3-氯-4H-噻吩并[3,2-b]吡咯-5-羧酸 | 332099-33-9

• 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: 3-氯-4H-噻吩并[3,2-b]吡咯-5-羧酸
• 英文名称: 3-Chloro-4H-thieno[3,2-b]pyrrole-5-carboxylic acid
• 英文别名: 5-Carboxy-3-chloro-4H-thieno[3,2-b]pyrrole
• CAS: 332099-33-9
• 化学式: C₇H₄ClNO₂S
• 分子量: 201.633
• InChiKey: FDGNVONVURZBLL-UHFFFAOYSA-N

物化性质

• 沸点：
  465.9±40.0 °C(Predicted)
• 密度：
  1.740±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  81.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-氯-4H-噻吩并[3,2-b]吡咯-5-羧酸 、 2-氨基-N-苯基乙酰胺 在 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.02h， 以67%的产率得到3-chloro-5-[N-(N-phenylcarbamoylmethyl)carbamoyl]-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
• 作为产物：
  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

文献信息

• Use of glycogen phosphorylase inhibitors
  申请人：——

  公开号：US20030004162A1

  公开（公告）日：2003-01-02

  The invention provides methods of treating prophylactically an individual in whom Type 2 diabetes mellitus has not yet presented, but in whom there is an increased risk of developing such condition, which methods comprise administering to an individual in need thereof an effective amount of a glycogen phosphorylase inhibitor; effective amounts of a glycogen phosphorylase inhibitor and a non-glycogen phosphorylase inhibiting anti-diabetic agent; or effective amounts of a glycogen phosphorylase inhibitor and an anti-obesity agent. The invention further provides methods of treating prophylactically an individual in whom Type 2 diabetes mellitus has not yet presented, but in whom there is an increased risk of developing such condition, which methods comprise administering to an individual in need thereof a pharmaceutical composition comprising effective amounts of a glycogen phosphorylase inhibitor and a non-glycogen phosphorylase inhibiting anti-diabetic agent; or effective amounts of a glycogen phosphorylase inhibitor and an anti-obesity agent.

  本发明提供了一种预防性地治疗尚未出现2型糖尿病但存在发展为该病风险的个体的方法，该方法包括向需要该方法的个体施用有效量的糖原磷酸化酶抑制剂；有效量的糖原磷酸化酶抑制剂和非糖原磷酸化酶抑制的抗糖尿病剂；或者有效量的糖原磷酸化酶抑制剂和抗肥胖剂。本发明还提供了一种预防性地治疗尚未出现2型糖尿病但存在发展为该病风险的个体的方法，该方法包括向需要该方法的个体施用包含有效量的糖原磷酸化酶抑制剂和非糖原磷酸化酶抑制的抗糖尿病剂的药物组合物；或者有效量的糖原磷酸化酶抑制剂和抗肥胖剂。
• [EN] SUBSTITUTED TRICYCLIC AMIDES, ANALOGUES THEREOF, AND METHODS USING SAME<br/>[FR] AMIDES TRICYCLIQUES SUBSTITUÉS, ANALOGUES DE CEUX-CI ET PROCÉDÉS LES METTANT EN OEUVRE
  申请人：ARBUTUS BIOPHARMA CORP

  公开号：WO2021229302A1

  公开（公告）日：2021-11-18

  The present disclosure includes substituted tricyclic amides, or analogues thereof of formula (I) (I), wherein X, Y, ring A, R1, R5, R6 and R7 are as defined herein, and compositions comprising compounds of formula (I) that can be used to treat or prevent hepatitis B virus (HBV) and/or hepatitis D virus (HDV) infections in a patient.

  本公开涵盖了替代三环酰胺，或其类似物的化合物，其化学式为(I)，其中X、Y、环A、R1、R5、R6和R7如本文所定义，并包括化合物(I)的组合物，可用于治疗或预防患者体内的乙型肝炎病毒（HBV）和/或丙型肝炎病毒（HDV）感染。
• [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。
• FLUORO-SUBSTITUTED INHIBITORS OF D-AMINO ACID OXIDASE
  申请人：Heffernan L. R. Michele

  公开号：US20080004327A1

  公开（公告）日：2008-01-03

  This invention provides novel inhibitors of the enzyme D-amino acid oxidase as well as pharmaceutical compositions including the compounds of the invention. The invention also provides methods for the treatment and prevention of neurological disorders, such as neuropsychiatric and neurodegenerative diseases, as well as pain, ataxia and convulsion. The compounds of the invention have the general structure: wherein A is NH or S. Q is a member selected from CR 1 and N. X and Y are members independently selected from O, S, CR 2 , N and NH. R 1 , R 2 and R 4 are members independently selected from H and F, provided that at least one member selected from R 1 , R 2 and R 4 is F. R 6 is a member selected from O − X + and OH, wherein X + is a positive ion, which is a member selected from inorganic positive ions and organic positive ions.

  这项发明提供了D-氨基酸氧化酶的新型抑制剂，以及包括该发明中化合物的药物组合物。该发明还提供了用于治疗和预防神经系统疾病，如神经精神病和神经退行性疾病，以及疼痛、共济失调和抽搐的方法。该发明中的化合物具有一般结构：其中A为NH或S。Q是从CR1和N中选择的成员。X和Y分别是从O、S、CR2、N和NH中独立选择的成员。R1、R2和R4是从H和F中独立选择的成员，前提是至少选择R1、R2和R4中的一个成员为F。R6是从O−X+和OH中选择的成员，其中X+是正离子，从无机正离子和有机正离子中选择的成员。