N-(4-chloroquinolin-6-yl)acetamide | 352205-96-0

• 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-chloroquinolin-6-yl)acetamide
• CAS: 352205-96-0
• 化学式: C₁₁H₉ClN₂O
• 分子量: 220.658
• InChiKey: JVKLYDQQSVDOJP-UHFFFAOYSA-N

物化性质

• 熔点：
  223-224 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  442.7±25.0 °C(Predicted)
• 密度：
  1.363±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 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：
  42
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(4-chloroquinolin-6-yl)acetamide 在 盐酸 、 氨 、 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 、 三氯氧磷 作用下， 生成 N-(4-chloroquinolin-6-yl)acetamide
  参考文献：
  名称：

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

  摘要：

  DOI：
• 作为试剂：
  描述：

  4-氯-6-氨基喹啉 、 乙酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 在 二氯甲烷 、 氯化钠 、 N-(4-chloroquinolin-6-yl)acetamide 作用下， 以 水 为溶剂， 反应 16.0h， 以A to obtain the title compound N-(4-chloroquinolin-6-yl)acetamide 16b (80 mg的产率得到N-(4-chloroquinolin-6-yl)acetamide
  参考文献：
  名称：

  CYCLOALKYL ACID DERIVATIVE, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL APPLICATION THEREOF

  摘要：

  本发明涉及环烷基酸衍生物及其制备方法和药用应用。具体地，本发明涉及一种由通式（I）表示的环烷基酸衍生物及其医用盐、其制备方法以及将该环烷基酸衍生物和其医用盐作为URAT1抑制剂的应用，特别是作为治疗与异常尿酸水平相关的疾病的治疗剂。其中，通式（I）中取代基团的定义与说明书中的定义相同。

  公开号：

  US20160108035A1

文献信息

• 사이클로알킬산 유도체, 그의 제조 방법, 및 그의 약학적 용도
  申请人：SHANGHAI HENGRUI PHARMACEUTICAL CO., LTD. 샹하이 헨그루이 파마수티컬 컴퍼니 리미티드(520080332544)

  公开号：KR20160006207A

  公开（公告）日：2016-01-18

  본 발명은 사이클로알킬산 유도체, 그의 제조 방법 및 그의 약학적 용도에 관한 것이며, 특히 본 발명은 하기 화학식 I에 의해 나타내는 사이클로알킬산 유도체 및 그의 의학적 염, 그의 제조 방법, 및 URAT1 억제제로서 및 특히 이상 요산 수준과 관련된 질병에 대한 치료제로서 상기 사이클로알킬산 유도체 및 그의 의학적 염의 용도에 관한 것이며, 여기에서 화학식 I의 치환체 그룹들의 정의는 명세서에서의 정의와 같다. 화학식 I

  这是一段关于某种环丙基酸衍生物的专利描述，涉及其制备方法和药用用途，特别是涉及由化学式I表示的环丙基酸衍生物及其医药盐、制备方法，以及作为URAT1抑制剂和特别是用于治疗与高尿酸水平相关的疾病的药物的用途。在此，化学式I中的取代基团的定义与规范中的定义相同。 化学式I
• 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。
• [EN] CYCLOALKYL ACID DERIVATIVE, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL APPLICATION THEREOF<br/>[FR] DÉRIVÉ D'ACIDE CYCLOALKYLIQUE, PROCÉDÉ DE PRÉPARATION ET UTILISATION PHARMACEUTIQUE DE CELUI-CI
  申请人：SHANGHAI HENGRUI PHARM CO LTD

  公开号：WO2014183555A1

  公开（公告）日：2014-11-20

  本发明涉及环烷基甲酸类衍生物、其制备方法及其在医药上的应用。具体而言，本发明涉及一种通式（I）所示环烷基甲酸类衍生物及其可药用盐，其制备方法以及它们作为URAT1抑制剂，特别是作为与尿酸水平异常相关的病症的治疗剂的用途，其中通式（I）中的各取代基的定义与说明书中的定义相同。
• Chemical compounds
  申请人：——

  公开号：US20030105129A1

  公开（公告）日：2003-06-05

  A compound of formula (I) 1 or a salt, ester, amide or prodrug thereof; R 5 is an optionally substituted 6 -membered aromatic ring containing at least one nitrogen atom, and R 1 , R 2 , R 3 , R 4 are independently selected from halogeno, cyano, nitro, C 1-3 alkysulphonyl, —N(OH)R 7 — (wherein R 7 is hydrogen, or C 1-3 alkyl), or R 9 X 1 — (wherein X 1 represents a direct bond, —O—, —CH 2 —, —OC(O)—, —C(O)—, —S—, —SO—, —SO 2 —, —NR 10 C(O)—, —C(O)NR 11 —, —SO 2 NR 12 —, —NR 13 SO 2 — or —NR 14 — (wherein R 10 , R 11 , R 12 , R 13 and R 14 each independently represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl), and R 9 is hydrogen, optionally substituted hydrocarbyl, optionally substituted heterocyclyl or optionally substituted alkoxy); provided that at least one of R 2 or R 3 is other than hydrogen. These compounds are inhibitors of aurora 2 kinase. Thus they, and pharmaceutical compositions containing them, are useful in methods of treatment of proliferative disease such as cancer and in particular cancers such as colorectal or breast cancer where aurora 2 is upregulated.

  化合物的公式（I）1或其盐、酯、酰胺或前药；其中R5是一个含有至少一个氮原子的可选取代的6成员芳香环，而R1、R2、R3、R4是独立选择的卤素基、氰基、硝基、C1-3烷基磺酰基、-N（OH）R7-（其中R7是氢或C1-3烷基）或R9X1-（其中X1表示直接键，-O-，-CH2-，-OC（O）-，-C（O）-，-S-，-SO-，-SO2-，-NR10C（O）-，-C（O）NR11-，-SO2NR12-，-NR13SO2-或-NR14-（其中R10、R11、R12、R13和R14各自独立地表示氢、C1-3烷基或C1-3烷氧基C2-3烷基），而R9是氢、可选取代的烃基、可选取代的杂环基或可选取代的烷氧基；前提是R2或R3至少有一个不是氢。这些化合物是aurora 2激酶的抑制剂。因此，它们及包含它们的药物组成物在治疗增殖性疾病如癌症以及特别是aurora 2上调的结直肠癌或乳腺癌的方法中是有用的。
• Discovery of potent and orally bioavailable inhibitors of Human Uric Acid Transporter 1 (hURAT1) and binding mode prediction using homology model
  作者：Jianbiao Peng、Qiyue Hu、Chunyan Gu、Bonian Liu、Fangfang Jin、Jijun Yuan、Jun Feng、Lei Zhang、Jiong Lan、Qing Dong、Guoqing Cao

  DOI：10.1016/j.bmcl.2015.12.040

  日期：2016.1

  This Letter describes the discovery of a series of potent inhibitors of Human Uric Acid Transporter 1 (hURAT1). Lead generation and optimization via 3D pharmacophore analysis resulted in compound 41. With an IC50 of 33.7 nM, 41 also demonstrated good oral bioavailability in rat (74.8%) and displayed a consistent PK profile across all species tested (rat, dog and monkey). (C) 2015 Published by Elsevier Ltd.