3-Chloro-5-methoxycarbonyl-4H-thieno[3,2-b]pyrrole | 403860-07-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡咯类
• 英文名称: 3-Chloro-5-methoxycarbonyl-4H-thieno[3,2-b]pyrrole
• 英文别名: Methyl 3-chloro-4H-thieno[3,2-b]pyrrole-5-carboxylate
• CAS: 403860-07-1
• 化学式: C₈H₆ClNO₂S
• 分子量: 215.66
• InChiKey: BEMUCZOBFBMGJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 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：

  3-Chloro-5-methoxycarbonyl-4H-thieno[3,2-b]pyrrole 在 甲醇 、 lithium hydroxide 、 水 、 盐酸 作用下， 以 水 为溶剂， 反应 1.25h， 以100%的产率得到3-氯-4H-噻吩并[3,2-b]吡咯-5-羧酸
  参考文献：
  名称：

  [EN] HETEROCYCLIC AMIDE DERIVATIVES AS INHIBITORS OF GLYCOGEN PHOSPHORYLASE
  [FR] DERIVES D'AMIDES HETEROCYCLIQUES COMME INHIBITEURS DE LA GLYCOGENE PHOSPHORYLASE

  摘要：

  式（1）的杂环酰胺，其中：X为N或CH；R4和R5一起是-S-C（R6）=C（R7）-或-C（R7）=C（R6）-S-；R6和R7可独立地选择自氢、卤素和C1-4烷基；A为苯基或杂芳基；n为0、1或2；R1可从卤素、硝基、氰基、羟基、羧基中选择；R2为氢、羟基或羧基；R3可从氢、羟基、芳基、杂环烷基和C1-4烷基中选择（可选地由1或2个R8基取代）；R8可从羟基、-COCOOR9、-C（O）N（R9）（R10）、-NHC（O）R9、（R9）（R10）N-和-COOR9中选择；R9和R10可从氢、羟基、C1-4烷基（可选地由1或2个R13取代）中选择；R13可从羟基、卤素、三卤甲基和C1-4烷氧基中选择；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中具有价值。描述了制备所述杂环酰胺衍生物和含有它们的药物组合物的方法。

  公开号：

  WO2003074532A1
• 作为产物：
  描述：

  4-氯-2-噻吩甲醛 在 叠氮乙酸乙酯 、 sodium methylate 、 ammonium chloride 作用下， 以 甲醇 、 水 、 xylene 为溶剂， 反应 16.5h， 以40%的产率得到3-Chloro-5-methoxycarbonyl-4H-thieno[3,2-b]pyrrole
  参考文献：
  名称：

  Bicyclic pyrrolyl amides as glucogen phosphorylase inhibitors

  摘要：

  杂环酰胺衍生物的化学式（I）：其中—X-Y-Z-选择自—S—CR4═CR5—，—CR4═CR5—S—，—O—CR4═CR5—，—CR4═CR5—O—，—N═CR4—S—，—S—CR4═N—，—NR6—CR4═CR5—和—CR4═CR5—NR6—；或其药学上可接受的盐或体内可水解酯；（附带条件）；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和含有它们的药物组合物的方法。

  公开号：

  US20030232875A1

文献信息

• [EN] HETEROCYCLIC AMIDE DERIVATIVES AS INHIBITORS OF GLYCOGEN PHOSPHORYLASE<br/>[FR] DERIVES D'AMIDES HETEROCYCLIQUES COMME INHIBITEURS DE LA GLYCOGENE PHOSPHORYLASE
  申请人：ASTRAZENECA AB

  公开号：WO2003074532A1

  公开（公告）日：2003-09-12

  Heterocyclic amides of formula (1) wherein: X is N or CH; R4 and R5 together are either -S-C(R6)=C(R7)- or -C(R7)=C(R6)-S-; R6 and R7 are independently selected from, for example hydrogen, halo and C1-4alkyl; A is phenylene or heteroarylene; n is 0, 1 or 2; R1 is selected from for example halo, nitro, cyano, hydroxy, carboxy; R2 is hydrogen, hydroxy or carboxy; R3 is selected from for example hydrogen, hydroxy, aryl, heterocyclyl and C1-4alkyl (optionally substituted by 1 or 2 R8 groups); R8 is selected from for example hydroxy, -COCOOR9, -C(O)N(R9)(R10), -NHC(O)R9, (R9)(R10)N- and -COOR9; R9 and R10 are selected from for example hydrogen, hydroxy, C1-4alkyl (optionally substituted by 1 or 2 R13); R13 is selected from hydroxy, halo, trihalomethyl and C1-4alkoxy; 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.

  式（1）的杂环酰胺，其中：X为N或CH；R4和R5一起是-S-C（R6）=C（R7）-或-C（R7）=C（R6）-S-；R6和R7可独立地选择自氢、卤素和C1-4烷基；A为苯基或杂芳基；n为0、1或2；R1可从卤素、硝基、氰基、羟基、羧基中选择；R2为氢、羟基或羧基；R3可从氢、羟基、芳基、杂环烷基和C1-4烷基中选择（可选地由1或2个R8基取代）；R8可从羟基、-COCOOR9、-C（O）N（R9）（R10）、-NHC（O）R9、（R9）（R10）N-和-COOR9中选择；R9和R10可从氢、羟基、C1-4烷基（可选地由1或2个R13取代）中选择；R13可从羟基、卤素、三卤甲基和C1-4烷氧基中选择；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中具有价值。描述了制备所述杂环酰胺衍生物和含有它们的药物组合物的方法。
• [EN] HETEROCYCLIC AMIDE DERIVATIVES HAVING GLYCOGEN PHOSPHORYLASE INHIBITORY ACTIVITY<br/>[FR] DERIVES D'AMIDES HETEROCYCLIQUES POSSEDANT UNE ACTIVITE D'INHIBITION DE LA GLYCOGENE PHOSPHORYLASE
  申请人：ASTRAZENECA AB

  公开号：WO2003074531A1

  公开（公告）日：2003-09-12

  Heterocyclic amides of formula (1) wherein: Z is CH or nitrogen; R4 and R5 together are either -S-C(R6)=C(R7)- or -C(R7)=C(R6)-S- ; R6 and R7 are selected from for example hydrogen, halo, C1-4alkyl, and C1-4alkanoyl; A is phenylene or heteroarylene; n is 0, 1 or 2; R1 is selected from for example halo, nitro, cyano, hydroxy, carboxy; r is 1 or 2; Y is -NR2R3 or -OR3; R2 and R3 are selected from for example hydrogen, hydroxy, aryl, heterocyclyl and C1-4alkyl (optionally substituted by 1 or 2 R8 groups); R4 is selected from for example hydrogen, halo, nitro, cyano, hydroxy, C1-4alkyl, and C1-4alkanoyl; R8 is selected from for example hydroxy, -COCOOR9, -C(O)N(R9)(R10), -NHC(O)R9 , (R9)(R10)N- and -COOR9 ; R9 and R10 are selected from for example hydrogen, hydroxy, C1-4alkyl (optionally substituted by 1 or 2 R13 ); R13 is selected from hydroxy, halo, trihalomethyl and C1-4alkoxy; 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.

  式（1）中的杂环酰胺，其中：Z为CH或氮；R4和R5共同为-S-C(R6)=C(R7)-或-C(R7)=C(R6)-S-；R6和R7从氢、卤素、C1-4烷基和C1-4醇酰中选择；A为苯基或杂环基；n为0、1或2；R1从卤素、硝基、氰基、羟基、羧基中选择；r为1或2；Y为-NR2R3或-OR3；R2和R3从氢、羟基、芳基、杂环基和C1-4烷基中选择（可选择性地由1或2个R8基团取代）；R4从氢、卤素、硝基、氰基、羟基、C1-4烷基和C1-4醇酰中选择；R8从羟基、-COCOOR9、-C(O)N(R9)(R10)、-NHC(O)R9、(R9)(R10)N-和-COOR9中选择；R9和R10从氢、羟基、C1-4烷基（可选择性地由1或2个R13取代）中选择；R13从羟基、卤素、三卤甲基和C1-4烷氧基中选择；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中具有价值。描述了制备所述杂环酰胺衍生物的方法和含有它们的药物组合物。
• Heterocyclic amide derivatives as inhibitors of glycogen phoshorylase
  申请人：Birch Martin Alan

  公开号：US20050131015A1

  公开（公告）日：2005-06-16

  Heterocyclic amides of formula (1) wherein: X is N or CH; 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 independently selected from, for example hydrogen, halo and C l-4 alkyl; A is phenylene or heteroarylene; n is 0, 1 or 2; R 1 is selected from for example halo, nitro, cyano, hydroxy, carboxy; R 2 is hydrogen, hydroxy or carboxy; R 3 is selected from for example hydrogen, hydroxy, aryl, heterocyclyl and C 1-4 alkyl(optionally substituted by 1 or 2 R 8 groups); 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.

  公式（1）的杂环酰胺，其中：X是N或CH；R4和R5一起是—S—C(R6)═C(R7)—或—C(R7)═C(R6)—S—；R6和R7独立选择自氢、卤素和Cl-4烷基；A是苯基或杂环芳基；n为0、1或2；R1选择自卤素、硝基、氰基、羟基、羧基；R2是氢、羟基或羧基；R3选择自氢、羟基、芳基、杂环芳基和C1-4烷基（可选地取代1或2个R8基）；R8选择自羟基、—COCOOR9、—C（O）N（R9）（R10）、—NHC（O）R9、（R9）（R10）N—和—COOR9；R9和R10选择自氢、羟基、C1-4烷基（可选地取代1或2个R13）；R13选择自羟基、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，因此在治疗与增加的糖原磷酸化酶活性相关的疾病状态中具有价值。还描述了制造该杂环酰胺衍生物的过程以及含有它们的制药组合物。
• 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。
• Heterocyclic amide derivatives as inhibitors of glycogen phosphorylase
  申请人：AstraZeneca AB

  公开号：US07276517B2

  公开（公告）日：2007-10-02

  Heterocyclic amides of formula (1) wherein: X is N or CH; R4 and R5 together are either —S—C(R6)═C(R7)— or —C(R7)═C(R6)—S—; R6 and R7 are independently selected from, for example hydrogen, halo and C1-4alkyl; A is phenylene or heteroarylene; n is 0, 1 or 2; R1 is selected from for example halo, nitro, cyano, hydroxy, carboxy; R2 is hydrogen, hydroxy or carboxy; R3 is selected from for example hydrogen, hydroxy, aryl, heterocyclyl and C1-4alkyl(optionally substituted by 1 or 2 R8 groups); R8 is selected from for example hydroxy, —COCOOR9, —C(O)N(R9)(R10), —NHC(O)R9, (R9)(R10)N— and —COOR9; R9 and R10 are selected from for example hydrogen, hydroxy, C1-4alkyl (optionally substituted by 1 or 2 R13); R13 is selected from hydroxy, halo, trihalomethyl and C1-4alkoxy; 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.

  公式（1）中的杂环酰胺，其中： X为N或CH; R4和R5一起是—S—C(R6)═C(R7)—或—C(R7)═C(R6)—S—; R6和R7独立选择自例如氢，卤素和C1-4烷基; A为苯基或杂环芳基; n为0，1或2; R1选择自例如卤素，硝基，氰基，羟基，羧基; R2为氢，羟基或羧基; R3选择自例如氢，羟基，芳基，杂环基和C1-4烷基（可选地取代1或2个R8基团）; 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（可选地取代1或2个R13）; 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。描述了制造该杂环酰胺衍生物的方法以及含有它们的制药组合物。