6-fluoro-3,4-dihydrospiro[chromene-2,4'-piperidine] hydrochloride | 936648-52-1

• 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: 6-fluoro-3,4-dihydrospiro[chromene-2,4'-piperidine] hydrochloride
• 英文别名: 6-Fluorospiro[chromane-2,4'-piperidine] hydrochloride；6-fluorospiro[3,4-dihydrochromene-2,4'-piperidine];hydrochloride
• CAS: 936648-52-1
• 化学式: C₁₃H₁₆FNO*ClH
• 分子量: 257.735
• InChiKey: LVIYPEDTJUXAOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.69
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  21.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-fluoro-3,4-dihydrospiro[chromene-2,4'-piperidine] hydrochloride 、 苯基[4-(三氟甲基)苯基]氨基甲酸酯 在 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 以65%的产率得到6-fluoro-N-[4-(trifluoromethyl)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：

  5-氟-2-羟基苯乙酮 在 四氢吡咯 、 三乙基硅烷 、 sodium tetrahydroborate 、 三氟乙酸 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 45.0h， 生成 6-fluoro-3,4-dihydrospiro[chromene-2,4'-piperidine] hydrochloride
  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

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。
• WO2007/54580
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.