6-amino-2-methyl-4-methylaminoquinoline | 244219-91-8

• 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
• 英文名称: 6-amino-2-methyl-4-methylaminoquinoline
• 英文别名: N⁴,2-methylquinolin-4,6-diamine；4-methylamino-6-amino-quinaldine；2,N⁴-dimethyl-quinoline-4,6-diyldiamine；2,N⁴-Dimethyl-chinolin-4,6-diyldiamin；N,2-dimethylquinoline-4,6-diamine；4-N,2-dimethylquinoline-4,6-diamine
• CAS: 244219-91-8
• 化学式: C₁₁H₁₃N₃
• 分子量: 187.244
• InChiKey: ZPTFYJKAWRUABO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  50.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-氯-4-氨基-6-甲基嘧啶 、 6-amino-2-methyl-4-methylaminoquinoline 生成 N⁶-(4-amino-6-methyl-pyrimidin-2-yl)-2,N⁴-dimethyl-quinoline-4,6-diyldiamine
  参考文献：
  名称：

  Process for preparing diquaternary salts of pyrimidylamino quinolines

  摘要：

  通过用季铵盐形成剂（例如甲基碘化物、二甲基硫酸酯和对甲苯磺酸甲酯等）处理含有三联氮嘧啶基氨基喹啉的化合物，可以制备具有抗锥虫作用的嘧啶基氨基喹啉的二季铵盐。在这些化合物中，三联氮嘧啶或喹啉化合物中的一个以季铵盐的形式存在，例如在2-、4-（或6-）位上被较低的烷基氨基（例如甲基和异丙基氨基）或氨基基团取代，在另一个这些位置上，被较低的烷基（例如甲基）或氨基基团或较低的烷基氨基取代，并与剩余的2-、4-（或6-）位上的连接-NH-基团相连。同时，喹啉核在4-位上被氨基或较低的烷基氨基（例如甲基氨基和乙基氨基）取代，进一步被较低的烷基或烷基组取代（例如2-甲基），并在6-位上带有连接-NH-基团。如果喹啉核中的4-取代基不是较低的烷基氨基，则三联氮嘧啶核必须包含较低的烷基氨基基团。所述的二季铵盐包括甲碘酸盐和甲基对甲苯磺酸盐，大多数最终转化为前者，从其他季铵盐中间体（例如甲基硫酸盐）中得到。作为初始材料使用的嘧啶基氨基喹啉及其单季铵盐，可以通过将适当取代的6-氨基喹啉或其季铵盐与4-氯嘧啶或其季铵盐缩合，必要时脱水得到单水合物，并在需要时替换季铵基团，例如从氢碘酸盐替换为甲碘酸盐。4-甲基和乙基氨基-6-氨基喹啉可以通过水解N-乙酰衍生物获得。参考规范658,203。

  公开号：

  US02585910A1
• 作为产物：
  描述：

  4′-氨基乙酰苯胺 在 盐酸 、 三氯氧磷 作用下， 以 甲醇 为溶剂， 反应 22.67h， 生成 6-amino-2-methyl-4-methylaminoquinoline
  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

• The synthesis and biological evaluation of new DNA-directed alkylating agents, phenyl N-mustard-4-anilinoquinoline conjugates containing a urea linker
  作者：Bhavin Marvania、Rajesh Kakadiya、Wilson Christian、Tai-Lin Chen、Ming-Hsi Wu、Sharda Suman、Kiran Tala、Te-Chang Lee、Anamik Shah、Tsann-Long Su

  DOI：10.1016/j.ejmech.2014.06.066

  日期：2014.8

  We synthesized a series of phenyl N-mustard-4-anilinoquinoline conjugates to study their antitumorigenic effects. These agents were prepared by the condensation of 4-[N,N-bis(2-chloroethyl)amino]phenyl isocyanate with 6-amino-4-methylamino or 4-anilinoquinolines. The structure–activity relationship (SAR) studies revealed that the C2-methylquinoline derivatives (18a–o) were generally more cytotoxic

  我们合成了一系列苯基N-芥子-4-苯胺喹啉共轭物，以研究其抗肿瘤作用。通过将4- [ N，N-双（2-氯乙基）氨基]苯基异氰酸酯与6-氨基-4-甲基氨基或4-苯胺基喹啉缩合来制备这些试剂。结构-活性关系（SAR）研究表明，C2-甲基喹啉衍生物（18a - o）通常比C2-苯基喹啉缀合物（23a - d）具有更高的细胞毒性。）在体外抑制各种人类肿瘤细胞系的细胞生长。但是，喹啉C4处的甲基氨基或苯胺取代基不影响细胞毒性作用。标题缀合物能够诱导DNA交联并促进G2 / M期的细胞周期停滞。这项研究表明，针对各种肿瘤细胞系的细胞生长，苯基N-芥子-4-苯胺喹啉偶联物通常比苯基N-芥子-4-苯胺喹啉偶联物更有效。
• 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。
• [EN] ARYLAMINE DERIVATIVES AND THEIR USE AS ANTI-TELOMERASE AGENT<br/>[FR] DERIVES ARYLAMINES ET LEUR APPLICATION COMME AGENT ANTITELOMERASE
  申请人：AVENTIS PHARMA SA

  公开号：WO2001040218A1

  公开（公告）日：2001-06-07

  La présente invention est relative à la thérapie du cancer et concerne de nouveaux agents anticancéreux ayant un mécanisme d'action bien particulier. Elle concerne aussi de nouveaux composés chimiques ainsi que leur application thérapeutique chez l'homme.

  本发明涉及癌症治疗，并涉及具有特定作用机制的新型抗癌剂。它还涉及新的化合物以及它们在人类治疗中的应用。
• 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。
• Chemical derivatives and their application as antitelomerase agent
  申请人：Aventis Pharms S.A.

  公开号：US20040053966A1

  公开（公告）日：2004-03-18

  The present invention relates to cancer therapy and to novel anticancer agent having a mechanism of action which is quite specific. It also relates to novel chemical compounds as well as their therapeutic application in humans.

  本发明涉及癌症治疗和具有相当特定作用机制的新型抗癌剂。它还涉及新的化学化合物以及它们在人类治疗中的治疗应用。