Structure–Activity Relationship Studies and Discovery of a Potent Transient Receptor Potential Vanilloid (TRPV1) Antagonist 4-[3-Chloro-5-[(1S)-1,2-dihydroxyethyl]-2-pyridyl]-N-[5-(trifluoromethyl)-2-pyridyl]-3,6-dihydro-2H-pyridine-1-carboxamide (V116517) as a Clinical Candidate for Pain Management
| العنوان: | Structure–Activity Relationship Studies and Discovery of a Potent Transient Receptor Potential Vanilloid (TRPV1) Antagonist 4-[3-Chloro-5-[(1S)-1,2-dihydroxyethyl]-2-pyridyl]-N-[5-(trifluoromethyl)-2-pyridyl]-3,6-dihydro-2H-pyridine-1-carboxamide (V116517) as a Clinical Candidate for Pain Management |
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| المؤلفون: | Yasuyoshi Iso, Shintani Takuya, John J. Engel, Akira Kato, Jianming Yu, Tsuyoshi Hasegawa, Toshiyuki Asaki, Yoshitaka Yamaguchi, Naoki Tsuno, Laykea Tafesse, Chiyou Ni, Noriyuki Kurose, Kevin C. Brown, Toshiyuki Kanemasa, Gang Wu, Manjunath S. Shet, Yuka Iwamoto, Aniket Patel, Donald J. Kyle, Xiaoming Zhou |
| المصدر: | Journal of Medicinal Chemistry. 57:6781-6794 |
| بيانات النشر: | American Chemical Society (ACS), 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Trifluoromethyl, medicine.drug_class, Stereochemistry, TRPV1, Antagonist, Carboxamide, Pharmacology, chemistry.chemical_compound, chemistry, Pharmacokinetics, Capsaicin, In vivo, Drug Discovery, medicine, Molecular Medicine, Structure–activity relationship, lipids (amino acids, peptides, and proteins) |
| الوصف: | A series of novel tetrahydropyridinecarboxamide TRPV1 antagonists were prepared and evaluated in an effort to optimize properties of previously described lead compounds from piperazinecarboxamide series. The compounds were evaluated for their ability to block capsaicin and acid-induced calcium influx in CHO cells expressing human TRPV1. The most potent of these TRPV1 antagonists were further characterized in pharmacokinetic, efficacy, and body temperature studies. On the basis of its pharmacokinetic, in vivo efficacy, safety, and toxicological properties, compound 37 was selected for further evaluation in human clinical trials. |
| تدمد: | 1520-4804 0022-2623 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::1e9a80de5389c83676a37a8b92fce8dc https://doi.org/10.1021/jm500818a |
| رقم الأكسشن: | edsair.doi...........1e9a80de5389c83676a37a8b92fce8dc |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15204804 00222623 |
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