tert-butyl 8-chloro-4-oxo-3,4-dihydrospiro[chromene-2,4'-piperidine]-1'-carboxylate | 1051383-39-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: tert-butyl 8-chloro-4-oxo-3,4-dihydrospiro[chromene-2,4'-piperidine]-1'-carboxylate
• 英文别名: tert-butyl 8-chloro-4-oxo-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxylate；tert-butyl 8-chloro-4-oxospiro[chromane-2,4'-peridine]-1'-carboxylate；Tert-butyl 8-chloro-4-oxospiro[chroman-2,4'-piperidine]-1'-carboxylate；tert-butyl 8-chloro-4-oxospiro[3H-chromene-2,4'-piperidine]-1'-carboxylate
• CAS: 1051383-39-1
• 化学式: C₁₈H₂₂ClNO₄
• 分子量: 351.83
• InChiKey: OGSPWJSNOLKNSY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 8-chloro-4-oxo-3,4-dihydrospiro[chromene-2,4'-piperidine]-1'-carboxylate 在 盐酸 、 三乙胺 作用下， 以 二甲基亚砜 、 乙酸乙酯 为溶剂， 反应 2.0h， 生成 8-chloro-4-oxo-N-[4-(trifluoromethoxy)phenyl]-3,4-dihydrospiro[chromene-2,4'-piperidine]-1'-carboxamide
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of novel N-aryl-3,4-dihydro-1′H-spiro[chromene-2,4′-piperidine]-1′-carboxamides as TRPM8 antagonists

  摘要：

  A novel series of N-aryl-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamides was identified as transient receptor potential melastatin 8 (TRPM8) channel blockers through analogue-based rational design, synthesis and screening. Details of the synthesis, effect of aryl groups and their substituents on in-vitro potency were studied. The effects of selected functional groups on the 4-position of the chromene ring were also studied, which showed interesting results. The 4-hydroxy derivatives showed excellent potency and selectivity. Optical resolution and screening of alcohols revealed that (R)-(-)-isomers were in general more potent than the corresponding (S)-(+)-isomers. The isomer (R)-(-)-10e (IC50: 8.9 nM) showed a good pharmacokinetic profile upon oral dosing at 10 mg/kg in Sprague-Dawley (SD) rats. The compound (R)-(-)-10e also showed excellent efficacy in relevant rodent models of neuropathic pain. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.08.031
• 作为产物：
  描述：

  1-(3-氯-2-羟苯基)乙基-1-酮 、 N-叔丁氧羰基-4-哌啶酮 在 四氢吡咯 作用下， 以 甲醇 为溶剂， 生成 tert-butyl 8-chloro-4-oxo-3,4-dihydrospiro[chromene-2,4'-piperidine]-1'-carboxylate
  参考文献：
  名称：

  新型螺[苯并二氢吡喃酮-2,4'-哌啶]-4-酮衍生物作为病原体脂肪酸合成的潜在抑制剂：设计、合成和生物学评价

  摘要：

  细菌的生存依赖于膜脂稳态，它能够调节脂质成分以适应和优化它们在不同环境中的生长。因此，干扰细菌脂肪酸合成过程的抑制剂的开发被认为是一种有前途的策略。在这项研究中，制备了 58 种新型螺环色满酮衍生物，并研究了它们的构效关系 (SAR)。生物测定结果表明，大多数化合物均表现出优异的生物活性，例如化合物B 14、C 1、B 15和B 13，它们对多种致病菌具有显着的抑制活性与EC0.78 μg/mL ∼3.48 μg/mL 的50 个值。通过一系列生化分析研究初步抗菌行为，包括但不限于荧光成像模式、GC - MS 分析、TEM 图像和荧光滴定实验。值得注意的是，化合物B 14降低了细胞膜的脂质含量，增加了细胞膜的通透性，从而破坏了细菌细胞膜的完整性。进一步的 qRT - PCR 结果表明化合物B 14干扰了脂肪酸合成过程中的 mRNA 表达水平-相关基因包括 ACC、ACP 和 Fab 家族基

  DOI：

  10.1016/j.ejmech.2023.115215

文献信息

• HETEROCYCLIC COMPOUND
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP2123652A1

  公开（公告）日：2009-11-25

  The present invention provides a compound having an ACC inhibitory action, which is useful for the prophylaxis or treatment of obesity, diabetes, hypertension, hyperlipidemia, cardiac failure, diabetic complications, metabolic syndrome, sarcopenia, cancer and the like, and has superior efficacy. The present invention provides a compound represented by the formula (I): wherein each symbol is as in the specification, or a salt thereof.

  本发明提供了一种具有ACC抑制作用的化合物，该化合物用于预防或治疗肥胖、糖尿病、高血压、高脂血症、心力衰竭、糖尿病并发症、代谢综合征、肌肉减少症、癌症等疾病，并具有优异的疗效。 本发明提供了一种由公式（I）表示的化合物： 其中每个符号如说明书所述，或其盐。
• [EN] NOVEL SPIRO COMPOUNDS USEFUL AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE<br/>[FR] NOUVEAUX COMPOSÉS SPIRO UTILES COMME INHIBITEURS DE LA STÉAROYL-COENZYME A DELTA-9 DÉSATURASE
  申请人：MERCK FROSST CANADA LTD

  公开号：WO2010094120A1

  公开（公告）日：2010-08-26

  Heteroaromatic compounds of structural formula (I) are selective inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD1) relative to other known stearoyl-coenzyme A desaturases. The compounds of the present invention are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease, such as atherosclerosis; obesity; diabetes; neurological disease; metabolic syndrome; insulin resistance; and liver steatosis.

  结构式（I）的杂环芳香化合物相对于其他已知的硬脂酰辅酶A去饱和酶（SCD1）具有选择性抑制作用。本发明的化合物可用于预防和治疗与异常脂质合成和代谢相关的疾病，包括心血管疾病，如动脉粥样硬化；肥胖；糖尿病；神经系统疾病；代谢综合征；胰岛素抵抗；以及肝脂肪变性。
• [EN] SPIROCYCLIC PIPERIDINE DERIVATIVES AS TRPM 8 MODULATORS<br/>[FR] DÉRIVÉS DE PIPÉRIDINE SPIROCYCLIQUES EN TANT QUE MODULATEURS DE TRPM8
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2010103381A1

  公开（公告）日：2010-09-16

  The present invention provides Transient Receptor Potential subfamily M, member 8 (TRPM8) modulators of formula (I). In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by TRPM8. Also provided herein are processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by TRPM8.

  本发明提供了公式（I）的瞬时受体电位亚家族M，成员8（TRPM8）调节剂。特别地，本文所描述的化合物对于治疗或预防TRPM8调节的疾病，状况和/或紊乱非常有用。本文还提供了制备所述化合物的过程，用于其合成的中间体，其制药组合物以及用于治疗或预防由TRPM8调节的疾病，状况和/或紊乱的方法。
• NOVEL SPIRO COMPOUNDS USEFUL AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
  申请人：Lachance Nicolas

  公开号：US20110312952A1

  公开（公告）日：2011-12-22

  Heteroaromatic compounds of structural formula (I) are selective inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD1) relative to other known stearoyl-coenzyme A desaturases. The compounds of the present invention are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease, such as atherosclerosis; obesity; diabetes; neurological disease; metabolic syndrome; insulin resistance; and liver steatosis.

  结构式（I）的杂环芳香化合物是选择性的硬脂酰辅酶A-Δ9-脱饱和酶（SCD1）抑制剂，相对于其他已知的硬脂酰辅酶A脱饱和酶。本发明的化合物对于预防和治疗与异常脂质合成和代谢相关的疾病非常有用，包括心血管疾病，如动脉粥样硬化；肥胖症；糖尿病；神经系统疾病；代谢综合征；胰岛素抵抗和肝脂肪变性。
• SPIRO DERIVATIVES FOR THE MODULATION OF STEAROYL-COA DESATURASE
  申请人：Dales Natalie

  公开号：US20120010135A1

  公开（公告）日：2012-01-12

  The present invention provides spiro derivatives that modulate the activity of stearoyl-CoA desaturase. Methods of using such derivatives to modulate the activity of stearoyl-CoA desaturase and pharmaceutical compositions comprising such derivatives are also encompassed.

  本发明提供了螺环衍生物，可以调节硬脂酰辅酶A脱饱和酶的活性。还包括使用这些衍生物调节硬脂酰辅酶A脱饱和酶的方法以及包含这些衍生物的制药组合物。