(R)-6-(3-hydroxypropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one | 1114088-40-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-6-(3-hydroxypropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one
• 英文别名: (6R)-6-(3-hydroxypropyl)-6-phenyl-3-[(1S)-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl]-1,3-oxazinan-2-one
• CAS: 1114088-40-2
• 化学式: C₂₇H₃₆BNO₅
• 分子量: 465.398
• InChiKey: UUEHOTMZRRETQX-CCLHPLFOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.56
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  68.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-溴吡啶 、 (R)-6-(3-hydroxypropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one 在 bis-triphenylphosphine-palladium(II) chloride 、 caesium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 生成 (R)-6-(3-hydroxypropyl)-6-phenyl-3-((S)-1-(4-(pyridin-4-yl)phenyl)ethyl)-1,3-oxazinan-2-one
  参考文献：
  名称：

  Discovery of BI 135585, an in vivo efficacious oxazinanone-based 11β hydroxysteroid dehydrogenase type 1 inhibitor

  摘要：

  A potent, in vivo efficacious 11 beta hydroxysteroid dehydrogenase type 1 (11 beta HSD1) inhibitor (11j) has been identified. Compound 11j inhibited 11 beta HSD1 activity in human adipocytes with an IC50 of 4.3 nM and in primary human adipose tissue with an IC80 of 53 nM. Oral administration of 11j to cynomolgus monkey inhibited 11 beta HSD1 activity in adipose tissue. Compound 11j exhibited >1000x selectivity over other hydroxysteroid dehydrogenases, displays desirable pharmacodynamic properties and entered human clinical trials in 2011. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.04.033
• 作为产物：
  描述：

  (R)-6-allyl-3-((S)-1-(4-bromophenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one 在 硼烷四氢呋喃络合物 、 potassium acetate 、 palladium dichloride 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 22.0h， 生成 (R)-6-(3-hydroxypropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one
  参考文献：
  名称：

  Discovery of BI 135585, an in vivo efficacious oxazinanone-based 11β hydroxysteroid dehydrogenase type 1 inhibitor

  摘要：

  A potent, in vivo efficacious 11 beta hydroxysteroid dehydrogenase type 1 (11 beta HSD1) inhibitor (11j) has been identified. Compound 11j inhibited 11 beta HSD1 activity in human adipocytes with an IC50 of 4.3 nM and in primary human adipose tissue with an IC80 of 53 nM. Oral administration of 11j to cynomolgus monkey inhibited 11 beta HSD1 activity in adipose tissue. Compound 11j exhibited >1000x selectivity over other hydroxysteroid dehydrogenases, displays desirable pharmacodynamic properties and entered human clinical trials in 2011. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.04.033

文献信息

• CYCLIC INHIBITORS OF 11BETA-HYDROXYSTEROID DEHYDROGENASE 1
  申请人：Renz Martin

  公开号：US20100331320A1

  公开（公告）日：2010-12-30

  This invention relates to novel compounds of the Formula Ik, Im 1 , Im 2 , Im 5 , In 1 , In 2 , In 5 , Io 1 , Io 2 , Io 5 , Ip 1 , Ip 3 , 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.

  这项发明涉及到Ik、Im1、Im2、Im5、In1、In2、In5、Io1、Io2、Io5、Ip1、Ip3的新化合物，以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。
• Cyclic inhibitors of 11β-hydroxysteroid dehydrogenase 1
  申请人：Boehringer Ingelheim International GmbH

  公开号：US08114868B2

  公开（公告）日：2012-02-14

  Disclosed is a compound represented by Formula (Im1) or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof. Also disclosed are pharmaceutical compositions comprising the compound of Formula (Im1) or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof and methods of inhibiting 11β-HSD1 activity comprising the step of administering to a mammal in need of such treatment an effective amount of a compound of Formulas (Im1), or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof.

  公开的是一种由式（Im1）表示的化合物或其药学上可接受的盐、对映体或非对映体。还公开了包括该式（Im1）化合物或其药学上可接受的盐、对映体或非对映体的制药组合物以及抑制11β-HSD1活性的方法，包括向需要此类治疗的哺乳动物施用该式（Im1）化合物或其药学上可接受的盐、对映体或非对映体的有效量。
• Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1
  申请人：Vitae Pharmaceuticals, Inc.

  公开号：US08138178B2

  公开（公告）日：2012-03-20

  Disclosed is a compound represented by Formula (Im1) or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof. Also disclosed are pharmaceutical compositions comprising the compound of Formula (Im1) or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof and methods of inhibiting 11β-HSD1 activity comprising the step of administering to a mammal in need of such treatment an effective amount of a compound of Formulas (Im1), or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof.

  揭示了一种由公式（Im1）表示的化合物或其药学上可接受的盐、对映体或二对映体。还揭示了包含公式（Im1）的化合物或其药学上可接受的盐、对映体或二对映体的制药组合物，以及抑制11β-HSD1活性的方法，其中包括向需要此类治疗的哺乳动物施用公式（Im1）的化合物或其药学上可接受的盐、对映体或二对映体的有效量。
• Cyclic Inhibitors Of 11Beta-Hydroxysteroid Dehydrogenase 1
  申请人：Claremon David A.

  公开号：US20110263583A1

  公开（公告）日：2011-10-27

  This invention relates to novel compounds of the Formula Il Ik, Im 3 , Im 4 , Im 6-12 , In 3 , In 4 , In 6-12 , lo 3 , lo 4 , lo 6-12 , Ip 2 , Ip 4-7 , 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。
• 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。