N-(4-amino-3-hydroxy-4-oxo-1-phenylbutan-2-yl)-2-(6-ethyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl)nicotinamide | 1466455-45-7

• 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: N-(4-amino-3-hydroxy-4-oxo-1-phenylbutan-2-yl)-2-(6-ethyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl)nicotinamide
• 英文别名: N-(4-Amino-3-hydroxy-4-oxo-1-phenylbutan-2-yl)-2-(6-ethyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl)nicotinamide；N-(4-amino-3-hydroxy-4-oxo-1-phenylbutan-2-yl)-2-(6-ethyl-5,7-dihydro-4H-pyrazolo[3,4-c]pyridin-2-yl)pyridine-3-carboxamide
• CAS: 1466455-45-7
• 化学式: C₂₄H₂₈N₆O₃
• 分子量: 448.525
• InChiKey: QHYRKUZSSWOXMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  126
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-(4-amino-3-hydroxy-4-oxo-1-phenylbutan-2-yl)-2-(4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl)nicotinamide hydrochloride 、 乙醛 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以85 mg的产率得到N-(4-amino-3-hydroxy-4-oxo-1-phenylbutan-2-yl)-2-(6-ethyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl)nicotinamide
  参考文献：
  名称：

  [EN] CARBOXAMIDE COMPOUNDS AND THEIR USE AS CALPAIN INHIBITORS V
  [FR] COMPOSÉS CARBOXAMIDES ET LEUR UTILISATION COMME INHIBITEURS DE CALPAÏNE V

  摘要：

  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和n具有所述权利要求和说明中提到的含义，Y是式(Y1)或(Y2)的基团，其中#表示Y与吡啶环的连接点，R3、R4、R5、Ry和m具有所述权利要求和说明中提到的含义，A是(CH2)p，其中p为1、2、3或4，其中一个或两个氢原子可以被基团R6取代，其中A连接到吡唑基团的3或4位，R6具有所述权利要求和说明中提到的含义；A1是(CH2)q，其中q为0、1、2或3，其中一个或两个氢原子可以被卤素或C1-C4烷基取代；A2是(CH2)r，其中r为0、1、2或3，其中一个或两个氢原子可以被卤素或C1-C4烷基取代，前提是r+q为2、3、4、5或6；它们的互变异构体、水合物、药学上适用的羧酰胺化合物(I)的盐、(I)的前药和前药的药学上适用的盐、互变异构体或水合物。

  公开号：

  WO2013149800A1

文献信息

• CARBOXAMIDE COMPOUNDS AND THEIR USE AS CALPAIN INHIBITORS V
  申请人：ABBVIE DEUTSCHLAND GMBH &CO. KG

  公开号：US20150065477A1

  公开（公告）日：2015-03-05

  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 and n have the meanings mentioned in the claims and the description, Y is a radical of the formulae (Y1) or (Y2) where # indicates the point of attachment of Y to the pyridine ring, R 3 , R 4 , R 5 , R y and m have the meanings mentioned in the claims and the description, A is (CH 2 ) p with p being 1, 2, 3 or 4, where one or two hydrogen atoms may be replaced by a radical R 6 , where A is attached to the 3- or 4-position of the pyrazole radical and R 6 has the meaning mentioned in the claims and the description; A 1 is (CH 2 )q with q being 0, 1, 2 or 3, where one or two hydrogen atoms may be replaced by halogen or C 1 -C 4 -alkyl; and A 2 is (CH 2 )r with r being 0, 1, 2 or 3, where one or two hydrogen atoms may be replaced by halogen or C 1 -C 4 -alkyl, provided that that r+q is 2, 3, 4, 5 or 6; their tautomers, the hydrates thereof, the pharmaceutically suitable salts of the carbox-amide compounds (I), the prodrugs of (I) and the pharmaceutically suitable salts of the prodrugs, tautomers or hydrates of (I).

  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。羧酰胺化合物是通式（I）的化合物，其中R1、R2和n具有所述权利要求和说明中提到的含义，Y是式（Y1）或（Y2）的基团，其中#表示Y与吡啶环的连接点，R3、R4、R5、Ry和m具有所述权利要求和说明中提到的含义，A是（CH2）p，其中p为1、2、3或4，其中一个或两个氢原子可以被基团R6替换，其中A连接到吡唑基团的3或4位，R6具有所述权利要求和说明中提到的含义；A1是（CH2）q，其中q为0、1、2或3，其中一个或两个氢原子可以被卤素或C1-C4烷基替换；A2是（CH2）r，其中r为0、1、2或3，其中一个或两个氢原子可以被卤素或C1-C4烷基替换，前提是r+q为2、3、4、5或6；它们的互变异构体，其水合物，羧酰胺化合物（I）的药学适用盐，（I）的前药和前药的药学适用盐，互变异构体或水合物。
• Carboxamide compounds and their use as calpain inhibitors V
  申请人：ABBVIE DEUTSCHLAND GMBH & CO. KG

  公开号：US09150545B2

  公开（公告）日：2015-10-06

  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 and n have the meanings mentioned in the claims and the description, Y is a radical of the formulae (Y1) or (Y2) where # indicates the point of attachment of Y to the pyridine ring, R3, R4, R5, Ry and m have the meanings mentioned in the claims and the description, A is (CH2)p with p being 1, 2, 3 or 4, where one or two hydrogen atoms may be replaced by a radical R6, where A is attached to the 3- or 4-position of the pyrazole radical and R6 has the meaning mentioned in the claims and the description; A1 is (CH2)q with q being 0, 1, 2 or 3, where one or two hydrogen atoms may be replaced by halogen or C1-C4-alkyl; and A2 is (CH2)r with r being 0, 1, 2 or 3, where one or two hydrogen atoms may be replaced by halogen or C1-C4-alkyl, provided that that r+q is 2, 3, 4, 5 or 6; their tautomers, the hydrates thereof, the pharmaceutically suitable salts of the carbox-amide compounds (I), the prodrugs of (I) and the pharmaceutically suitable salts of the prodrugs, tautomers or hydrates of (I).

  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)中的化合物，其中R1、R2和n具有所述权利要求和说明中提到的含义，Y是式(Y1)或(Y2)的基团，其中#表示Y与吡啶环的连接点，R3、R4、R5、Ry和m具有所述权利要求和说明中提到的含义，A为(CH2)p，其中p为1、2、3或4，其中一个或两个氢原子可以被基团R6替换，其中A连接到吡唑基团的3或4位，R6具有所述权利要求和说明中提到的含义；A1为(CH2)q，其中q为0、1、2或3，其中一个或两个氢原子可以被卤素或C1-C4烷基替换；A2为(CH2)r，其中r为0、1、2或3，其中一个或两个氢原子可以被卤素或C1-C4烷基替换，前提是r+q为2、3、4、5或6；它们的互变异构体，其水合物，羧酰胺化合物(I)的药物适用盐，(I)的前药物以及前药物的药物适用盐，互变异构体或其水合物。
• US9150545B2
  申请人：——

  公开号：US9150545B2

  公开（公告）日：2015-10-06
• [EN] CARBOXAMIDE COMPOUNDS AND THEIR USE AS CALPAIN INHIBITORS V<br/>[FR] COMPOSÉS CARBOXAMIDES ET LEUR UTILISATION COMME INHIBITEURS DE CALPAÏNE V
  申请人：ABBVIE DEUTSCHLAND

  公开号：WO2013149800A1

  公开（公告）日：2013-10-10

  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 and n have the meanings mentioned in the claims and the description, Y is a radical of the formulae (Y1) or (Y2) where # indicates the point of attachment of Y to the pyridine ring, R3, R4, R5, Ry and m have the meanings mentioned in the claims and the description, A is is (CH2)p with p being 1, 2, 3 or 4, where one or two hydrogen atoms may be replaced by a radical R6, where A is attached to the 3-or 4-positon of the pyrazole radical and R6 has the meaning mentioned in the claims and the description; A1 is (CH2)q with q being 0, 1, 2 or 3, where one or two hydrogen atoms may be replaced by halogen or C1-C4-alkyl; and A2 is (CH2)r with r being 0, 1, 2 or 3, where one or two hydrogen atoms may be replaced by halogen or C1-C4-alkyl, provided that that r + q is 2, 3, 4, 5 or 6; their tautomers, the hydrates thereof, the pharmaceutically suitable salts of the carbox-amide compounds (I), the prodrugs of (I) and the pharmaceutically suitable salts of the prodrugs, tautomers or hydrates of (I).

  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和n具有所述权利要求和说明中提到的含义，Y是式(Y1)或(Y2)的基团，其中#表示Y与吡啶环的连接点，R3、R4、R5、Ry和m具有所述权利要求和说明中提到的含义，A是(CH2)p，其中p为1、2、3或4，其中一个或两个氢原子可以被基团R6取代，其中A连接到吡唑基团的3或4位，R6具有所述权利要求和说明中提到的含义；A1是(CH2)q，其中q为0、1、2或3，其中一个或两个氢原子可以被卤素或C1-C4烷基取代；A2是(CH2)r，其中r为0、1、2或3，其中一个或两个氢原子可以被卤素或C1-C4烷基取代，前提是r+q为2、3、4、5或6；它们的互变异构体、水合物、药学上适用的羧酰胺化合物(I)的盐、(I)的前药和前药的药学上适用的盐、互变异构体或水合物。