3-{(S)-1-[4-(1-cyclopropylmethyl-6-oxo-1,6-dihydropyridazin-3-yl)phenyl]ethyl}-(S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl[1,3]oxazinan-2-one | 1114573-54-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3-{(S)-1-[4-(1-cyclopropylmethyl-6-oxo-1,6-dihydropyridazin-3-yl)phenyl]ethyl}-(S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl[1,3]oxazinan-2-one
• 英文别名: 3-{(S)-1-[4-(1-Cyclopropylmethyl-6-oxo-1,6-dihydro-pyridazin-3-yl)-phenyl]-ethyl}-(S)-6-(2-hydroxy-2-methyl-propyl)-6-phenyl-[1,3]oxazinan-2-one；(6S)-3-[(1S)-1-[4-[1-(cyclopropylmethyl)-6-oxopyridazin-3-yl]phenyl]ethyl]-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one
• CAS: 1114573-54-4
• 化学式: C₃₀H₃₅N₃O₄
• 分子量: 501.626
• InChiKey: IYVALPSKVAMDMH-JRPXNJEYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  82.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (S)-3-((S)-1-(4-(1,5-dimethyl-6-oxo-1,6-dihydropyridazin-3-yl)phenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one 、 6-chloro-2-cyclopropylmethyl-2H-pyridazin-3-one 生成 3-{(S)-1-[4-(1-cyclopropylmethyl-6-oxo-1,6-dihydropyridazin-3-yl)phenyl]ethyl}-(S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl[1,3]oxazinan-2-one
  参考文献：
  名称：

  Cyclic Inhibitors Of 11Beta-Hydroxysteroid Dehydrogenase 1

  摘要：

  本发明涉及一种新的化合物，其中包括公式Il Ik，Im3，Im4，Im6-12，In3，In4，In6-12，lo3，lo4，lo6-12，Ip2，Ip4-7的化合物及其药学上可接受的盐和药物组合物。这些化合物对于治疗与哺乳动物中11β-HSD1的调节或抑制相关的疾病非常有用。本发明进一步涉及这些新化合物的药物组合物以及在细胞中减少或控制皮质醇的产生或抑制皮质酮转化为皮质醇的方法。

  公开号：

  US20110263583A1

文献信息

• [EN] CYCLIC INHIBITORS OF 11ß-HYDROXYSTERIOD DEHYDROGENASE 1<br/>[FR] INHIBITEURS CYCLIQUES DE LA 11?-HYDROXYSTÉROÏDE DÉSHYDROGÉNASE 1
  申请人：VITAE PHARMACEUTICALS INC

  公开号：WO2009017664A1

  公开（公告）日：2009-02-05

  This invention relates to novel compounds of the Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih); (Ii); (Ij), (Ik), (II) pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11 β-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of cortisol in a cell or the inhibition of the conversion of cortisone to cortisol in a cell.

  本发明涉及式(I)、(Ia)、(Ib)、(Ic)、(Id)、(Ie)、(If)、(Ig)、(Ih)；(Ii)；(Ij)，(Ik)，(II)的新颖化合物，其药用可接受的盐以及药物组合物，这些化合物对于治疗与调节或抑制哺乳动物中的11β-HSD1相关的疾病是有用的。本发明进一步涉及新颖化合物的药物组合物及其在减少或控制细胞中皮质醇的产生或抑制细胞中将可的松转化为皮质醇的方法。
• INHIBITORS OF 11beta-HYDROXYSTEROID DEHYDROGENASE 1
  申请人：Himmelsbach Frank

  公开号：US20120108578A1

  公开（公告）日：2012-05-03

  This invention relates to novel compounds of the Formula (I), (Ia 1-10 ), (Ib 1-10 ), (Ic 1-10 ), (Id 1-7 ), (Ie 1-5 ) pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11β-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of cortisol in a cell or the inhibition of the conversion of cortisone to cortisol in a cell.

  这项发明涉及公式（I）、（Ia1-10）、（Ib1-10）、（Ic1-10）、（Id1-7）、（Ie1-5）的新化合物，其药学上可接受的盐，以及其药物组合物，这些化合物对于治疗与哺乳动物中11β-HSD1的调节或抑制相关的疾病是有用的。该发明还涉及这些新化合物的药物组合物和它们在细胞中减少或控制皮质醇的产生或抑制皮质醇酮转化为皮质醇的方法的用途。
• SYNTHESIS OF INHIBITORS OF 11ß-HYDROXYSTEROID DEHYDROGENASE TYPE 1
  申请人：Xu Zhenrong

  公开号：US20100256363A1

  公开（公告）日：2010-10-07

  Disclosed are syntheses of 11 β-HSD1 inhibitors and corresponding intermediates that are promising for the treatment of a variety of disease states including diabetes, metabolic syndrome, obesity, glucose intolerance, insulin resistance, hyperglycemia, hypertension, hypertension-related cardiovascular disorders, hyperlipidemia, deleterious gluco-corticoid effects on neuronal function (e.g. cognitive impairment, dementia, and/or depression), elevated intra-ocular pressure, various forms of bone disease (e.g., osteoporosis), tuberculosis, leprosy (Hansen's disease), psoriasis, and impaired wound healing (e.g., in patients that exhibit impaired glucose tolerance and/or type 2 diabetes).

  本发明涉及11β-HSD1抑制剂及其中间体的合成，可用于治疗多种疾病，包括糖尿病、代谢综合征、肥胖症、葡萄糖不耐受、胰岛素抵抗、高血糖、高血压、高血压相关的心血管疾病、高血脂症、糖皮质激素对神经功能的有害影响（例如认知障碍、痴呆和/或抑郁症）、眼内压升高、各种骨疾病（例如骨质疏松症）、结核病、麻风病（汉生病）、牛皮癣和受损伤口愈合不良（例如在表现出糖耐量受损和/或2型糖尿病的患者中）。
• Cyclic inhibitors of 11BETA-hydroxysteroid dehydrogenase 1
  申请人：Claremon David A.

  公开号：US08592410B2

  公开（公告）日：2013-11-26

  This invention relates to novel compounds of the Formula Il Ik, Im3, Im4, Im6-12, In3, In4, In6-12, lo3, lo4, lo6-12, Ip2, Ip4-7, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11β-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of Cortisol in a cell or the inhibition of the conversion of cortisone to Cortisol in a cell.

  本发明涉及公式Il Ik，Im3，Im4，Im6-12，In3，In4，In6-12，lo3，lo4，lo6-12，Ip2，Ip4-7的新化合物，及其药学上可接受的盐和制药组合物，用于治疗与哺乳动物中11β-HSD1的调节或抑制相关的疾病。本发明还涉及新化合物的制药组合物和其在细胞中减少或控制皮质醇的产生或抑制皮质酮转化为皮质醇的方法。
• CYCLIC INHIBITORS OF 11BETA-HYDROXYSTEROID DEHYDROGENASE 1
  申请人：Claremon David A.

  公开号：US20110015157A1

  公开（公告）日：2011-01-20

  This invention relates to novel compounds of the Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih); (Ii); (Ij), (Ik), (II) pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11 β-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of cortisol in a cell or the inhibition of the conversion of cortisone to cortisol in a cell.

  本发明涉及式(I)、(Ia)、(Ib)、(Ic)、(Id)、(Ie)、(If)、(Ig)、(Ih)、(Ii)、(Ij)、(Ik)、(II)的新化合物，以及其药学上可接受的盐和制药组合物，用于治疗与哺乳动物11β-HSD1调节或抑制相关的疾病。本发明还涉及新化合物的制药组合物以及其在细胞中减少或控制皮质醇的产生或抑制皮质酮转化为皮质醇的方法。