5-氟嘧啶-2-羧酸甲酯 | 1227575-47-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 5-氟嘧啶-2-羧酸甲酯
• 中文别名: 5-氟嘧啶-2-甲酸甲酯
• 英文名称: methyl 5-fluoropyrimidine-2-carboxylate
• CAS: 1227575-47-4
• 化学式: C₆H₅FN₂O₂
• 分子量: 156.116
• InChiKey: BAWZGVWTHJYDFE-UHFFFAOYSA-N

物化性质

• 沸点：
  256.3±32.0 °C(Predicted)
• 密度：
  1.323±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  52.1
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  5-氟嘧啶-2-羧酸甲酯 在 吡啶 、 lithium hydroxide monohydrate 、 水 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 53.0h， 生成 (R)-N-(2,8-dimethylimidazo[1,2-a]pyrazin-6-yl)-5-(3-(methylamino)pyrrolidin-1-yl)pyrimidine-2-carboxamide
  参考文献：
  名称：

  [EN] HTT MODULATORS FOR TREATING HUNTINGTON'S DISEASE
  [FR] MODULATEURS HTT POUR LE TRAITEMENT DE LA MALADIE DE HUNTINGTON

  摘要：

  以下提供了一些作为HTT调节剂有用的化合物。这些化合物在亨廷顿病的治疗中很有用。

  公开号：

  WO2021231571A1
• 作为产物：
  描述：

  甲醇 、 2-氰基-5-氟嘧啶 在 盐酸 作用下， 以 水 为溶剂， 反应 2.0h， 以40%的产率得到5-氟嘧啶-2-羧酸甲酯
  参考文献：
  名称：

  Iminothiadiazine Dioxide Compounds as BACE Inhibitors, Compositions and Their Use

  摘要：

  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。

  公开号：

  US20150307465A1

文献信息

• [EN] COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH APJ RECEPTOR ACTIVITY<br/>[FR] COMPOSÉS ET COMPOSITIONS DESTINÉS AU TRAITEMENT D'ÉTATS PATHOLOGIQUES ASSOCIÉS À UNE ACTIVITÉ DU RÉCEPTEUR DE L'APJ
  申请人：ANNAPURNA BIO INC

  公开号：WO2019169193A1

  公开（公告）日：2019-09-06

  This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt and/or hydrate and/or prodrug of the compound) that modulate (e.g., agonize) the apelin receptor (also referred to herein as the APJ receptor; gene symbol "APLNR"). This disclosure also features compositions containing the same as well as other methods of using and making the same. The chemical entities are useful, e.g., for treating a subject (e.g., a human) having a disease, disorder, or condition in which a decrease in APJ receptor activity (e.g., repressed or impaired APJ receptor signaling; e.g., repressed or impaired apelin-APJ receptor signaling) or downregulation of endogenous apelin contributes to the pathology and/or symptoms and/or progression of the disease, disorder, or condition. Non-limiting examples of such diseases, disorders, or conditions include: (i) cardiovascular disease; (ii) metabolic disorders; (iii) diseases, disorders, and conditions associated with vascular pathology; and (iv) organ failure; (v) diseases, disorders, and conditions associated with infections (e.g., microbial infections); and (vi) diseases, disorders, or conditions that are sequela or comorbid with any of the foregoing or any disclosed herein. More particular non-limiting examples of such diseases, disorders, or conditions include pulmonary hypertension (e.g., PAH); heart failure; type II diabetes; renal failure; sepsis; and systemic hypertension.

  本公开涉及化学实体（例如，化合物或药学上可接受的盐和/或水合物和/或化合物的前药），其调节（例如，激活）apelin受体（在此处也称为APJ受体；基因符号“APLNR”）。本公开还涉及含有相同化学实体的组合物，以及使用和制备相同的其他方法。这些化学实体可用于治疗患有减少APJ受体活性（例如，抑制或受损的APJ受体信号传导；例如，抑制或受损的apelin-APJ受体信号传导）或内源性apelin下调导致疾病、障碍或病症的主体（例如，人类）。此类疾病、障碍或病症的非限定示例包括：（i）心血管疾病；（ii）代谢紊乱；（iii）与血管病变相关的疾病、障碍和病症；（iv）器官功能衰竭；（v）与感染（例如，微生物感染）相关的疾病、障碍和病症；以及（vi）与前述任何疾病、障碍或病症或在此处公开的任何疾病、障碍或病症并发或合并的疾病、障碍或病症。此类疾病、障碍或病症的更为具体的非限定示例包括肺动脉高压（例如，PAH）；心力衰竭；2型糖尿病；肾功能衰竭；败血症；和全身性高血压。
• IMINOTHIADIAZINE DIOXIDE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS AND THEIR USE
  申请人：Scott Jack D.

  公开号：US20120183563A1

  公开（公告）日：2012-07-19

  In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): (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 Alzheimers disease, are also disclosed.

  在其多种实施方式中，本发明提供了某些亚硫酰二氮杂环化合物，包括化合物式（I）：（I）及其立体异构体和所述化合物立体异构体的药学上可接受的盐，其中R1、R2、R3、R4、R5、R9、环A、环B、m、n、p、-L1-、L2-和L3-各自独立选择并如所定义。本发明的新型亚硫酰二氮杂环化合物出人意料地表现出预期的性质，使它们作为BACE抑制剂和/或用于治疗和预防与β-淀粉样蛋白（Aβ）产生相关的各种病理学具有优势。还公开了包括一种或多种这样的化合物（单独和与一种或多种其他活性剂的组合）的制药组合物，以及用于治疗与淀粉样β（Aβ）蛋白相关的病理学，包括阿尔茨海默病的方法。
• IMINOTHIADIAZINE DIOXIDE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE
  申请人：Scott Jack D.

  公开号：US20140296221A1

  公开（公告）日：2014-10-02

  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.

  在其多种实施方式中，本发明提供了某些亚氨基噻二嗪二氧化物化合物，包括化合物公式（I）的化合物：以及其立体异构体和该化合物立体异构体的药学上可接受的盐，其中每个R1、R2、R3、R4、R5、R9、环A、环B、m、n、p、-L1-、-L2-和-L3-独立选择并在此定义。本发明的新型亚氨基噻二嗪二氧化物化合物出乎意料地表现出有利于作为BACE抑制剂和/或用于治疗和预防与β-淀粉样蛋白（“Aβ”）产生相关的各种病理的性质。还公开了包括一个或多个此类化合物（单独和与一个或多个其他活性剂的组合）的制药组合物，以及用于治疗与淀粉样β（Aβ）蛋白相关的病理，包括阿尔茨海默病的制备和使用方法。
• 5,6,7,8,9,10-hexahydro-6,10-epimino[1,2,4]triazolo[4,3-a]azocines as P2X7 modulators
  申请人：Janssen Pharmaceutica NV

  公开号：US09102686B2

  公开（公告）日：2015-08-11

  The present invention is directed to a compound of Formula (I): The invention also relates to pharmaceutical compositions comprising compounds of Formula (I). Methods of making and using the compounds of Formula (I) are also within the scope of the invention.

  本发明涉及一种式（I）的化合物。本发明还涉及包括式（I）化合物的制药组合物。制备和使用式（I）化合物的方法也在本发明的范围内。
• P2X7 MODULATORS
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：US20160039836A1

  公开（公告）日：2016-02-11

  The present invention is directed to a compound of Formula (I): wherein: The present invention is directed to a compound of Formula (I): wherein: n is an integer from 0-1; X is CH2 when n is 0, or X is CH2 or oxygen when n is 1; R 1 is phenyl or pyridinyl, wherein the phenyl or pyridinyl is optionally substituted with from 1 to 4 substituents independently selected from halogen and alkyl; and R 2 is S phenyl, pyridinyl, pyrazinyl, pyradizinyl, pyrimidinyl, pyrrolyl, pyrazolyl, thiazolyl or thiophenyl, wherein the phenyl, pyridinyl, pyrazinyl, pyradizinyl, pyrimidinyl, pyrrolyl, pyrazolyl, thiazolyl or thiophenyl is optionally substituted with from 1 to 2 substituents independently selected from the group consisting of halogen, alkyl, hydroxy and alkoxy. The invention also relates to pharmaceutical compositions comprising compounds of Formula (I). The compounds of formula (I) are useful as P2X7 modulators.

  本发明涉及一种式（I）的化合物：其中：n是0-1的整数；当n为0时，X是CH2，当n为1时，X是 或氧；R1是苯基或吡啶基，其中苯基或吡啶基可选地被1-4个取代基独立地选自卤素和烷基取代；R2是S苯基、吡啶基、吡嗪基、吡啶并嗪基、嘧啶基、吡咯基、吡唑基、噻唑基或噻吩基，其中苯基、吡啶基、吡嗪基、吡啶并嗪基、嘧啶基、吡咯基、吡唑基、噻唑基或噻吩基可选地被1-2个取代基独立地选自卤素、烷基、羟基和烷氧基。本发明还涉及包含式（I）化合物的药物组合物。式（I）化合物可用作P2X7调节剂。