2-甲基-5-[[(2R)-环氧乙烷-2-基]甲氧基]-1,3-苯并噻唑 | 678982-27-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 中文名称: 2-甲基-5-[[(2R)-环氧乙烷-2-基]甲氧基]-1,3-苯并噻唑
• 英文名称: 5-(((R)-oxiran-2-yl)methoxy)-2-methylbenzo[d]thiazole
• 英文别名: 5-[((2R)oxiran-2-yl)methoxy]-2-methylbenzothiazole；2-(2R)-methyl-5-(oxiran-2-ylmethoxy)benzothiazole；2-methyl-5-(R)-(oxiran-2-ylmethoxy)benzothiazole；2-methyl-5-[[(2R)-oxiran-2-yl]methoxy]-1,3-benzothiazole
• CAS: 678982-27-9
• 化学式: C₁₁H₁₁NO₂S
• 分子量: 221.28
• InChiKey: YSPRCDGVFRVBED-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  62.9
• 氢给体数：
  0
• 氢受体数：
  4

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  2-甲基-5-苯并噻唑	2-methyl-5-benzothiazolol	68867-14-1	C8H7NOS	165.216

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(2R)-3-(2-methylbenzothiazol-5-yloxy)-1-piperazinylpropan-2-ol	678981-82-3	C15H21N3O2S	307.417
  1-[(2R)-2-羟基-3-(2-甲基苯并噻唑-5-氧基)丙基]哌啶-4-酮	1-[(2R)-2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]piperidin-4-one	1044674-27-2	C16H20N2O3S	320.412
  ——	(2R)-3-((3S)-3-methylpiperazinyl)-1-(2-methylbenzothiazol-5-yloxy)propan-2-ol	——	C16H23N3O2S	321.444
  ——	4-[2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]-piperazine-1-carboxylic acid tert-butyl ester	737790-75-9	C20H29N3O4S	407.534
  ——	tert-butyl 4-[(2R)-2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl](3S)-3-methylpiperazinecarboxylate	737790-76-0	C21H31N3O4S	421.561
  ——	N-(2-{4-[(2R)-2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]piperazinyl}ethyl)[4-(trifluoromethyl)phenyl]carboxamide	——	C25H29F3N4O3S	522.591
  ——	(R)-CVT 3501	——	C25H32N4O3S	468.62

反应信息

• 作为反应物：
  描述：

  2-甲基-5-[[(2R)-环氧乙烷-2-基]甲氧基]-1,3-苯并噻唑 在 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 2-{4-[(R)-2-Hydroxy-3-(2-methyl-benzothiazol-5-yloxy)-propyl]-piperazin-1-yl}-N-(4-methoxy-phenyl)-acetamide
  参考文献：
  名称：

  New fatty acid oxidation inhibitors with increased potency lacking adverse metabolic and electrophysiological properties

  摘要：

  New inhibitors of palmitoylCoA oxidation were synthesized based on a structurally novel lead, CVT-3501 (1). Investigation of structure-activity relationships was conducted with respect to potency of inhibition of cardiac mitochondrial palmitoylCoA oxidation and metabolic stability. Potent and metabolically stable analogues 33, 42, and 43 were evaluated in vitro for cytochrome P450 inhibition and potentially adverse electrophysiological effects. Compound 33 was also found to have favorable pharmacokinetic properties in rat. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.093
• 作为产物：
  描述：

  2-甲基-5-苯并噻唑 、 右旋环氧氯丙烷 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 生成 2-甲基-5-[[(2R)-环氧乙烷-2-基]甲氧基]-1,3-苯并噻唑
  参考文献：
  名称：

  [EN] SUBSTITUTED HETEROCYCLIC COMPOUNDS USEFUL IN THE TREATMENT OF CARDIOVASCULAR DISEASES
  [FR] COMPOSES HETEROCYCLIQUES SUBSTITUES UTILES POUR LE TRAITEMENT DE MALADIES CARDIO-VASCULAIRES

  摘要：

  其中：a.o. T是氧、硫或NR11，其中R11是氢或较低的烷基；V是-N<，-CH<或-NH-CH<；X1是氢，可选择取代的较低烷基，可选择取代的环烷基，可选择取代的芳基或可选择取代的杂芳基；X2是可选择取代的芳基或可选择取代的杂芳基；Y是可选择取代的二氢杂芳基；Z1和Z2分别是1-4个碳原子的可选择取代的烷基，用于治疗各种疾病状态，特别是心血管疾病，如心房和心室心律失常、间歇性跛行、普林兹梅塔（变异）心绞痛、稳定和不稳定心绞痛、运动诱发性心绞痛、充血性心脏病和心肌梗死。这些化合物还可用于治疗糖尿病。

  公开号：

  WO2004069818A1

文献信息

• [EN] 1-AKAN-2-OL SUBSTITUTED PIPERAZINE AND PIPERIDINE COMPOUNDS<br/>[FR] COMPOSES PIPERAZINE ET PIPERAZINE 1-AKAN-2-OL SUBSTITUES
  申请人：CV THERAPEUTICS INC

  公开号：WO2005061470A1

  公开（公告）日：2005-07-07

  Disclosed are novel substituted heterocyclic derivatives having the structure of Formula (I): The compounds are useful for the treatment of various disease states, in particular cardiovascular diseases such as atrial and ventricular arrhythmias, intermittent claudication, Prinzmetal's (variant) angina, stable and unstable angina, exercise induced angina, congestive heart disease, diabetes, and myocardial infarction.

  揭示了具有以下结构的新型取代杂环衍生物（I）的化合物：这些化合物对于治疗各种疾病状态有用，特别是心血管疾病，如心房和心室心律失常，间歇性跛行，普林兹梅塔（变异）心绞痛，稳定和不稳定心绞痛，运动诱发性心绞痛，充血性心脏病，糖尿病和心肌梗死。
• Substituted heterocyclic compounds
  申请人：——

  公开号：US20030176447A1

  公开（公告）日：2003-09-18

  Disclosed are novel heterocyclic derivatives, useful for the treatment of various disease states, in particular cardiovascular diseases such as atrial and ventricular arrhythmias, intermittent claudication, Prinzmetal's (variant) angina, stable and unstable angina, exercise induced angina, congestive heart disease, and myocardial infarction. The compounds are also useful in the treatment of diabetes, and for increasing HDL plasma levels in mammals.

  揭示了一种新颖的杂环衍生物，用于治疗各种疾病状态，特别是心血管疾病，如心房和心室心律失常、间歇性跛行、普林兹梅塔（变异）心绞痛、稳定和不稳定心绞痛、运动诱发性心绞痛、充血性心力衰竭和心肌梗死。这些化合物还可用于治疗糖尿病，并可增加哺乳动物的高密度脂蛋白血浆水平。
• [EN] UREA DERIVATIVES OF PIPERAZINES AND PIPERIDINES AS FATTY ACID OXIDATION INHIBITORS<br/>[FR] DERIVES D'UREE DE PIPERAZINES ET DE PIPERIDINES COMME INHIBITEURS DE L'OXYDATION D'ACIDES GRAS
  申请人：CV THERAPEUTICS INC

  公开号：WO2005000826A1

  公开（公告）日：2005-01-06

  Disclosed are novel piperazine derivatives, useful for the treatment of various disease states, in particular cardiovascular diseases such as atrial and ventricular arrhythmias, intermittent claudication, Prinzmetal's (variant) angina, stable and unstable angina, exercise induced angina, congestive heart disease, and myocardial infarction.

  揭示了一种新型哌嗪衍生物，可用于治疗各种疾病状态，特别是心血管疾病，如心房和心室心律失常、间歇性跛行、普林兹梅塔（变异）心绞痛、稳定和不稳定心绞痛、运动诱发性心绞痛、充血性心脏病和心肌梗死。
• [EN] SUBSTITUTED HETEROCYCLIC COMPOUNDS USEFUL IN THE TREATMENT OF CARDIOVASCULAR DISEASES<br/>[FR] COMPOSES HETEROCYCLIQUES SUBSTITUES UTILES POUR LE TRAITEMENT DE MALADIES CARDIO-VASCULAIRES
  申请人：CV THERAPEUTICS INC

  公开号：WO2004069818A1

  公开（公告）日：2004-08-19

  wherein: a.o. T is oxygen, sulfur, or NR11 , in which R11 is hydrogen or lower alkyl; V is -N<, -CH<, or -NH-CH<; X1 is hydrogen, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl; X2 is optionally substituted aryl or optionally substituted heteroaryl; Y is optionally substituted dihydroheteroarcyl; and Z1 and Z2 are independently optionally substituted alkylene of 1-4 carbon atoms, useful for the treatment of various disease states, in particular cardiovascular diseases such as atrial and ventricular arrhythmias, intermittent claudication, Prinzmetal’s (variant) angina, stable and unstable angina, exercise induced angina, congestive heart disease, and myocardial infarction. The compounds are also useful in the treatment of diabetes.

  其中：a.o. T是氧、硫或NR11，其中R11是氢或较低的烷基；V是-N<，-CH<或-NH-CH<；X1是氢，可选择取代的较低烷基，可选择取代的环烷基，可选择取代的芳基或可选择取代的杂芳基；X2是可选择取代的芳基或可选择取代的杂芳基；Y是可选择取代的二氢杂芳基；Z1和Z2分别是1-4个碳原子的可选择取代的烷基，用于治疗各种疾病状态，特别是心血管疾病，如心房和心室心律失常、间歇性跛行、普林兹梅塔（变异）心绞痛、稳定和不稳定心绞痛、运动诱发性心绞痛、充血性心脏病和心肌梗死。这些化合物还可用于治疗糖尿病。
• [EN] SUBSTITUTED PIPERAZINE COMPOUNDS AND THEIR USE AS FATTY ACID OXIDATION INHIBITORS<br/>[FR] COMPOSES DE PIPERAZINE SUBSTITUES ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE L'OXYDATION D'ACIDES GRAS
  申请人：CV THERAPEUTICS INC

  公开号：WO2003008411A1

  公开（公告）日：2003-01-30

  Disclosed are novel heterocyclic derivatives of the formula (I), wherein amongst others R?1, R2, R3, R4, R5, R6, R7, and R8¿ are hydrogen; T is oxygen, sulfur, or NR11, in which R11 is hydrogen or lower alkyl; V is N<, -CH<, or N-CH<; X1 is hydrogen, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl; X2 is optionally substituted aryl or optionally substituted heteroaryl; Y is optionally substituted monocyclic heteroarylenyl; and Z?1 and Z2¿ are independently optionally substituted alkylene or 1-4 carbon atoms. The compounds are useful for the treatment of various disease states, in particular cardiovascular diseases such as atrial and ventricular arrhythmias, intermittent claudication, Prinzmetal's (variant) angina, stable and unstable angina, exercise induced angina, congestive heart disease, and myocardial infarction. The compounds are also useful in the treatment of diabetes, and for increasing HDL plasma levels in mammals.

  本发明涉及一种新型杂环衍生物的公开式（I），其中，R1、R2、R3、R4、R5、R6、R7和R8中的一些是氢；T为氧、硫或NR11，其中R11为氢或低碳基；V为N<、-CH<或N-CH<；X1为氢、可选取代的低碳基、可选取代的环烷基、可选取代的芳基或可选取代的杂环芳基；X2为可选取代的芳基或可选取代的杂环芳基；Y为可选取代的单环杂芳基；Z1和Z2独立地为可选取代的烷基或1-4碳原子。该化合物可用于治疗各种疾病状态，特别是心血管疾病，如心房和心室心律失常、间歇性跛行、普林兹梅塔尔（变异型）心绞痛、稳定和不稳定性心绞痛、运动诱发性心绞痛、充血性心力衰竭和心肌梗死。该化合物还可用于治疗糖尿病，并可提高哺乳动物的高密度脂蛋白血浆水平。