N-(4-hydroxy-[6]quinolyl)-acetamide | 874499-36-2

• 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: N-(4-hydroxy-[6]quinolyl)-acetamide
• 英文别名: N-(4-Hydroxy-[6]chinolyl)-acetamid；N-(4-oxo-1H-quinolin-6-yl)acetamide
• CAS: 874499-36-2
• 化学式: C₁₁H₁₀N₂O₂
• 分子量: 202.213
• InChiKey: XGTBQMJWOMDGLR-UHFFFAOYSA-N

物化性质

• 熔点：
  280-282 °C
• 沸点：
  507.0±30.0 °C(Predicted)
• 密度：
  1.363±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(4-hydroxy-[6]quinolyl)-acetamide 在 盐酸 、 氨 、 三氯氧磷 、 苯酚 作用下， 生成 4,6-喹啉二胺
  参考文献：
  名称：

  Jensch, Justus Liebigs Annalen der Chemie, 1950, vol. 568, p. 73,79

  摘要：

  DOI：
• 作为产物：
  描述：

  6-氨基-4-羟基-2-喹啉羧酸 在 喹啉 、 铜 作用下， 生成 N-(4-hydroxy-[6]quinolyl)-acetamide
  参考文献：
  名称：

  Jensch, Justus Liebigs Annalen der Chemie, 1950, vol. 568, p. 73,79

  摘要：

  DOI：

文献信息

• [EN] COMPOSITION AND METHODS FOR INHIBITING MAMMALIAN STERILE 20-LIKE KINASE 1<br/>[FR] COMPOSITION ET MÉTHODES POUR INHIBER LA KINASE 1 STÉRILE DE MAMMIFÈRE DE TYPE 20
  申请人：CALIFORNIA INST BIOMEDICAL RES

  公开号：WO2016210345A1

  公开（公告）日：2016-12-29

  Disclosed herein are compounds, compositions, and methods of their use for the treatment of diabetes.

  本文披露了用于治疗糖尿病的化合物、组合物及其使用方法。
• Quaternary salts of pyrimidylaminoquinolines
  申请人：ICI LTD

  公开号：US02585905A1

  公开（公告）日：1952-02-19

  Mono- and di-quaternary salts of pyrimidylaminoquinolines, possessing trypanocidal activity and of the general formula Pq-NH-A, (wherein P represents a 2-, 4- (or 6-) amino-substituted pyrimidine nucleus which is attached to the -NH- linkage at another of the 2-, 4- (or 6-) positions and which may be further substituted in the remaining 2-, 4- (or 6-) position by an alkyl radical of not more than 5 carbon atoms or an amino group, A represents Q or Qq where Q is a quinoline nucleus which is substituted in the 2- or 4- position by an amino group and may be further substituted by an alkyl group of not more than 5 carbon atoms, and which bears the linking-NH- group in the 6-position, and the symbols q indicate that the preceding nuclei P and Q respectively are in the form of their quaternary salts), or tantomeric forms thereof, are manufactured by reacting a compound of the formula PqX (wherein X represents a halogen atom or a group -SR, R being a hydrocarbon radical, obtainable by the process of Specification 634,471) with a compound of the formula NH2A, or a salt thereof, or a substance which will give rise thereto under the reaction conditions (e.g. an acyl derivative thereof). The reaction may be effected by heating the reactants together, advantageously in a liquid medium and in the presence of an acid. In examples: (1) 2 - chloro - 4 - methyl - 6 - aminopyrimidine 3-methiodide is boiled with 4 : 6-diaminoquinaldine methochloride in dilute hydrochloric acid to produce 4-amino-6-(61-amino - 41 - methylpyrimidyl - 21 - amino) - quinaldine 1 : 31-dimethiodide; (2) 4-chloro-2-amino-6-methylpyrimidine 1-methiodide is boiled in water with 4 : 6-diaminoquinaldine methochloride hydrochloride, yielding 4-amino-6-(21-amino-61-methylpyrimidyl-41-amino) p -quinaldine 1 : 11-dimethiodide, or the tantomeric 4-amino-6-(21-imino-11 : 61-dimethyl-11 : 21-dihydropyrimidyl-41-amino)-quinaldine 1-methiodide hydriodide or 4-imino-1-methyl-6-(21-amino-61-methylpyrimidyl -41-amino)-1 : 4-dihydroquinaldine 11-methiodide hydriodide or 4-imino-1-methyl-6-(21-imino-11 : 61-dimethyldihydropyrimidyl-41-amino)-1 : 4-dihydroquinaldine dihydriodide; the product may be converted into the dimethochloride by treating an aqueous solution thereof with hydrochloric acid or sodium chloride, or into the dimethobromide by analogous treatment; (3) the pyrimidine reactant in (2) is replaced by 4-iodo-2-amino-6-methylpyrimidine 3-methiodide, producing the corresponding 1 : 31-dimethiodide, which may be converted with silver chloride into the dimethochloride and with sodium carbonate solution into 4-amino-6-(21-imino-31 : 61-dimethyl-2 : 3-dihydropyrimidyl-41-amino)-quinaldine 1-methiodide; (4) 4 : 6-diaminoquinaldine methochloride is heated with 2-amino-4-methylthio6-methylpyrimidine 1-methiodide to give the product of (2); (5) the quinaldine reactant in (3) is replaced by 4 : 6-diaminoquinaldine methiodide; (6) the pyrimidine reactant in (5) is replaced by 4-chloro-2 : 6-diaminopyrimidine 3-methiodide, and (7) by the corresponding 1-methiodide; (8) 4 : 6-diaminoquinoline methiodide is reacted as in (2); (9) the quinaldine reactant of (2) is replaced by 2 : 6-diaminolepidine methiodide; (10) 4-amino-6-acetylaminoquinaldine 1-metho-methylsulphate and 4-chloro-2-amino-6-methylpyrimidine 1-methomethylsulphate are reacted as in (1) and the product is treated with hydrochloric acid to give the dimethochloride of (2); (11) the pyrimidine reactant of (10) is replaced by the 1-methiodide; (12) 4 : 6-diaminoquinaldine and 4-chloro-2 : 6-diaminopyrimidine 3-methiodide are reacted as in (1) to produce 4-amino-6-(21 : 61-diaminopyrimidyl-41-amino)-quinaldine 31-methiodide hydriodide; (13) 4 : 6 - diaminoquinaldine ethiodide is reacted as in (2). Specification 634,531 also is referred to. 4 : 6-Diaminoquinaldinium salts.-The methochloride hydrochloride is obtainable by treating 4-amino-6-acetylaminoquinaldine with dimethyl sulphate in nitrobenzene and refluxing the product with aqueous hydrochloric acid. It may be converted into the methochloride by the action of sodium carbonate solution and into the methiodide by the action of a solution of sodium carbonate and excess of potassium iodide. The ethiodide is obtainable by treating 4-amino-6-acetylaminoquinaldine with diethyl sulphate in nitrobenzene, treating the product with sodium iodide solution, hydrolysing with hydrochloric acid and adding sodium carbonate and sodium iodide. 4 : 6-Diaminoquinoline methiodide is obtainable from ethyl 6-acetylamino-4-hydroxyquinoline-2-carboxylate by saponification, decarboxylation, treatment with phosphorous oxychloride and then with ammonia in the presence of phenol, quaternation of the resulting 4-amino-6-acetylaminoquinoline by means of dimethyl sulphate in nitrobenzene, hydrolysis with hydrochloric acid and treatment with sodium carbonate and sodium iodide. 2 : 6-Diaminolepidine methiodide is obtainable from 2-chloro-6-nitrolepidine by treatment with ammonia in the presence of phenol and acetamide, quaternation with dimethyl sulphate in nitrobenzene, treatment with excess of sodium chloride, reduction of the nitro group with iron and methanolic hydrochloric acid and treatment with sodium carbonate and sodium iodide.

  具有抗锥虫活性的嘧啶基氨基喹啉的单、双季铵盐，其一般式为Pq-NH-A（其中P代表2-、4-（或6-）氨基取代的嘧啶核，该核附着在另一个2-、4-（或6-）位置的-NH-连接处，并且在其余的2-、4-（或6-）位置上可能进一步取代为不超过5个碳原子的烷基或氨基，A代表Q或Qq，其中Q是一个喹啉核，在2-或4-位置上被氨基取代，并且可能进一步被不超过5个碳原子的烷基取代，其在6-位置带有连接-NH-基团，符号q表示前面的核P和Q分别以其季铵盐的形式存在，或其异构体，可以通过将公式PqX（其中X代表卤素原子或由规范634,471的过程获得的-SR基团，其中R是一个碳氢基团）与公式NH2A或其盐或在反应条件下将产生该物质的物质（例如，其酰基衍生物）反应制备。反应可以通过加热反应物一起进行，优选在液体介质中，在酸的存在下进行。在例子中：（1）2-氯-4-甲基-6-氨基嘧啶3-碘化物在稀盐酸中与4：6-二氨基喹啉甲基氯化物沸腾，产生4-氨基-6-（6-氨基-4-甲基嘧啶-2-氨基）-喹啉1：3-二碘化物；（2）4-氯-2-氨基-6-甲基嘧啶1-碘甲烷酸盐在水中与4：6-二氨基喹啉甲基氯化物盐酸盐沸腾，产生4-氨基-6-（2-氨基-6-甲基嘧啶-4-氨基）-喹啉1：1-二碘化物，或其异构体4-氨基-6-（2-亚氨基-1，1：6，1-二甲基-2，3-二氢嘧啶-4-氨基）-喹啉1-碘甲烷酸盐，或4-亚氨基-1-甲基-6-（2-氨基-6-甲基嘧啶-4-氨基）-1：4-二氢喹啉11-碘甲烷酸盐，或4-亚氨基-1-甲基-6-（2-亚氨基-1，1：6，1-二甲基嘧啶-4-氨基）-1：4-二氢喹啉二碘化物；可以通过用盐酸或氯化钠处理其水溶液将产物转化为二甲基氯化物或类似处理将其转化为二甲基溴化物；（3）（2）中的嘧啶反应物被4-碘-2-氨基-6-甲基嘧啶3-碘甲烷酸盐所取代，产生相应的1：3-二碘化物，该化合物可以与氯化银转化为二甲基氯化物，或与碳酸钠溶液转化为4-氨基-6-（2-亚氨基-3,1：6,1-二甲基嘧啶-4-氨基）-喹啉1-碘甲烷酸盐；（4）4：6-二氨基喹啉甲基氯化物与2-氨基-4-甲硫基-6-甲基嘧啶1-碘甲烷酸盐加热，产生（2）的产物；（5）（3）中的喹啉反应物被4：6-二氨基喹啉甲烷酸盐所取代；（6）（5）中的嘧啶反应物被4-氯-2：6-二氨基嘧啶3-碘甲烷酸盐所取代，（7）被相应的1-碘甲烷酸盐所取代；（8）4：6-二氨基喹啉甲烷酸盐如（2）中所述反应；（9）（2）中的喹啉反应物被2：6-二氨基乙二噻啶甲烷酸盐所取代；（10）4-氨基-6-乙酰氨基喹啉1-甲硫酸盐和4-氯-2-氨基-6-甲基嘧啶1-甲硫酸盐如（1）中所述反应，产物用盐酸处理后得到（2）的二甲基氯化物；（11）（10）中的嘧啶反应物被1-甲烷基碘化物所取代；（12）4：6-二氨基喹啉和4-氯-2：6-二氨基嘧啶3-碘甲烷酸盐如（1）中所述反应，产生4-氨基-6-（2：4-二氨基嘧啶-6,1-二氨基）-喹啉3-碘甲烷酸盐；（13）4：6-二氨基喹啉乙碘化物如（2）中所述反应。规范634,531也被提到。4：6-二氨基喹啉盐-甲基氯化物盐酸盐可以通过将4-氨基-6-乙酰氨基喹啉与硫酸二甲酯在硝基苯中处理，并将产物与水合盐酸回流处理得到。它可以通过钠碳酸溶液的作用转化为甲基氯化物，通过钠碘化物溶液和过量的碘化钾的作用转化为甲基碘化物。乙碘化物可以通过将4-氨基-6-乙酰氨基喹啉与硫酸二乙酯在硝基苯中处理，用碘化钠溶液处理产物，水解并加入碳酸钠和碘化钠得到。4：6-二氨基喹啉甲烷酸盐可以通过将乙基6-乙酰氨基-4-羟基喹啉-2-羧酸酯皂化、脱羧、用氯化亚磷酰处理，然后在苯酚存在下与氨一起处理，用硝基苯中的二甲基硫酸盐季铵化得到4-氨基-6-乙酰氨基喹啉，用盐酸水解并用碳酸钠和碘化钠处理得到。2：6-二氨基乙二噻啶甲烷酸盐可以通过用苯酚和乙酰胺处理2-氯-6-硝基乙二噻啶，用硝基苯中的二甲基硫酸盐季铵化，过量的氯化钠处理，铁和甲醇盐酸还原硝基基团，然后用碳酸钠和碘化钠处理得到。
• 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。
• Composition and methods for inhibiting mammalian sterile 20-like kinase 1
  申请人：The Scripps Research Institute

  公开号：US10774068B2

  公开（公告）日：2020-09-15

  Disclosed herein are compounds, compositions, and methods of their use for the treatment of diabetes.

  本文公开了用于治疗糖尿病的化合物、组合物及其使用方法。
• DE831697
  申请人：——

  公开号：——

  公开（公告）日：——