3-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridine | 1357142-80-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 3-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridine
• 英文别名: 3-Bromo-1-methyl-1H-pyrrolo[3,2-b]pyridine；3-bromo-1-methylpyrrolo[3,2-b]pyridine
• CAS: 1357142-80-3
• 化学式: C₈H₇BrN₂
• 分子量: 211.061
• InChiKey: SFABSAOTNYQZIU-UHFFFAOYSA-N

物化性质

• 沸点：
  323.5±22.0 °C(Predicted)
• 密度：
  1.60±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridine 在 正丁基锂 、 水 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.83h， 生成 (R)-8-chloro-4-((1-(1-methyl-1H-pyrrolo[3,2-b]pyridine-3-carbonyl)piperidin-4-yl)methyl)-3-(pyridin-2-ylmethyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione
  参考文献：
  名称：

  [EN] NOVEL CLOSTRIDIUM DIFFICILE TOXIN INHIBITORS
  [FR] NOUVEAUX INHIBITEURS DE TOXINE DE CLOSTRIDIUM DIFFICILE

  摘要：

  本发明涉及式(I)的苯二氮卓衍生物化合物，或其药学上可接受的盐。目前的苯二氮卓衍生物在治疗人类的克罗斯特氏梭菌感染中是有用的抑制剂。本发明提供了一种含有式(I)的苯二氮卓化合物的药物组合物，以及制备该药物组合物的方法和使用该药物组合物治疗感染克罗斯特氏梭菌的患者的方法。本发明的化合物可以与额外的抗生素或抗毒素抗体药物结合使用。

  公开号：

  WO2017214359A1
• 作为产物：
  描述：

  4-氮杂吲哚 在 N-溴代丁二酰亚胺(NBS) 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 2.25h， 生成 3-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridine
  参考文献：
  名称：

  设计，合成和药理学评价新型多环杂芳基醚作为PDE10A抑制剂：第二部分

  摘要：

  我们报告设计和合成新型的吡咯并[3,2- b ]喹啉含有杂芳烃醚作为PDE10A抑制剂，具有优异的效能，选择性和代谢稳定性。该主要系列的进一步优化导致鉴定出1-甲基-3-（4-{[3-（吡啶-4-基）吡嗪-2-基]氧基}苯基）-1 H-吡咯并[3,2 - b ]吡啶13A具有良好hPDE10A效力（IC 50：6.3 nM），对其他相关PDE的优异选择性和理想的理化性质。在啮齿动物中口服给药后，该化合物表现出较高的外周水平和足够的大脑水平。该化合物在与精神疾病，特别是精神分裂症有关的多种临床前动物模型中也显示出优异的功效。

  DOI：

  10.1016/j.bmcl.2014.06.028

文献信息

• [EN] FUSED HETEROCYCLIC COMPOUNDS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES CONDENSÉS
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2012018909A1

  公开（公告）日：2012-02-09

  The present invention provides a compound which has the effect of PDE 10A inhibition, and which is useful as a medicament for preventing or treating schizophrenia or so on. A compound represented by the formula (1'): wherein, Ring A' represents an optionally substituted pyridine ring, an optionally substituted pyridazine ring, a pyrimidine ring, or 10 a pyrazine ring, R1' represents (1) wherein, R1a' represents an optionally substituted phenyl group, or an optionally substituted 5- to 10-membered heterocyclic group, Ring B2 represents a bond, -S-, -0-, -CO-, an optionally substituted methylene group, or -NRa'- (Ra' represents a hydrogen atom, or an optionally substituted C1-6 alkyl group), and Ring B1' represents an optionally further substituted 6- to 10- membered aromatic hydrocarbon ring, or an optionally further substituted 5- to 10-membered aromatic heterocyclic ring, or alternatively, L' and R1a' may be taken together to form an optionally substituted bicyclic or tricyclic fused heterocyclic group, or (2), wherein, R1b' represents an optionally substituted phenyl group, or an optionally substituted 5- to 10-membered heterocyclic group, Ring B2' represents an optionally substituted benzene ring, an optionally substituted pyridine ring, an optionally substituted pyrimidine ring, an optionally substituted pyrazine ring, or an optionally substituted pyridazine ring, Ring D' represents an optionally further substituted 5- or 6- membered ring, R2' represents a hydrogen atom, or a substituent, X' represents =N- or =CRb'- (Rb' represents a hydrogen atom, or a substituent), _ _ _ _ _ represents that Rb' and R2' may form, taken together with the carbon atom and the nitrogen atom to which they are each adjacent, an optionally substituted 5- to 7-membered ring when.X' is =CRb'-, or a salt thereof.

  本发明提供了一种具有PDE 10A抑制作用的化合物，可用作预防或治疗精神分裂症等疾病的药物。化合物的结构如下（1'）：其中，环A'代表可选择取代的吡啶环、可选择取代的吡啉环、嘧啶环或吡嗪环，R1'代表（1）其中，R1a'代表可选择取代的苯基或可选择取代的5-至10-成员杂环基，环B2代表键、-S-、-O-、-CO-、可选择取代的亚甲基基团或-NRa'-（Ra'代表氢原子或可选择取代的C1-6烷基基团），环B1'代表可选择进一步取代的6-至10-成员芳香碳氢环、或可选择进一步取代的5-至10-成员芳香杂环环，或者，L'和R1a'可以结合形成可选择取代的双环或三环融合杂环基，或（2）其中，R1b'代表可选择取代的苯基或可选择取代的5-至10-成员杂环基，环B2'代表可选择取代的苯环、可选择取代的吡啶环、可选择取代的嘧啶环、可选择取代的吡嗪环或可选择取代的吡啉环，环D'代表可选择进一步取代的5-或6-成员环，R2'代表氢原子或取代基，X'代表=N-或=CRb'-（Rb'代表氢原子或取代基），_ _ _ _ _代表Rb'和R2'可能形成，与它们各自相邻的碳原子和氮原子一起，当X'为=CRb'-时，形成可选择取代的5-至7-成员环，或其盐。
• FUSED HETEROCYCLIC COMPOUNDS
  申请人：Raker Joseph

  公开号：US20130172292A1

  公开（公告）日：2013-07-04

  The present invention provides a compound which has the effect of PDE 10A inhibition, and which is useful as a medicament for preventing or treating schizophrenia or so on. A compound represented by the formula (1′): wherein, Ring A′ represents an optionally substituted pyridine ring, an optionally substituted pyridazine ring, a pyrimidine ring, or 10 a pyrazine ring, R1′ represents (1) wherein, R 1a′ represents an optionally substituted phenyl group, or an optionally substituted 5- to 10-membered heterocyclic group, Ring B2 represents a bond, —S—, -0-, —CO—, an optionally substituted methylene group, or —NR a′ -(R a′ represents a hydrogen atom, or an optionally substituted C 1-6 alkyl group), and Ring B 1′ represents an optionally further substituted 6- to 10-membered aromatic hydrocarbon ring, or an optionally further substituted 5- to 10-membered aromatic heterocyclic ring, or alternatively, L′ and R 1a′ may be taken together to form an optionally substituted bicyclic or tricyclic fused heterocyclic group, or (2), wherein, R 1b′ represents an optionally substituted phenyl group, or an optionally substituted 5- to 10-membered heterocyclic group, Ring B 2′ represents an optionally substituted benzene ring, an optionally substituted pyridine ring, an optionally substituted pyrimidine ring, an optionally substituted pyrazine ring, or an optionally substituted pyridazine ring, Ring D′ represents an optionally further substituted 5- or 6-membered ring, R 2′ represents a hydrogen atom, or a substituent, X′ represents ═N— or ═CR b′ —(R b′ represents a hydrogen atom, or a substituent), - - - - - represents that R b′ and R 2′ may form, taken together with the carbon atom and the nitrogen atom to which they are each adjacent, an optionally substituted 5- to 7-membered ring when.X′ is ═CR b′ , or a salt thereof.

  本发明提供一种具有PDE 10A抑制作用的化合物，可用作预防或治疗精神分裂症等药物。化合物表示为公式（1'）：其中，环A'表示可选取取代的吡啶环、可选取取代的吡嗪环、嘧啶环或吡嗪环，R1'表示（1）其中，R1a'表示可选取取代的苯基或可选取取代的5-至10-成员杂环基，环B2表示键、-S-、-O-、可选取取代的亚甲基基或-NRa'（Ra'表示氢原子或可选取取代的C1-6烷基基），环B1'表示可选进一步取代的6-至10-成员芳香烃环或可选进一步取代的5-至10-成员芳香杂环环，或者，L'和R1a'可取代成为可选取代的双环或三环融合杂环基，或（2），其中，R1b'表示可选取取代的苯基或可选取取代的5-至10-成员杂环基，环B2'表示可选取取代的苯环、可选取取代的吡啶环、可选取取代的嘧啶环、可选取取代的吡嗪环或可选取取代的吡嗪环，环D'表示可选进一步取代的5-或6-成员环，R2'表示氢原子或取代基，X'表示═N-或═CRb'-（Rb'表示氢原子或取代基），- - - - - 表示当X'为═CRb'时，Rb'和R2'可与它们各自相邻的碳原子和氮原子一起形成可选取代的5-至7-成员环，或其盐。
• Fused heterocyclic compounds
  申请人：Raker Joseph

  公开号：US09029536B2

  公开（公告）日：2015-05-12

  The present invention provides a compound which has the effect of PDE 10A inhibition, and which is useful as a medicament for preventing or treating schizophrenia or so on. A compound represented by the formula (1′): wherein, Ring A′ represents an optionally substituted pyridine ring, an optionally substituted pyridazine ring, a pyrimidine ring, or 10 a pyrazine ring, R1′ represents (1) wherein, R1a′ represents an optionally substituted phenyl group, or an optionally substituted 5- to 10-membered heterocyclic group, Ring B2 represents a bond, —S—, -0-, —CO—, an optionally substituted methylene group, or —NRa′— (Ra′ represents a hydrogen atom, or an optionally substituted C1-6 alkyl group), and Ring B1′ represents an optionally further substituted 6- to 10-membered aromatic hydrocarbon ring, or an optionally further substituted 5- to 10-membered aromatic heterocyclic ring, or alternatively, L′ and R1a′ may be taken together to form an optionally substituted bicyclic or tricyclic fused heterocyclic group, or (2), wherein, R1b′ represents an optionally substituted phenyl group, or an optionally substituted 5- to 10-membered heterocyclic group, Ring B2′ represents an optionally substituted benzene ring, an optionally substituted pyridine ring, an optionally substituted pyrimidine ring, an optionally substituted pyrazine ring, or an optionally substituted pyridazine ring, Ring D′ represents an optionally further substituted 5- or 6-membered ring, R2′ represents a hydrogen atom, or a substituent, X′ represents ═N— or ═CRb′—(Rb′ represents a hydrogen atom, or a substituent), - - - - - represents that Rb′ and R2′ may form, taken together with the carbon atom and the nitrogen atom to which they are each adjacent, an optionally substituted 5- to 7-membered ring when.X′ is ═CRb′, or a salt thereof.

  本发明提供了一种具有PDE 10A抑制作用的化合物，可用作预防或治疗精神分裂症等药物。化合物的结构式为（1'）：其中，环A'表示可选取取代的吡啶环、可选取取代的吡嗪环、嘧啶环或吡嗪环，R1'表示（1），其中R1a'表示可选取取代的苯基或可选取取代的5-至10-成员杂环基，环B2表示键、-S-、-O-、可选取取代的亚甲基基或-NRa'-(Ra'表示氢原子或可选取取代的C1-6烷基基)，环B1'表示可选取进一步取代的6-至10-成员芳香碳环或可选取进一步取代的5-至10-成员芳香杂环，或者，L'和R1a'可取代成为可选取代的双环或三环融合杂环基，或（2），其中R1b'表示可选取取代的苯基或可选取取代的5-至10-成员杂环基，环B2'表示可选取取代的苯环、可选取取代的吡啶环、可选取取代的嘧啶环、可选取取代的吡嗪环或可选取取代的吡嗪嗪环，环D'表示可选进一步取代的5-或6-成员环，R2'表示氢原子或取代基，X'表示═N-或═CRb'-（Rb'表示氢原子或取代基），- - - - - 表示当X'为═CRb'时，Rb'和R2'可以与它们各自相邻的碳原子和氮原子一起形成可选取代的5-至7-成员环，或其盐。
• 2-arylamino pyridine, pyrimidine or triazine derivatives, preparation method and use thereof
  申请人：Wuxi Shuangliang Biotechnology Co., Ltd.

  公开号：US10377747B2

  公开（公告）日：2019-08-13

  The present disclosure relates to 2-arylamino pyridine, pyrimidine, or triazine derivatives, and the preparation method and use thereof. The 2-arylamino pyridine, pyrimidine, or triazine derivatives may act on certain mutated forms of epidermal growth factor receptor, for example the L858R activating mutant, the delE746_A750 mutant, the Exonl9 deletion activating mutant, and the T790M resistance mutant, so as to be used for treatment and prevention of diseases and medical conditions. The 2-arylamino pyridine, pyrimidine, or triazine derivatives may be used for treatment and prevention of cancer. The present disclosure also relates to a pharmaceutical composition comprising 2-arylamino pyridine, pyrimidine, or triazine derivatives, intermediates useful in the manufacture of 2-arylamino pyridine, pyrimidine, or triazine derivatives, and to methods of treatment of diseases mediated by various different forms of EGFR using 2-arylamino pyridine, pyrimidine, or triazine derivatives.

  本公开涉及 2-芳基氨基吡啶、嘧啶或三嗪衍生物及其制备方法和用途。2-芳基氨基吡啶、嘧啶或三嗪衍生物可作用于表皮生长因子受体的某些突变形式，例如 L858R 激活突变体、delE746_A750 突变体、Exonl9 缺失激活突变体和 T790M 抗性突变体，从而可用于治疗和预防疾病和病症。2-芳基氨基吡啶、嘧啶或三嗪衍生物可用于治疗和预防癌症。本公开还涉及包含 2-芳基氨基吡啶、嘧啶或三嗪衍生物的药物组合物，用于制造 2-芳基氨基吡啶、嘧啶或三嗪衍生物的中间体，以及使用 2-芳基氨基吡啶、嘧啶或三嗪衍生物治疗由各种不同形式的表皮生长因子受体介导的疾病的方法。
• Clostridium difficile toxin inhibitors
  申请人：Venenum Biodesign, LLC

  公开号：US10669242B2

  公开（公告）日：2020-06-02

  The present invention relates to benzodiazepine derivative compounds of formula (I), or pharmaceutically acceptable salts thereof. The present benzodiazepine compounds are useful Clostridium difficile inhibitors in the treatment of Clostridium difficile infection in humans. The present invention provides a pharmaceutical composition containing benzodiazepine compounds of formula (I) and a method of making as well as a method of using the same in treating patients infected with Clostridium difficile infection by administering the same. The compounds of the present invention may be used in combination with additional antibiotics or anti-toxin antibody drugs.

  本发明涉及式（I）的苯二氮杂卓衍生物化合物或其药学上可接受的盐类。本发明的苯二氮杂卓化合物是治疗人类艰难梭菌感染的有用的艰难梭菌抑制剂。本发明提供了一种含有式（I）苯并二氮杂卓化合物的药物组合物及其制造方法，以及通过给药治疗感染艰难梭菌的患者的方法。本发明的化合物可与其他抗生素或抗毒素抗体药物联合使用。