Kynurenamines as Neural Nitric Oxide Synthase Inhibitors
To find new compounds with potential neuroprotective activity, we have designed, synthesized, and characterized a series of neural nitric oxide synthase (nNOS) inhibitors with a kynurenamine structure. Among them, N-[3-(2-amino-5-methoxyphenyl)-3-oxopropyl]acetamide is the main melatonin metabolite...
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| Veröffentlicht in: | Journal of medicinal chemistry 2005-12, Vol.48 (26), p.8174-8181 |
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| container_title | Journal of medicinal chemistry |
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| creator | Entrena, Antonio Camacho, M. Encarnación Carrión, M. Dora López-Cara, Luisa C Velasco, Guillermo León, Josefa Escames, Germaine Acuña-Castroviejo, Darío Tapias, Víctor Gallo, Miguel A Vivó, Antonio Espinosa, Antonio |
| description | To find new compounds with potential neuroprotective activity, we have designed, synthesized, and characterized a series of neural nitric oxide synthase (nNOS) inhibitors with a kynurenamine structure. Among them, N-[3-(2-amino-5-methoxyphenyl)-3-oxopropyl]acetamide is the main melatonin metabolite in the brain and shows the highest activity in the series, with an inhibition percentage of 65% at a 1 mM concentration. The structure−activity relationship of the new series partially reflects that of the previously reported 2-acylamido-4-(2-amino-5-methoxyphenyl)-4-oxobutyric acids, endowed with a kynurenine-like structure. Structural comparisons between these new kinurenamine derivatives, kynurenines, and 1-acyl-3-(2-amino-5-methoxyphenyl)-4,5-dihydro-1H-pyrazole derivatives also reported confirm our previous model for the nNOS inhibition. |
| doi_str_mv | 10.1021/jm050740o |
| format | Article |
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Encarnación ; Carrión, M. Dora ; López-Cara, Luisa C ; Velasco, Guillermo ; León, Josefa ; Escames, Germaine ; Acuña-Castroviejo, Darío ; Tapias, Víctor ; Gallo, Miguel A ; Vivó, Antonio ; Espinosa, Antonio</creator><creatorcontrib>Entrena, Antonio ; Camacho, M. Encarnación ; Carrión, M. Dora ; López-Cara, Luisa C ; Velasco, Guillermo ; León, Josefa ; Escames, Germaine ; Acuña-Castroviejo, Darío ; Tapias, Víctor ; Gallo, Miguel A ; Vivó, Antonio ; Espinosa, Antonio</creatorcontrib><description>To find new compounds with potential neuroprotective activity, we have designed, synthesized, and characterized a series of neural nitric oxide synthase (nNOS) inhibitors with a kynurenamine structure. Among them, N-[3-(2-amino-5-methoxyphenyl)-3-oxopropyl]acetamide is the main melatonin metabolite in the brain and shows the highest activity in the series, with an inhibition percentage of 65% at a 1 mM concentration. The structure−activity relationship of the new series partially reflects that of the previously reported 2-acylamido-4-(2-amino-5-methoxyphenyl)-4-oxobutyric acids, endowed with a kynurenine-like structure. Structural comparisons between these new kinurenamine derivatives, kynurenines, and 1-acyl-3-(2-amino-5-methoxyphenyl)-4,5-dihydro-1H-pyrazole derivatives also reported confirm our previous model for the nNOS inhibition.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm050740o</identifier><identifier>PMID: 16366599</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Animals ; Biological and medical sciences ; Corpus Striatum - drug effects ; Corpus Striatum - enzymology ; Enzyme Inhibitors - chemical synthesis ; Enzyme Inhibitors - pharmacology ; Kynuramine - analogs & derivatives ; Kynuramine - chemical synthesis ; Kynuramine - pharmacology ; Kynurenine 3-Monooxygenase - antagonists & inhibitors ; Medical sciences ; Molecular Conformation ; Neuropharmacology ; Neuroprotective agent ; Nitric Oxide Synthase Type I - antagonists & inhibitors ; Pharmacology. 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Encarnación</creatorcontrib><creatorcontrib>Carrión, M. Dora</creatorcontrib><creatorcontrib>López-Cara, Luisa C</creatorcontrib><creatorcontrib>Velasco, Guillermo</creatorcontrib><creatorcontrib>León, Josefa</creatorcontrib><creatorcontrib>Escames, Germaine</creatorcontrib><creatorcontrib>Acuña-Castroviejo, Darío</creatorcontrib><creatorcontrib>Tapias, Víctor</creatorcontrib><creatorcontrib>Gallo, Miguel A</creatorcontrib><creatorcontrib>Vivó, Antonio</creatorcontrib><creatorcontrib>Espinosa, Antonio</creatorcontrib><title>Kynurenamines as Neural Nitric Oxide Synthase Inhibitors</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>To find new compounds with potential neuroprotective activity, we have designed, synthesized, and characterized a series of neural nitric oxide synthase (nNOS) inhibitors with a kynurenamine structure. 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Structural comparisons between these new kinurenamine derivatives, kynurenines, and 1-acyl-3-(2-amino-5-methoxyphenyl)-4,5-dihydro-1H-pyrazole derivatives also reported confirm our previous model for the nNOS inhibition.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Corpus Striatum - drug effects</subject><subject>Corpus Striatum - enzymology</subject><subject>Enzyme Inhibitors - chemical synthesis</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Kynuramine - analogs & derivatives</subject><subject>Kynuramine - chemical synthesis</subject><subject>Kynuramine - pharmacology</subject><subject>Kynurenine 3-Monooxygenase - antagonists & inhibitors</subject><subject>Medical sciences</subject><subject>Molecular Conformation</subject><subject>Neuropharmacology</subject><subject>Neuroprotective agent</subject><subject>Nitric Oxide Synthase Type I - antagonists & inhibitors</subject><subject>Pharmacology. 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Dora ; López-Cara, Luisa C ; Velasco, Guillermo ; León, Josefa ; Escames, Germaine ; Acuña-Castroviejo, Darío ; Tapias, Víctor ; Gallo, Miguel A ; Vivó, Antonio ; Espinosa, Antonio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a412t-1f979a706cf147873545103cec6dc3bb2f0f55685aa3e0eae4fb1b1e70e4fff73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Corpus Striatum - drug effects</topic><topic>Corpus Striatum - enzymology</topic><topic>Enzyme Inhibitors - chemical synthesis</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Kynuramine - analogs & derivatives</topic><topic>Kynuramine - chemical synthesis</topic><topic>Kynuramine - pharmacology</topic><topic>Kynurenine 3-Monooxygenase - antagonists & inhibitors</topic><topic>Medical sciences</topic><topic>Molecular Conformation</topic><topic>Neuropharmacology</topic><topic>Neuroprotective agent</topic><topic>Nitric Oxide Synthase Type I - antagonists & inhibitors</topic><topic>Pharmacology. 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Encarnación</au><au>Carrión, M. Dora</au><au>López-Cara, Luisa C</au><au>Velasco, Guillermo</au><au>León, Josefa</au><au>Escames, Germaine</au><au>Acuña-Castroviejo, Darío</au><au>Tapias, Víctor</au><au>Gallo, Miguel A</au><au>Vivó, Antonio</au><au>Espinosa, Antonio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Kynurenamines as Neural Nitric Oxide Synthase Inhibitors</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2005-12-29</date><risdate>2005</risdate><volume>48</volume><issue>26</issue><spage>8174</spage><epage>8181</epage><pages>8174-8181</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>To find new compounds with potential neuroprotective activity, we have designed, synthesized, and characterized a series of neural nitric oxide synthase (nNOS) inhibitors with a kynurenamine structure. 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| subjects | Animals Biological and medical sciences Corpus Striatum - drug effects Corpus Striatum - enzymology Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - pharmacology Kynuramine - analogs & derivatives Kynuramine - chemical synthesis Kynuramine - pharmacology Kynurenine 3-Monooxygenase - antagonists & inhibitors Medical sciences Molecular Conformation Neuropharmacology Neuroprotective agent Nitric Oxide Synthase Type I - antagonists & inhibitors Pharmacology. Drug treatments Rats |
| title | Kynurenamines as Neural Nitric Oxide Synthase Inhibitors |
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