دورية أكاديمية
Progress in the development of oxytocin antagonists for use in preterm labor.
| العنوان: | Progress in the development of oxytocin antagonists for use in preterm labor. |
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| المؤلفون: | Pettibone DJ; Department of New Lead Pharmacology, Merck Research Laboratories, West Point, PA 19486, USA., Guidotti M, Harrell CM, Jasper JR, Lis EV, O'Brien JA, Reiss DR, Woyden CJ, Bock MG, Evans BE, et. al. |
| المصدر: | Advances in experimental medicine and biology [Adv Exp Med Biol] 1995; Vol. 395, pp. 601-12. |
| نوع المنشور: | Journal Article; Review |
| اللغة: | English |
| بيانات الدورية: | Publisher: Kluwer Academic/Plenum Publishers Country of Publication: United States NLM ID: 0121103 Publication Model: Print Cited Medium: Print ISSN: 0065-2598 (Print) Linking ISSN: 00652598 NLM ISO Abbreviation: Adv Exp Med Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1998- : New York : Kluwer Academic/Plenum Publishers Original Publication: New York, Plenum Press. |
| مواضيع طبية MeSH: | Hormone Antagonists/*therapeutic use , Obstetric Labor, Premature/*drug therapy , Oxytocin/*antagonists & inhibitors , Tocolytic Agents/*therapeutic use, Animals ; Benzoxazines ; Camphanes/administration & dosage ; Camphanes/chemistry ; Camphanes/therapeutic use ; Dogs ; Female ; Hormone Antagonists/administration & dosage ; Hormone Antagonists/chemistry ; Humans ; In Vitro Techniques ; Macaca mulatta ; Molecular Structure ; Obstetric Labor, Premature/physiopathology ; Oxazines/chemistry ; Oxazines/therapeutic use ; Pan troglodytes ; Piperazines/administration & dosage ; Piperazines/chemistry ; Piperazines/therapeutic use ; Piperidines/chemistry ; Piperidines/therapeutic use ; Pregnancy ; Rats ; Tocolytic Agents/administration & dosage ; Tocolytic Agents/chemistry ; Uterine Contraction/drug effects |
| مستخلص: | From a targeted screening effort and medicinal chemistry program, L-368,899 was selected as the first orally-active oxytocin (OT) antagonist to enter clinical trials. In animal studies, L-368,899 was shown to be a potent and selective OT antagonist and was orally bioavailable in rats, dogs and chimpanzees. L-368,899 was further shown to be a potent OT antagonist in pregnant rhesus and to inhibit spontaneous nocturnal uterine contractions. In Phase I human studies, L-368,899 was generally well-tolerated given intravenously and showed significant plasma levels after oral administration. In addition, L-368,899 blocked OT-stimulated uterine activity in postpartum women with a potency similar to that in the pregnant rhesus monkey. More recently, another structural series has been pursued, represented by L-371,257 [1-(1-(4-(N-acetyl-4-piperidinyloxy)-2-methoxybenzoyl)pip eridin-4-yl)- 1,2-dihydro-4(H)-3,1-benzoxazin-2-one]. L-371,257 exhibits high affinity (Ki, 4.6 nM) for human uterine OT receptors with high selectivity vs. human vasopressin receptors. In rat tissues in vitro, L-371,257 is a potent and competitive OT antagonist (pA2, 8.4) and, in vivo, blocks OT-stimulated uterine activity given both i.v. and intraduodenally. L-371,257 highlights the promise of this novel structural class. |
| Number of References: | 49 |
| المشرفين على المادة: | 0 (Benzoxazines) 0 (Camphanes) 0 (Hormone Antagonists) 0 (L 371257) 0 (Oxazines) 0 (Piperazines) 0 (Piperidines) 0 (Tocolytic Agents) 50-56-6 (Oxytocin) ER33G946JT (L 368899) |
| تواريخ الأحداث: | Date Created: 19950101 Date Completed: 19960919 Latest Revision: 20191210 |
| رمز التحديث: | 20231215 |
| PMID: | 8714024 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 0065-2598 |
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