tert-butyl 6-fluoro-4-hydroxy-3,4-dihydrospiro[chromene-2,4'-piperidine]-1'-carboxylate | 936648-45-2

• 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 6-fluoro-4-hydroxy-3,4-dihydrospiro[chromene-2,4'-piperidine]-1'-carboxylate
• 英文别名: tert-butyl-6-fluoro-4-hydroxyspiro[chromane-2,4'-piperidine]-1'-carboxylate；Tert-butyl 6-fluoro-4-hydroxyspiro[chroman-2,4'-piperidine]-1'-carboxylate；tert-butyl 6-fluoro-4-hydroxyspiro[3,4-dihydrochromene-2,4'-piperidine]-1'-carboxylate
• CAS: 936648-45-2
• 化学式: C₁₈H₂₄FNO₄
• 分子量: 337.391
• InChiKey: XPSOOGPODJERSO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 6-fluoro-4-hydroxy-3,4-dihydrospiro[chromene-2,4'-piperidine]-1'-carboxylate 在 三乙基硅烷 、 三氟乙酸 作用下， 反应 14.0h， 以65%的产率得到6-氟-3,4-二氢螺[2H-1-苯并吡喃-2,4'-哌啶]
  参考文献：
  名称：

  [EN] HDAC INHIBITORS
  [FR] INHIBITEURS DE HDAC

  摘要：

  本公开涉及色满烷化合物、表现出HDAC抑制作用的色满烷化合物及其制药组合物。其他实施例包括使用色满烷化合物的方法。例如，本公开包括抑制细胞中组蛋白乙酰化的方法，包括将该细胞与本公开中的色满烷化合物接触。其他实施例包括治疗需要抑制组蛋白乙酰化的患者的可治疗疾病的方法，包括给予本公开中的色满烷化合物。

  公开号：

  WO2022120048A1
• 作为产物：
  描述：

  tert-butyl 6-fluoro-4-oxo-3,4-dihydrospiro[chromene-2,4'-piperidine]-1'-carboxylate 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 生成 tert-butyl 6-fluoro-4-hydroxy-3,4-dihydrospiro[chromene-2,4'-piperidine]-1'-carboxylate
  参考文献：
  名称：

  鉴定螺[色烯-2,4'-哌啶]作为有效、选择性和 Gq 偏向的 5-HT2C 受体部分激动剂

  摘要：

  基于我们之前的先导化合物1，通过结构修饰设计和合成了一系列螺哌啶，并通过细胞信号转导测定进行评估，以发现具有 G q偏向的 5-HT 2C受体 (5-HT 2C R) 选择性激动剂。螺哌啶的构效关系 (SAR) 研究发现螺[色烯-2,4′-哌啶]是一种新型 5-HT 2C R 选择性激动剂化学型。在这个新系列中，7-氯类似物8被确定为最有效和最具选择性的 5-HT 2C R 部分激动剂 ( E max = 71.09%)，EC 50值为 121.5 nM，并且没有观察到对 5-HT 2A的活性R 或 5-HT 2B R。此外，化合物8对 β-arrestin 没有表现出募集活性，并且在 10 μM 时表现出对 hERG 的低抑制作用。这些发现可能为开发更有效的 G q偏向 5-HT 2C R 部分激动剂作为有用的药理学工具化合物或潜在的候选药物铺平道路。

  DOI：

  10.1021/acsmedchemlett.3c00454

文献信息

• N-sulfamoyl-N'-benzopyranpiperidine compounds and uses thereof
  申请人：Antel Jochen

  公开号：US20070117823A1

  公开（公告）日：2007-05-24

  N-sulfamoyl-N′-benzopyranpiperidine compounds of formula I and their physiologically acceptable acid addition salts, pharmaceutical compositions comprising them, processes for their preparation, and their use for the treatment and/or inhibition of glaucoma, epilepsy, bipolar disorders, migraine, neuropathic pain, obesity, type II diabetes, metabolic syndrome, alcohol dependence, and/or cancer, and related concomitant and/or secondary diseases or conditions.

  式I的N-磺胺基-N'-苯并吡啶啉化合物及其生理上可接受的酸盐，包含它们的药物组合物，其制备方法，以及它们用于治疗和/或抑制青光眼、癫痫、双相情感障碍、偏头痛、神经痛、肥胖症、2型糖尿病、代谢综合征、酒精依赖症和/或癌症的用途，以及相关的并发和/或继发疾病或症状。
• 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。
• Synthesis and pharmacological evaluation of novel N-aryl-3,4-dihydro-1′H-spiro[chromene-2,4′-piperidine]-1′-carboxamides as TRPM8 antagonists
  作者：Sachin S. Chaudhari、Ashok B. Kadam、Neelima Khairatkar-Joshi、Indranil Mukhopadhyay、Pallavi V. Karnik、Anupindi Raghuram、Shobha S. Rao、Thamil Selvan Vaiyapuri、Dinesh P. Wale、Vikram M. Bhosale、Girish S. Gudi、Ramchandra R. Sangana、Abraham Thomas

  DOI：10.1016/j.bmc.2013.08.031

  日期：2013.11

  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.
• Novel spiropiperidine-based stearoyl-CoA desaturase-1 inhibitors: Identification of 1′-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-5-(trifluoromethyl)-3,4-dihydrospiro[chromene-2,4′-piperidine]
  作者：Yoshikazu Uto、Yohei Kiyotsuka、Yuko Ueno、Yuriko Miyazawa、Hitoshi Kurata、Tsuneaki Ogata、Tsuneo Deguchi、Makiko Yamada、Nobuaki Watanabe、Masahiro Konishi、Nobuya Kurikawa、Toshiyuki Takagi、Satoko Wakimoto、Keita Kono、Jun Ohsumi

  DOI：10.1016/j.bmcl.2009.11.043

  日期：2010.1

  Cyclization of the benzoylpiperidine in lead compound 2 generated a series of novel and highly potent spiropiperidine-based stearoyl-CoA desaturase (SCD)-1 inhibitors. Among them, 1'-6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-5-(trifluoromethyl)-3,4-dihydrospiro[chromene-2,4'-piperidine] (19) demonstrated the most powerful inhibitory activity against SCD-1, not only in vitro but also in vivo (C57BL/6 J mice). With regard to the pharmacological evaluation, 19 showed powerful reduction of the desaturation index in the plasma of C57BL/6 J mice on a non-fat diet after a 7-day oral administration (q.d.) without causing notable abnormalities in the eyes or skin up to the highest dose (3 mg/kg) in our preliminary analysis. (C) 2009 Elsevier Ltd. All rights reserved.
• 4-(Phenylsulfonyl)piperidines:  Novel, Selective, and Bioavailable 5-HT_2A Receptor Antagonists
  作者：Stephen R. Fletcher、Frank Burkamp、Peter Blurton、Susan K. F. Cheng、Robert Clarkson、Desmond O'Connor、Daniel Spinks、Matthew Tudge、Monique B. van Niel、Smita Patel、Kerry Chapman、Rose Marwood、Sara Shepheard、Graham Bentley、Gina P Cook、Linda J Bristow、Jose L. Castro、Peter H. Hutson、Angus M. MacLeod

  DOI：10.1021/jm011030v

  日期：2002.1.1

  On the basis of a spirocyclic ether screening lead, a series of acyclic sulfones have been identifed as high-affinity, selective 5-HT2A receptor antagonists. Bioavailability lacking in the parent, 1-(2-(2,4-difluorophenyl)ethyl)-4-(phenylsulfonyl)piperidine (12), was introduced by using stability toward rat liver microsomes as a predictor of bioavailability. By this means, the 4-cyano- and 4-carboxamidophenylsulfonyl derivatives 26 and 31 were identified as orally bioavailable, brain-penetrant analogues suitable for evaluation in animal models. Bioavailability was also attainable by N substitution leading to the N-phenacyl derivative 35. IKr activity detected through counterscreening was reduced to insignificant levels in vivo with the latter compound.