Loading…
Muscarinic subtypes profile modulation within a series of new antagonists, bridged bicyclic derivatives of 2,2-Diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine
A set of new muscarinic antagonists, bridged bicyclic derivatives of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine ( 1), was synthesized and tested to evaluate their affinity and selectivity for M 1, M 2, M 3 and M 4 receptor subtypes. The conformational constraint of 1 in a bicyclic structur...
Saved in:
| Published in: | Bioorganic & medicinal chemistry 2003-09, Vol.11 (18), p.3901-3911 |
|---|---|
| Main Authors: | , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | |
|---|---|
| cites | cdi_FETCH-LOGICAL-c254t-f40d7ac88c91c8b86c522a69ee7161d6d5b4494be84ce156618e018ecdf826563 |
| container_end_page | 3911 |
| container_issue | 18 |
| container_start_page | 3901 |
| container_title | Bioorganic & medicinal chemistry |
| container_volume | 11 |
| creator | Piergentili, Alessandro Gentili, Francesco Ghelfi, Francesca Marucci, Gabriella Pigini, Maria Quaglia, Wilma Giannella, Mario |
| description | A set of new muscarinic antagonists, bridged bicyclic derivatives of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine (
1), was synthesized and tested to evaluate their affinity and selectivity for M
1, M
2, M
3 and M
4 receptor subtypes. The conformational constraint of
1 in a bicyclic structure, and the variation in distance and stereochemistry of the active functions allowed us to modulate the selectivity of interaction with the M
1–M
3 receptor subtypes. The most interesting compound was (
cis,
trans)-2-(2,2-diphenylethyl)-5-methyl-tetrahydro-[1,3]dioxolo[4,5-
c]pyrrole oxalate (
6), which is equipotent with Pirenzepine on rabbit vas deferens (M
1-putative) but shows a better selectivity profile.
The
trans stereoisomer
6 (
n=1,
m=1) is a muscarinic antagonist equipotent with Pirenzepine on rabbit vas deferens (M
1-putative) but shows a better selectivity profile. |
| doi_str_mv | 10.1016/S0968-0896(03)00431-0 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_73594553</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0968089603004310</els_id><sourcerecordid>73594553</sourcerecordid><originalsourceid>FETCH-LOGICAL-c254t-f40d7ac88c91c8b86c522a69ee7161d6d5b4494be84ce156618e018ecdf826563</originalsourceid><addsrcrecordid>eNqFkc9u1DAQxi0EotuFRwD5AgJpDXZie5MTQi3_pCIOwAkhy7En3UGJs7WTLXkaXhW3WdEjh9GM5N83M56PkCeCvxJc6Ndfea0rxqtav-DlS85lKRi_R1ZCasnKshb3yeofckJOU_rFOS9kLR6SE1HUxbZSfEX-fJ6SsxEDOpqmZpz3kOg-Di12QPvBT50dcQj0GscdBmppgogZGVoa4JraMNrLIWAa04Y2Ef0leNqgm12XG_rMHrL-sAiKTcHOcb-DMHfsh9iUP5nH4ffQ2cAkm7sexl1-8bgUtscAj8iD1nYJHh_zmnx__-7b2Ud28eXDp7O3F8wVSo6sldxvrasqVwtXNZV2qiisrgG2QguvvWqkrGUDlXQglNaiAp7D-bYqtNLlmjxf-ua_X02QRtNjctDl3WCYktmWqpZKlRlUC-jikFKE1uwj9jbORnBz44y5dcbcnN3w0tw6k4s1eXocMDU9-DvV0YoMPDsCNjvStdEGh-mOU1xKXcjMvVk4yOc4IESTHEJw4DGCG40f8D-r_AXuYa1z</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>73594553</pqid></control><display><type>article</type><title>Muscarinic subtypes profile modulation within a series of new antagonists, bridged bicyclic derivatives of 2,2-Diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine</title><source>ScienceDirect Journals</source><creator>Piergentili, Alessandro ; Gentili, Francesco ; Ghelfi, Francesca ; Marucci, Gabriella ; Pigini, Maria ; Quaglia, Wilma ; Giannella, Mario</creator><creatorcontrib>Piergentili, Alessandro ; Gentili, Francesco ; Ghelfi, Francesca ; Marucci, Gabriella ; Pigini, Maria ; Quaglia, Wilma ; Giannella, Mario</creatorcontrib><description>A set of new muscarinic antagonists, bridged bicyclic derivatives of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine (
1), was synthesized and tested to evaluate their affinity and selectivity for M
1, M
2, M
3 and M
4 receptor subtypes. The conformational constraint of
1 in a bicyclic structure, and the variation in distance and stereochemistry of the active functions allowed us to modulate the selectivity of interaction with the M
1–M
3 receptor subtypes. The most interesting compound was (
cis,
trans)-2-(2,2-diphenylethyl)-5-methyl-tetrahydro-[1,3]dioxolo[4,5-
c]pyrrole oxalate (
6), which is equipotent with Pirenzepine on rabbit vas deferens (M
1-putative) but shows a better selectivity profile.
The
trans stereoisomer
6 (
n=1,
m=1) is a muscarinic antagonist equipotent with Pirenzepine on rabbit vas deferens (M
1-putative) but shows a better selectivity profile.</description><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/S0968-0896(03)00431-0</identifier><identifier>PMID: 12927850</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Animals ; Biological and medical sciences ; Bridged Bicyclo Compounds - chemical synthesis ; Bridged Bicyclo Compounds - chemistry ; Cholinergic system ; Dioxolanes - chemical synthesis ; Dioxolanes - chemistry ; Dioxolanes - pharmacology ; Guinea Pigs ; Hydrocarbons, Iodinated - chemistry ; Ileum - drug effects ; Ileum - metabolism ; In Vitro Techniques ; Male ; Medical sciences ; Muscarinic Antagonists - chemical synthesis ; Muscarinic Antagonists - pharmacology ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; Oxalates - chemistry ; Pharmacology. Drug treatments ; Rabbits ; Receptors, Muscarinic - classification ; Receptors, Muscarinic - drug effects ; Receptors, Muscarinic - metabolism ; Stereoisomerism ; Structure-Activity Relationship ; Vas Deferens - drug effects ; Vas Deferens - metabolism</subject><ispartof>Bioorganic & medicinal chemistry, 2003-09, Vol.11 (18), p.3901-3911</ispartof><rights>2003 Elsevier Ltd</rights><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c254t-f40d7ac88c91c8b86c522a69ee7161d6d5b4494be84ce156618e018ecdf826563</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15044624$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12927850$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Piergentili, Alessandro</creatorcontrib><creatorcontrib>Gentili, Francesco</creatorcontrib><creatorcontrib>Ghelfi, Francesca</creatorcontrib><creatorcontrib>Marucci, Gabriella</creatorcontrib><creatorcontrib>Pigini, Maria</creatorcontrib><creatorcontrib>Quaglia, Wilma</creatorcontrib><creatorcontrib>Giannella, Mario</creatorcontrib><title>Muscarinic subtypes profile modulation within a series of new antagonists, bridged bicyclic derivatives of 2,2-Diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem</addtitle><description>A set of new muscarinic antagonists, bridged bicyclic derivatives of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine (
1), was synthesized and tested to evaluate their affinity and selectivity for M
1, M
2, M
3 and M
4 receptor subtypes. The conformational constraint of
1 in a bicyclic structure, and the variation in distance and stereochemistry of the active functions allowed us to modulate the selectivity of interaction with the M
1–M
3 receptor subtypes. The most interesting compound was (
cis,
trans)-2-(2,2-diphenylethyl)-5-methyl-tetrahydro-[1,3]dioxolo[4,5-
c]pyrrole oxalate (
6), which is equipotent with Pirenzepine on rabbit vas deferens (M
1-putative) but shows a better selectivity profile.
The
trans stereoisomer
6 (
n=1,
m=1) is a muscarinic antagonist equipotent with Pirenzepine on rabbit vas deferens (M
1-putative) but shows a better selectivity profile.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Bridged Bicyclo Compounds - chemical synthesis</subject><subject>Bridged Bicyclo Compounds - chemistry</subject><subject>Cholinergic system</subject><subject>Dioxolanes - chemical synthesis</subject><subject>Dioxolanes - chemistry</subject><subject>Dioxolanes - pharmacology</subject><subject>Guinea Pigs</subject><subject>Hydrocarbons, Iodinated - chemistry</subject><subject>Ileum - drug effects</subject><subject>Ileum - metabolism</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Muscarinic Antagonists - chemical synthesis</subject><subject>Muscarinic Antagonists - pharmacology</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>Oxalates - chemistry</subject><subject>Pharmacology. Drug treatments</subject><subject>Rabbits</subject><subject>Receptors, Muscarinic - classification</subject><subject>Receptors, Muscarinic - drug effects</subject><subject>Receptors, Muscarinic - metabolism</subject><subject>Stereoisomerism</subject><subject>Structure-Activity Relationship</subject><subject>Vas Deferens - drug effects</subject><subject>Vas Deferens - metabolism</subject><issn>0968-0896</issn><issn>1464-3391</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNqFkc9u1DAQxi0EotuFRwD5AgJpDXZie5MTQi3_pCIOwAkhy7En3UGJs7WTLXkaXhW3WdEjh9GM5N83M56PkCeCvxJc6Ndfea0rxqtav-DlS85lKRi_R1ZCasnKshb3yeofckJOU_rFOS9kLR6SE1HUxbZSfEX-fJ6SsxEDOpqmZpz3kOg-Di12QPvBT50dcQj0GscdBmppgogZGVoa4JraMNrLIWAa04Y2Ef0leNqgm12XG_rMHrL-sAiKTcHOcb-DMHfsh9iUP5nH4ffQ2cAkm7sexl1-8bgUtscAj8iD1nYJHh_zmnx__-7b2Ud28eXDp7O3F8wVSo6sldxvrasqVwtXNZV2qiisrgG2QguvvWqkrGUDlXQglNaiAp7D-bYqtNLlmjxf-ua_X02QRtNjctDl3WCYktmWqpZKlRlUC-jikFKE1uwj9jbORnBz44y5dcbcnN3w0tw6k4s1eXocMDU9-DvV0YoMPDsCNjvStdEGh-mOU1xKXcjMvVk4yOc4IESTHEJw4DGCG40f8D-r_AXuYa1z</recordid><startdate>20030901</startdate><enddate>20030901</enddate><creator>Piergentili, Alessandro</creator><creator>Gentili, Francesco</creator><creator>Ghelfi, Francesca</creator><creator>Marucci, Gabriella</creator><creator>Pigini, Maria</creator><creator>Quaglia, Wilma</creator><creator>Giannella, Mario</creator><general>Elsevier Ltd</general><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>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20030901</creationdate><title>Muscarinic subtypes profile modulation within a series of new antagonists, bridged bicyclic derivatives of 2,2-Diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine</title><author>Piergentili, Alessandro ; Gentili, Francesco ; Ghelfi, Francesca ; Marucci, Gabriella ; Pigini, Maria ; Quaglia, Wilma ; Giannella, Mario</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c254t-f40d7ac88c91c8b86c522a69ee7161d6d5b4494be84ce156618e018ecdf826563</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Bridged Bicyclo Compounds - chemical synthesis</topic><topic>Bridged Bicyclo Compounds - chemistry</topic><topic>Cholinergic system</topic><topic>Dioxolanes - chemical synthesis</topic><topic>Dioxolanes - chemistry</topic><topic>Dioxolanes - pharmacology</topic><topic>Guinea Pigs</topic><topic>Hydrocarbons, Iodinated - chemistry</topic><topic>Ileum - drug effects</topic><topic>Ileum - metabolism</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Muscarinic Antagonists - chemical synthesis</topic><topic>Muscarinic Antagonists - pharmacology</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>Oxalates - chemistry</topic><topic>Pharmacology. Drug treatments</topic><topic>Rabbits</topic><topic>Receptors, Muscarinic - classification</topic><topic>Receptors, Muscarinic - drug effects</topic><topic>Receptors, Muscarinic - metabolism</topic><topic>Stereoisomerism</topic><topic>Structure-Activity Relationship</topic><topic>Vas Deferens - drug effects</topic><topic>Vas Deferens - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Piergentili, Alessandro</creatorcontrib><creatorcontrib>Gentili, Francesco</creatorcontrib><creatorcontrib>Ghelfi, Francesca</creatorcontrib><creatorcontrib>Marucci, Gabriella</creatorcontrib><creatorcontrib>Pigini, Maria</creatorcontrib><creatorcontrib>Quaglia, Wilma</creatorcontrib><creatorcontrib>Giannella, Mario</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>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Piergentili, Alessandro</au><au>Gentili, Francesco</au><au>Ghelfi, Francesca</au><au>Marucci, Gabriella</au><au>Pigini, Maria</au><au>Quaglia, Wilma</au><au>Giannella, Mario</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Muscarinic subtypes profile modulation within a series of new antagonists, bridged bicyclic derivatives of 2,2-Diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2003-09-01</date><risdate>2003</risdate><volume>11</volume><issue>18</issue><spage>3901</spage><epage>3911</epage><pages>3901-3911</pages><issn>0968-0896</issn><eissn>1464-3391</eissn><abstract>A set of new muscarinic antagonists, bridged bicyclic derivatives of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine (
1), was synthesized and tested to evaluate their affinity and selectivity for M
1, M
2, M
3 and M
4 receptor subtypes. The conformational constraint of
1 in a bicyclic structure, and the variation in distance and stereochemistry of the active functions allowed us to modulate the selectivity of interaction with the M
1–M
3 receptor subtypes. The most interesting compound was (
cis,
trans)-2-(2,2-diphenylethyl)-5-methyl-tetrahydro-[1,3]dioxolo[4,5-
c]pyrrole oxalate (
6), which is equipotent with Pirenzepine on rabbit vas deferens (M
1-putative) but shows a better selectivity profile.
The
trans stereoisomer
6 (
n=1,
m=1) is a muscarinic antagonist equipotent with Pirenzepine on rabbit vas deferens (M
1-putative) but shows a better selectivity profile.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>12927850</pmid><doi>10.1016/S0968-0896(03)00431-0</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0968-0896 |
| ispartof | Bioorganic & medicinal chemistry, 2003-09, Vol.11 (18), p.3901-3911 |
| issn | 0968-0896 1464-3391 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_73594553 |
| source | ScienceDirect Journals |
| subjects | Animals Biological and medical sciences Bridged Bicyclo Compounds - chemical synthesis Bridged Bicyclo Compounds - chemistry Cholinergic system Dioxolanes - chemical synthesis Dioxolanes - chemistry Dioxolanes - pharmacology Guinea Pigs Hydrocarbons, Iodinated - chemistry Ileum - drug effects Ileum - metabolism In Vitro Techniques Male Medical sciences Muscarinic Antagonists - chemical synthesis Muscarinic Antagonists - pharmacology Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Oxalates - chemistry Pharmacology. Drug treatments Rabbits Receptors, Muscarinic - classification Receptors, Muscarinic - drug effects Receptors, Muscarinic - metabolism Stereoisomerism Structure-Activity Relationship Vas Deferens - drug effects Vas Deferens - metabolism |
| title | Muscarinic subtypes profile modulation within a series of new antagonists, bridged bicyclic derivatives of 2,2-Diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T12%3A31%3A43IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Muscarinic%20subtypes%20profile%20modulation%20within%20a%20series%20of%20new%20antagonists,%20bridged%20bicyclic%20derivatives%20of%202,2-Diphenyl-%5B1,3%5D-dioxolan-4-ylmethyl-dimethylamine&rft.jtitle=Bioorganic%20&%20medicinal%20chemistry&rft.au=Piergentili,%20Alessandro&rft.date=2003-09-01&rft.volume=11&rft.issue=18&rft.spage=3901&rft.epage=3911&rft.pages=3901-3911&rft.issn=0968-0896&rft.eissn=1464-3391&rft_id=info:doi/10.1016/S0968-0896(03)00431-0&rft_dat=%3Cproquest_cross%3E73594553%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c254t-f40d7ac88c91c8b86c522a69ee7161d6d5b4494be84ce156618e018ecdf826563%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=73594553&rft_id=info:pmid/12927850&rfr_iscdi=true |