N-(4-氯-2-甲基喹啉-6-基)乙酰胺 | 59611-57-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: N-(4-氯-2-甲基喹啉-6-基)乙酰胺
• 英文名称: 6-acetamide-4-chloro-2-methylquinoline
• 英文别名: N-(4-chloro-2-methyl-[6]quinolyl)-acetamide；N-(4-Chlor-2-methyl-[6]chinolyl)-acetamid；N-(4-chloro-2-methyl-6-quinolyl)acetamide；6-Acetamino-4-chlor-chinaldin；N-(4-chloro-2-methylquinolin-6-yl)acetamide
• CAS: 59611-57-3
• 化学式: C₁₂H₁₁ClN₂O
• 分子量: 234.685
• InChiKey: CGKDHJPGFCSXQP-UHFFFAOYSA-N

物化性质

• 熔点：
  209-210 °C
• 沸点：
  442.1±40.0 °C(Predicted)
• 密度：
  1.317±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933499090

反应信息

• 作为反应物：
  描述：

  N-(4-氯-2-甲基喹啉-6-基)乙酰胺 在 哌啶 、 sodium hydrogensulfite 作用下， 生成 6-acetylamino-2-trans-styryl-quinoline-4-sulfonic acid
  参考文献：
  名称：

  Rubzow; Bunina, Zhurnal Obshchei Khimii, 1944, vol. 14, p. 1128,1132

  摘要：

  DOI：
• 作为产物：
  描述：

  4′-氨基乙酰苯胺 在 三氯氧磷 作用下， 以 甲醇 为溶剂， 反应 17.67h， 生成 N-(4-氯-2-甲基喹啉-6-基)乙酰胺
  参考文献：
  名称：

  4-Aminoquinolines:  Novel Nociceptin Antagonists with Analgesic Activity

  摘要：

  Small-molecule nociceptin antagonists were synthesized to examine their therapeutic potential. After a 4-aminoquinoline derivative was found to bind with the human ORL1 receptor, a series of 4-aminoquinolines and related compounds were synthesized and their binding was evaluated. Elucidation of structure-activity relationships eventually led to the optimum compounds. One of the se compounds, N-(4-amino-2-methylquinolin-6-yl) -2-(4-ethylphenoxymethyl)benzamide hydrochloride (11) not only antagonized nociceptin-induced allodynia in mice but also showed analgesic effect in a hot plate test using mice and in a formalin test using rats. Its analgesic effect was not antagonized by the opioid antagonist naloxone. These results indicate that this nociceptin antagonist has the potential to become a novel type of analgesic that differs from mu -opioid agonists.

  DOI：

  10.1021/jm0002073

文献信息

• Amide derivatives and nociceptin antagonists
  申请人：Japan Tobacco Inc.

  公开号：US06410561B1

  公开（公告）日：2002-06-25

  The present invention relates to a compound of the formula [1′] wherein R2 is lower alkyl optionally substituted by hydroxy, amino and the like, ring B is phenyl, thienyl and the like, E is a single bond, —O—, —S— and the like, ring G is aryl, heterocyclic group and the like, R5 is halogen atom, hydroxy, lower alkyl optionally substituted by halogen atom etc., and the like, t is 0 or an integer of 1 to 5, when t is an integer of 2 to 5, each R5 may be the same or different, m is 0 or an integer of 1 to 8, and n is 0 or an integer of 1 to 4, and a nociceptin antagonist containing compound [1′] as an active ingredient. The compound [1′] shows, due to nociceptin antagonistic action, analgesic effect against sharp pain such as postoperative pain and the like. The present invention also relates to the use of certain amide derivative inclusive of compound [1′] as a nociceptin antagonist or analgesic.

  本发明涉及一种化合物的公式为[1′]，其中R2是可选择地由羟基、氨基等取代的较低烷基，环B是苯基、噻吩基等，E是单键，—O—，—S—等，环G是芳基、杂环基等，R5是卤原子、羟基、可选择地由卤原子等取代的较低烷基等，t为0或1至5的整数，当t为2至5的整数时，每个R5可以相同或不同，m为0或1至8的整数，n为0或1至4的整数，以及包含化合物[1′]作为活性成分的一种痛觉受体拮抗剂。该化合物[1′]由于痛觉受体拮抗作用，对于术后疼痛等剧痛具有镇痛效果。本发明还涉及某些酰胺衍生物的使用，包括化合物[1′]作为痛觉受体拮抗剂或镇痛剂。
• Quaternary salts of pyrimidylaminoquinolines
  申请人：MURIEL RUTH CURD

  公开号：US02585909A1

  公开（公告）日：1952-02-19

  Mono- and di-quaternary salts of pyrimidylaminoquinolines having trypanocidal activity are made by reacting a quaternary salt of pyrimidine substituted in the 2-, 4- (or 6-) positions by amino or lower alkylamino-groups, in another of the 2-, 4- (or 6-) positions by a lower alkyl-, amino-, or lower alkylamino-group, and in one of the remaining 2-, 4- (or 6-) groups by a halogen atom or -SR group, R being hydrocarbon, with an amino-quinoline, substituted in the 4-position by amino-, or lower alkylamino, and which may be further substituted by lower alkyl groups, or with a quaternary salt thereof, in presence of an acid with or without a liquid medium. The amino-quinoline may be in the form of a salt thereof, or in the form of substances which will give rise to it under the reaction conditions. The products must contain at least an alkylamino-substituent in the pyrimidine nucleus or in 4-position of the quinoline nucleus. In examples, the quaternary salts of aminopyrimidines substituted by chlorine, bromine or iodine or thioalkyl in the 2- or 4-position, and with other groups as defined, are treated with 4- or 6-aminoquinolines having other substituents as defined above, or with their acetyl derivatives or quaternary salts, to give the mono- or di-salts of the corresponding pyrimidylaminoquinolines, in which the-NH-group is attached at the 2-, 4-, or 6-positions of the pyrimidine nucleus and the 6-positions of the quinoline nucleus, and the alkyl groups may be methyl, ethyl, isopropyl and butyl. The products include 4-alkylamino- or amino-6-(21-amino- or alkylamino-61-alkyl- or amino-pyrimidyl-41-amino)-methyl quinoline-dimethiodides, dimethochlorides, &c., and the corresponding quinolines. 4 - Alkylamino 6 - acetyl - aminoquinaldines are obtained by the action of alkylamines on the 4-chloro-compound and may be hydrolysed and quaternated; the corresponding methylaminequinoline derivative is obtained by hydrolysis of 4-hydroxy-6-acetylamino-quinoline with POCl3 to give the 2-chloro derivative, and condensation with methylamine, and may be quaternated. Specifications 658,202 and 658,204 are referred to.

  制备具有抗锥虫活性的嘧啶基氨基喹啉的单和双季铵盐，通过将2-、4-（或6-）位置取代氨基或较低烷基氨基基团的嘧啶季铵盐与2-、4-（或6-）位置中的较低烷基、氨基或较低烷基氨基基团以及剩余的2-、4-（或6-）位置中的卤素原子或-SR基（R为碳氢）取代的氨基喹啉或其季铵盐在酸性介质中或无液体介质的情况下反应制得。氨基喹啉可以是其盐的形式，或者是在反应条件下会产生其形式的物质。产品必须至少含有嘧啶核或喹啉核4-位置的烷基氨基取代基。例如，用氯、溴或碘或硫代烷基在2-或4-位置取代的氨基嘧啶季铵盐，以及具有上述其他取代基的4-或6-氨基喹啉或其乙酰衍生物或季铵盐进行反应，制备相应的嘧啶基氨基喹啉的单或双季铵盐，其中-NH基团附在嘧啶核的2-、4-或6-位置和喹啉核的6-位置，烷基可以是甲基、乙基、异丙基和丁基。产品包括4-烷基氨基或氨基-6-(2-氨基或烷基氨基-6-烷基或氨基-嘧啶基-4-氨基)-甲基喹啉二甲硫醇盐、二甲氯化物等，以及相应的喹啉。通过在4-氯化合物上作用烷基胺得到4-烷基氨基-6-乙酰氨基喹啉，可以水解和季铵化；通过将4-羟基-6-乙酰氨基喹啉与POCl3水解以得到2-氯衍生物，再与甲基胺缩合，可以得到相应的甲胺喹啉衍生物，并可以季铵化。参考规范658,202和658,204。
• Process for the manufacture of diquaternary salts of pyrimidylaminoquinolines
  申请人：MURIEL RUTH CURD

  公开号：US02585972A1

  公开（公告）日：1952-02-19

  Quaternary salts of pyrimidylaminoquinolines in which either the 2-position of the pyrimidine nucleus or the 4-position of the quinoline nucleus, or both, are substituted by an amino- or lower alkylamino-group, the -NH- linking is in the 4 : 61-positions respectively, and each nucleus may be optionally substituted by alkyl groups, are obtained by heating the quaternary compound bearing ether and/or thioether groups in the above-mentioned 2- and/or 4-positions with ammonia or lower alkylamines in a solvent. In examples, pyrimidylaminoquinoline quaternary salts having methyl thio-, or benzylthio in the 2-pyrimidyl, and 4-quinoline, positions, and/or having methoxy, ethoxy, or phenoxy in the 4-quinoline position, with amino and methyl groups as other substituents are converted into the corresponding amine or alkylamine with ammonia or ethylamine in various solvents. There is described also the preparation, as starting materials, of the quaternary satls of pyrimidylamino-quinolines substituted as required above by amino, and methyl groups and having methylthio, benzylthio, alkoxy or phenoxy groups in the required positions by the condensation of the corresponding halogenated pyrimidine ether or thioether with an aminoquinoline, or the halogenated pyrimidine with an aminoquinoline ether or thioether, non-reacting amino groups being acetylated and later hydrolysed, if necessary, and with intermediate or subsequent conversion to the quaternary salts. 6-Acetylamino and 6-amino-4-methyl, 4-benzylthio-ethers, or 4-methyl, ethyl and phenyl ethers of quinoline or quinaldine are obtained by the action of the corresponding mercaptan-, alcohol- or phenol-sodium salt or a mixture producing these, on the 4-halogen- or 4-hydroxy-quinoline compound, followed if necessary by hydrolysing the acetylamino-group. Specifications 634,531, 634,818, 658,203 and 658,204 are referred to.

  2-吡咯啉基氨基喹啉的第四价盐，在其中吡咯啉核的2-位置或喹啉核的4-位置或两者都被氨基或较低的烷基氨基取代，-NH-连接分别在4:6或1-位置，每个核也可以选择性地被烷基取代。通过在溶剂中用氨或较低的烷基胺加热带有醚和/或硫醚基团的第四价化合物，可以获得这些盐。例如，具有2-吡咯啉中甲硫基或苄基硫基和4-喹啉位置的吡咯啉基氨基喹啉四价盐，并/或具有4-喹啉位置的甲氧基、乙氧基或苯氧基，具有氨基和甲基基团作为其他取代基的盐，可以用氨或乙基胺在各种溶剂中转化为相应的胺或烷基胺。还描述了作为起始材料的吡咯啉基氨基喹啉的第四价盐，这些盐如上所述被氨基和甲基基团取代，并在所需位置具有甲硫基、苄基硫基、烷氧基或苯氧基，通过相应卤代吡咯啉醚或硫醚和氨基喹啉的缩合或卤代吡咯啉和氨基喹啉醚或硫醚，非反应性氨基被乙酰化，如果需要，后来水解，并通过中间或后续转化成第四价盐。通过在4-卤代或4-羟基喹啉化合物上作用相应的巯基醇盐、醇盐或酚盐或产生这些的混合物，然后如有必要水解乙酰氨基基团，可以获得6-乙酰氨基和6-氨基-4-甲基、4-苄基硫醚、或4-甲基、乙基和苯基醚的喹啉或喹啉醛醚。参考规范634,531、634,818、658,203和658,204。
• N-methylene malonate of tetrahydroquinoline and derivatives thereof
  申请人：Riker Laboratories, Inc.

  公开号：US03969463A1

  公开（公告）日：1976-07-13

  Certain substituted 6,7-dihydro-1-oxo-1H,5H-benzo[ij]-quinolizine-2-carboxylic acids and hydrazides, esters, amides and salts thereof, intermediates therefor, and a process for their preparation are described; the compounds are active as anti-microbial agents.

  本文描述了某些取代的6,7-二氢-1-氧代-1H,5H-苯并[ij]-喹啉-2-羧酸及其肼衍生物、酯、酰胺和盐，中间体以及它们的制备方法。这些化合物具有抗微生物活性。
• Substituted benzo[ij]quinolinzine-2-carboxylic acids and derivatives
  申请人：Riker Laboratories, Inc.

  公开号：US03985882A1

  公开（公告）日：1976-10-12

  Certain substituted 6,7-dihydro-1-oxo-1H,5H-benzo[ij]-quinolizine-2-carboxylic acids and hydrazides, esters, amides and salts thereof, intermediates therefor, and a process for their preparation are described; the compounds are active as anti-microbial agents.

  本文介绍了某些取代的6,7-二氢-1-氧代-1H,5H-苯并[ij]-喹啉-2-羧酸及其肼、酯、酰胺和盐，其中间体及其制备方法；这些化合物具有抗微生物活性。