ethyl 2-(2H-indazol-2-yl)pyridine-3-carboxylate | 1037828-69-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: ethyl 2-(2H-indazol-2-yl)pyridine-3-carboxylate
• 英文别名: ethyl 2-(2H-indazol-2-yl)nicotinate；ethyl 2-indazol-2-ylpyridine-3-carboxylate
• CAS: 1037828-69-5
• 化学式: C₁₅H₁₃N₃O₂
• 分子量: 267.287
• InChiKey: YNAGDTSSHBEZEM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  57
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 2-(2H-indazol-2-yl)pyridine-3-carboxylate 在 1-羟基苯并三唑 、 二甲基亚砜 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.25h， 生成 N-(4-amino-3,4-dioxo-1-phenylbutan-2-yl)-2-(2H-indazol-2-yl)nicotinamide
  参考文献：
  名称：

  发现新型和高度选择性的钙蛋白酶抑制剂可治疗阿尔茨海默氏病：2-（3-苯基-1 H-吡唑-1-基）-烟酰胺

  摘要：

  钙蛋白酶的过度激活与多种病理疾病有关，包括缺血/再灌注损伤，白内障形成和神经退行性疾病，例如阿尔茨海默氏病（AD）。在本文中，我们描述了我们的努力，从而导致了基于酮酰胺的2-（3-苯基-1 H-吡唑-1-基）烟酰胺与相关半胱氨酸蛋白酶组织蛋白酶，其他蛋白酶和与之相关的半胱氨酸蛋白酶的选择性具有很高的选择性。受体。在一系列与AD相关的临床前模型中，广泛的疗效表明，抑制钙蛋白酶代表了一种有吸引力的方法，具有治疗AD的潜在益处。

  DOI：

  10.1021/acs.jmedchem.7b00731
• 作为产物：
  描述：

  2-氯烟酸乙酯 、 吲唑 在 18-冠醚-6 、 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 ethyl 2-(2H-indazol-2-yl)pyridine-3-carboxylate
  参考文献：
  名称：

  发现新型和高度选择性的钙蛋白酶抑制剂可治疗阿尔茨海默氏病：2-（3-苯基-1 H-吡唑-1-基）-烟酰胺

  摘要：

  钙蛋白酶的过度激活与多种病理疾病有关，包括缺血/再灌注损伤，白内障形成和神经退行性疾病，例如阿尔茨海默氏病（AD）。在本文中，我们描述了我们的努力，从而导致了基于酮酰胺的2-（3-苯基-1 H-吡唑-1-基）烟酰胺与相关半胱氨酸蛋白酶组织蛋白酶，其他蛋白酶和与之相关的半胱氨酸蛋白酶的选择性具有很高的选择性。受体。在一系列与AD相关的临床前模型中，广泛的疗效表明，抑制钙蛋白酶代表了一种有吸引力的方法，具有治疗AD的潜在益处。

  DOI：

  10.1021/acs.jmedchem.7b00731

文献信息

• Carboxamide compounds and their use as calpain inhibitors
  申请人：Kling Andreas

  公开号：US20080234330A1

  公开（公告）日：2008-09-25

  The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. The carboxamide compounds are compounds of the general formula I in which R 1 , R 2 , R 3a , R 3b , W, Y and X have the meanings mentioned in the claims and the description, the tautomers thereof and the pharmaceutically suitable salts thereof. In particular, the compounds have the general formula I-A.a′ and I-A.a″ in which m, E, R 1 , R 3a , R 3b , R 2 , R y , R w and R w6 * have the meanings mentioned in the claims, n is 0, 1 or 2, the tautomers thereof and the pharmaceutically suitable salts thereof.

  本发明涉及新型羧酰胺化合物及其用于制备药物的用途。这些羧酰胺化合物是钙蛋白酶（依赖于钙的半胱氨酸蛋白酶）的抑制剂。因此，本发明还涉及利用这些羧酰胺化合物治疗与升高的钙蛋白酶活性相关的疾病。这些羧酰胺化合物是具有一般式I的化合物，其中R1、R2、R3a、R3b、W、Y和X具有所述权利要求书和说明中提到的含义，其互变异构体和药用盐。具体而言，这些化合物具有一般式I-A.a′和I-A.a″，其中m、E、R1、R3a、R3b、R2、Ry、Rw和Rw6*具有权利要求书中提到的含义，n为0、1或2，其互变异构体和药用盐。
• Carboxamide compounds and their use as calpain inhibitors V
  申请人：Kling Andreas

  公开号：US09062027B2

  公开（公告）日：2015-06-23

  The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. The carboxamide compounds are compounds of the general formula (I) in which R1, R2, R3, R4, X, m and n have the meanings mentioned in the claims and the description, the tautomers thereof, the hydrates thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein R1 is optionally substituted benzyl or hetaryl-methyl, X is a single bond or an oxygen atom, R2 is C1-C4-alkyl, C1-C4-haloalkyl, C2-C4-alkenyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C2-alkyl, C3-C6-heterocycloalkyl-C1-C2-alkyl, phenyl, phenyl-C1-C3-alkyl, pyridin-2-yl-C1-C3-alkyl or CH2—C(O)OCH3, R3 and R4 independently of one another are halogen, CN, CF3, CHF2, CH2F, C1-C2-alkyl or C1-C2-alkoxy, and m and n independently of one another are 0 or 1.

  本发明涉及新型羧酰胺化合物及其用于制备药物的用途。这些羧酰胺化合物是钙依赖性半胱氨酸蛋白酶(calpain)的抑制剂。因此，本发明还涉及使用这些羧酰胺化合物治疗与升高的calpain活性相关的疾病。这些羧酰胺化合物是通式(I)的化合物，其中R1、R2、R3、R4、X、m和n在权利要求书和说明书中所述的含义，其互变异构体、水合物和药学上适宜的盐。在这些化合物中，首选R1为可选的取代苯甲基或杂环甲基，X为单键或氧原子，R2为C1-C4烷基、C1-C4卤代烷基、C2-C4烯基、C3-C6环烷基、C3-C6环烷基-C1-C2烷基、C3-C6杂环烷基-C1-C2烷基、苯基、苯基-C1-C3烷基、吡啶-2-基-C1-C3烷基或CH2—C(O)OCH3，R3和R4相互独立地为卤素、CN、CF3、CHF2、 F、C1-C2烷基或C1-C2烷氧基，m和n相互独立地为0或1。
• CARBOXAMIDE COMPOUNDS AND THEIR USE AS CALPAIN INHIBITORS V
  申请人：Kling Andreas

  公开号：US20140005227A1

  公开（公告）日：2014-01-02

  The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. The carboxamide compounds are compounds of the general formula (I) in which R 1 , R 2 , R 3 , R 4 , X, m and n have the meanings mentioned in the claims and the description, the tautomers thereof, the hydrates thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein R 1 is optionally substituted benzyl or hetaryl-methyl, X is a single bond or an oxygen atom, R 2 is C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 2 -C 4 -alkenyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkyl-C 1 -C 2 -alkyl, C 3 -C 6 -heterocycloalkyl-C 1 -C 2 -alkyl, phenyl, phenyl-C 1 -C 3 -alkyl, pyridin-2-yl-C 1 -C 3 -alkyl or CH 2 —C(O)OCH 3 , R 3 and R 4 independently of one another are halogen, CN, CF 3 , CHF 2 , CH 2 F, C 1 -C 2 -alkyl or C 1 -C 2 -alkoxy, and m and n independently of one another are 0 or 1.

  本发明涉及新型羧酰胺化合物及其用于制造药物的用途。这些羧酰胺化合物是钙依赖性半胱氨酸蛋白酶（calpain）的抑制剂。因此，本发明还涉及使用这些羧酰胺化合物治疗与升高的calpain活性相关的疾病。这些羧酰胺化合物是一般式（I）的化合物，其中R1、R2、R3、R4、X、m和n具有权利要求书和说明中提到的含义，它们的互变异构体、水合物和药学上适宜的盐也属于本发明的保护范围。其中，R1为可选取代苄基或杂环基甲基，X为单键或氧原子，R2为C1-C4烷基、C1-C4卤代烷基、C2-C4烯基、C3-C6环烷基、C3-C6环烷基-C1-C2烷基、C3-C6杂环环烷基-C1-C2烷基、苯基、苯基-C1-C3烷基、吡啶-2-基-C1-C3烷基或CH2—C（O）OCH3，R3和R4独立地为卤素、CN、CF3、CHF2、 F、C1-C2烷基或C1-C2烷氧基，m和n独立地为0或1。
• CARBOXAMIDE COMPOUNDS AND THEIR USE AS CALPAIN INHIBITORS
  申请人：Abbott GmbH & Co. KG

  公开号：US20130245003A1

  公开（公告）日：2013-09-19

  The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. The carboxamide compounds are compounds of the general formula I in which R 1 , R 2 , R 3a , R 3b , W, Y and X have the meanings mentioned in the claims and the description, the tautomers thereof and the pharmaceutically suitable salts thereof. In particular, the compounds have the general formula I-A.a′ and I-A.a″ in which m, E, R 1 , R 3a , R 3b , R 2 , R y , R w and R w6 * have the meanings mentioned in the claims, n is 0, 1 or 2, the tautomers thereof and the pharmaceutically suitable salts thereof.

  本发明涉及新型羧酰胺化合物及其用于制造药物的用途。这些羧酰胺化合物是钙依赖性半胱氨酸蛋白酶（calpain）的抑制剂。因此，本发明还涉及使用这些羧酰胺化合物治疗与升高的calpain活性相关的疾病的用途。这些羧酰胺化合物是具有一般式I的化合物，其中R1、R2、R3a、R3b、W、Y和X具有权利要求书和说明书中提到的含义，其互变异构体和药学上适宜的盐。特别地，这些化合物具有一般式I-A.a'和I-A.a"，其中m、E、R1、R3a、R3b、R2、Ry、Rw和Rw6*具有权利要求书中提到的含义，n为0、1或2，其互变异构体和药学上适宜的盐。
• [EN] CARBOXAMIDE COMPOUNDS AND THEIR USE AS CALPAIN INHIBITORS V<br/>[FR] COMPOSÉS DE CARBOXAMIDE ET LEUR UTILISATION COMME INHIBITEURS V DE LA CALPAÏNE
  申请人：ABBOTT GMBH & CO KG

  公开号：WO2012076639A1

  公开（公告）日：2012-06-14

  The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. The carboxamide compounds are compounds of the general formula (I) in which R1, R2, R3 R4, X, m and n have the meanings mentioned in the claims and the description, the tautomers thereof, the hydrates thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein R1 is optionally substituted benzyl or hetaryl-methyl, X is a single bond or an oxygen atom, R2 is C1-C4- alkyl, C1-C4-haloalkyl, C2-C4-alkenyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C2-alkyl, C3-C6-heterocycloalkyl-C1-C2-alkyl, phenyl, phenyl-C1-C3-alkyl, pyridin-2-yl-C1-C3-alkyl or CH2-C(O)OCH3,R3 and R4 independently of one another are halogen, CN, CF3, CHF2, CH2F, C1-C2-alkyl or C1-C2-alkoxy, and m and n independently of one another are 0 or 1.

  本发明涉及新型羧酰胺化合物及其用于制造药物的用途。这些羧酰胺化合物是钙依赖性半胱氨酸蛋白酶(calpain)的抑制剂。因此，本发明还涉及使用这些羧酰胺化合物治疗与升高的calpain活性相关的疾病。这些羧酰胺化合物是通式(I)中R1、R2、R3、R4、X、m和n的化合物，其中这些化合物的自异构体、水合物和药学上适宜的盐也包括在内。其中，R1为可选的取代苯甲基或杂环甲基，X为单键或氧原子，R2为C1-C4烷基、C1-C4卤代烷基、C2-C4烯基、C3-C6环烷基、C3-C6环烷基-C1-C2烷基、C3-C6杂环环烷基-C1-C2烷基、苯基、苯基-C1-C3烷基、吡啶-2-基-C1-C3烷基或CH2-C（O）OCH3，R3和R4分别是卤素、CN、CF3、CHF2、 F、C1-C2烷基或C1-C2烷氧基，m和n分别是0或1。