4(5)-(1'-hydroxy-2',2',2'-trifluoroethyl)imidazole | 105480-21-5

• 英文名称: 4(5)-(1'-hydroxy-2',2',2'-trifluoroethyl)imidazole
• 英文别名: 2,2,2-trifluoro-1-(1H-imidazol-5-yl)ethanol
• CAS: 105480-21-5
• 化学式: C₅H₅F₃N₂O
• 分子量: 166.103
• InChiKey: UEYYZTGTKXAZTJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  48.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4(5)-(1'-hydroxy-2',2',2'-trifluoroethyl)imidazole 以42%的产率得到
  参考文献：
  名称：

  FUJII, SHOZO;MAKI, YASUO;KIMOTO, HIROSHI, J. FLUOR. CHEM., 1986, 30, N 4, 415-428

  摘要：

  DOI：
• 作为产物：
  描述：

  咪唑 、 三氟乙醛缩甲基半醇 反应 2.0h， 以37.3%的产率得到4(5)-(1'-hydroxy-2',2',2'-trifluoroethyl)imidazole
  参考文献：
  名称：

  咪唑与三氟乙醛的热缩合

  摘要：

  在三氟乙醛的甲基半缩醛回流（100°C）时容易发生标题缩合，提供37.3％的4（5）-（1'-羟基-2'，2'，2'-三氟乙基）咪唑为主要产物以及8.8％的2-（1'-羟基-2'，2'，2'-三氟乙基）咪唑，7.2％的2,4（5）-双-（1'-羟基-2'，2' ，2'-三氟乙基）咪唑和0.4％的4,5-双产物。通过这些缩合产物的氧化来制备（三氟乙酰基）咪唑。缩合产物的硝化和溴化分别得到相应的硝基咪唑和溴咪唑。

  DOI：

  10.1016/s0022-1139(00)85096-4

文献信息

• [EN] INDOLIN-2-ONE OR PYRROLO-PYRIDIN/PYRIMIDIN-2-ONE DERIVATIVES<br/>[FR] DÉRIVÉS INDOLIN-2-ONE OU PYRROLO-PYRIDIN/PYRIMIDIN-2-ONE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2014202493A1

  公开（公告）日：2014-12-24

  The present invention is concerned with 2-oxo-2,3-dihydro-indoles of general formula (I) wherein Ar is a heteroaryl group, containing one, two or three heteroatoms, selected from N, S or O; R1 is hydrogen, lower alkyl, halogen, amino, dimethylamino, cyano, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy, CH(OH)CF3, (CH2)o-lower alkoxy, cycloalkyl optionally substituted by CF3, or heterocycloalkyl optionally substituted by lower alkyl; R2 is hydrogen, lower alkyl, (CH2)o-cycloalkyl, (CH2)o-O-cycloalkyl, (CH2)o-lower alkoxy, CH2)o-lower alkoxy substituted by halogen, (CH2)o-heterocycloalkyl optionally substituted by lower alkyl, (CH2)o-S(O)2-cycloalkyl, lower alkyl substituted by one or two hydroxy, lower alkyl substituted by one or two lower alkoxy, (CH2)o-S(O)2-lower alkyl, lower alkyl substituted by halogen or CH2CH(OH)CF3; R3 is halogen or lower alkyl; X is CH or N; X1 is CH or N; n is 1 or 2; o is 0, 1, 2 or 3; m is 0, 1 or 2; and the dotted line is a bond or not; as well as with a pharmaceutically acceptable salts thereof, with a racemic mixture, or with its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof The compounds may be used for the treatment of certain central nervous system disorders which are positive (psychosis) and negative symptoms of schizophrenia, substance abuse, alcohol and drug addiction, obsessive-compulsive disorders, cognitive impairment, bipolar disorders, mood disorders, major depression, treatment resistant depression, anxiety disorders, Alzheimer's disease, autism, Parkinson's disease, chronic pain, borderline personality disorder, sleep disturbances, chronic fatigue syndrome, stiffness, antiinflammatory effects in arthritis and balance problems.

  本发明涉及通式（I）中的2-氧代-2,3-二氢吲哚，其中Ar是一个杂环烃基，含有一个、两个或三个杂原子，选自N、S或O；R1是氢、低碳基、卤素、氨基、二甲胺基、氰基、被卤素取代的低碳基、被羟基取代的低碳基、CH(OH)CF3、（CH2）o-低碳醚、环烷基（可选地被 取代）、或杂环烷基（可选地被低碳基取代）；R2是氢、低碳基、（ ）o-环烷基、（ ）o-O-环烷基、（ ）o-低碳醚、被卤素取代的（ ）o-低碳醚、（ ）o-杂环烷基（可选地被低碳基取代）、（ ）o-S(O)2-环烷基、被一个或两个羟基取代的低碳基、被一个或两个低碳醚取代的低碳基、（ ）o-S(O)2-低碳基、被卤素或 CH(OH) 取代的低碳基；R3是卤素或低碳基；X是CH或N；X1是CH或N；n是1或2；o是0、1、2或3；m是0、1或2；虚线是键或非键；以及其在药学上可接受的盐、消旋混合物、或其相应的对映体和/或光学异构体和/或立体异构体。这些化合物可用于治疗某些中枢神经系统障碍，包括精神病（阳性和阴性症状）、精神分裂症、物质滥用、酒精和药物成瘾、强迫症、认知障碍、双相情感障碍、情绪障碍、重性抑郁症、治疗难治性抑郁症、焦虑障碍、阿尔茨海默病、自闭症、帕金森病、慢性疼痛、边缘人格障碍、睡眠障碍、慢性疲劳综合征、僵硬、关节炎的抗炎作用和平衡问题。
• INDOLIN-2-ONE OR PYRROLO-PYRIDIN/PYRIMIDIN-2-ONE DERIVATIVES
  申请人：Hoffmann-La Roche Inc.

  公开号：US20160095844A1

  公开（公告）日：2016-04-07

  The present invention is concerned with 2-oxo-2,3-dihydro-indoles of general formula wherein Ar is a 6-membered heteroaryl group, containing one or two N-atoms, which are the groups, pyridinyl, pyrimidinyl, pyridazinyl, or a 5-membered heteroaryl group containing from 1 to 3 heteroatoms, selected from N, S or O, which groups are imidazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadazolyl, isoxazolyl, oxazolyl, 1,3,4-thiadiazolyl or pyrazolyl; R 1 is hydrogen, lower alkyl, halogen, amino, dimethylamino, cyano, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy, CH(OH)CF 3 , (CH 2 ) o -lower alkoxy, cycloalkyl optionally substituted by CF 3 , or heterocycloalkyl optionally substituted by lower alkyl; R 2 is hydrogen, lower alkyl, (CH 2 ) o -cycloalkyl, (CH 2 ) o —O-cycloalkyl, (CH 2 ) o -lower alkoxy, CH 2 ) o -lower alkoxy substituted by halogen, (CH 2 ) o -heterocycloalkyl optionally substituted by lower alkyl, (CH 2 ) o —S(O) 2 -cycloalkyl, lower alkyl substituted by one or two hydroxy, lower alkyl substituted by one or two lower alkoxy, (CH 2 ) o —S(O) 2 -lower alkyl, lower alkyl substituted by halogen or CH 2 CH(OH)CF 3 ; R 3 is halogen or lower alkyl; X is CH or N; X 1 is CH or N; n is 1 or 2; is 0, 1, 2 or 3; m is 0, 1 or 2; and the dotted line indicates a bond may or may not be present; or, a pharmaceutically acceptable salts thereof, with a racemic mixture, or with its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof The compounds may be used for the treatment of certain central nervous system disorders which are positive (psychosis) and negative symptoms of schizophrenia, substance abuse, alcohol and drug addiction, obsessive-compulsive disorders, cognitive impairment, bipolar disorders, mood disorders, major depression, treatment resistant depression, anxiety disorders, Alzheimer's disease, autism, Parkinson's disease, chronic pain, borderline personality disorder, sleep disturbances, chronic fatigue syndrome, stiffness, antiinflammatory effects in arthritis and balance problems.

  本发明涉及一般式为的2-氧代-2,3-二氢吲哚，其中Ar是6元杂环芳基基团，含有一个或两个N原子，该基团为吡啶基，嘧啶基，吡嗪基或含有1至3个杂原子的5元杂环芳基基团，所述杂原子选自N，S或O，该基团为咪唑基，1,2,4-噁二唑基，1,3,4-噁二唑基，异噁唑基，噁唑基，1,3,4-噻二唑基或吡唑基；R1为氢，低碳基，卤素，氨基，二甲氨基，氰基，低碳基取代的卤素，低碳基取代的羟基，CH（OH）CF3，（CH2）o-低碳基氧基，环烷基（可选）取代 或杂环烷基（可选）取代低碳基；R2为氢，低碳基，（ ）o-环烷基，（ ）o—O-环烷基，（ ）o-低碳基氧基，（ ）o-低碳基取代的卤素，（ ）o-杂环烷基（可选）取代低碳基，（ ）o—S（O）2-环烷基，低碳基取代1或2个羟基，低碳基取代1或2个低碳基氧基，（ ）o—S（O）2-低碳基，低碳基取代卤素或 CH（OH） ；R3为卤素或低碳基；X为CH或N；X1为CH或N；n为1或2；为0,1,2或3；m为0,1或2；虚线表示可能存在或不存在键；或其药学上可接受的盐，与外消旋混合物或其对应的对映体和/或光学异构体和/或立体异构体一起使用。这些化合物可用于治疗某些中枢神经系统紊乱，包括精神病（阳性症状）和阴性症状的精神分裂症，物质滥用，酒精和药物成瘾，强迫症，认知障碍，双相障碍，情绪障碍，重度抑郁症，治疗难治性抑郁症，焦虑症，阿尔茨海默病，自闭症，帕金森病，慢性疼痛，边缘人格障碍，睡眠障碍，慢性疲劳综合症，僵硬，关节炎的抗炎作用和平衡问题的治疗。