5-(cyclopropylmethoxy)pyrazine-2-carboxylic acid | 1286777-19-2

• 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: 5-(cyclopropylmethoxy)pyrazine-2-carboxylic acid
• CAS: 1286777-19-2
• 化学式: C₉H₁₀N₂O₃
• mdl: MFCD20284638
• 分子量: 194.19
• InChiKey: UTKCEOFCDHLKRM-UHFFFAOYSA-N

物化性质

• 沸点：
  353.2±37.0 °C(Predicted)
• 密度：
  1.370±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.444
• 拓扑面积：
  72.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-4-(5-amino-2-fluorophenyl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine 、 5-(cyclopropylmethoxy)pyrazine-2-carboxylic acid 生成 5-cyclopropylmethoxy-pyrazine-2-carboxylic acid [3-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-4-fluoro-phenyl]-amide
  参考文献：
  名称：

  2-amino-5,5-difluoro-5,6-dihydro-4H-[1,3]oxazin-4-yl)-phenyl]-amides

  摘要：

  本发明涉及具有BACE1和/或BACE2抑制活性的2-氨基-5,5-二氟-5,6-二氢-4H-[1,3]噁唑-4-基]-苯基]-酰胺的化合物，其制造、含有它们的制药组合物以及它们作为治疗活性物质的用途。本发明的活性化合物在治疗和/或预防阿尔茨海默病和2型糖尿病等方面具有用途。

  公开号：

  US08389513B2
• 作为产物：
  描述：

  羟甲基环丙烷 、 5-氯吡嗪-2-羧酸 在 potassium hydroxide 、 柠檬酸 作用下， 以 二甲基亚砜 、 水 为溶剂， 反应 1.5h， 以27%的产率得到5-(cyclopropylmethoxy)pyrazine-2-carboxylic acid
  参考文献：
  名称：

  2-AMINO-5,5-DIFLUORO-5,6-DIHYDRO-4H-[1,3]OXAZIN-4-YL)-PHENYL]-AMIDES

  摘要：

  本发明涉及具有BACE1和/或BACE2抑制活性的2-氨基-5,5-二氟-5,6-二氢-4H-[1,3]噁唑-4-基)-苯基]-酰胺的化合物，其制备方法，含有它们的药物组合物以及它们作为治疗活性物质的用途。本发明的活性化合物可用于治疗和/或预防例如阿尔茨海默病和2型糖尿病。

  公开号：

  US20110144097A1

文献信息

• Iminothiadiazine Dioxide Compounds as BACE Inhibitors, Compositions and Their Use
  申请人：Merck Sharp & Dohme Corp.

  公开号：US20150307465A1

  公开（公告）日：2015-10-29

  In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R 1 , R 2 , R 3 , R 4 , R 5 , R 9 , ring A, ring B, m, n, p, -L 1 -, -L 2 -, and -L 3 - is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related to β-amyloid (“Aβ”) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimer's disease, are also disclosed.

  本发明提供了多种形式的亚氨基噻二唑二氧化物化合物，包括公式(I)的化合物： 包括它们的立体异构体，以及所述立体异构体的药用可接受盐，其中R1、R2、R3、R4、R5、R9、环A、环B、m、n、p、-L1-、-L2-和-L3-都是独立选择且按本文定义。发明的新型亚氨基噻二唑二氧化物化合物出人意料地被发现具有预期的特性，使其作为BACE抑制剂以及/或用于治疗和预防与β-淀粉样蛋白（“Aβ”）生成相关的各种病理学具有优势。还公开了包含一个或多个此类化合物（单独使用和与一个或多个其他活性成分组合使用）的药物组合物，以及它们的制备方法和用于治疗与淀粉样β（Aβ）蛋白相关的病理学，包括阿尔茨海默病的方法。
• AMINO-DIHYDROTHIAZINE AND AMINO-DIOXIDO DIHYDROTHIAZINE COMPOUNDS AS BETA-SECRETASE ANTAGONISTS AND METHODS OF USE
  申请人：Amgen Inc.

  公开号：US20140107109A1

  公开（公告）日：2014-04-17

  The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A 4 , A 5 , A 6 , A 8 , R 1 , R 2 , R 3 , R 7 and n of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and corresponding uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formula II and sub-formula embodiments thereof, intermediates and processes and methods useful for the preparation of compounds of Formulas I-II.

  本发明提供了一类新的化合物，用于调节β-分泌酶（BACE）活性。这些化合物具有一般的化学式I： 其中化学式I中的变量A4、A5、A6、A8、R1、R2、R3、R7和n在此独立地被定义。该发明还提供了包含这些化合物的药物组合物，以及这些化合物和组合物用于治疗与A-beta斑块形成和沉积相关的疾病和/或症状的对应用途，这些疾病和症状是由BACE的生物活性引起的。这种由BACE介导的疾病包括阿尔茨海默病、认知缺陷、认知障碍、精神分裂症和其他中枢神经系统疾病。该发明还提供了化学式II的化合物及其亚式化合物，中间体和用于制备化学式I-II化合物的有用过程和方法。
• [EN] PYRAZINE DERIVATIVES<br/>[FR] DÉRIVÉS DE PYRAZINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2014072257A1

  公开（公告）日：2014-05-15

  The present invention relates to compounds of formula (I), wherein R1R2 are hydrogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, lower alkoxy substituted by halogen, cycloalkyl, OCH2-cycloalkyl or heterocycloalkyl which is optionally substituted by halogen, with the proviso that one of R1 and R2 is hydrogen, or R1 and R2 form together with the carbon atom to which they are attach a phenyl ring, which may be optionally substituted by lower alkyl; R3/R4 are hydrogen, halogen or cyano; with the proviso that one of R3 and R4 is hydrogen; or to a pharmaceutically suitable acid addition salt thereof, to all racemic mixtures, all their corresponding enantiomers and/or optical isomers, which may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse, metabolic disorders, eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

  本发明涉及式(I)的化合物，其中R1R2为氢、较低的烷基、较低的烷氧基、受卤素取代的较低烷基、受卤素取代的较低烷氧基、环烷基、OCH2-环烷基或杂环烷基，该杂环烷基可以选择性地受卤素取代，但R1和R2中的一个为氢，或者R1和R2与它们连接的碳原子一起形成苯环，该苯环可以选择性地受较低烷基取代；R3/R4为氢、卤素或氰基；但R3和R4中的一个为氢；或其药学上适宜的酸盐，所有的外消旋混合物，它们对应的对映体和/或光学异构体，可用于治疗抑郁症、焦虑症、躁郁症、注意缺陷多动障碍（ADHD）、与压力有关的疾病、精神疾病、精神分裂症、神经系统疾病、帕金森病、神经退行性疾病、阿尔茨海默病、癫痫、偏头痛、高血压、物质滥用、代谢紊乱、进食障碍、糖尿病、糖尿病并发症、肥胖症、血脂异常、能量消耗和吸收障碍、体温稳态障碍、睡眠和昼夜节律障碍，以及心血管疾病。
• BICYCLIC COMPOUND
  申请人：TAKEDA PHARMACEUTICAL COMPANY LIMITED

  公开号：US20140243310A1

  公开（公告）日：2014-08-28

  The present invention provides a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.

  本发明提供了一种由以下公式（I）表示的化合物：其中每个符号如规范中定义的，或其盐。
• 1,3-OXAZINES AS BACE1 AND/OR BACE2 INHIBITORS
  申请人：Hilpert Hans

  公开号：US20120258962A1

  公开（公告）日：2012-10-11

  The present invention provides 4-(3-Amino-phenyl)-5,6-dihydro-4H-[1,3]oxazin-2-ylamines of formula I having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease and type 2 diabetes.

  本发明提供了具有BACE1和/或BACE2抑制活性的式I的4-(3-氨基苯基)-5,6-二氢-4H-[1,3]噁嗪-2-胺，其制备方法，含有它们的药物组合物以及它们作为治疗活性物质的用途。本发明的活性化合物在治疗和/或预防治疗阿尔茨海默病和2型糖尿病等疾病方面是有用的。