potency for nNOS. Significantly, the selectivities for nNOS over eNOS (endothelial NOS), and iNOS (inducible NOS) are greatly increased in these series. The most potent nNOS inhibitor among these compounds is (4S)-N-(4-amino-5-[aminoethyl]aminopentyl)-N‘-nitroguanidine (7) (Ki = 120 nM), which also shows the highest selectivity over eNOS (greater than 2500-fold) and 320-fold selectivity over iNOS. The reduced amide bond is an excellent surrogate of the amide bond, and it will facilitate the design of new potent and selective inhibitors of nNOS. | en_US |
dc.description.sponsorship | The authors are grateful to the National Institutes of Health (Grant GM49725) for financial support of this research. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | AMER CHEMICAL SOC | en_US |
dc.title | Reduced Amide Bond Peptidomimetics. (4S)-N-(4-Amino-5-[aminoalkyl]aminopentyl)-N'-nitroguanidines, Potent and Highly Selective Inhibitors of Neuronal Nitric Oxide Synthase | en_US |
dc.type | Article | en_US |
dc.relation.volume | 44 | - |
dc.identifier.doi | 10.1021/jm0101491 | - |
dc.relation.page | 2667-2670 | - |
dc.relation.journal | JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.contributor.googleauthor | Hah, Jung-Mi | - |
dc.contributor.googleauthor | Roman, Linda J. | - |
dc.contributor.googleauthor | Pavel Martásek | - |
dc.contributor.googleauthor | Silverman, Richard B. | - |
dc.relation.code | 2009205413 | - |
dc.sector.campus | E | - |
dc.sector.daehak | COLLEGE OF PHARMACY[E] | - |
dc.sector.department | DEPARTMENT OF PHARMACY | - |
dc.identifier.pid | jhah | - |
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