N-(3-((4aS,5R,7aS)-2-amino-5-methyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-7a-yl)-4-fluorophenyl)-5-(difluoromethyl)pyrazine-2-carboxamide | 1388651-30-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3-((4aS,5R,7aS)-2-amino-5-methyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-7a-yl)-4-fluorophenyl)-5-(difluoromethyl)pyrazine-2-carboxamide
• 英文别名: N-[3-((4aS,5R,7aS)-2-amino-5-methyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-7a-yl)-4-fluorophenyl]-5-difluoromethylpyrazine-2-carboxamide；elenbecestat；E-2609；N-[3-[(4aS,5R,7aS)-2-amino-5-methyl-4,4a,5,7-tetrahydrofuro[3,4-d][1,3]thiazin-7a-yl]-4-fluorophenyl]-5-(difluoromethyl)pyrazine-2-carboxamide
• CAS: 1388651-30-6
• 化学式: C₁₉H₁₈F₃N₅O₂S
• 分子量: 437.445
• InChiKey: AACUJFVOHGRMTR-DPXNYUHVSA-N

物化性质

• 密度：
  1.61±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：≥ 250 mg/mL（571.51 mM）

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  9

制备方法与用途

生物活性方面，Elenbecestat（E2609）是一种新型的BACE1抑制剂，单次给药后能够长效降低血浆中β-淀粉样蛋白的水平。

反应信息

• 作为产物：
  描述：

  (±)-tert-butyl 2-(but-3-en-2-yloxy)acetate 在 吡啶 、 盐酸 、 正丁基锂 、 甲酸 、 氯化亚砜 、 三氟甲磺酸酐 、 硫酸 、 盐酸羟胺 、 硝酸 、 sodium acetate 、 铁粉 、 potassium carbonate 、 氯化铵 、 溶剂黄146 、 对苯二酚 、 N,N'-羰基二咪唑 、 三氟乙酸 、 sodium hydroxide 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 5,5-dimethyl-1,3-cyclohexadiene 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 反应 29.75h， 生成 N-(3-((4aS,5R,7aS)-2-amino-5-methyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-7a-yl)-4-fluorophenyl)-5-(difluoromethyl)pyrazine-2-carboxamide
  参考文献：
  名称：

  JP2016121177A5

  摘要：

  公开号：

  JP2016121177A5

文献信息

• FUSED AMINODIHYDROTHIAZINE DERIVATIVES
  申请人：SUZUKI Yuichi

  公开号：US20090209755A1

  公开（公告）日：2009-08-20

  A compound represented by the general formula: or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein Ring A is a C 6-14 aryl group or the like, L is —NR e CO— or the like (wherein R e is a hydrogen atom or the like), Ring B is a C 6-14 aryl group or the like, X is a C 1-3 alkylene group or the like, Y is a single bond or the like, Z is a C 1-3 alkylene group or the like, R 1 and R 2 are each independently a hydrogen atom or the like, and R 3 , R 4 , R 5 and R 6 are independently a hydrogen atom, a halogen atom or the like, has an Aβ production inhibitory effect or a BACE1 inhibitory effect and is useful as a prophylactic or therapeutic agent for a neurodegenerative disease caused by Aβ and typified by Alzheimer-type dementia.

  一个由以下通用公式表示的化合物：或其药用可接受的盐或其溶剂化物，其中环A是C6-14芳基或类似物，L是—NReCO—或类似物（其中Re是氢原子或类似物），环B是C6-14芳基或类似物，X是C1-3烷基烯基或类似物，Y是单键或类似物，Z是C1-3烷基烯基或类似物，R1和R2各自独立地是氢原子或类似物，而R3、R4、R5和R6各自独立地是氢原子、卤原子或类似物，具有Aβ产生抑制作用或BACE1抑制作用，并且可用作由Aβ引起的以阿尔茨海默型痴呆为特征的神经退行性疾病的预防或治疗剂。
• Fused aminodihydrothiazine derivatives
  申请人：Eisai R&D Management Co., Ltd.

  公开号：US08946211B2

  公开（公告）日：2015-02-03

  A compound represented by the general formula: or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein Ring A is a C6-14 aryl group or the like, L is —NReCO— or the like (wherein Re is a hydrogen atom or the like), Ring B is a C6-14 aryl group or the like, X is a C1-3 alkylene group or the like, Y is a single bond or the like, Z is a C1-3 alkylene group or the like, R1 and R2 are each independently a hydrogen atom or the like, and R3, R4, R5 and R6 are independently a hydrogen atom, a halogen atom or the like, has an Aβ production inhibitory effect or a BACE1 inhibitory effect and is useful as a prophylactic or therapeutic agent for a neurodegenerative disease caused by Aβ and typified by Alzheimer-type dementia.

  一种化合物，其通式为：或其药学上可接受的盐或溶剂，其中环A是C6-14芳基或类似物，L是-NReCO-或类似物（其中Re是氢原子或类似物），环B是C6-14芳基或类似物，X是C1-3烷基或类似物，Y是单键或类似物，Z是C1-3烷基或类似物，R1和R2各自独立地是氢原子或类似物，而R3、R4、R5和R6则各自独立地是氢原子、卤素原子或类似物。该化合物具有Aβ生成抑制效应或BACE1抑制效应，并可用作预防或治疗由Aβ引起的神经退行性疾病，如阿尔茨海默型痴呆的药物。
• METHODS AND COMPOUNDS USEFUL IN THE SYNTHESIS OF FUSED AMINODIHYDROTHIAZINE DERIVATIVES
  申请人：Mitasev Branko

  公开号：US20120190848A1

  公开（公告）日：2012-07-26

  Provided are compounds and methods useful for the preparation of compounds useful as inhibitors of beta-site amyloid precursor protein (APP)-cleaving enzyme.

  提供了化合物和方法，用于制备用作beta-位点淀粉样前体蛋白(APP)裂解酶抑制剂的化合物。
• METHODS AND COMPOUNDS USEFUL IN THE SYNTHESIS OF FUSED AMINODIHYDROTHIAZINE DERIVATIVES
  申请人：Eisai R&D Management Co., Ltd.

  公开号：US20140309429A1

  公开（公告）日：2014-10-16

  Provided are compounds and methods useful for the preparation of compounds useful as inhibitors of beta-site amyloid precursor protein (APP)-cleaving enzyme.

  提供了化合物和方法，用于制备作为beta-位点淀粉样前体蛋白(APP)裂解酶抑制剂有用的化合物。
• CONDENSED AMINODIHYDROTHIAZINE DERIVATIVE
  申请人：Suzuki Yuichi

  公开号：US20100317850A1

  公开（公告）日：2010-12-16

  Disclosed is a compound represented by General formula (I), a pharmaceutically acceptable salt thereof, or a solvate of the compound or the pharmaceutically acceptable salt, which has an inhibitory activity of the production of Aβ or a BACE1-inhibiting activity, and is therefore useful as a prophylactic or therapeutic agent for Aβ-induced neurodegenerative diseases typified by Alzheimer-type dementia. Wherein the ring A represents a C 6-14 aryl group or the like; L represents —NR e CO— [wherein R e represents a hydrogen atom or the like] or the like; the ring B represents a C 6-14 aryl group or the like; X represents a C 1-3 alkylene group or the like; Y represents a single bond or the like; Z represents a C 1-3 alkylene group or the like; R 1 and R 2 independently represent a hydrogen atom or the like; and R 3 , R 4 , R 5 and R 6 independently represent a hydrogen atom, a halogen atom or the like.

  本发明涉及一种由通式（I）表示的化合物，其药学上可接受的盐或该化合物或药学上可接受的盐的溶剂，该化合物具有抑制Aβ产生或BACE1抑制活性，因此可用作治疗由阿尔茨海默病等Aβ诱导的神经退行性疾病的预防或治疗剂。其中，环A表示C6-14芳基或类似物；L表示—NReCO—[其中Re表示氢原子或类似物]或类似物；环B表示C6-14芳基或类似物；X表示C1-3烷基或类似物；Y表示单键或类似物；Z表示C1-3烷基或类似物；R1和R2独立地表示氢原子或类似物；而R3、R4、R5和R6独立地表示氢原子、卤素原子或类似物。