trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT2 receptor family
A strategy to replace the ethylamine side chain of 2,5-dimethoxy-4-iodoamphetamine (DOI, 1a), and 2,5-dimethoxy-4-bromoamphetamine (DOB, 1b) with a cyclopropylamine moiety was successful in leading to compounds with high affinity at the 5-HT2 family of receptors; and the more potent stereoisomer of...
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| Format: | Article |
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Beilstein-Institut
2012-10-01
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| Series: | Beilstein Journal of Organic Chemistry |
| Subjects: | |
| Online Access: | https://doi.org/10.3762/bjoc.8.194 |
| _version_ | 1818733372410691584 |
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| author | Adam Pigott Stewart Frescas John D. McCorvy Xi-Ping Huang Bryan L. Roth David E. Nichols |
| author_facet | Adam Pigott Stewart Frescas John D. McCorvy Xi-Ping Huang Bryan L. Roth David E. Nichols |
| author_sort | Adam Pigott |
| collection | DOAJ |
| description | A strategy to replace the ethylamine side chain of 2,5-dimethoxy-4-iodoamphetamine (DOI, 1a), and 2,5-dimethoxy-4-bromoamphetamine (DOB, 1b) with a cyclopropylamine moiety was successful in leading to compounds with high affinity at the 5-HT2 family of receptors; and the more potent stereoisomer of the cyclopropane analogues had the expected (−)-(1R,2S)-configuration. Screening for affinity at various serotonin receptor subtypes, however, revealed that the cyclopropane congeners also had increased affinity at several sites in addition to the 5-HT2A and 5-HT2B receptors. Therefore, at appropriate doses – although (−)-4 and (−)-5 may be useful as tools to probe 5-HT2 receptor function – one would need to be mindful that their selectivity for 5-HT2A receptors is somewhat less than for DOI itself. |
| first_indexed | 2024-12-17T23:48:25Z |
| format | Article |
| id | doaj.art-e4a4e65219af4ebc8b2d67f16ff7a98c |
| institution | Directory Open Access Journal |
| issn | 1860-5397 |
| language | English |
| last_indexed | 2024-12-17T23:48:25Z |
| publishDate | 2012-10-01 |
| publisher | Beilstein-Institut |
| record_format | Article |
| series | Beilstein Journal of Organic Chemistry |
| spelling | doaj.art-e4a4e65219af4ebc8b2d67f16ff7a98c2022-12-21T21:28:15ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972012-10-01811705170910.3762/bjoc.8.1941860-5397-8-194trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT2 receptor familyAdam Pigott0Stewart Frescas1John D. McCorvy2Xi-Ping Huang3Bryan L. Roth4David E. Nichols5Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN 47907, USADepartment of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN 47907, USADepartment of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN 47907, USANational Institute of Mental Health, Psychoactive Drug Screening Program, Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USANational Institute of Mental Health, Psychoactive Drug Screening Program, Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USADepartment of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN 47907, USAA strategy to replace the ethylamine side chain of 2,5-dimethoxy-4-iodoamphetamine (DOI, 1a), and 2,5-dimethoxy-4-bromoamphetamine (DOB, 1b) with a cyclopropylamine moiety was successful in leading to compounds with high affinity at the 5-HT2 family of receptors; and the more potent stereoisomer of the cyclopropane analogues had the expected (−)-(1R,2S)-configuration. Screening for affinity at various serotonin receptor subtypes, however, revealed that the cyclopropane congeners also had increased affinity at several sites in addition to the 5-HT2A and 5-HT2B receptors. Therefore, at appropriate doses – although (−)-4 and (−)-5 may be useful as tools to probe 5-HT2 receptor function – one would need to be mindful that their selectivity for 5-HT2A receptors is somewhat less than for DOI itself.https://doi.org/10.3762/bjoc.8.194cyclopropanationdiazomethanehallucinogen5-HT2A agonistreceptor probetrans-2-phenylcyclopropylamines |
| spellingShingle | Adam Pigott Stewart Frescas John D. McCorvy Xi-Ping Huang Bryan L. Roth David E. Nichols trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT2 receptor family Beilstein Journal of Organic Chemistry cyclopropanation diazomethane hallucinogen 5-HT2A agonist receptor probe trans-2-phenylcyclopropylamines |
| title | trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT2 receptor family |
| title_full | trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT2 receptor family |
| title_fullStr | trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT2 receptor family |
| title_full_unstemmed | trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT2 receptor family |
| title_short | trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT2 receptor family |
| title_sort | trans 2 2 5 dimethoxy 4 iodophenyl cyclopropylamine and trans 2 2 5 dimethoxy 4 bromophenyl cyclopropylamine as potent agonists for the 5 ht2 receptor family |
| topic | cyclopropanation diazomethane hallucinogen 5-HT2A agonist receptor probe trans-2-phenylcyclopropylamines |
| url | https://doi.org/10.3762/bjoc.8.194 |
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