Aza analogues of thalidomide : Synthesis and evaluation as inhibitors of tumor necrosis factor-α production in vitro
A synthetic entry to derivatives of the new classes of 5-phthalimidouracils and 5-phthalimidobarbituric acids is reported. These 5-phthalimidopyrimidines as well as phthalimido-2,4-difluorobenzenes were designed as analogues of thalidomide, a well known inhibitor of TNF-alpha production. A prelimina...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry 2001-04, Vol.9 (4), p.1059-1065 |
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| container_title | Bioorganic & medicinal chemistry |
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| creator | GÜTSCHOW, Michael HECKER, Thomas THIELE, Andrea HAUSCHILDT, Sunna EGER, Kurt |
| description | A synthetic entry to derivatives of the new classes of 5-phthalimidouracils and 5-phthalimidobarbituric acids is reported. These 5-phthalimidopyrimidines as well as phthalimido-2,4-difluorobenzenes were designed as analogues of thalidomide, a well known inhibitor of TNF-alpha production. A preliminary in vitro investigation of the compounds as inhibitors of the TNF-alpha production was performed. Among the compounds of the present series, 5-ethyl-1-phenyl-5-(tetrafluorophthalimido)barbituric acid and 2-(2,4-difluorophenyl)-4,5,6,7-tetrafluoro-1H-isoindole-1,3(2H)-dione were proved to be potent inhibitors. Both compounds showed inhibitory activity in the lower micromolar range on the LPS-induced TNF-alpha production in human monocytes. |
| doi_str_mv | 10.1016/S0968-0896(00)00323-0 |
| format | Article |
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These 5-phthalimidopyrimidines as well as phthalimido-2,4-difluorobenzenes were designed as analogues of thalidomide, a well known inhibitor of TNF-alpha production. A preliminary in vitro investigation of the compounds as inhibitors of the TNF-alpha production was performed. Among the compounds of the present series, 5-ethyl-1-phenyl-5-(tetrafluorophthalimido)barbituric acid and 2-(2,4-difluorophenyl)-4,5,6,7-tetrafluoro-1H-isoindole-1,3(2H)-dione were proved to be potent inhibitors. Both compounds showed inhibitory activity in the lower micromolar range on the LPS-induced TNF-alpha production in human monocytes.</description><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/S0968-0896(00)00323-0</identifier><identifier>PMID: 11354662</identifier><language>eng</language><publisher>Oxford: Elsevier Science</publisher><subject>Aza Compounds - chemical synthesis ; Aza Compounds - pharmacology ; Biological and medical sciences ; Humans ; Immunomodulators ; In Vitro Techniques ; Lipopolysaccharides - pharmacology ; Medical sciences ; Monocytes - drug effects ; Monocytes - metabolism ; Pharmacology. 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Both compounds showed inhibitory activity in the lower micromolar range on the LPS-induced TNF-alpha production in human monocytes.</description><subject>Aza Compounds - chemical synthesis</subject><subject>Aza Compounds - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Humans</subject><subject>Immunomodulators</subject><subject>In Vitro Techniques</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Medical sciences</subject><subject>Monocytes - drug effects</subject><subject>Monocytes - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Thalidomide - analogs & derivatives</subject><subject>Thalidomide - chemical synthesis</subject><subject>Thalidomide - pharmacology</subject><subject>Tumor Necrosis Factor-alpha - antagonists & inhibitors</subject><subject>Tumor Necrosis Factor-alpha - biosynthesis</subject><issn>0968-0896</issn><issn>1464-3391</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo90EtOwzAQBmALgWgpHAFkCQnBImDHj9jsqoqXVIlFYR1NY5saJXGJk0rlVlyEMxFo6WoW8_2jmUHolJJrSqi8mREtVUKUlpeEXBHCUpaQPTSkXPKEMU330XBHBugoxndCSMo1PUQDSpngUqZD1I0_AUMNZXjrbMTB4XYBpTeh8sbiWzxb1-3CRh97ZLBdQdlB60ONIWJfL_zct6HZ5LoqNLi2RRN-uYOi7yTfX3jZBNMVfyFf45Vvm3CMDhyU0Z5s6wi93t-9TB6T6fPD02Q8TZZUZm2iQKVS2oxabqXmcyacEtYwrYXgGU0zISgnmhPhMmUMOJly5wprFIN5kQIboYvN3H6Hj_6-Nq98LGxZQm1DF_OMKKG5ED0828JuXlmTLxtfQbPO_x_Vg_MtgFhA6RqoCx93TmeEMcV-AEAHehw</recordid><startdate>20010401</startdate><enddate>20010401</enddate><creator>GÜTSCHOW, Michael</creator><creator>HECKER, Thomas</creator><creator>THIELE, Andrea</creator><creator>HAUSCHILDT, Sunna</creator><creator>EGER, Kurt</creator><general>Elsevier Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20010401</creationdate><title>Aza analogues of thalidomide : Synthesis and evaluation as inhibitors of tumor necrosis factor-α production in vitro</title><author>GÜTSCHOW, Michael ; HECKER, Thomas ; THIELE, Andrea ; HAUSCHILDT, Sunna ; EGER, Kurt</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p167t-8a8266e71e4e694b35f85ed3995547127551409405f78ddaf624ffced83abc2a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Aza Compounds - chemical synthesis</topic><topic>Aza Compounds - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Humans</topic><topic>Immunomodulators</topic><topic>In Vitro Techniques</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Medical sciences</topic><topic>Monocytes - drug effects</topic><topic>Monocytes - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Thalidomide - analogs & derivatives</topic><topic>Thalidomide - chemical synthesis</topic><topic>Thalidomide - pharmacology</topic><topic>Tumor Necrosis Factor-alpha - antagonists & inhibitors</topic><topic>Tumor Necrosis Factor-alpha - biosynthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GÜTSCHOW, Michael</creatorcontrib><creatorcontrib>HECKER, Thomas</creatorcontrib><creatorcontrib>THIELE, Andrea</creatorcontrib><creatorcontrib>HAUSCHILDT, Sunna</creatorcontrib><creatorcontrib>EGER, Kurt</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>GÜTSCHOW, Michael</au><au>HECKER, Thomas</au><au>THIELE, Andrea</au><au>HAUSCHILDT, Sunna</au><au>EGER, Kurt</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aza analogues of thalidomide : Synthesis and evaluation as inhibitors of tumor necrosis factor-α production in vitro</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2001-04-01</date><risdate>2001</risdate><volume>9</volume><issue>4</issue><spage>1059</spage><epage>1065</epage><pages>1059-1065</pages><issn>0968-0896</issn><eissn>1464-3391</eissn><abstract>A synthetic entry to derivatives of the new classes of 5-phthalimidouracils and 5-phthalimidobarbituric acids is reported. These 5-phthalimidopyrimidines as well as phthalimido-2,4-difluorobenzenes were designed as analogues of thalidomide, a well known inhibitor of TNF-alpha production. A preliminary in vitro investigation of the compounds as inhibitors of the TNF-alpha production was performed. Among the compounds of the present series, 5-ethyl-1-phenyl-5-(tetrafluorophthalimido)barbituric acid and 2-(2,4-difluorophenyl)-4,5,6,7-tetrafluoro-1H-isoindole-1,3(2H)-dione were proved to be potent inhibitors. Both compounds showed inhibitory activity in the lower micromolar range on the LPS-induced TNF-alpha production in human monocytes.</abstract><cop>Oxford</cop><pub>Elsevier Science</pub><pmid>11354662</pmid><doi>10.1016/S0968-0896(00)00323-0</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Bioorganic & medicinal chemistry, 2001-04, Vol.9 (4), p.1059-1065 |
| issn | 0968-0896 1464-3391 |
| language | eng |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Aza Compounds - chemical synthesis Aza Compounds - pharmacology Biological and medical sciences Humans Immunomodulators In Vitro Techniques Lipopolysaccharides - pharmacology Medical sciences Monocytes - drug effects Monocytes - metabolism Pharmacology. Drug treatments Thalidomide - analogs & derivatives Thalidomide - chemical synthesis Thalidomide - pharmacology Tumor Necrosis Factor-alpha - antagonists & inhibitors Tumor Necrosis Factor-alpha - biosynthesis |
| title | Aza analogues of thalidomide : Synthesis and evaluation as inhibitors of tumor necrosis factor-α production in vitro |
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