螺[色烯-2,4-哌啶]-1-羧酸叔丁酯 | 1207163-67-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 中文名称: 螺[色烯-2,4-哌啶]-1-羧酸叔丁酯
• 英文名称: tert-butyl spiro[chromene-2,4'-piperidine]-1'-carboxylate
• 英文别名: tert-butyl 1'H-spiro[chromene-2,4'-piperidine]-1'-carboxylate
• CAS: 1207163-67-4
• 化学式: C₁₈H₂₃NO₃
• 分子量: 301.386
• InChiKey: VBXFQESAJFYACP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  螺[色烯-2,4-哌啶]-1-羧酸叔丁酯 在 盐酸 、 水 作用下， 以 1,4-二氧六环 为溶剂， 生成 spiro[chromene-2,4'-piperidine] hydrochloride
  参考文献：
  名称：

  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]

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2009.11.043
• 作为产物：
  描述：

  4-氧代-2-螺(N-叔丁基哌啶-4-基)-吡喃 在 甲醇 、 sodium tetrahydroborate 、 对甲苯磺酸 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 、 甲苯 为溶剂， 反应 22.0h， 生成 螺[色烯-2,4-哌啶]-1-羧酸叔丁酯
  参考文献：
  名称：

  基于全细胞筛选鉴定具有有效抗结核特性的螺哌啶

  摘要：

  在复制和非复制（NRP）条件下进行的基于全细胞的筛选，以鉴定抗结核分枝杆菌（Mtb）的命中物，从而鉴定出具有有效抗结核特性的多种新颖但与结构相关的螺哌啶。这些化合物可进一步分为三类，即3-（3-芳基-1,2,4-恶二唑-5-基）-1'-烷基螺[茚-1,4'-哌啶]（螺环茚）， 4-（3-芳基-1,2,4-恶二唑-5-基）-1'-烷基螺[色烯-2,4'-哌啶]（螺螺铬烯）和1'-苄基螺[吲哚-1,4 ′-哌啶] -2（1 H）-1 （螺旋螺吲哚）。螺茚显示⩾4log 10在复制的Mtb上杀死（2–12μM），但在非复制条件下具有中等活性。螺环茚抗性突变体的全基因组测序工作导致鉴定了MmpL3（大分枝杆菌膜蛋白）中的I292L突变，这是将霉菌酸组装到Mtb的细胞壁核心中所必需的。MIC调制研究表明，该突变体对螺环色酮具有交叉抗性，但对螺线吲哚酮不具有交叉抗性。该信函描述了铅鉴定工作，旨在提高效

  DOI：

  10.1016/j.bmcl.2015.05.087

文献信息

• [EN] CHROMAN - SPIROCYCLIC PIPERIDINE AMIDES AS MODULATORS OF ION CHANNELS<br/>[FR] AMIDES DE PIPÉRIDINE SPIROCYCLIQUE CHROMANIQUE EN TANT QUE MODULATEURS DES CANAUX IONIQUES
  申请人：VERTEX PHARMA

  公开号：WO2012112743A1

  公开（公告）日：2012-08-23

  The invention relates to chroman spirocyclic piperidine amide derivatives useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

  这项发明涉及用于抑制离子通道的螺环色满烷酰胺衍生物。该发明还提供了包含本发明化合物的药用可接受组合物，以及使用这些组合物治疗各种疾病的方法。
• CHROMAN-SPIROCYCLIC PIPERIDINE AMIDES AS MODULATORS OF ION CHANNELS
  申请人：HADIDA-RUAH Sara Sabina

  公开号：US20120245136A1

  公开（公告）日：2012-09-27

  The invention relates to chroman spirocyclic piperidine amide derivatives useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

  本发明涉及一种用作离子通道抑制剂的色满环螺环己烷酰胺衍生物。本发明还提供了包括本发明化合物的药学上可接受的组合物，并提供了使用这些组合物治疗各种疾病的方法。
• Chroman-spirocyclic piperidine amides as modulators of ion channels
  申请人：Hadida-Ruah Sara Sabina

  公开号：US10385070B2

  公开（公告）日：2019-08-20

  The invention relates to chroman spirocyclic piperidine amide derivatives useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

  本发明涉及可用作离子通道抑制剂的铬螺环哌啶酰胺衍生物。本发明还提供了包含本发明化合物的药学上可接受的组合物，以及使用该组合物治疗各种疾病的方法。
• Synthesis and evaluation of novel stearoyl-CoA desaturase 1 inhibitors: 1′-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-3,4-dihydrospiro[chromene-2,4′-piperidine] analogs
  作者：Yoshikazu Uto、Yuko Ueno、Yohei Kiyotsuka、Yuriko Miyazawa、Hitoshi Kurata、Tsuneaki Ogata、Makiko Yamada、Tsuneo Deguchi、Masahiro Konishi、Toshiyuki Takagi、Satoko Wakimoto、Jun Ohsumi

  DOI：10.1016/j.ejmech.2010.07.044

  日期：2010.11

  In continuation of our investigation on novel stearoyl-CoA desaturase (SCD) 1 inhibitors, we have already reported on the structural modification of the benzoylpiperidines that led to a series of novel and highly potent spiropiperidine-based SCD1 inhibitors. In this report, we would like to extend the scope of our previous investigation and disclose details of the synthesis, SAR, ADME, PK, and pharmacological evaluation of the spiropiperidines with high potency for SCD1 inhibition. Our current efforts have culminated in the identification of 5-fluoro-1'-6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-3,4-dihydrospiro[chromene-2,4'-piperidine] (10e), which demonstrated a very strong potency for liver SCD1 inhibition (ID(50) = 0.6 mg/kg). This highly efficacious inhibition is presumed to be the result of a combination of strong enzymatic inhibitory activity (IC(50) (mouse)= 2 nM) and good oral bioavailability (F >95%). Pharmacological evaluation of 10e has demonstrated potent, dose-dependent reduction of the plasma desaturation index in C57BL/6J mice on a high carbohydrate diet after a 7-day oral administration (q.d.). In addition, it did not cause any noticeable skin abnormalities up to the highest dose (10 mg/kg). (C) 2010 Elsevier Masson SAS. All rights reserved.
• CHROMAN - SPIROCYCLIC PIPERIDINE AMIDES AS MODULATORS OF ION CHANNELS
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：EP2675812B1

  公开（公告）日：2017-08-30