cis-1,2,3a,4,5,9b-Hexahydro-3H-benz[e] indoles: Synthesis and In Vitro Binding Affinity at Dopamine D1 and D2 Receptors
cis-1,2,3a,4,5,9b-Hexahydro-3H-benz[e]indoles were synthesized and evaluated for in vitro dopamine D1 and D2 receptor binding affinity. The target compounds 21-25 were readily prepared by reduction of the air-sensitive tricyclic enamines 10-14. Reduction of 10-14 with sodium borohydride, sodium cyan...
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| Veröffentlicht in: | Journal of pharmaceutical sciences 1993-03, Vol.82 (3), p.334-339 |
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| container_title | Journal of pharmaceutical sciences |
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| creator | Cruse, Sharon F. Lear, Jennifer Klein, Cheryl L. Andersen, Peter H. Dick, Ronald M. Michael Crider, A. |
| description | cis-1,2,3a,4,5,9b-Hexahydro-3H-benz[e]indoles were synthesized and evaluated for in vitro dopamine D1 and D2 receptor binding affinity. The target compounds 21-25 were readily prepared by reduction of the air-sensitive tricyclic enamines 10-14. Reduction of 10-14 with sodium borohydride, sodium cyanoborohydride, palladium on carbon in ethanol, and platinum oxide in ethanol or acetic acid gave only the cis(3a,9b) 1,2,3a,4,5,9b-hexahydro-3H-benz[e]indoles. The stereochemistry was confirmed by single-crystal X-ray analysis. In the 6-hydroxy series, the binding affinity at D1 and D2 receptors was of the order 22 (W-n-butyl) >21 (N-n-propyl) >23 (N-H). The compounds demonstrated greater binding affinity at D2 receptors than at D1 binding sites. In contrast, 8-OH derivatives exhibited affinity only for D2 receptors, with 25 (N-n-butyl) having slightly greater affinity than 24 (N-n-propyl). |
| doi_str_mv | 10.1002/jps.2600820324 |
| format | Article |
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The target compounds 21-25 were readily prepared by reduction of the air-sensitive tricyclic enamines 10-14. Reduction of 10-14 with sodium borohydride, sodium cyanoborohydride, palladium on carbon in ethanol, and platinum oxide in ethanol or acetic acid gave only the cis(3a,9b) 1,2,3a,4,5,9b-hexahydro-3H-benz[e]indoles. The stereochemistry was confirmed by single-crystal X-ray analysis. In the 6-hydroxy series, the binding affinity at D1 and D2 receptors was of the order 22 (W-n-butyl) >21 (N-n-propyl) >23 (N-H). The compounds demonstrated greater binding affinity at D2 receptors than at D1 binding sites. In contrast, 8-OH derivatives exhibited affinity only for D2 receptors, with 25 (N-n-butyl) having slightly greater affinity than 24 (N-n-propyl).</description><identifier>ISSN: 0022-3549</identifier><identifier>EISSN: 1520-6017</identifier><identifier>DOI: 10.1002/jps.2600820324</identifier><identifier>PMID: 8095545</identifier><identifier>CODEN: JPMSAE</identifier><language>eng</language><publisher>Washington: Elsevier Inc</publisher><subject>Animals ; Benzazepines - metabolism ; Benzazepines - pharmacology ; Biological and medical sciences ; Catecholaminergic system ; Corpus Striatum - drug effects ; Corpus Striatum - metabolism ; Dopamine Agents - chemical synthesis ; Dopamine Agents - metabolism ; Dopamine Agents - pharmacology ; Indoles - chemical synthesis ; Indoles - metabolism ; Indoles - pharmacology ; Male ; Medical sciences ; Models, Biological ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; Pharmacology. Drug treatments ; Rats ; Rats, Wistar ; Receptors, Dopamine D1 - metabolism ; Receptors, Dopamine D2 - metabolism ; Spiperone - metabolism ; Spiperone - pharmacology ; Structure-Activity Relationship ; Tritium</subject><ispartof>Journal of pharmaceutical sciences, 1993-03, Vol.82 (3), p.334-339</ispartof><rights>1993 Wiley-Liss, Inc., A Wiley Company</rights><rights>Copyright © 1993 Wiley‐Liss, Inc., A Wiley Company</rights><rights>1993 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3714-6f4d6c214e2662b5655c8f746068c50f9c09a4502a1f2c3218ae436afa6637a83</citedby><cites>FETCH-LOGICAL-c3714-6f4d6c214e2662b5655c8f746068c50f9c09a4502a1f2c3218ae436afa6637a83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjps.2600820324$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjps.2600820324$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4756487$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8095545$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cruse, Sharon F.</creatorcontrib><creatorcontrib>Lear, Jennifer</creatorcontrib><creatorcontrib>Klein, Cheryl L.</creatorcontrib><creatorcontrib>Andersen, Peter H.</creatorcontrib><creatorcontrib>Dick, Ronald M.</creatorcontrib><creatorcontrib>Michael Crider, A.</creatorcontrib><title>cis-1,2,3a,4,5,9b-Hexahydro-3H-benz[e] indoles: Synthesis and In Vitro Binding Affinity at Dopamine D1 and D2 Receptors</title><title>Journal of pharmaceutical sciences</title><addtitle>J. Pharm. Sci</addtitle><description>cis-1,2,3a,4,5,9b-Hexahydro-3H-benz[e]indoles were synthesized and evaluated for in vitro dopamine D1 and D2 receptor binding affinity. The target compounds 21-25 were readily prepared by reduction of the air-sensitive tricyclic enamines 10-14. Reduction of 10-14 with sodium borohydride, sodium cyanoborohydride, palladium on carbon in ethanol, and platinum oxide in ethanol or acetic acid gave only the cis(3a,9b) 1,2,3a,4,5,9b-hexahydro-3H-benz[e]indoles. The stereochemistry was confirmed by single-crystal X-ray analysis. In the 6-hydroxy series, the binding affinity at D1 and D2 receptors was of the order 22 (W-n-butyl) >21 (N-n-propyl) >23 (N-H). The compounds demonstrated greater binding affinity at D2 receptors than at D1 binding sites. In contrast, 8-OH derivatives exhibited affinity only for D2 receptors, with 25 (N-n-butyl) having slightly greater affinity than 24 (N-n-propyl).</description><subject>Animals</subject><subject>Benzazepines - metabolism</subject><subject>Benzazepines - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Catecholaminergic system</subject><subject>Corpus Striatum - drug effects</subject><subject>Corpus Striatum - metabolism</subject><subject>Dopamine Agents - chemical synthesis</subject><subject>Dopamine Agents - metabolism</subject><subject>Dopamine Agents - pharmacology</subject><subject>Indoles - chemical synthesis</subject><subject>Indoles - metabolism</subject><subject>Indoles - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Models, Biological</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptors, Dopamine D1 - metabolism</subject><subject>Receptors, Dopamine D2 - metabolism</subject><subject>Spiperone - metabolism</subject><subject>Spiperone - pharmacology</subject><subject>Structure-Activity Relationship</subject><subject>Tritium</subject><issn>0022-3549</issn><issn>1520-6017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM1v0zAYhyMEGt3gyg3JB8QpLv5Owm20sA4mmDZgB4Qs13nDvKVOZqds4a_H0KqIA-L0Ht7n9348WfaEkiklhL246uOUKUJKRjgT97IJlYxgRWhxP5skgGEuRfUw24_xihCiiJR72V5JKimFnGS31kVMc5Zzk4tc5tUSL-DOXI516DBf4CX4H1_gK3K-7lqIL9H56IdLiC4i42t07NFnN4QOvUqA89_QYdM474YRmQHNu96snAc0p7_hOUNnYKEfuhAfZQ8a00Z4vK0H2ac3rz_OFvjkw9Hx7PAEW15QgVUjamUZFcCUYkuppLRlUwhFVGklaSpLKiMkYYY2zHJGSwOCK9MYpXhhSn6QPd_M7UN3s4Y46JWLFtrWeOjWURdSUS4ET-B0A9rQxRig0X1wKxNGTYn-ZVon0_qP6RR4up28Xq6g3uFbtan_bNs30Zq2CcYn1ztMpM2iLBJWbbBb18L4n6X67en5XyfgTdbFAe52WROutSp4IfXF-yN9urg4q9S7mSaJLzc8JOPfHQQdrQNvoXYB7KDrzv3r259nobTx</recordid><startdate>199303</startdate><enddate>199303</enddate><creator>Cruse, Sharon F.</creator><creator>Lear, Jennifer</creator><creator>Klein, Cheryl L.</creator><creator>Andersen, Peter H.</creator><creator>Dick, Ronald M.</creator><creator>Michael Crider, A.</creator><general>Elsevier Inc</general><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><general>American Pharmaceutical Association</general><scope>BSCLL</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>199303</creationdate><title>cis-1,2,3a,4,5,9b-Hexahydro-3H-benz[e] indoles: Synthesis and In Vitro Binding Affinity at Dopamine D1 and D2 Receptors</title><author>Cruse, Sharon F. ; Lear, Jennifer ; Klein, Cheryl L. ; Andersen, Peter H. ; Dick, Ronald M. ; Michael Crider, A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3714-6f4d6c214e2662b5655c8f746068c50f9c09a4502a1f2c3218ae436afa6637a83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Animals</topic><topic>Benzazepines - metabolism</topic><topic>Benzazepines - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Catecholaminergic system</topic><topic>Corpus Striatum - drug effects</topic><topic>Corpus Striatum - metabolism</topic><topic>Dopamine Agents - chemical synthesis</topic><topic>Dopamine Agents - metabolism</topic><topic>Dopamine Agents - pharmacology</topic><topic>Indoles - chemical synthesis</topic><topic>Indoles - metabolism</topic><topic>Indoles - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Models, Biological</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptors, Dopamine D1 - metabolism</topic><topic>Receptors, Dopamine D2 - metabolism</topic><topic>Spiperone - metabolism</topic><topic>Spiperone - pharmacology</topic><topic>Structure-Activity Relationship</topic><topic>Tritium</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cruse, Sharon F.</creatorcontrib><creatorcontrib>Lear, Jennifer</creatorcontrib><creatorcontrib>Klein, Cheryl L.</creatorcontrib><creatorcontrib>Andersen, Peter H.</creatorcontrib><creatorcontrib>Dick, Ronald M.</creatorcontrib><creatorcontrib>Michael Crider, A.</creatorcontrib><collection>Istex</collection><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>Journal of pharmaceutical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cruse, Sharon F.</au><au>Lear, Jennifer</au><au>Klein, Cheryl L.</au><au>Andersen, Peter H.</au><au>Dick, Ronald M.</au><au>Michael Crider, A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>cis-1,2,3a,4,5,9b-Hexahydro-3H-benz[e] indoles: Synthesis and In Vitro Binding Affinity at Dopamine D1 and D2 Receptors</atitle><jtitle>Journal of pharmaceutical sciences</jtitle><addtitle>J. Pharm. Sci</addtitle><date>1993-03</date><risdate>1993</risdate><volume>82</volume><issue>3</issue><spage>334</spage><epage>339</epage><pages>334-339</pages><issn>0022-3549</issn><eissn>1520-6017</eissn><coden>JPMSAE</coden><abstract>cis-1,2,3a,4,5,9b-Hexahydro-3H-benz[e]indoles were synthesized and evaluated for in vitro dopamine D1 and D2 receptor binding affinity. The target compounds 21-25 were readily prepared by reduction of the air-sensitive tricyclic enamines 10-14. Reduction of 10-14 with sodium borohydride, sodium cyanoborohydride, palladium on carbon in ethanol, and platinum oxide in ethanol or acetic acid gave only the cis(3a,9b) 1,2,3a,4,5,9b-hexahydro-3H-benz[e]indoles. The stereochemistry was confirmed by single-crystal X-ray analysis. In the 6-hydroxy series, the binding affinity at D1 and D2 receptors was of the order 22 (W-n-butyl) >21 (N-n-propyl) >23 (N-H). The compounds demonstrated greater binding affinity at D2 receptors than at D1 binding sites. In contrast, 8-OH derivatives exhibited affinity only for D2 receptors, with 25 (N-n-butyl) having slightly greater affinity than 24 (N-n-propyl).</abstract><cop>Washington</cop><pub>Elsevier Inc</pub><pmid>8095545</pmid><doi>10.1002/jps.2600820324</doi><tpages>6</tpages></addata></record> |
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| ispartof | Journal of pharmaceutical sciences, 1993-03, Vol.82 (3), p.334-339 |
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| language | eng |
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| source | MEDLINE; Access via Wiley Online Library; Alma/SFX Local Collection |
| subjects | Animals Benzazepines - metabolism Benzazepines - pharmacology Biological and medical sciences Catecholaminergic system Corpus Striatum - drug effects Corpus Striatum - metabolism Dopamine Agents - chemical synthesis Dopamine Agents - metabolism Dopamine Agents - pharmacology Indoles - chemical synthesis Indoles - metabolism Indoles - pharmacology Male Medical sciences Models, Biological Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Pharmacology. Drug treatments Rats Rats, Wistar Receptors, Dopamine D1 - metabolism Receptors, Dopamine D2 - metabolism Spiperone - metabolism Spiperone - pharmacology Structure-Activity Relationship Tritium |
| title | cis-1,2,3a,4,5,9b-Hexahydro-3H-benz[e] indoles: Synthesis and In Vitro Binding Affinity at Dopamine D1 and D2 Receptors |
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