2-(2-Chloro-ethoxy)-6-nitro-phenylamine | 211739-06-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(2-Chloro-ethoxy)-6-nitro-phenylamine
• 英文别名: 2-(2-chloroethoxy)-6-nitrophenylamine；2-(2-chloroethoxy)-6-nitro-phenylamine；2-(2-chloroethoxy)-6-nitroaniline
• CAS: 211739-06-9
• 化学式: C₈H₉ClN₂O₃
• 分子量: 216.624
• InChiKey: KAGMABJVGLXKLQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  81.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(2-Chloro-ethoxy)-6-nitro-phenylamine 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 15.0h， 生成 3-{2-[3-(5-fluoro-1H-indol-3-yl)propylamino]ethoxy}benzene-1,2-diamine
  参考文献：
  名称：

  Studies toward the Discovery of the Next Generation of Antidepressants. 3. Dual 5-HT_1A and Serotonin Transporter Affinity within a Class of N-Aryloxyethylindolylalkylamines

  摘要：

  N-Aryloxylethylindolealkylamines (5) having dual 5-HT transporter and 5-HT1A affinity are described. These compounds represent truncated analogues of our previously reported piperidinyl derivatives (3). Compounds in this investigation were found to have more similar affinities and functional activities for the 5-HT1A receptor and 5-HT transporter. Though 5-HT1A antagonism is not consistently observed throughout series 5, several molecular features were found to be essential to obtain high and balanced activities. The proper placement of a heteroatom in the aryl ring and the length of the linkage used to tether the indole moiety had significant influence on 5-HT1A and 5-HT transporter affinities. Introduction of a halogen into the aryl ring usually lowered intrinsic activity and in some cases led to full 5-HT1A antagonists. Compounds 33 and 34 were observed to be full 5-HT1A antagonists with K-i values of approximately 30 nM for the 5-HT1A receptor and K-i values of 5 and 0.5 nM for the 5-HT transporter, respectively. Unfortunately, similar to our previous series (3), compounds in this report also had high affinity for the alpha(1) receptor.

  DOI：

  10.1021/jm0304010
• 作为产物：
  描述：

  2-氨基-3-硝基苯酚 、 1,2-二氯乙烷 在 potassium carbonate 作用下， 以 丁酮 为溶剂， 反应 24.0h， 以85%的产率得到2-(2-Chloro-ethoxy)-6-nitro-phenylamine
  参考文献：
  名称：

  New generation dopaminergic agents. 7. Heterocyclic bioisosteres that exploit the 3-OH-phenoxyethylamine D2 template

  摘要：

  The synthesis of several bioisosteric analogs based on the 3-OH-phenoxyethylamine dopamine D-2 agonist template (i.e., 3) is described. The benzimidazol-2-ones and benzthioimidazol-2-ones (7-10) and 2-trifluoromethyl-benzimidazole (13) were observed to have excellent affinity for the Dp receptor. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00434-5

文献信息

• [EN] 4-AMINOALKOXY-1H-BENZIMIDAZOLE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS DOPAMINE AUTORECEPTOR (D2) AGONISTS<br/>[FR] DERIVES DE 4-AMINOALCOXY-1H-BENZIMIDAZOLE, LEUR PREPARATION ET LEUR UTILISATION COMME AGONISTES DES AUTORECEPTEURS DE LA DOPAMINE (D2)
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：WO1998035945A1

  公开（公告）日：1998-08-20

  (EN) This invention relates to D2 dopaminergic compounds of formula (I), wherein R1 is hydrogen, trifluoromethyl, pentafluoroethyl, heptafluoropropyl, straight-chain or branched alkyl group having up to 6 carbons or benzyl optionally substituted by one to three substituents selected from halogen, amino, nitro, hydroxy, C1-C6 alkoxy; R2 is hydrogen or C1-C6 alkyl. R3 is hydrogen, straight-chain or branched alkyl group having up to 10 carbon atoms, cyclohexylmethyl, -(CH2)mAr, where Ar is phenyl, thienyl, furanyl, or pyridinyl, each optionally substituted by one to two substituents selected from halogen, C1-C6 alkoxy, trifluoromethyl or C1-C6 alkyl; or NR2R3 is 1,2,3,4-tetrahydroquinolin-1-yl or 1,2,3,4-tetrahydroisoquinolin-2-yl; Y = halogen, lower alkyl, amino, and lower alkoxy; n = 1-5; or a pharmaceutically acceptable salt thereof. These D2 dopaminergic compounds are useful in the treatment of schizophrenia, Parkinson's disease, Tourette's syndrome, and drug or alcohol addiction.(FR) L'invention concerne des composés dopaminergiques D2 de formule (I) dans laquelle R1 est hydrogène, trifluorométhyle, pentafluoroéthyle, heptafluoropropyle, un groupe alkyle à chaîne droite ou ramifié possédant jusqu'à 6 carbones, ou bien benzyle éventuellement substitué par un à trois substituants choisis parmi halogène, amino, nitro, hydroxy, alcoxy C1-C6; R2 est hydrogène ou alkyle C1-C6. R3 est hydrogène, un groupe alkyle à chaîne droite ou ramifié possédant jusqu'à 10 atomes de carbone, cyclohéxylméthyle, -(CH2)mAr où Ar est phényle, thiényle, furanyle, ou bien pyridinyle, éventuellement substitués par un à deux substituants choisis parmi halogène, alcoxy C1-C6, trifluorométhyle ou alkyle C1-C6; ou bien NR2R3 est 1,2,3,4-tétrahydroquinoléin-1-yle ou bien 1,2,3,4-tétrahydroisoquinoléin-2-yle; Y = halogène, alkyle inférieur, amino, et alcoxy inférieur; n = 1-5. L'invention concerne également un sel pharmaceutiquement acceptable de ces composés. Ces composés dopaminergiques D2 sont utiles dans le traitement de la schizophrénie, de la maladie de Parkinson, de la maladie de Gilles de La Tourette, et de la toxicomanie ou de l'alcoolisme.

  本发明涉及公式（I）中的D2多巴胺化合物，其中R1是氢，三氟甲基，五氟乙基，七氟丙基，直链或支链碳数不超过6的烷基或苄基，可选地被一到三个卤素，氨基，硝基，羟基，C1-C6烷氧基取代；R2是氢或C1-C6烷基。R3是氢，直链或支链碳数不超过10的烷基，环己基甲基，-(CH2)mAr，其中Ar是苯基，噻吩基，呋喃基或吡啶基，每个可选地被一到两个卤素，C1-C6烷氧基，三氟甲基或C1-C6烷基取代；或NR2R3是1,2,3,4-四氢喹啉-1-基或1,2,3,4-四氢异喹啉-2-基；Y = 卤素，低烷基，氨基和低烷氧基；n = 1-5；或其药学上可接受的盐。这些D2多巴胺化合物在治疗精神分裂症，帕金森病，托瑞特综合征以及药物或酒精成瘾方面有用。
• 4-aminoalkoxy-1,3-dihydrobenzoimidazol-2-one dopamine autoreceptor
  申请人：American Home Products Corporation

  公开号：US06103744A1

  公开（公告）日：2000-08-15

  Disclosed are compounds of the formula ##STR1## wherein: R.sup.1 is hydrogen or C.sub.1 -C.sub.6 alkyl; R.sup.2 is selected from hydrogen, straight-chain and branched C.sub.1 -C.sub.10 alkyl, cyclohexylmethyl or --(CH.sub.2).sub.m Ar where Ar is phenyl, naphthyl, thienyl, furanyl or pyridinyl, each optionally substituted by one or two substituents selected independently from C.sub.1 -C.sub.6 alkyl, halogen, C.sub.1 -C.sub.6 alkoxide and trifluoromethyl; or NR.sup.1 R.sup.2 is 1, 2, 3, 4-tetrahydroquinolin-1-yl or 1, 2, 3, 4-tetrahydroisoquinolin-2-yl; m is 1-5; n is 1 or 2; R.sup.3 is hydrogen or C.sub.1 -C.sub.6 alkyl; Y is halogen, C.sub.1 -C.sub.6 alkyl, and C.sub.1 -C.sub.6 alkoxy; or a pharmaceutically acceptable salt thereof, which are dopamine autoreceptor agonists and as such are useful in the treatment of schizophrenia, Parkinson's disease, Tourette's syndrome, alcohol addiction and drug addiction.

  本发明涉及的化合物的化学式为##STR1##其中：R.sup.1表示氢或C.sub.1-C.sub.6烷基；R.sup.2选自氢、直链和支链C.sub.1-C.sub.10烷基、环己基甲基或--(CH.sub.2).sub.m Ar，其中Ar为苯基、萘基、噻吩基、呋喃基或吡啶基，每个基团可选地被一个或两个基团独立地选自C.sub.1-C.sub.6烷基、卤素、C.sub.1-C.sub.6烷氧基和三氟甲基取代；或NR.sup.1R.sup.2是1,2,3,4-四氢喹啉-1-基或1,2,3,4-四氢异喹啉-2-基；m为1-5；n为1或2；R.sup.3表示氢或C.sub.1-C.sub.6烷基；Y为卤素、C.sub.1-C.sub.6烷基和C.sub.1-C.sub.6烷氧基；或其药学上可接受的盐。这些化合物是多巴胺自身受体激动剂，因此在治疗精神分裂症、帕金森病、图雷特综合症、酒精成瘾和药物成瘾方面有用。
• N-aryloxyethylamine derivatives for the treatment of depression
  申请人：American Home Products Corp.

  公开号：US06110956A1

  公开（公告）日：2000-08-29

  Compounds effective in treating disorders of the serotonin-affected neurological systems are provided, such compounds having the following formula: ##STR1## wherein: R.sub.1 and R.sub.2 are each, independently, hydrogen, halogen, CF.sub.3, lower alkyl, lower alkoxy, MeSO.sub.2, or together can form a 5-7 membered carbocyclic or heterocyclic ring; R.sub.3 is alkoxy, halogen, hydrogen or carbamoyl; R.sub.4 is hydrogen, hydroxy, lower alkyl, or lower alkoxy; R.sub.5 is hydrogen, lower alkyl, or halogen; R.sub.6 is hydrogen, lower alkyl, or phenyl; R.sub.7 is hydrogen, lower alkyl, lower alkoxy, halogen, CN, CF.sub.3, or hydroxy; and X is (CH.sub.2).sub.n, wherein n is 0 to 3; or pharmaceutically acceptable salts thereof.

  提供了用于治疗受血清素影响的神经系统疾病的化合物，该化合物具有以下结构式：##STR1## 其中：R.sub.1和R.sub.2各自独立地是氢、卤素、CF.sub.3、较低的烷基、较低的烷氧基、MeSO.sub.2，或者一起形成5-7个成员的碳环或杂环；R.sub.3是烷氧基、卤素、氢或者氨基甲酰基；R.sub.4是氢、羟基、较低的烷基或较低的烷氧基；R.sub.5是氢、较低的烷基或卤素；R.sub.6是氢、较低的烷基或苯基；R.sub.7是氢、较低的烷基、较低的烷氧基、卤素、CN、CF.sub.3或羟基；X是(CH.sub.2).sub.n，其中n为0至3；或其药学上可接受的盐。
• 4-aminoalkoxy-1H-benzoimidazoles
  申请人：American Home Products Corporation

  公开号：US06127380A1

  公开（公告）日：2000-10-03

  This invention relates to D.sub.2 dopaminergic compounds of the formula ##STR1## wherein: R.sup.1 is hydrogen, trifluoromethyl, pentafluoroethyl, heptafluoropropyl, straight-chain or branched alkyl group having up to 6 carbons or benzyl optionally substituted by one to three substituents selected from halogen, amino, nitro, hydroxy, and C.sub.1 -C.sub.6 alkoxy; R.sup.2 is hydrogen or C.sub.1 -C.sub.6 alkyl; R.sup.3 is hydrogen, straight-chain or branched alkyl group having up to 10 carbon atoms, cyclohexylmethyl, --(CH.sub.2).sub.m Ar where Ar is phenyl, naphthalenyl, thienyl, furanyl, or pyridinyl, each optionally substituted by one to two substituents selected from halogen, C.sub.1 -C.sub.6 alkoxy, trifluoromethyl and C.sub.1 -C.sub.6 alkyl, and m is 1-3 or NR.sup.2 R.sup.3 is 1,2,3,4-tetrahydroquinolin-1-yl or 1,2,3,4-tetrahydroisoquinolin-2-yl; Y is hydrogen, halogen, lower alkyl, amino, or lower alkoxy; n is 1-5: or a pharmaceutically acceptable salt thereof. These D.sub.2 dopaminergic compounds are useful in the treatment of schizophrenia, Parkinson's disease, Tourette's syndrome, and drug or alcohol addiction.

  本发明涉及D.sub.2多巴胺化合物的公式##STR1##其中：R.sup.1是氢，三氟甲基，五氟乙基，七氟丙基，直链或支链烷基，具有高达6个碳或苄基，可选择由卤素，氨基，硝基，羟基和C.sub.1-C.sub.6烷氧基中的一到三个取代基取代；R.sup.2是氢或C.sub.1-C.sub.6烷基；R.sup.3是氢，直链或支链烷基，具有高达10个碳原子，环己基甲基，--(CH.sub.2).sub.m Ar，其中Ar是苯基，萘基，噻吩基，呋喃基或吡啶基，每个基团可选择由卤素，C.sub.1-C.sub.6烷氧基，三氟甲基和C.sub.1-C.sub.6烷基中的一到两个取代基取代，m为1-3或NR.sup.2 R.sup.3为1,2,3,4-四氢喹啉-1-基或1,2,3,4-四氢异喹啉-2-基；Y是氢，卤素，低烷基，氨基或低烷氧基；n为1-5：或其药学上可接受的盐。这些D.sub.2多巴胺能化合物可用于治疗精神分裂症，帕金森病，图雷特综合症和药物或酒精成瘾。
• 5-aminoalkoxy-1, 4-dihydroquinoxaline-2, 3-diones
  申请人：American Home Products Corporation

  公开号：US05922715A1

  公开（公告）日：1999-07-13

  This invention relates to compounds of Formula I ##STR1## wherein: R.sup.1 and R.sup.2 are independently selected from hydrogen, straight-chain and branched alkyl group having up to 10 carbon atoms or --(CH.sub.2).sub.m Ar where Ar is phenyl, naphthyl or thienyl, each optionally substituted by one or two substituents selected independently from C.sub.1 -C.sub.6 alkyl, halogen, C.sub.1 -C.sub.6 alkoxide and trifluoromethyl; or NR.sup.1 R.sup.2 is 1, 2, 3, 4-tetrahydroquinolin-1-yl or 1, 2, 3, 4-tetrahydroisoquinoline-2-yl; m is 1-5; n is 1 or 2; Y is hydrogen, C.sub.1 -C.sub.6 alkyl, and C.sub.1 -C.sub.6 alkoxy; or the pharmaceutically acceptable salts thereof, which are dopamine D.sub.2 agonists and therefore useful in the treatment of psychoses and Parkinson's disease.

  本发明涉及I式化合物：##STR1##其中：R.sup.1和R.sup.2独立地选自具有最多10个碳原子的直链和支链烷基或--(CH.sub.2).sub.m Ar，其中Ar是苯基，萘基或噻吩基，每个可选地由C.sub.1-C.sub.6烷基，卤素，C.sub.1-C.sub.6烷氧基和三氟甲基中的一个或两个取代基选自；或NR.sup.1 R.sup.2是1,2,3,4-四氢喹啉-1-基或1,2,3,4-四氢异喹啉-2-基；m为1-5；n为1或2；Y为氢，C.sub.1-C.sub.6烷基和C.sub.1-C.sub.6烷氧基；或其药学上可接受的盐，它们是多巴胺D.sub.2激动剂，因此在治疗精神病和帕金森病方面有用。