3-(bromomethyl)-6-phenylpyridazine | 1187451-22-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3-(bromomethyl)-6-phenylpyridazine
• CAS: 1187451-22-4
• 化学式: C₁₁H₉BrN₂
• 分子量: 249.11
• InChiKey: OEVNGVJNXOHGNE-UHFFFAOYSA-N

物化性质

• 沸点：
  414.5±33.0 °C(Predicted)
• 密度：
  1.459±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  双(叔丁氧羰基)胺 、 3-(bromomethyl)-6-phenylpyridazine 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以97%的产率得到3-[bis(tert-butoxycarbony)aminomethyl]-6-phenylpyridazine
  参考文献：
  名称：

  PYRIDYLAMINOACETIC ACID COMPOUND

  摘要：

  公开号：

  EP2264009B1
• 作为产物：
  描述：

  3-methyl-6-phenylpyridazine 在 N-溴代丁二酰亚胺(NBS) 、 过氧化苯甲酰 作用下， 以 四氯化碳 为溶剂， 以4%的产率得到3-(bromomethyl)-6-phenylpyridazine
  参考文献：
  名称：

  Cushing’s Syndrome: Development of Highly Potent and Selective CYP11B1 Inhibitors of the (Pyridylmethyl)pyridine Type

  摘要：

  Potent and selective CYP11B1 inhibitors could be promising therapeutics for the treatment of Cushing's syndrome. Optimization of Ref 1 (5-((1H-imidazol-1-yl)methyl)-2-phenylpyridine) led to compound 44 (5-((5-methylpyridin-3-yl)methyl)-2-phenylpyridine) with a 50-fold improved IC50 value of 2 nM toward human CYP11B1 and an enhanced inhibition of the rat enzyme (IC50 = 2440 nM) compared to Ref 1 (IC50 > 10000 nM). Furthermore, selectivities over CYP11B2, CYP17, and CYP19 were observed, as well as satisfying metabolic stability not only in human and rat plasma but also in liver S9 fraction. Investigation of cytotoxicity and inhibition of hepatic CYP2A6 and CYP3A4 showed that 44 fulfills first safety criteria and can be considered for further in vivo evaluation in rats.

  DOI：

  10.1021/jm400240r

文献信息

• [EN] SELECTIVE CYP11B1 INHIBITORS FOR THE TREATMENT OF CORTISOL DEPENDENT DISEASES<br/>[FR] INHIBITEURS SÉLECTIFS DE CYP11B1 POUR LE TRAITEMENT DE MALADIES DÉPENDANTES DU CORTISOL
  申请人：UNIV SAARLAND

  公开号：WO2012052540A1

  公开（公告）日：2012-04-26

  The present invention relates to compounds which selectively inhibit CYP11B1. Preferably, the compounds of the present invention do not substantially inhibit CYP11B2. Moreover, the compounds of the present invention do not substantially inhibit CYP17 and/or CYP19, either. Amongst other applications of the compounds of the present invention, they can be used for the treatment of Cushing's syndrome or metabolic disease.

  本发明涉及选择性抑制CYP11B1的化合物。优选，本发明的化合物不显著抑制CYP11B2。此外，本发明的化合物也不显著抑制CYP17和/或CYP19。在本发明的化合物的其他应用中，它们可用于治疗库欣综合症或代谢性疾病。
• MEDICAL COMPOSITION FOR TREATMENT OR PROPHYLAXIS OF GLAUCOMA
  申请人：Hagihara Masahiko

  公开号：US20120190852A1

  公开（公告）日：2012-07-26

  The present invention is to provide a medical composition for the treatment or prophylaxis of glaucoma which comprises a pyridylaminoacetic acid compound represented by the formula (1): wherein R 1 , R 2 and R 3 each independently represent a hydrogen atom or C 1 -C 6 alkyl group, Y represents a bicyclic heteroaromatic ring group which may be substituted by a group(s) selected from the group consisting of a halogen atom, C 1 -C 6 alkyl group, halogeno C 1 -C 6 alkyl group, C 1 -C 6 alkoxyl group, halogeno C 1 -C 6 alkoxyl group and C 1 -C 6 alkylthio group or a group -Q 1 -Q 2 wherein Q 1 represents an arylene group or 5- to 6-membered heteroarylene group, Q 2 represents an aromatic group or a 5- to 6-membered ring heterocyclic group each of which may be substituted by a group(s) selected from the group consisting of a halogen atom, hydroxyl group, C 1 -C 6 alkyl group, halogeno C 1 -C 6 alkyl group, C 1 -C 6 alkoxyl group and halogeno C 1 -C 6 alkoxyl group, Z represents an aromatic group or a 5- to 6-membered heteroaromatic ring group each of which may be substituted by a group(s) selected from the group consisting of a halogen atom, C 1 -C 6 alkyl group, halogeno C 1 -C 6 alkyl group, C 1 -C 6 alkoxyl group and halogeno C 1 -C 6 alkoxyl group, or a pharmaceutically acceptable salt thereof as an effective ingredient.

  本发明提供了一种用于治疗或预防青光眼的医用组合物，该组合物包括以下式子（1）所表示的吡啶基氨基乙酸化合物：其中，R1、R2和R3各自独立地表示氢原子或C1-C6烷基；Y表示一个双环杂芳基环基，该环基可以被选自卤素原子、C1-C6烷基、卤代C1-C6烷基、C1-C6烷氧基、卤代C1-C6烷氧基和C1-C6烷基硫基或-Q1-Q2基团所取代；其中，Q1表示芳烃基或5-至6-成员杂芳烃基，Q2表示芳香基或5-至6-成员环杂芳基，每个基团都可以被选自卤素原子、羟基、C1-C6烷基、卤代C1-C6烷基、C1-C6烷氧基和卤代C1-C6烷氧基的基团所取代；Z表示芳香基或5-至6-成员杂芳基环基，每个基团都可以被选自卤素原子、C1-C6烷基、卤代C1-C6烷基、C1-C6烷氧基和卤代C1-C6烷氧基的基团所取代，或其药学上可接受的盐作为有效成分。
• SELECTIVE CYP11B1 INHIBITORS FOR THE TREATMENT OF CORTISOL DEPENDENT DISEASES
  申请人：Hartmann Rolf

  公开号：US20140155407A1

  公开（公告）日：2014-06-05

  The present invention relates to compounds which selectively inhibit CYP11B1. Preferably, the compounds of the present invention do not substantially inhibit CYP11B2. Moreover, the compounds of the present invention do not substantially inhibit CYP17 and/or CYP19, either. Amongst other applications of the compounds of the present invention, they can be used for the treatment of Cushing's syndrome or metabolic disease.

  本发明涉及一种选择性抑制CYP11B1的化合物。优选地，本发明的化合物不会显著抑制CYP11B2。此外，本发明的化合物也不会显著抑制CYP17和/或CYP19。在本发明化合物的其他应用中，它们可用于治疗库欣综合征或代谢疾病。
• Medical composition for treatment or prophylaxis of glaucoma
  申请人：Hagihara Masahiko

  公开号：US08685986B2

  公开（公告）日：2014-04-01

  The present invention is to provide a medical composition for the treatment or prophylaxis of glaucoma which comprises a pyridylaminoacetic acid compound represented by the formula (1): wherein R1, R2, R3, Y, and Z are defined in the specification.

  本发明提供了一种医用组合物，用于治疗或预防青光眼，其包含一种由式（1）表示的吡啶基氨基乙酸化合物：其中R1、R2、R3、Y和Z在规范中有定义。
• Pyridylaminoacetic acid compound
  申请人：Iwamura Ryo

  公开号：US08648097B2

  公开（公告）日：2014-02-11

  The present invention provides a novel pyridylaminoacetic acid compound represented by the following formula (1): (wherein R1, R2, R3, Y and Z are as defined in the description and claims), or a pharmacologically acceptable salt thereof. The pyridylaminoacetic acid compound has EP2 agonistic action and is therefore useful as a therapeutic and/or prophylactic agent for respiratory diseases such as asthma or chronic obstructive pulmonary disease.

  本发明提供了一种新型吡啶基氨基乙酸化合物，其化学式如下（1）所示：（其中R1、R2、R3、Y和Z如说明书和权利要求所定义），或其药学上可接受的盐。该吡啶基氨基乙酸化合物具有EP2受体激动作用，因此可用作治疗和/或预防哮喘或慢性阻塞性肺疾病等呼吸系统疾病的药物。