2-氯-6H-噻吩并[2,3-B]吡咯-5-羧酸甲酯 | 403860-10-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡咯类
• 中文名称: 2-氯-6H-噻吩并[2,3-B]吡咯-5-羧酸甲酯
• 英文名称: methyl 2-chloro-6H-thieno[2,3-b]pyrrole-5-carboxylate
• 英文别名: 2-chloro-5-methoxycarbonyl-6H-thieno[2,3-b]pyrrole
• CAS: 403860-10-6
• 化学式: C₈H₆ClNO₂S
• mdl: MFCD18837597
• 分子量: 215.66
• InChiKey: PUVPNBQYYYYQCY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  70.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-氯-6H-噻吩并[2,3-B]吡咯-5-羧酸甲酯 在 sodium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 5.0h， 以97%的产率得到2-Chloro-6H-thieno[2,3-b]pyrrole-5-carboxylic acid
  参考文献：
  名称：

  [EN] HETEROCYCLIC AMIDE DERIVATIVES WHICH POSSES GLYCOGEN PHOSPHORYLASE INHIBITORY ACTIVITY
  [FR] DERIVES D'AMIDE HETEROCYCLIQUE AYANT UNE ACTIVITE INHIBITRICE DE LA GLYCOGENE PHOSPHORYLASE

  摘要：

  一种化合物的分子式（1）或其药用可接受的盐，其中：R4和R5一起是-S-C(R6)=C(R7)-或-C(R7)=C(R6)-S-；A是苯基或杂环芳基；R1例如被选择自卤素、硝基、氰基、羟基、羧基、氨基甲酰基、N-(1-4C)烷基甲酰基、N-(1-4C)烷基磺酰基、(1-4C)烷基、(1-4C)烷氧基、(1-4C)烷酰基、(1-4C)烷酰氧基、羟基(1-4C)烷基、氟甲基和-NHSO2(1-4C)烷基；或者，当n为2时，两个R1基团与它们连接的A的碳原子一起，可以形成一个含有1或2个杂原子（独立选择自O、S和N）的4至7个成员饱和环；R2和R3与它们连接的氮一起形成一个可选地取代的4至7个成员的杂环环；具有糖原磷酸化酶抑制活性，因此在治疗与增加的糖原磷酸化酶活性相关的疾病状态中具有价值。描述了制备化合物和含有它们的药物组合物的过程。

  公开号：

  WO2005020986A1
• 作为产物：
  描述：

  3-噻吩甲醛 在 N-氯代丁二酰亚胺 、 sodium methylate 作用下， 以 甲醇 、 氯仿 、 甲苯 为溶剂， 反应 6.75h， 生成 2-氯-6H-噻吩并[2,3-B]吡咯-5-羧酸甲酯
  参考文献：
  名称：

  [EN] FAAH INHIBITORS
  [FR] INHIBITEURS DE FAAH

  摘要：

  本公开涉及具有以下结构式（I）的N-苄基吡咯类化合物，可用作脂肪酸酰胺水解酶（FAAH）的抑制剂。本公开还提供了包括本公开化合物的药学上可接受的组合物，以及使用这些组合物在治疗或预防各种疾病中的方法。

  公开号：

  WO2011071996A1

文献信息

• [EN] HETEROCYCLIC AMIDE DERIVATIVES WHICH POSSES GLYCOGEN PHOSPHORYLASE INHIBITORY ACTIVITY<br/>[FR] DERIVES D'AMIDE HETEROCYCLIQUES AYANT UNE ACTIVITE INHIBITRICE DE LA GLYCOGENE PHOSPHORYLASE
  申请人：ASTRAZENECA AB

  公开号：WO2005020987A1

  公开（公告）日：2005-03-10

  Heterocyclic amides of formula (1) wherein: B is selected from R4 and R 5 together are either -S-C(R 6)=C(R 7)_ or _C(R7)=C(R6)_S_; A is a pyridylene ring; m is 0, 1 or 2; n is 0 or 1; R 2 is for example selected from (I -4C)alkyl, hydroxy(l -4C)alkyl, dihydroxy(2-4C)alkyl and (1 -4C)aIkoxy(1 -4C)alkyl. or a pharmaceutically acceptable salt possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity. Processes for the manufacture of said heterocyclic amide derivatives, intermediates in said processes and pharmaceutical compositions containing the heterocyclic amide derivatives are described.

  式（1）中的杂环酰胺，其中：B选自R4和R5，R4和R5一起是-S-C（R6）=C（R7）_或_C（R7）=C（R6）_S_；A是吡啶基环；m为0、1或2；n为0或1；R2例如选自（1-4C）烷基、羟基（1-4C）烷基、二羟基（2-4C）烷基和（1-4C）氧基（1-4C）烷基，或者是药学上可接受的盐，具有糖原磷酸化酶抑制活性，因此在治疗与糖原磷酸化酶活性增加相关的疾病状态中具有价值。描述了制备所述杂环酰胺衍生物的方法、所述方法中的中间体以及含有所述杂环酰胺衍生物的药物组合物。
• [EN] HETEROCYCLIC AMIDE DERIVATIVES WHICH POSSES GLYCOGEN PHOSPHORYLASE INHIBITORY ACTIVITY<br/>[FR] DERIVES D'AMIDE HETEROCYCLIQUE AYANT UNE ACTIVITE INHIBITRICE DE LA GLYCOGENE PHOSPHORYLASE
  申请人：ASTRAZENECA AB

  公开号：WO2005020986A1

  公开（公告）日：2005-03-10

  A compound of the formula (1) or a pharmaceutically-acceptable salt thereof wherein: R4 and R5 together are either -S-C(R6)=C(R7)- or -C(R7)=C(R6)-S-; A is phenylene or heteroarylene; R1 is for example selected from halo, nitro, cyano, hydroxy, carboxy, carbamoyl, N-(1-4C)alkylcarbamoyl, N-(1-4C)alkylsulphamoyl, (1-4C)alkyl, (1-4C)alkoxy, (1-4C)alkanoyl, (1-4C)alkanoyloxy, hydroxy(1-4C)alkyl, fluoromethyl, and -NHSO2(1-4C)alkyl; or, when n is 2, the two R1 groups, together with the carbon atoms of A to which they are attached, may form a 4 to 7 membered saturated ring, optionally containing 1 or 2 heteroatoms independently selected from O, S and N; R2 and R3 together with the nitrogen to which they are attached form an optionally substituted 4- to 7-membered, heterocyclic ring; possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity. Processes for the manufacture of compounds and pharmaceutical compositions containing them are described.

  一种化合物的分子式（1）或其药用可接受的盐，其中：R4和R5一起是-S-C(R6)=C(R7)-或-C(R7)=C(R6)-S-；A是苯基或杂环芳基；R1例如被选择自卤素、硝基、氰基、羟基、羧基、氨基甲酰基、N-(1-4C)烷基甲酰基、N-(1-4C)烷基磺酰基、(1-4C)烷基、(1-4C)烷氧基、(1-4C)烷酰基、(1-4C)烷酰氧基、羟基(1-4C)烷基、氟甲基和-NHSO2(1-4C)烷基；或者，当n为2时，两个R1基团与它们连接的A的碳原子一起，可以形成一个含有1或2个杂原子（独立选择自O、S和N）的4至7个成员饱和环；R2和R3与它们连接的氮一起形成一个可选地取代的4至7个成员的杂环环；具有糖原磷酸化酶抑制活性，因此在治疗与增加的糖原磷酸化酶活性相关的疾病状态中具有价值。描述了制备化合物和含有它们的药物组合物的过程。
• [EN] HETEROCYCLIC AMIDE DERIVATIVES WHICH POSSESS GLYCOGEN PHOSPHORYLASE INHIBITORY ACTIVITY<br/>[FR] DERIVES AMIDES HETEROCYCLIQUES POSSEDANT UNE ACTIVITE INHIBITRICE DE GLYCOGENE PHOSPHORYLASE
  申请人：ASTRAZENECA AB

  公开号：WO2005018637A1

  公开（公告）日：2005-03-03

  A compound of the formula (1) or a pharmaceutically-acceptable salt, or pro-drug thereof; (1) wherein, for example: R4 and R5 together are either -S-C(R6=C(R7)- or -C(R7)=C(R6)-S- ; R6 and R7 are independently selected from hydrogen and halo; A is phenylene or heteroarylene; n is 0, 1 or 2; R1 is halo, cyano or carboxy; R2 is for example methyl; R3 is for example selected from halo(1-4C)alkyl, dihalo(1-4C)alkyl, trifluoromethyl, hydroxy(1-4C)alkyl, dihydroxy(2-4C)alkyl, trihydroxy(3-4C)alkyl, cyano(1-4C)alkyl (optionally substituted on alkyl with hydroxy), (1-4C)alkoxy(1-4C)alkyl, (1-4C)alkoxy(1-4C)alkoxy(1-4C)alkyl, di[(1-4C)alkoxy](1-4C)alkyl, (hydroxy)[(1-4C)alkoxy](1-4C)alkyl; possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity. Processes for the manufacture of compounds and pharmaceutical compositions containing them are described.

  该化合物的分子式为（1）或其药用可接受的盐或前药；（1）其中，例如：R4和R5一起是-S-C(R6=C(R7)-或-C(R7)=C(R6)-S-；R6和R7分别选择自氢和卤素；A是苯基或杂环芳基；n为0、1或2；R1为卤素、氰基或羧基；R2为例如甲基；R3为例如选择自卤(1-4C)烷基、二卤(1-4C)烷基、三氟甲基、羟基(1-4C)烷基、二羟基(2-4C)烷基、三羟基(3-4C)烷基、氰基(1-4C)烷基（在烷基上可选择性地取代羟基）、（1-4C)烷氧基(1-4C)烷基、（1-4C)烷氧基(1-4C)烷氧基(1-4C)烷基、二[(1-4C)烷氧](1-4C)烷基、(羟基)[(1-4C)烷氧](1-4C)烷基；具有糖原磷酸化酶抑制活性，因此在治疗与糖原磷酸化酶活性增加相关的疾病状态中具有价值。描述了制备化合物和含有它们的药物组合物的方法。
• [EN] PROCESS AND INTERMEDIATES FOR THE PREPARATION OF THE THIENOPYRROLE DERIVATIVES<br/>[FR] PROCEDE ET PRODUITS INTERMEDIAIRES POUR LA PREPARATION DE DERIVES DE THIENOPYRROLE
  申请人：ASTRAZENECA AB

  公开号：WO2004031194A1

  公开（公告）日：2004-04-15

  A process for preparing a compound of formula (I) where R4 and R5 are as defined in the specification; and R6 is hydrogen or a protecting group, which process comprises cyclisation of a compound of formula (II) where R4, R5and R6 are as defined in relation to formula (I) and R7is a nitrogen-protecting group, and removing protecting group R7-, and thereafter if desired or necessary, removing any protecting group R6 to obtain the corresponding carboxylic acid. Novel intermediates and the use of the products in the preparation of pharmaceutical compounds is also described and claimed.

  一种制备式（I）化合物的方法，其中R4和R5如规范所定义；R6为氢或保护基，该方法包括将式（II）化合物环化，其中R4，R5和R6如相对于式（I）所定义，R7为氮保护基，并去除保护基R7-，然后如有需要，去除任何保护基R6以获得相应的羧酸。还描述和声明了新的中间体和产品在制备药物化合物方面的用途。
• Heterocyclic amide derivatives having glycogen phosphorylase inhibitory activity
  申请人：Whittamore Robert Owen Paul

  公开号：US20050131052A1

  公开（公告）日：2005-06-16

  Heterocyclic amides of formula (1) wherein: Z is CH or nitrogen; R 4 and R 5 together are either —S—C(R 6 )═C(R 7 )— or —C(R 7 )═C(R 6 )—S—; R 6 and R 7 are selected from for example hydrogen, halo, C 1-4 alkyl, and C 1-4 alkanoyl; A is phenylene or heteroarylene; n is 0, 1 or 2; R 1 is selected from for example halo, nitro, cyano, hydroxy, carboxy; r is 1 or 2; Y is —NR 2 R 3 or —OR 3 ; R 2 and R 3 are selected from for example hydrogen, hydroxy, aryl, heterocyclyl and C 1-4 alkyl(optionally substituted by 1 or 2 R 8 groups); R 4 is selected from for example hydrogen, halo, nitro, cyano, hydroxy, C 1-4 alkyl, and C 1-4 alkanoyl; R 8 is selected from for example hydroxy, —COCOOR 9 , —C(O)N(R 9 )(R 10 ), —NHC(O)R 9 , (R 9 )(R 10 )N— and —COOR 9 ; R 9 and R 10 are selected from for example hydrogen, hydroxy, C 1-4 alkyl (optionally substituted by 1 or 2 R 13 ); R 13 is selected from hydroxy, halo, trihalomethyl and C 1-4 alkoxy; or a pharmaceutically acceptable salt or pro-drug thereof; possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity. Processes for the manufacture of said heterocyclic amide derivatives and pharmaceutical compositions containing them are described.

  化合物的异环酰胺式（1），其中：Z为CH或氮；R4和R5一起是—S—C（R6）═C（R7）—或—C（R7）═C（R6）—S—；R6和R7选择自例如氢，卤素，C1-4烷基和C1-4烷酰基；A为苯撑或杂芳撑；n为0，1或2；R1选择自例如卤素，硝基，氰基，羟基，羧基；r为1或2；Y为—NR2R3或—OR3；R2和R3选择自例如氢，羟基，芳基，杂环基和C1-4烷基（可选地被1或2个R8基替代）；R4选择自例如氢，卤素，硝基，氰基，羟基，C1-4烷基和C1-4烷酰基；R8选择自例如羟基，—COCOOR9，—C（O）N（R9）（R10），—NHC（O）R9，（R9）（R10）N—和—COOR9；R9和R10选择自例如氢，羟基，C1-4烷基（可选地被1或2个R13取代）；R13选择自例如羟基，卤素，三卤甲基和C1-4烷氧基；或其药学上可接受的盐或前药；具有糖原磷酸化酶抑制活性，因此在治疗与糖原磷酸化酶活性增加相关的疾病状态方面具有价值。描述了制造该异环酰胺衍生物的工艺和含有它们的制药组合物。