N-[3-amino-2,3-dioxo-1-(phenylmethyl)propyl]-2-thiochromeno[4,3-c]pyrazol-2(4H)-ylpyridine-3-carboxamide | 1037828-23-1

• 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-amino-2,3-dioxo-1-(phenylmethyl)propyl]-2-thiochromeno[4,3-c]pyrazol-2(4H)-ylpyridine-3-carboxamide
• 英文别名: N-(4-amino-3,4-dioxo-1-phenylbutan-2-yl)-2-(4H-thiochromeno[4,3-c]pyrazol-2-yl)pyridine-3-carboxamide
• CAS: 1037828-23-1
• 化学式: C₂₆H₂₁N₅O₃S
• 分子量: 483.55
• InChiKey: NRNHVASCPLBXJN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  145
• 氢给体数：
  2
• 氢受体数：
  6

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
  申请人：Hornberger Wilfried

  公开号：US20110059968A1

  公开（公告）日：2011-03-10

  The present invention relates to novel carboxamide compounds of the formula I and their use for the manufacture of a medicament. The carboxamide compounds are prodrugs of 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. R 1 is C 1 -C 10 -alkyl, C 2 -C 10 -alkenyl, C 2 -C 10 -alkynyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 4 -alkyl, aryl, hetaryl, aryl-C 1 -C 6 -alkyl, aryl-C 2 -C 6 -alkenyl, hetaryl-C 1 -C 4 -alkyl or hetaryl-C 2 -C 6 -alkenyl, R 2 is C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 4 -alkyl, aryl, O-aryl, O—CH 2 -aryl, hetaryl, aryl-C 1 -C 6 -alkyl, aryl-C 2 -C 6 -alkenyl, hetaryl-C 1 -C 4 -alkyl or hetaryl-C 2 -C 6 -alkenyl, R 3a and R 3b together form a moiety S-Alk-S, O-Alk-S or O-Alk-O, wherein Alk is linear C 2 -C 5 -alkandiyl, which may be unsubstituted or substituted with 1, 2, 3 or 4 radicals selected from C 1 -C 4 -alkyl or halogen; X is a radical of the formulae C(═O)—O—R x1 , C(═O)—NR x2 R x3 , C(═O)—N(R x4 )—(C 1 -C 6 -alkylene)-NR x2 R x3 , C(═O)—N(R x4 )NR x2 R x3 , n is 0, 1 or 2, one of the variables Y 1 , Y 2 , Y 3 or Y 4 is a nitrogen atom, and the remaining variables Y 1 , Y 2 , Y 3 or Y 4 are CH; R y is e.g. OH, SH, halogen, NO 2 , NH 2 , CN, CF 3 , CHF 2 , CH 2 F, O—CF 3 , O—CHF 2 , O—CH 2 F, COON, OCH 2 COOH, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, C 1 -C 6 -alkylthio etc. W is a radical of the formulae W1 or W2 which is linked via nitrogen: in which * means the linkage to the 6-membered heteroaromatic ring, and # means the linkage to R 2 , m is 0, 1 or 2, and R w is e.g. OH, SH, halogen, NO 2 , NH 2 , CN, CF 3 , CHF 2 , CH 2 F, O—CF 3 , O—CHF 2 , O—CH 2 F, COOH, OCH 2 COOH.

  本发明涉及公式I的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抑制剂的前药。因此，本发明还涉及使用这些羧酰胺化合物治疗与升高的半胱氨酸蛋白酶活性相关的疾病。其中，R1是C1-C10烷基，C2-C10烯基，C2-C10炔基，C3-C7环烷基，C3-C7环烷基-C1-C4烷基，芳基，杂芳基，芳基-C1-C6烷基，芳基-C2-C6烯基，杂芳基-C1-C4烷基或杂芳基-C2-C6烯基；R2是C3-C7环烷基，C3-C7环烷基-C1-C4烷基，芳基，O-芳基，O—CH2-芳基，杂芳基，芳基-C1-C6烷基，芳基-C2-C6烯基，杂芳基-C1-C4烷基或杂芳基-C2-C6烯基；R3a和R3b一起形成S-Alk-S、O-Alk-S或O-Alk-O的基团，其中Alk是线性C2-C5-烷二基，可以是未取代或取代的，取代基包括1、2、3或4个选择自C1-C4烷基或卤素的基团；X是公式C(═O)—O—Rx1、C(═O)—NRx2Rx3、C(═O)—N(Rx4)—(C1-C6-烷基)-NRx2Rx3、C(═O)—N(Rx4)NRx2Rx3的基团，n为0、1或2，变量Y1、Y2、Y3或Y4中的一个是氮原子，其余变量Y1、Y2、Y3或Y4为CH；Ry例如为OH、SH、卤素、NO2、NH2、CN、CF3、CHF2、 F、O— 、O— 、O— F、COON、O COOH、C1-C6烷基、C1-C6烷氧基、C1-C6烷氧基-C1-C4烷基、C1-C6烷硫基等；W是通过氮原子连接的公式W1或W2的基团：其中*表示连接到6元杂环芳基环，#表示连接到R2，m为0、1或2，Rw例如为OH、SH、卤素、 、NH2、CN、 、 、 F、O— 、O— 、O— F、COOH、O COOH。
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