Synthesis and pharmacological evaluation of carbamic acid 1-phenyl-3-(4-phenyl-piperazine-1-yl)-propyl ester derivatives as new analgesic agents
| Autor: | Hong-sik Moon, Yeonjung Choi, Hyeon Cho, Hanju Yi, Kiho Lee, Eunhee Chae |
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| Rok vydání: | 2012 |
| Předmět: |
Drug
media_common.quotation_subject Clinical Biochemistry Analgesic Pain Pharmaceutical Science Pharmacology Biochemistry Piperazines Mice Structure-Activity Relationship chemistry.chemical_compound Carbamic acid Pharmacokinetics In vivo Drug Discovery Animals Molecular Biology Pain Measurement media_common Analgesics Molecular Structure Morphine Organic Chemistry Esters In vitro Rats Piperazine chemistry Molecular Medicine Carbamates Serotonin Antagonists Receptors Serotonin 5-HT2 Antagonism |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 22:2434-2439 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2012.02.023 |
| Popis: | A series of carbamic acid 1-phenyl-3-(4-phenyl-piperazine-1-yl)-propyl ester derivatives were synthesized through discovery strategies for balancing target-based in vitro screening and phenotypic in vivo screening. All the newly synthesized compounds were screened for their analgesic activities and compared with standard drug morphine. Among them, compound 44r, a potent analgesic agent that has favorable pharmacokinetic properties in rats and most importantly, has a wide safety margin. We demonstrated with in vitro and in vivo functional assays that its analgesic activity might be through 5-HT2A antagonism to some extent. Hence, it is concluded that there is ample scope for further study in developing compound 44r as a good lead candidate for an analgesic agent. |
| Databáze: | OpenAIRE |
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