Novel vasopressin V2 receptor-selective antagonists, pyrrolo[2,1-a]quinoxaline and pyrrolo[2,1-c][1,4]benzodiazepine derivatives
| العنوان: | Novel vasopressin V2 receptor-selective antagonists, pyrrolo[2,1-a]quinoxaline and pyrrolo[2,1-c][1,4]benzodiazepine derivatives |
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| المؤلفون: | Daisuke Morizono, Hisashi Hasegawa, Yasuhiro Ohtake, Akira Naito, Yoko Tanaka, Kenji Naito, Yohji Ezure, Hidehiko Matsukawa, Yoshihiro Tsuriya, Makoto Taniguchi, Katsuhiro Kawano, Touru Oguma |
| المصدر: | Bioorganicmedicinal chemistry. 7(6) |
| سنة النشر: | 1999 |
| مصطلحات موضوعية: | Stereochemistry, medicine.drug_class, Vasopressins, Clinical Biochemistry, Pharmaceutical Science, Pyrrolobenzodiazepine, Carboxamide, In Vitro Techniques, Biochemistry, Chemical synthesis, chemistry.chemical_compound, Benzodiazepines, Structure-Activity Relationship, Quinoxaline, Arginine vasopressin receptor 2, Quinoxalines, Drug Discovery, medicine, Structure–activity relationship, Animals, Pyrroles, Diuretics, Molecular Biology, chemistry.chemical_classification, Organic Chemistry, Diuresis, Rats, chemistry, Lactam, Molecular Medicine, Antidiuretic Hormone Receptor Antagonists, Tricyclic |
| الوصف: | The intent of the work was to study the structure-activity relationships of AVP receptor antagonists bearing a chiral ring as a partial structure since such studies had been reported for only achiral compounds. In the present paper, we deal with compounds consisting of the chiral tricyclic hetero ring (1,2,3,3a,4,5-hexahydropyrrolo[1,2-a]quinoxaline and 1,2,3,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine) and 2-phenylbenzanilide analogues. These compounds exhibited a highly selective affinity for V2 receptor, and their stereochemical configuration had a great influence on V2 receptor binding. VP-343 (N-[4-[[(2S,3aR)-2-hydroxy-2,3,3a,4-tetrahydropyrrolo[1,2-a] quinoxalin-5(1H)-yl]carbonyl]phenyl]-4'-methyl[1,1'-biphenyl]-2-ca rboxamide), VP-365 (N-[4-[[(11aS)-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benz odiazepin-10(5H)-yl]carbonyl]phenyl][1,1'-biphenyl-2-carboxamide) and VP-339 (N-[4-[[(11aS)-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]+ ++benzodiazepin-10(5H)-yl]carbonyl]phenyl][1,1'-biphenyl]-2-carboxami de) were the most potent compounds in vitro and in vivo. The IC50 values of VP-343, VP-365 and VP-339 against V2 receptor were 0.772, 1.18 and 0.216 nM, respectively. The ED300 values (dose required to increase three times the urine volume of the control rats; oral administration) of VP-343, VP-365 and VP-339 were 0.22, 0.31 and 0.78 mg/kg, respectively. |
| تدمد: | 0968-0896 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::89f556356aa45cee1ad6d1d016419884 https://pubmed.ncbi.nlm.nih.gov/10428398 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....89f556356aa45cee1ad6d1d016419884 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 09680896 |
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