4,6-喹啉二胺 | 40107-09-3

• 物质功能分类: 医药中间体 - 喹啉类化合物
• 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: 4,6-喹啉二胺
• 英文名称: quinoline-4,6-diyldiamine
• 英文别名: Chinolin-4,6-diyldiamin；4,5-Diamino-chinolin；4,6-Quinolinediamine；quinoline-4,6-diamine
• CAS: 40107-09-3
• 化学式: C₉H₉N₃
• mdl: MFCD11849297
• 分子量: 159.191
• InChiKey: IKWVYRACZMFUHI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  64.9
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2933499090

反应信息

• 作为反应物：
  描述：

  4,6-喹啉二胺 在 硫酸 、 sodium nitrite 作用下， 生成 4-amino-quinolin-6-ol
  参考文献：
  名称：

  Mizoguchi, Pharmaceutical Bulletin, 1955, vol. 3, p. 227

  摘要：

  DOI：
• 作为产物：
  描述：

  4,6-二硝基喹啉1-氧化物 在 盐酸 、 palladium on activated charcoal 作用下， 生成 4,6-喹啉二胺
  参考文献：
  名称：

  Naito, Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1945, vol. 65, p. Ausg. B, S. 446, 447

  摘要：

  DOI：

文献信息

• Di-quaternary salts of pyrimidylaminoquinolines
  申请人：ICI LTD

  公开号：US02591545A1

  公开（公告）日：1952-04-01

  The invention comprises diquaternary salts of pyrimidylaminoquinolines of the general formula Pq-NH-Qq, wherein P represents a 2-, 4- (or 6-) amino- or 1-5C-alkylamino-substituted pyrimidine nucleus attached to the -NH- bridge at another of the 2,4- (or 6-) positions and substituted by halogen in the third, Q represents a quinoline nucleus attached to the -NH- bridge in the 6-position, substituted in the 4-position by an amino or 1-5C-alkylamino group, and optionally further substituted by one or more 1-5C-alkyl groups, and the symbols q indicate that the nuclei P and Q are in the form of quaternary salts, and the manufacture thereof by reacting one or more substances of the formula P-NH-Q or P-NH-Qq with a quaternary salt-forming agent, or, in the case of quaternary salts other than methyl p-toluenesulphonates, by treating the corresponding compounds in which at least one of the quaternary salt groups is in the form of a methyl p-toluenesulphonate, with a water-soluble salt (e.g. an inorganic halide). The products are useful as intermediates for the production of trypanocidal compounds, e.g. by replacing the halogen atom by hydrogen by a reduction process, or by an amino or alkylamino group by reaction with ammonia or an alkylamine. In examples: (1) and (2) 4-amino-6 - (61 - chloro - 21 - aminopyrimidyl - 41 - amino)-quinaldine or its 1-methochloride is reacted with methyl p-toluenesulphonate in nitrobenzene and the product is dissolved in aqueous alcohol and reacted with sodium iodide to give the 1 : 11-dimethiodide; (3) 4 - amino - 6 - (41 - chloro - 61 - methylaminopyrimidyl - 21 - amino) - quinaldine is quaternated as in (1), yielding the 1 : 31 - di - (metho - p - toluenesulphonate); (4) 4-amino-6-(61-chloro-21-aminopyrimidyl-41-amino) -quinoline is quaternated as in (1) and the product is dissolved in aqueous sodium bicarbonate solution and treated with sodium chloride to give the 1 : 11-dimethochloride; (5) 4-methylamino-6-(61-chloro-21-methylaminopyrimidyl - 41 - amino) - quinaldine 1 - methochloride is quaternated as in (1), giving the 1 : 11-bis-metho-p-toluenesulphonate. 4 - Amino - 6 - (61 - chloro - 21 - aminopyrimidyl - 41 - amino) - quinaldine and its 1-methochloride are obtainable by refluxing 4 : 6-diaminoquinaldine with 4 : 6-dichloro-2-aminopyridine in dilute hydrochloric acid or with its methochloride hydrochloride in water. 4 - Amino - 6 - (41 - chloro - 61 - methylaminopyrimidyl - 21 - amino) - quinaldine is obtainable similarly from 2 : 4-dichloro-6-methylaminopyrimidine. 4 - Amino - 6 - (61 - chloro - 21 - aminopyrimidyl - 41 - amino) - quinoline is obtainable by refluxing 4 : 6-diaminoquinoline with 2-amino-4 : 6-dichloropyrimidine in dilute hydrochloric acid. 4 - Methylamino - 6 - (61 - chloro - 21 - methylaminopyrimidyl - 41 - amino) - quinaldine 1-methochloride is obtainable by refluxing 6-amino-4-methylaminoquinaldine 1-methochloride dihydrate with 4 : 6-dichloro-2-methylaminopyrimidine in dilute hydrochloric acid.

  这个发明包括通式Pq-NH-Qq的嘧啶基氨基喹啉的二季铵盐，其中P代表连接到-NH-桥另一个2-，4-（或6-）位置并在第三位置被卤素取代的2-，4-（或6-）氨基或1-5C-烷基氨基取代的嘧啶核，Q代表连接到6-位置的喹啉核，在4-位置被氨基或1-5C-烷基氨基取代，并且可选择地进一步被一个或多个1-5C-烷基基团取代，符号q表示核P和Q以季铵盐的形式存在，并通过将通式P-NH-Q或P-NH-Qq的一个或多个物质与季铵盐形成剂反应来制备该二季铵盐，或者，对于除了甲基对甲苯磺酸盐以外的季铵盐，通过处理相应的化合物，其中至少一个季铵盐基团以甲基对甲苯磺酸盐的形式存在，与水溶性盐（例如无机卤化物）处理。这些产品可用作生产试虫药化合物的中间体，例如通过还原过程将卤素原子替换为氢，或通过与氨或烷基胺反应将氨基或烷基氨基团替换。在示例中：（1）和（2）4-氨基-6-（61-氯-21-氨基嘧啶基-41-氨基）-喹啉或其1-甲氯化物在硝基苯中与甲基对甲苯磺酸盐反应，产物溶解在水醇中，并与碘化钠反应得到1:11-二甲碘化物；（3）4-氨基-6-（41-氯-61-甲基氨基嘧啶基-21-氨基）-喹啉如同（1）进行季铵化，产生1:31-二（甲氧-对甲苯磺酸盐）；（4）4-氨基-6-（61-氯-21-氨基嘧啶基-41-氨基）-喹啉如同（1）进行季铵化，产物溶解在水碳酸氢钠溶液中，并与氯化钠处理得到1:11-二甲氯化物；（5）4-甲基氨基-6-（61-氯-21-甲基氨基嘧啶基-41-氨基）-喹啉1-甲氯化物如同（1）进行季铵化，得到1:11-双甲氧-对甲苯磺酸盐。4-氨基-6-（61-氯-21-氨基嘧啶基-41-氨基）-喹啉及其1-甲氯化物可通过在稀盐酸中回流4:6-二氨基喹啉与4:6-二氯-2-氨基吡啶或其甲氯化物盐酸盐反应或与水中的甲氯化物盐酸盐反应得到。类似地，4-氨基-6-（41-氯-61-甲基氨基嘧啶基-21-氨基）-喹啉可从2:4-二氯-6-甲基氨基嘧啶中获得。4-氨基-6-（61-氯-21-氨基嘧啶基-41-氨基）-喹啉可通过在稀盐酸中回流4:6-二氨基喹啉与2-氨基-4:6-二氯嘧啶反应获得。4-甲基氨基-6-（61-氯-21-甲基氨基嘧啶基-41-氨基）-喹啉1-甲氯化物可通过在稀盐酸中回流6-氨基-4-甲基氨基喹啉1-甲氯化物二水合物与4:6-二氯-2-甲基氨基嘧啶反应获得。
• 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 quaternary salts of pyrimidylamino quinolines
  申请人：ICI LTD

  公开号：US02585979A1

  公开（公告）日：1952-02-19

  Quaternary sulphates and sulphonates of substituted pyrimidylaminoquinolines useful as trypanocides, are obtained by heating the corresponding halogen acid di-quaternary salts with lower alkyl esters of sulphuric acid, or sulphonic acids, preferably in a solvent having a higher boiling-point than the alkyl halide formed. In examples, methochlorides or methiodides of pyrimidylaminoquinolines joined in the 4-pyrimidyl-position to the -NH- link, and substituted in the 2-pyrimidine position by amino, in the 6-position by methyl, and in the quinoline nucleus by 4-amino and methylamino, and methyl, and joined in the 6-position to the -NH-, are converted into methomethylsulphate, methomethanesulphonate, and metho - p - toluenesulphonate. Generally, the compounds may be substituted in the 2-, 4- or 6-position by amino or lower alkyl amino, attached to the linking -NH- group at another of these positions and further substituted in the remaining 2-, 4- or 6-position by lower alkyl, amino, or lower alkylamino. 4 - Amino - 6(21-aminopyrimidyl - 41 - amino) quinoline monohydrate is obtained by the action of 4 : 6-diaminoquinoline on 4-chloro-2-aminopyrimidine, in presence of hydrochloric acid, rendering alkaline and crystallizing, and may be converted via di-methylsulphate and sodium chloride to the di-methochloride trihydrate.

  通过加热相应的卤素酸二季铵盐和低级烷基硫酸酯或磺酸，可以制备取代嘧啶基氨基喹啉的四价硫酸盐和磺酸盐，其可用作抗锥虫药物。最好使用沸点高于生成的烷基卤化物的溶剂。例如，将连接到4-嘧啶基位置的嘧啶基氨基喹啉的甲氧氯化物或甲氧碘化物，以及在2-嘧啶基位置上通过氨基取代，在6-位置上通过甲基取代，在喹啉核中通过4-氨基和甲基氨基取代，以及连接到- NH-的6-位置上，转化为甲氧甲磺酸盐、甲氧甲磺酸盐和甲基-p-甲苯磺酸盐。通常，这些化合物可以在2-、4-或6-位置上通过氨基或低级烷基氨基取代，在连接的-NH-基团的另一个位置上，并在剩余的2-、4-或6-位置上进一步通过低级烷基、氨基或低级烷基氨基取代。通过4:6-二氨基喹啉和4-氯-2-氨基嘧啶在盐酸存在下反应，使其碱化和结晶，可以得到4-氨基-6（21-氨基嘧啶-41-氨基）喹啉一水合物，并通过二甲基硫酸盐和氯化钠转化为二甲氧氯化物三水合物。
• [EN] 4-AMINOQUINOLINE COMPOUNDS<br/>[FR] COMPOSES 4-AMINOQUINOLEINES
  申请人：MERCK & CO INC

  公开号：WO2003045920A1

  公开（公告）日：2003-06-05

  The present invention is concerned with compounds of the general Formula I : and pharmaceutically acceptable salts thereof, which are useful as melanin concentrating hormone receptor antagonists, particularly MCH-1R antagonists. As such, compounds of the present invention are useful for the treatment or prevention of obesity or eating disorders associated with excessive food intake and complications thereof, osteoarthritis, certain cancers, AIDS wasting, cachexia, frailty (particularly in elderly), mental disorders stress, cognitive disorders, sexual function, reproductive function, kidney function, locomotor disorders, attention deficit disorder (ADD), substance abuse disorders and dyskinesias, Huntington s disease, epilepsy, memory function, and spinal muscular atrophy. Compounds of formula I may therefore be used in the treatment of these conditions, and in the manufacture of a medicament useful in treating these conditions. Pharmaceutical formulations comprising one of the compounds of formula (I) as an active ingredient are disclosed, as are processes for preparing these compounds.

  本发明涉及一般式I的化合物及其药学上可接受的盐，这些化合物可用作黑色素浓集激素受体拮抗剂，尤其是MCH-1R拮抗剂。因此，本发明的化合物可用于治疗或预防与过度进食及其并发症相关的肥胖症或进食障碍、骨关节炎、某些癌症、艾滋病消耗症、消瘦、虚弱（尤其是老年人）、心理障碍、压力、认知障碍、性功能、生殖功能、肾功能、运动障碍、注意力缺陷障碍（ADD）、物质滥用障碍和运动障碍、亨廷顿病、癫痫、记忆功能和脊髓肌萎缩症。因此，I式化合物可用于治疗这些疾病，并用于制造用于治疗这些疾病的药物。本发明披露了包含一种I式化合物作为活性成分的制药配方，以及制备这些化合物的过程。
• Amide derivatives and nociceptin antagonists
  申请人：Japan Tobacco Inc.

  公开号：US20030055087A1

  公开（公告）日：2003-03-20

  The present invention relates to a compound of the formula [1′] 1 wherein R 2 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, R 5 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 R 5 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，其化学式为[1′]1，其中R2是低碳基，可选择性地被羟基、氨基等取代，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是卤素原子、羟基、低碳基，可选择性地被卤素原子等取代，t为0或1至5的整数，当t为2至5的整数时，每个R5可能相同也可能不同，m为0或1至8的整数，n为0或1至4的整数，以及一种含有化合物[1′]作为活性成分的镇痛剂。由于其镇痛剂作用，化合物[1′]对于术后疼痛等尖锐疼痛具有镇痛效果。本发明还涉及某些酰胺衍生物的使用，其中包括化合物[1′]作为镇痛剂或镇痛剂拮抗剂。