A critical review of both the synthesis approach and the receptor profile of the 8-chloro-1-(2′,4′-dichlorophenyl)-N-piperidin-1-yl-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide and analogue derivatives
| العنوان: | A critical review of both the synthesis approach and the receptor profile of the 8-chloro-1-(2′,4′-dichlorophenyl)-N-piperidin-1-yl-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide and analogue derivatives |
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| المؤلفون: | Nadine Jagerovic, Ilaria Manca, Ruth A. Ross, Paula Morales, Paolo Lazzari, Marilena Pira, Gérard Aimé Pinna, Gemma L. Baillie, Matteo Zanda, Gabriele Murineddu, Matteo Falzoi, Monica Sani, Rita Distinto |
| المصدر: | European journal of medicinal chemistry 121 (2016): 194–208. doi:10.1016/j.ejmech.2016.05.011 info:cnr-pdr/source/autori:Lazzari P.; Distinto R.; Manca I.; Baillie G.; Murineddu G.; Pira M.; Falzoi M.; Sani M.; Morales P.; Ross R.; Zanda M.; Jagerovic N.; Pinna G.A./titolo:A critical review of both the synthesis approach and the receptor profile of the 8-chloro-1-(2',4'-dichlorophenyl)-N-piperidin-1-yl-1,4,5,6-Tetrahydrobenzo[6,7]cyclohepta[1,2-c ]pyrazole-3-carboxamide and analogue derivatives/doi:10.1016%2Fj.ejmech.2016.05.011/rivista:European journal of medicinal chemistry/anno:2016/pagina_da:194/pagina_a:208/intervallo_pagine:194–208/volume:121 |
| بيانات النشر: | Elsevier BV, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Cannabinoid receptor binding assays, 0301 basic medicine, Cannabinoid receptor, Intrinsic activity, medicine.drug_class, Stereochemistry, cyclohepta[1, Carboxamide, 7], Pyrazole, 40-dichlorophenyl)-Npiperidin-1-yl-1, cannabinoids, Structure-Activity Relationship, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Piperidines, Receptor, Cannabinoid, CB1, Drug Discovery, medicine, 8-Chloro-1-(20, Structure–activity relationship, CB1 receptor ligands, 6-Tetrahydrobenzo[6, Receptor, Pharmacology, Drug discovery, Organic Chemistry, Antagonist, 2-c]pyrazole-3-carboxamide, General Medicine, 030104 developmental biology, chemistry, Pyrazoles, Endocannabinoid system (ECS), 030217 neurology & neurosurgery, Protein Binding |
| الوصف: | 8-Chloro-1-(2?,4?-dichlorophenyl)-N-piperidin-1-yl-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide 9a was discovered as potent and selective CB1 antagonist by part of our group few years ago. In particular it was reported to have an affinity towards the CB1 cannabinoid receptor (CB1R), expressed as Ki, of 0.00035 nM. Nevertheless significantly divergent data were reported for the same compound from other laboratories. To unequivocally define the receptor profile of 9a, we have critically reviewed both its synthesis approach and binding data. Here we report that, in contrast to our previously reported data, 9a showed a Ki value for CB1R in the order of nanomolar rather than of fentomolar range. The new determined receptor profile of 9a was also ascertained for analogue derivatives 9b-i, as well as for 12. Moreover, the structural features of the synthesized compounds necessary for CB1R were investigated. Amongst the novel series, effects on CB1R intrinsic activity was highlighted due to the substituents at the position 3 of the pyrazole ring of the 1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole scaffold. Although the cannabinoid receptor profile of 9a was reviewed in this work, the relevance of this compound in CB1R antagonist based drug discovery is confirmed. |
| تدمد: | 0223-5234 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eea8e6fe135fe0e3f2913f3cd98abc8d https://doi.org/10.1016/j.ejmech.2016.05.011 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....eea8e6fe135fe0e3f2913f3cd98abc8d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 02235234 |
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