(±)-(4aR*,8aR*)-octahydro-2H-1,4-benzoxazine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: (±)-(4aR*,8aR*)-octahydro-2H-1,4-benzoxazine
• 英文别名: (4aSR,8aSR)-octahydrobenzo[1,4]oxazine；(4AS,8aS)-octahydro-2H-benzo[b][1,4]oxazine；(4aS,8aS)-3,4,4a,5,6,7,8,8a-octahydro-2H-benzo[b][1,4]oxazine
• 化学式: C₈H₁₅NO
• 分子量: 141.213
• InChiKey: AGYZKRGPZJEWPN-YUMQZZPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (±)-(4aR*,8aR*)-octahydro-2H-1,4-benzoxazine 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、379.21 kPa 条件下， 反应 22.0h， 生成 (4-aminophenyl)-(4aSR,8aSR)octahydrobenzo[1,4]oxazin-4-ylmethanone
  参考文献：
  名称：

  Perhydroquinolylbenzamides as Novel Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1

  摘要：

  High-throughput screening identified 5 as a weak inhibitor of 11 beta-HSD1. Optimization of the structure led to a series of perhydroquinolylbenzamides, some with low nanomolar inhibitory potency. A tertiary benzamide is required for biological activity and substitution of the terminal benzamide with either electron-donating or -withdrawing groups is tolerated. The majority of the compounds show selectivity of > 20 to > 700-fold over 11 beta-HSD2. Analogues which showed >50% inhibition of 11 beta-HSD1 at 1 mu M in an cellular assay were screened in an ADX mouse model. A maximal response of > 70% reduction of liver corticosterone levels was observed for three compounds; 9m, 25 and 49.

  DOI：

  10.1021/jm058228q
• 作为产物：
  描述：

  rac-trans-Octahydro-2H-1,4-benzoxazin-3-one 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以82%的产率得到(±)-(4aR*,8aR*)-octahydro-2H-1,4-benzoxazine
  参考文献：
  名称：

  高效合成取代的吗啉

  摘要：

  摘要 已经开发了一种简单有效的方法，用于通过容易获得的氨基醇和α-卤代酰氯的一系列偶联，环化和还原反应来合成取代的吗啉。通过单一方法在相似的反应条件下以良好的产率合成了各种单，二和三取代的吗啉，螺型吗啉和环稠合的吗啉，以及吗啉同系物。该方法还用于（3 S）-3-甲基吗啉的多谱合成。 已经开发了一种简单有效的方法，用于通过容易获得的氨基醇和α-卤代酰氯的一系列偶联，环化和还原反应来合成取代的吗啉。通过单一方法在相似的反应条件下以良好的产率合成了各种单，二和三取代的吗啉，螺型吗啉和环稠合的吗啉，以及吗啉同系物。该方法还用于（3 S）-3-甲基吗啉的多谱合成。

  DOI：

  10.1055/s-0034-1379641

文献信息

• CYCLIC AMIDE DERIVATIVES AS INHIBITORS OF 11 - BETA - HYDROXYSTEROID DEHYDROGENASE AND USES THEREOF
  申请人：CONNEXIOS LIFE SCIENCES PVT. LTD.

  公开号：US20150158860A1

  公开（公告）日：2015-06-11

  The present invention relates to certain amide derivatives that have the ability to inhibit 11-β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) and which are therefore useful in the treatment of certain disorders that can be prevented or treated by inhibition of this enzyme. In addition the invention relates to the compounds, methods for their preparation, pharmaceutical compositions containing the compounds and the uses of these compounds in the treatment of certain disorders. It is expected that the compounds of the invention will find application in the treatment of conditions such as non-insulin dependent type 2 diabetes mellitus (NIDDM), insulin resistance, obesity, impaired fasting glucose, impaired glucose tolerance, lipid disorders such as dyslipidemia, hypertension and as well as other diseases and conditions.

  本发明涉及某些酰胺衍生物，这些衍生物具有抑制11-β-羟基类固醇脱氢酶1型（11β-HSD-1）的能力，因此在预防和治疗可以通过抑制该酶来预防或治疗的某些疾病中是有用的。此外，发明还涉及这些化合物的制备方法、含有这些化合物的药物组合物以及这些化合物在治疗某些疾病中的用途。预计本发明的化合物将在治疗非胰岛素依赖型2型糖尿病（NIDDM）、胰岛素抵抗、肥胖、空腹血糖受损、葡萄糖耐量受损、脂质紊乱（如血脂异常）、高血压以及其他疾病和状况中找到应用。
• [EN] AMIDE DERIVATIVES AND THEIR USE AS INHIBITORS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1<br/>[FR] DERIVES AMIDO ET LEUR UTILISATION COMME INHIBITEURS DE LA 11-BETA-HYDROXYSTEROIDE DESHYDROGENASE DE TYPE 1
  申请人：NOVARTIS AG

  公开号：WO2004065351A1

  公开（公告）日：2004-08-05

  Compounds of the formula (I) provide pharmacological agents which lower intracellular glucocorticoid concentrations in mammals, in particular, intracellular cortisol levels in humans. Therefore, the compounds of the instant invention improve insulin sensitivity in the muscle and the adipose tissue, and reduce lipolysis and free fatty acid production in the adipose tissue. The compounds of the invention lower hepatic glucocorticoid concentration in mammals, in particular, hepatic cortisol concentration in humans, resulting in inhibition of hepatic gluconeogenesis and lowering of plasma glucose levels. Thus, the compounds of the instant invention may be particularly useful in mammals as hypoglycemic agents for the treatment and prevention of conditions in which hyperglycemia and/or insulin resistance are implicated, such as type-2 diabetes. The compounds of the invention may also be used to treat other glucocorticoid associated disorders, such as Syndrome-X, dyslipidemia, hypertension and central obesity. The invention furthermore relates to the use of the compounds according to the invention for the preparation of medicaments, in particular of medicaments useful for the treatment and prevention of glucocorticoid associated disorders, by improving insulin sensitivity, reducing plasma glucose levels, reducing lipolysis and free fatty acid production, and by decreasing visceral adipose tissue formation.

  化合物的化学式（I）提供了降低哺乳动物细胞内糖皮质激素浓度的药物，特别是降低人类细胞内皮质醇水平的药物。因此，本发明的化合物改善了肌肉和脂肪组织中的胰岛素敏感性，并减少了脂肪组织中的脂解和游离脂肪酸产生。本发明的化合物降低了哺乳动物肝脏内的糖皮质激素浓度，特别是降低了人类肝脏内的皮质醇浓度，从而抑制了肝葡萄糖生成和降低了血浆葡萄糖水平。因此，本发明的化合物可能特别适用于哺乳动物作为降糖药物，用于治疗和预防高血糖和/或胰岛素抵抗等疾病，如2型糖尿病。本发明的化合物还可用于治疗其他与糖皮质激素相关的疾病，如X综合症、血脂异常、高血压和中心性肥胖。此外，本发明还涉及根据本发明的化合物用于制备药物，特别是用于治疗和预防与糖皮质激素相关疾病的药物，通过改善胰岛素敏感性、降低血浆葡萄糖水平、减少脂解和游离脂肪酸产生，以及减少内脏脂肪组织形成。
• Synthesis and absolute configuration of substituted morpholines
  作者：Giancarlo Bettoni、Carlo Franchini、Roberto Perrone、Vincenzo Tortorella

  DOI：10.1016/0040-4020(80)87009-8

  日期：——

  We studied methods of stereospecific synthesis that enabled us to obtain variously substituted morpholinic compounds and to determine their absolute configuration. From a study of the chiroptical properties of synthetic N-[2-pyridyl-N-oxide] derivatives of optically active morpholines, it was possible to correlate the sign of the Cotton effect with the absolute configuration. This correlation agrees

  我们研究了立体有择合成方法，使我们能够获得各种取代的吗啉代化合物并确定其绝对构型。通过对光学活性吗啉的合成N- [2-吡啶基-N-氧化物]衍生物的手性性质的研究，可以将Cotton效应的征兆与绝对构型相关联。这种相关性与先前针对哌啶类型的衍生物建立的相关性一致。通过评估位置2和3上取代基对棉花效应的各种贡献，我们建立了在上述两个位置上缩合的双环化合物的绝对构型。
• [EN] HETEROCYCLIC COMPOUNDS AS MTOR INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES EN TANT QU'INHIBITEURS DE MTOR
  申请人：ANGEX PHARMACEUTICAL INC

  公开号：WO2021133509A1

  公开（公告）日：2021-07-01

  The present disclosure describes novel heterocyclic mTOR inhibitors and methods for preparing them. The pharmaceutical compositions comprising such mTOR inhibitors and methods of using them for treating cancer, infectious diseases, and other mTOR associated disorders are also described.

  本公开描述了新颖的杂环mTOR抑制剂以及其制备方法。还描述了包含这些mTOR抑制剂的药物组合物以及治疗癌症、传染病和其他mTOR相关疾病的使用方法。
• Amide derivatives and their use as inhibitors of 11-beta-hydroxysteroid dehydrogenase type I
  申请人：Coppola Mark Gary

  公开号：US20060205772A1

  公开（公告）日：2006-09-14

  Compounds of the formula (I) provide pharmacological agents which lower intracellular glucocorticoid concentrations in mammals, in particular, intracellular cortisol levels in humans. Therefore, the compounds of the instant invention improve insulin sensitivity in the muscle and the adipose tissue, and reduce lipolysis and free fatty acid production in the adipose tissue. The compounds of the invention lower hepatic glucocorticoid concentration in mammals, in particular, hepatic cortisol concentration in humans, resulting in inhibition of hepatic gluconeogenesis and lowering of plasma glucose levels. Thus, the compounds of the instant invention may be particularly useful in mammals as hypoglycemic agents for the treatment and prevention of conditions in which hyperglycemia and/or insulin resistance are implicated, such as type-2 diabetes. The compounds of the invention may also be used to treat other glucocorticoid associated disorders, such as Syndrome-X, dyslipidemia, hypertension and central obesity. The invention furthermore relates to the use of the compounds according to the invention for the preparation of medicaments, in particular of medicaments useful for the treatment and prevention of glucocorticoid associated disorders, by improving insulin sensitivity, reducing plasma glucose levels, reducing lipolysis and free fatty acid production, and by decreasing

  化合物(I)的配方提供了降低哺乳动物细胞内糖皮质激素浓度的药物，特别是降低人类细胞内皮质醇水平的药物。因此，本发明的化合物改善了肌肉和脂肪组织中的胰岛素敏感性，并减少了脂肪组织中的脂解和游离脂肪酸产生。本发明的化合物降低了哺乳动物肝脏中的糖皮质激素浓度，特别是人类肝脏中的皮质醇浓度，从而抑制了肝糖异生并降低了血浆葡萄糖水平。因此，本发明的化合物在哺乳动物中可能特别有用作为降糖药物，用于治疗和预防与高血糖和/或胰岛素抵抗有关的疾病，例如2型糖尿病。本发明的化合物还可用于治疗其他与糖皮质激素相关的疾病，例如综合征X、血脂异常、高血压和中心性肥胖。此外，本发明还涉及使用根据本发明的化合物制备药物，特别是用于改善胰岛素敏感性、降低血浆葡萄糖水平、减少脂解和游离脂肪酸产生，并通过降低糖皮质激素浓度来降低肝糖异生的药物，用于治疗和预防糖皮质激素相关疾病。