N-去甲基化贝达喹啉 | 861709-47-9

• 物质功能分类: 医药中间体 - 杂环化合物 - 喹啉类化合物
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 中文名称: N-去甲基化贝达喹啉
• 英文名称: N-Monodesmethyl bedaquiline
• 英文别名: (1R,2S)-1-(6-bromo-2-methoxyquinolin-3-yl)-4-(methylamino)-2-naphthalen-1-yl-1-phenylbutan-2-ol
• CAS: 861709-47-9
• 化学式: C₃₁H₂₉BrN₂O₂
• 分子量: 541.487
• InChiKey: GOBOQBZOZDRXCQ-BVRKHOPBSA-N

物化性质

• 沸点：
  706.5±60.0 °C(Predicted)
• 密度：
  1.336±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  54.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-desmethyl bedaquiline 生成 (1S,2R)-1-(6-bromo-2-methoxyquinolin-3-yl)-4-(methylamino)-2-naphthalen-1-yl-1-phenylbutan-2-ol 、 N-去甲基化贝达喹啉
  参考文献：
  名称：

  [EN] SUBSTITUTED QUINOLINES AND THEIR USE AS MYCOBACTERIAL INHIBITORS
  [FR] QUINOLINES SUBSTITUEES ET LEUR UTILISATION COMME INHIBITEURS MYCOBACTERIENS

  摘要：

  本发明涉及根据一般式(Ia)或一般式(Ib)的新型取代喹啉衍生物，其盐、季铵盐、立体化学异构体形式、互变异构体形式和其N-氧化物形式，其中R1为氢、卤素、卤代烷基、氰基、羟基、Ar、Het、烷基、烷氧基、硫代烷基、烷氧基烷基、硫代烷基烷基、Ar-烷基或二(Ar)烷基；p为1、2、3或4；R2为氢、羟基、硫代基、烷氧基、烷氧基烷氧基、硫代烷基、单烷基或双(烷基)氨基或具有式(Ic)的基团；R3为烷基、Ar、Ar-烷基、Het或Het-烷基；R4为氢、烷基或苄基；R5为氢、卤素、卤代烷基、羟基、Ar、烷基、烷氧基、硫代烷基、烷氧基烷基、硫代烷基烷基、Ar-烷基或二(Ar)烷基；或两个邻R5基团可一起与它们所连接的苯环一起形成一个萘基；r为1、2、3、4或5；R6为氢、烷基、Ar或Het；R7为氢或烷基；R8为氧化物；或R7和R8一起形成基团-CH=CH-N=；Z为CH2或C(=O)。所述化合物可用于治疗结核分枝杆菌病等疾病，特别是由致病性分枝杆菌引起的疾病，如结核分枝杆菌、牛结核分枝杆菌、埃氏分枝杆菌、烟瘿分枝杆菌和海洋分枝杆菌。还声明了含有本发明化合物的药物组合物，所述化合物或组合物用于制造治疗结核分枝杆菌病的药物以及制备所述化合物的方法。

  公开号：

  WO2005070924A1

文献信息

• Novel mycobacterial inhibitors
  申请人：Guillemont Emile, Georges Jerome

  公开号：US20070082895A1

  公开（公告）日：2007-04-12

  The present invention relates to novel substituted quinoline derivatives according to the general formula (Ia) or the general formula (Ib) salts, quaternary amines, stereochemically isomeric forms, tautomeric forms and N-oxide forms thereof, wherein R 1 is hydrogen, halo, haloalkyl, cyano, hydroxy, Ar, Het, alkyl, alkyloxy, alkylthio, alkyloxyalkyl, alkylthioalkyl, Ar-alkyl or di(Ar)alkyl; p is 1, 2, 3 or 4; R 2 is hydrogen, hydroxy, thio, alkyloxy, alkyloxyalkyloxy, alkylthio, mono or di(alkyl)amino or a radical of formula R 3 is alkyl, Ar, Ar-alkyl, Het or Het-alkyl; R 4 is hydrogen, alkyl or benzyl; R 5 is hydrogen, halo, haloalkyl, hydroxy, Ar, alkyl, alkyloxy, alkylthio, alkyloxyalkyl, alkylthioalkyl, Ar-alkyl or di(Ar)alkyl; or two vicinal R 5 radicals may be taken together to form together with the phenyl ring to which they are attached a naphthyl; r is 1, 2, 3, 4 or 5; R 6 is hydrogen, alkyl, Ar or Het; R 7 is hydrogen or alkyl; R 8 is oxo; or R 7 and R 8 taken together form the radical CH═CH—N═; Z is CH 2 or C(═O). The claimed compounds are useful for the treatment of mycobacterial diseases, particularly those diseases caused by pathogenic mycobacteria such as M. tuberculosis, M. bovis, M. avium, M. smegmatis and M. marinum. Also claimed is a pharmaceutical composition containing a compound of the present invention, the use of the claimed compounds or compositions for the manufacture of a medicament for the treatment of mycobacterial diseases and a process for preparing the claimed compounds.
• [EN] SUBSTITUTED QUINOLINES AND THEIR USE AS MYCOBACTERIAL INHIBITORS<br/>[FR] QUINOLINES SUBSTITUEES ET LEUR UTILISATION COMME INHIBITEURS MYCOBACTERIENS
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2005070924A1

  公开（公告）日：2005-08-04

  The present invention relates to novel substituted quinoline derivatives according to the general formula (Ia) or the general formula (Ib) salts, quaternary amines, stereochemically isomeric forms, tautomeric forms and N­-oxide forms thereof, wherein R1 is hydrogen, halo, haloalkyl, cyano, hydroxy, Ar, Het, alkyl, alkyloxy, alkylthio, alkyloxyalkyl, alkylthioalkyl, Ar-alkyl or di(Ar)alkyl ; p is 1, 2, 3 or 4 ; R2 is hydrogen, hydroxy, thio, alkyloxy, alkyloxyalkyloxy, alkylthio, mono or di(alkyl)amino or a radical of formula (Ic); R3 is alkyl, Ar, Ar-alkyl, Het or Het-alkyl; R4 is hydrogen, alkyl or benzyl; R5 is hydrogen, halo, haloalkyl, hydroxy, Ar, alkyl, alkyloxy, alkylthio, alkyloxyalkyl, alkylthioalkyl, Ar-alkyl or di(Ar)alkyl ; or two vicinal R5 radicals may be taken together to form together with the phenyl ring to which they are attached a naphthyl; r is 1, 2, 3, 4 or 5 ; R6 is hydrogen, alkyl, Ar or Het R7 is hydrogen or alkyl; R8 is oxo ; or R7 and R8 taken together form the radical - CH=CH-N=; Z is CH2 or C(=O). The claimed compounds are useful for the treatment of mycobacterial diseases, particularly those diseases caused by pathogenic mycobacteria such as M. tuberculosis, M. bovis, M. avium, M. smegmatis and M. marinum. Also claimed is a pharmaceutical composition containing a compound of the present invention, the use of the claimed compounds or compositions for the manufacture of a medicament for the treatment of mycobacterial diseases and a process for preparing the claimed compounds.

  本发明涉及根据一般式(Ia)或一般式(Ib)的新型取代喹啉衍生物，其盐、季铵盐、立体化学异构体形式、互变异构体形式和其N-氧化物形式，其中R1为氢、卤素、卤代烷基、氰基、羟基、Ar、Het、烷基、烷氧基、硫代烷基、烷氧基烷基、硫代烷基烷基、Ar-烷基或二(Ar)烷基；p为1、2、3或4；R2为氢、羟基、硫代基、烷氧基、烷氧基烷氧基、硫代烷基、单烷基或双(烷基)氨基或具有式(Ic)的基团；R3为烷基、Ar、Ar-烷基、Het或Het-烷基；R4为氢、烷基或苄基；R5为氢、卤素、卤代烷基、羟基、Ar、烷基、烷氧基、硫代烷基、烷氧基烷基、硫代烷基烷基、Ar-烷基或二(Ar)烷基；或两个邻R5基团可一起与它们所连接的苯环一起形成一个萘基；r为1、2、3、4或5；R6为氢、烷基、Ar或Het；R7为氢或烷基；R8为氧化物；或R7和R8一起形成基团-CH=CH-N=；Z为CH2或C(=O)。所述化合物可用于治疗结核分枝杆菌病等疾病，特别是由致病性分枝杆菌引起的疾病，如结核分枝杆菌、牛结核分枝杆菌、埃氏分枝杆菌、烟瘿分枝杆菌和海洋分枝杆菌。还声明了含有本发明化合物的药物组合物，所述化合物或组合物用于制造治疗结核分枝杆菌病的药物以及制备所述化合物的方法。