Rigidized 1-aryl sulfonyl tryptamines: Synthesis and pharmacological evaluation as 5-HT₆ receptor ligands
A series of N₁-arylsulfonyl-3-(pyrrolidin-3-yl)-1H-indole and N₁-arylsulfonyl-3-(4-chloro-2,5-dihydro-1H-pyrrol-3-yl)-1H-indole derivatives (tryptamine derivatives with rigidized side chain) have been prepared and tested for their binding affinity to 5-HT₆ receptor. Several compounds displayed poten...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2011-08, Vol.21 (15), p.4577-4580 |
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| creator | Nirogi, Ramakrishna Dwarampudi, Adireddy Kambhampati, Ramasastry Bhatta, Venugopalarao Kota, Laxman Shinde, Anil Badange, Rajesh Jayarajan, Pradeep Bhyrapuneni, Gopinadh Dubey, P.K |
| description | A series of N₁-arylsulfonyl-3-(pyrrolidin-3-yl)-1H-indole and N₁-arylsulfonyl-3-(4-chloro-2,5-dihydro-1H-pyrrol-3-yl)-1H-indole derivatives (tryptamine derivatives with rigidized side chain) have been prepared and tested for their binding affinity to 5-HT₆ receptor. Several compounds displayed potent binding affinity for the 5-HT₆ receptor when tested in in vitro binding assay. The primary SAR indicates that rigidification of dimethylamino alkyl chain at C₃ of indole carbon maintains the binding affinity to 5-HT₆R. The lead compound N₁-benzenesulfonyl-3-(4-chloro-1-methyl-2,5-dihydro-1H-pyrrol-3-yl)-1H-indole, 10a (Kb=0.1nM) has shown excellent in vitro affinity and was active in animal models of cognition like NORT and water maze. |
| doi_str_mv | 10.1016/j.bmcl.2011.05.106 |
| format | Article |
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Several compounds displayed potent binding affinity for the 5-HT₆ receptor when tested in in vitro binding assay. The primary SAR indicates that rigidification of dimethylamino alkyl chain at C₃ of indole carbon maintains the binding affinity to 5-HT₆R. The lead compound N₁-benzenesulfonyl-3-(4-chloro-1-methyl-2,5-dihydro-1H-pyrrol-3-yl)-1H-indole, 10a (Kb=0.1nM) has shown excellent in vitro affinity and was active in animal models of cognition like NORT and water maze.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2011.05.106</identifier><identifier>PMID: 21724392</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>Administration, Oral ; animal models ; Animals ; binding capacity ; Biological and medical sciences ; carbon ; chemistry ; cognition ; Cognition Disorders - drug therapy ; Disease Models, Animal ; Indoles - chemical synthesis ; Indoles - pharmacokinetics ; Indoles - therapeutic use ; Ligands ; Male ; Medical sciences ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; Pharmacology. Drug treatments ; Protein Binding ; Rats ; Rats, Wistar ; Receptors, Serotonin - chemistry ; Receptors, Serotonin - metabolism ; Serotoninergic system ; Structure-Activity Relationship ; Sulfonamides - chemical synthesis ; Sulfonamides - pharmacokinetics ; Sulfonamides - therapeutic use ; tryptamine ; Tryptamines - chemistry ; Tryptamines - pharmacokinetics ; Tryptamines - therapeutic use</subject><ispartof>Bioorganic & medicinal chemistry letters, 2011-08, Vol.21 (15), p.4577-4580</ispartof><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier Ltd. 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Several compounds displayed potent binding affinity for the 5-HT₆ receptor when tested in in vitro binding assay. The primary SAR indicates that rigidification of dimethylamino alkyl chain at C₃ of indole carbon maintains the binding affinity to 5-HT₆R. 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Drug treatments</subject><subject>Protein Binding</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptors, Serotonin - chemistry</subject><subject>Receptors, Serotonin - metabolism</subject><subject>Serotoninergic system</subject><subject>Structure-Activity Relationship</subject><subject>Sulfonamides - chemical synthesis</subject><subject>Sulfonamides - pharmacokinetics</subject><subject>Sulfonamides - therapeutic use</subject><subject>tryptamine</subject><subject>Tryptamines - chemistry</subject><subject>Tryptamines - pharmacokinetics</subject><subject>Tryptamines - therapeutic use</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkMFu1DAURS0EokPhB1iAN4hVhufY8STsqgooUiUk2krsrGfHnnpw4mAnSMOSBR_Kl-DRDLCy9XzuffIh5DmDNQMm3-zWejBhXQNja2jKTD4gKyakqLiA5iFZQSehajvx5Yw8yXkHwAQI8Zic1WxTC97VK_L1s9_63v-wPWUVpn2geQkujuUyp_004-BHm9_Sm_0439vsM8Wxp9M9pgFNDHHrDQZqv2NYcPZxpJhpU13d_v75iyZr7DTHRIPfllR-Sh45DNk-O53n5O79u9vLq-r604ePlxfXlalbOVeSOdsAGKmNcYZ3reucaVytNUDvWmeFFVx31rhOQ3mSuuGgeY9s41BKzc_J62PvlOK3xeZZDT4bGwKONi5ZtZsWeOmtC1kfSZNizsk6NSU_FA2KgTo4Vjt1cKwOjhU0ZSZL6MWpftGD7f9F_kotwKsTgLnYcQlH4_N_TvANcGgL9_LIOYwKt6kwdzdlU_k84w0D4H8A2smSig</recordid><startdate>20110801</startdate><enddate>20110801</enddate><creator>Nirogi, Ramakrishna</creator><creator>Dwarampudi, Adireddy</creator><creator>Kambhampati, Ramasastry</creator><creator>Bhatta, Venugopalarao</creator><creator>Kota, Laxman</creator><creator>Shinde, Anil</creator><creator>Badange, Rajesh</creator><creator>Jayarajan, Pradeep</creator><creator>Bhyrapuneni, Gopinadh</creator><creator>Dubey, P.K</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>FBQ</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20110801</creationdate><title>Rigidized 1-aryl sulfonyl tryptamines: Synthesis and pharmacological evaluation as 5-HT₆ receptor ligands</title><author>Nirogi, Ramakrishna ; Dwarampudi, Adireddy ; Kambhampati, Ramasastry ; Bhatta, Venugopalarao ; Kota, Laxman ; Shinde, Anil ; Badange, Rajesh ; Jayarajan, Pradeep ; Bhyrapuneni, Gopinadh ; Dubey, P.K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c286t-61fe500c6bccfc398f9fc5f2bb00df8fe4e43b9ecf9b09fc6b530b3da17fa66b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Administration, Oral</topic><topic>animal models</topic><topic>Animals</topic><topic>binding capacity</topic><topic>Biological and medical sciences</topic><topic>carbon</topic><topic>chemistry</topic><topic>cognition</topic><topic>Cognition Disorders - drug therapy</topic><topic>Disease Models, Animal</topic><topic>Indoles - chemical synthesis</topic><topic>Indoles - pharmacokinetics</topic><topic>Indoles - therapeutic use</topic><topic>Ligands</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. 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Several compounds displayed potent binding affinity for the 5-HT₆ receptor when tested in in vitro binding assay. The primary SAR indicates that rigidification of dimethylamino alkyl chain at C₃ of indole carbon maintains the binding affinity to 5-HT₆R. The lead compound N₁-benzenesulfonyl-3-(4-chloro-1-methyl-2,5-dihydro-1H-pyrrol-3-yl)-1H-indole, 10a (Kb=0.1nM) has shown excellent in vitro affinity and was active in animal models of cognition like NORT and water maze.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>21724392</pmid><doi>10.1016/j.bmcl.2011.05.106</doi><tpages>4</tpages></addata></record> |
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| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2011-08, Vol.21 (15), p.4577-4580 |
| issn | 0960-894X 1464-3405 |
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| subjects | Administration, Oral animal models Animals binding capacity Biological and medical sciences carbon chemistry cognition Cognition Disorders - drug therapy Disease Models, Animal Indoles - chemical synthesis Indoles - pharmacokinetics Indoles - therapeutic use Ligands Male Medical sciences Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Pharmacology. Drug treatments Protein Binding Rats Rats, Wistar Receptors, Serotonin - chemistry Receptors, Serotonin - metabolism Serotoninergic system Structure-Activity Relationship Sulfonamides - chemical synthesis Sulfonamides - pharmacokinetics Sulfonamides - therapeutic use tryptamine Tryptamines - chemistry Tryptamines - pharmacokinetics Tryptamines - therapeutic use |
| title | Rigidized 1-aryl sulfonyl tryptamines: Synthesis and pharmacological evaluation as 5-HT₆ receptor ligands |
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