L-372662 是一种有效的具有口服活性的非肽催产素拮抗剂，其 Ki 值为 4.8。野生型 hOTR 和[A318G]OTR 的 L-372662 的 Kd 值分别为 5.8 nM 和 73 nM。L-372,662 对 OTR:V1a 具有选择性。
L-372662 is a potent and orally active non-peptide oxytocin antagonist with a Ki value of 4.8. The Kd value of L-372662 for wild-type hOTR and [A318G]OTR is 5.8 nM and 73 nM. L-372662 shows selectivity to OTR:V1aR[1][2].
L-372662 is an antagonist of oxytocin-induced uterine contractions in late gestation pregnant rhesus monkeys (AD50 = 36 micrograms/kg), oral bioavailability (F = 90% in dogs), and aqueous solubility (10 mg/mL).
[1]. Bell, I. M., Erb, J. M., Freidinger, R. M., Gallicchio, S. N., Guare, J. P., Guidotti, M. T., … Woyden, C. J. (1998). Development of Orally Active Oxytocin Antagonists: Studies on 1-(1-{4-[1-(2-Methyl-1-oxidopyridin-3-ylmethyl)piperidin-4-yloxy]-2- methoxybenzoyl}piperidin-4-yl)-1,4-dihydrobenz[d][1,3]oxazin-2-one (L-372,662) and Related Pyridines. Journal of Medicinal Chemistry, 41(12), 2146-2163.
[2]. Hawtin SR, et al. A Gly/Ala switch contributes to high affinity binding of benzoxazinone-based non-peptide oxytocin receptor antagonists. FEBS Lett. 2005;579(2):349-356.
[3]. Williams PD, et al. Progress in the development of oxytocin antagonists for use in preterm labor. Adv Exp Med Biol. 1998;449:473-479.
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