4-chlorophenoxyoxirane | 122023-60-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-chlorophenoxyoxirane
• 英文别名: rac-(4-chlorophenoxy)oxirane；2-(4-chlorophenoxy)oxirane
• CAS: 122023-60-3
• 化学式: C₈H₇ClO₂
• 分子量: 170.595
• InChiKey: NWTPTMIECBVULD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  21.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-chlorophenoxyoxirane 在 ammonium chloride 作用下， 以 水 、 乙腈 为溶剂， 以7<SP>6</SP>%的产率得到rac-1-azido-3-(4-chloro-phenoxy)-propane
  参考文献：
  名称：

  4-IMIDAZOLINES

  摘要：

  本发明涉及式I的化合物，其中R1，R2，X，Y和Ar如此定义，并且它们的药物活性盐，但排除外消旋化合物4-苄基-4,5-二氢-1H-咪唑或其互变异构体（CAS 131548-83-9）。式I的化合物具有良好的迹胺相关受体（TAARs）亲和力，尤其是对TAAR1，可用于治疗抑郁症，焦虑症，双相情感障碍，注意力缺陷多动障碍（ADHD），与压力相关的障碍，精神障碍，如精神分裂症，神经疾病，如帕金森病，神经退行性疾病，如阿尔茨海默病，癫痫，偏头痛，高血压，物质滥用和代谢性疾病，如进食障碍，糖尿病，糖尿病并发症，肥胖症，脂质代谢异常，能量消耗和吸收障碍，体温稳态障碍和功能障碍，睡眠和昼夜节律障碍，以及心血管疾病。

  公开号：

  US20090012138A1
• 作为产物：
  描述：

  1-氯-4-(乙烯基氧基)苯 在 过氧化氢苯甲酰 作用下， 以 氯仿 为溶剂， 反应 0.17h， 以10%的产率得到4-chlorophenoxyoxirane
  参考文献：
  名称：

  Sone, Tomomichi; Isobe, Masakazu; Takabatake, Eigo, Chemical and pharmaceutical bulletin, 1989, vol. 37, # 7, p. 1922 - 1924

  摘要：

  DOI：

文献信息

• 1,3-heterocyclic-substituted alkane
  申请人：Imperial Chemical Industries PLC

  公开号：US04957934A1

  公开（公告）日：1990-09-18

  A 2-propanol derivative of the formula I, wherein R.sup.1 and R.sup.5, which may be the same or different, are each a triazolyl, imidazolyl, pyridyl or pyrimidinyl radical; R.sup.2, R.sup.3 and R.sup.4, which may be the same or different, are each a hydrogen atom, a 1-6C alkyl, halogenoalkyl or alkoxy radical, a 3-8C cycloalkyl radical, or a phenyl, naphthyl, phenoxy, naphthyloxy or phenyl (1-6C alkyl) radical, in each of which the aryl group optionally bears one or more substituents selected from halogen atoms, amino, carboxamido, cyano and nitro radicals, 1-6C alkyl, halogenoalkyl, alkoxy, halogenoalkoxy and alkylamino radicals, 3-8C cycloalkyl radicals, di(1-6C alkyl)amino radicals and 2-6C alkoxycarbonyl radicals; R.sup.6 is a phenyl or naphthyl radical optionally bearing one or more substituents as defined above; X is a direct bond, an alkylene, alkenylene or alkynylene radical, or an oxyalkylene or thioalkylene radical wherein respectively the oxygen or sulphur atom is bonded to R.sup.6 or a phenylalkylene radical in which the phenyl group bears one or more substituents as defined above for R.sup.6 ; and Y is a hydrogen or halogen atom, a hydroxy, cyano or carbamoyl radical, or a phenyl(1-6C alkoxy) radical in which the phenyl group bears one or more substituents as defined above for R.sup.6 ; provided that, when Y is a cyano or carbamoyl radical, neither R.sup.2, R.sup.3 nor R.sup.4 may be an alkoxy or aryloxy radical, and either R.sup.2 is a hydrogen atom, or R.sup.3 and R.sup.4 are both hydrogen atoms; and provided that, when R.sup.1 and R.sup.5 are each a 1,2,4-triazol-1-yl radical, R.sup.2 is hydrogen and Y is a hydroxy radical, R.sup.3 and R.sup.4 may not be hydrogen or methyl when X is a direct bond, and R.sup.3 and R.sup.4 may not be hydrogen when X is a methylene radical; and for those compounds which contain a basic nitrogen atom, the pharmaceutically acceptable acid additon salts thereof.

  化学式I的2-丙醇衍生物，其中R.sup.1和R.sup.5，可以相同也可以不同，分别是三唑基、咪唑基、吡啶基或嘧啶基基团；R.sup.2、R.sup.3和R.sup.4，可以相同也可以不同，分别是氢原子、1-6碳烷基、卤代烷基或烷氧基基团、3-8碳环烷基基团，或苯基、萘基、苯氧基、萘氧基或苯（1-6碳烷基）基团，其中芳基基团可选地带有一个或多个卤素原子、氨基、羧酰胺基、氰基和硝基基团、1-6碳烷基、卤代烷基、烷氧基、卤代烷氧基和烷基氨基基团、3-8碳环烷基基团、二（1-6碳烷基）氨基基团和2-6碳氧羰基基团；R.sup.6是一个苯基或萘基基团，可选地带有如上所定义的一个或多个取代基；X是一个直链键、烷基、烯基或炔基基团，或氧烷基或硫烷基基团，其中氧或硫原子分别与R.sup.6或一个苯基烷基基团结合，该苯基带有如上所定义的一个或多个取代基；Y是氢原子或卤素原子、羟基、氰基或氨基甲酰基基团，或苯（1-6碳烷氧基）基团，其中苯基带有如上所定义的一个或多个取代基；但是，当Y是氰基或氨基甲酰基基团时，R.sup.2、R.sup.3或R.sup.4不能是烷氧基或芳基氧基基团，且要么R.sup.2是氢原子，要么R.sup.3和R.sup.4都是氢原子；此外，当R.sup.1和R.sup.5分别是1,2,4-三唑-1-基基团时，R.sup.2是氢，Y是羟基，当X是直链键时，R.sup.3和R.sup.4不能是氢或甲基，当X是亚甲基基团时，R.sup.3和R.sup.4不能是氢；对于含有碱性氮原子的化合物，其药学上可接受的酸盐。
• [EN] 4-IMIDAZOLINES AND THEIR USE AS ANTIDEPRESSANTS<br/>[FR] 4-IMIDAZOLINES ET LEUR UTILISATION COMME ANTIDÉPRESSEURS
  申请人：HOFFMANN LA ROCHE

  公开号：WO2009003867A1

  公开（公告）日：2009-01-08

  The present invention relates to compounds of formula (I) wherein R1 is hydrogen, halogen or lower alkyl; R2 is hydrogen or amino; X-Y is -(CH2)n-, N(R)-CH2-, -O-CH2- or -S-CH2-; Ar is phenyl or naphthyl; n is 1 or 2; R is hydrogen or lower alkyl; and to their pharmaceutically active salts, with the exclusion of the racemic compound 4-benzyl-4,5-dihydro-lH-imidazole or its tautomer (CAS 131548-83-9). It has been found that the compounds of formula (I) have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

  本发明涉及式(I)的化合物，其中R1是氢，卤素或较低的烷基; R2是氢或氨基; X-Y是-(CH2)n-，N(R)- -，-O- -或-S- -; Ar是苯基或萘基; n为1或2; R是氢或较低的烷基; 以及它们的药物活性盐，排除了外消旋化合物4-苄基-4,5-二氢-1H-咪唑或其互变异构体（CAS 131548-83-9）。发现式(I)的化合物对痕量胺相关受体（TAARs）具有良好的亲和力，特别是对TAAR1。这些化合物可用于治疗抑郁症、焦虑症、双相情感障碍、注意力缺陷多动障碍（ADHD）、与压力相关的障碍、精神障碍如精神分裂症、神经疾病如帕金森病、神经退行性疾病如阿尔茨海默病、癫痫、偏头痛、高血压、物质滥用和代谢障碍如进食障碍、糖尿病、糖尿病并发症、肥胖症、血脂异常、能量消耗和吸收障碍、体温稳态障碍和功能障碍、睡眠和昼夜节律障碍以及心血管疾病。
• 4-imidazolines
  申请人：Hoffman-La Roche Inc.

  公开号：US07812047B2

  公开（公告）日：2010-10-12

  The present invention relates to compounds of formula wherein R1, R2, X, Y and Ar are as defined herein and to their pharmaceutically active salts, with the exclusion of the racemic compound 4-benzyl-4,5-dihydro-1H-imidazole or its tautomer (CAS 131548-83-9). Compounds of formula I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1 and are useful for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

  本发明涉及式I的化合物，其中R1、R2、X、Y和Ar的定义如下，并且涉及它们的药物活性盐，但排除了外消旋化合物4-苄基-4,5-二氢-1H-咪唑或其互变异构体（CAS 131548-83-9）。式I的化合物具有良好的亲和力，特别是对TAAR1的痕量胺相关受体（TAARs），并可用于治疗抑郁症、焦虑症、双相情感障碍、注意力缺陷多动障碍（ADHD）、与压力相关的障碍、精神障碍如精神分裂症、神经疾病如帕金森病、神经退行性疾病如阿尔茨海默病、癫痫、偏头痛、高血压、物质滥用和代谢性疾病如进食障碍、糖尿病、糖尿病并发症、肥胖症、脂质代谢异常、能量消耗和吸收障碍、体温稳态障碍和功能障碍、睡眠和昼夜节律障碍以及心血管疾病。
• Heterocyclic Compounds
  申请人：IMPERIAL CHEMICAL INDUSTRIES PLC

  公开号：EP0299684A1

  公开（公告）日：1989-01-18

  A 2-propanol derivative of the formula I, wherein R' and R5, which may be the same or different, are each a triazolyl, imidazolyl, pyridyl or pyrimidinyl radical; R2, R3 and R4, which may be the same or different, are each a hydrogen atom, a 1-6C alkyl, halogenoalkyl or alkoxy radical, a 3-8C cycloalkyl radical, or a phenyl, naphthyl, phenoxy, naphthyloxy or phenyl(1-6C alkyl) radical, in each of which the aryl group optionally bears one or more substituents selected from halogen atoms, amino, carboxamido, cyano and nitro radicals, 1-6C alkyl, halogenoalkyl, alkoxy, halogenoalkoxy and alkylamino radicals, 3-8C cycloalkyl radicals, di(1-6C alkyl)amino radicals and 2-6C alkoxycarbonyl radicals; R6 is a phenyl or naphthyl radical optionally bearing one or more substituents as defined above; X is a direct bond, an alkylene, alkenylene or alkynylene radical, or an oxyalkylene or thioalkylene radical wherein respectively the oxygen or sulphur atom is bonded to R6 or a phenylalkenylene radical in which the phenyl group bears one or more substituents as defined above for R6; and Y is a hydrogen or halogen atom, a hydroxy, cyano or carbamoyl radical, or a phenyl(1-6C alkoxy) radical in which the phenyl group bears one or more substituents as defined above for R6; provided that, when Y is a cyano or carbamoyl radical, neither R2, R3 nor R4 may be an alkoxy or aryloxy radical, and either R2 is a hydrogen atom, or R3 and R4 are both hydrogen atoms; and provided that, when R' and R5 are each a 1,2,4-triazol-1-yl radical, R2 is , hydrogen and Y is a hydroxy radical, R3 arid R4 may not be hydrogen or methyl when X is a direct bond, and R3 and R4- may not be hydrogen when X is a methylene radical; and for those compounds which contain a basic nitrogen atom, the pharmaceutically acceptable acid addition salts thereof.

  式 I 的 2-丙醇衍生物，其中 R'和 R5（可以相同或不同）各自是三唑基、咪唑基、吡啶基或嘧啶基；R2、R3 和 R4（可以相同或不同）各自是氢原子、1-6C 烷基、卤代烷基或烷氧基、3-8C 环烷基或苯基、萘基、苯氧基、萘氧基或苯基（1-6C 烷基）基、其中每个芳基任选带有一个或多个选自卤素原子、氨基、羧基、氰基和硝基、1-6C 烷基、卤代烷基、烷氧基、卤代烷氧基和烷基氨基、3-8C 环烷基、二（1-6C 烷基）氨基和 2-6C 烷氧基羰基的取代基；R6 是苯基或萘基，可选择带有一个或多个如上定义的取代基；X 是直接键、亚烷基、亚烯基或亚炔基，或氧亚烷基或硫代亚烷基，其中氧原子或硫原子分别与 R6 或苯基亚烯基键合，其中苯基带有一个或多个如上文对 R6 所定义的取代基；以及 Y 是氢原子或卤素原子、羟基、氰基或氨基甲酰基，或苯基（1-6C 烷氧基）基，其中苯基带有一个或多个如上文对 R6 所定义的取代基；但当 Y 为氰基或氨基甲酰基时，R2、R3 或 R4 均不得为烷氧基或芳氧基基，且 R2 为氢原子，或 R3 和 R4 均为氢原子；当 R'和 R5 各为 1,2,4-三唑-1-基时，R2 为氢原子，Y 为羟基，当 X 为直接键时，R3 和 R4 不得为氢原子或甲基，当 X 为亚甲基时，R3 和 R4- 不得为氢原子。
• SONE, TOMOMICHI;ISOBE, MASAKAZU;TAKABATAKE, EIGO, CHEM. AND PHARM. BULL., 37,(1989) N, C. 1922-1924
  作者：SONE, TOMOMICHI、ISOBE, MASAKAZU、TAKABATAKE, EIGO

  DOI：——

  日期：——