1-isobutyl-3-methyl-2,4-dioxo-6-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carboxylic acid | 491614-13-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 1-isobutyl-3-methyl-2,4-dioxo-6-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carboxylic acid
• 英文别名: 1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-2,4-dioxo-6-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)thieno[2,3-d]pyrimidine-5-carboxylic acid；1,2,3,4-Tetrahydro-3-methyl-1 (isobutyl)-2,4-dioxo-6-(1h-pyrrolo[2,3,b]pyridin-3-ylmethyl)thieno[2,3,d]pyrimidine-5-carboxylic acid；3-methyl-1-(2-methylpropyl)-2,4-dioxo-6-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)thieno[2,3-d]pyrimidine-5-carboxylic acid
• CAS: 491614-13-2
• 化学式: C₂₀H₂₀N₄O₄S
• 分子量: 412.469
• InChiKey: PBSPZLGNYOUELC-UHFFFAOYSA-N

物化性质

• 密度：
  1.425±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  135
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-isobutyl-3-methyl-2,4-dioxo-6-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carboxylic acid 、 (R)-3-羟基吡咯烷盐酸盐 生成 5-{[(3R)-3-hydroxypyrrolidin-1-yl]carbonyl}-3-methyl-1-(2-methylpropyl)-6-{1H-pyrrolo[2,3-b]pyridin-3-ylmethyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione
  参考文献：
  名称：

  Potent blockers of the monocarboxylate transporter MCT1: Novel immunomodulatory compounds

  摘要：

  A novel series of potent blockers of the monocarboxylate transporter, MCT1, is disclosed. From very potent but lipophilic lead compounds, systematic changes to all parts of the molecule, targeting reduction in log D, afforded compounds with significantly improved overall properties. These Compounds show potent immunomodulatory activity. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.01.024
• 作为产物：
  描述：

  methyl 6-bromomethyl-1-isobutyl-3-methyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carboxylate 在 sodium hydroxide 、 sodium hydride 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 生成 1-isobutyl-3-methyl-2,4-dioxo-6-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carboxylic acid
  参考文献：
  名称：

  Potent blockers of the monocarboxylate transporter MCT1: Novel immunomodulatory compounds

  摘要：

  A novel series of potent blockers of the monocarboxylate transporter, MCT1, is disclosed. From very potent but lipophilic lead compounds, systematic changes to all parts of the molecule, targeting reduction in log D, afforded compounds with significantly improved overall properties. These Compounds show potent immunomodulatory activity. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.01.024

文献信息

• [EN] THIENOPYRIMIDINEDIONES AND THEIR USE IN THE MODULATION OF AUTOIMMUNE DISEASE<br/>[FR] THIENOPYRIMIDINEDIONES ET LEUR UTILISATION DANS LA MODULATION DE MALADIES AUTO-IMMUNES
  申请人：ASTRAZENECA AB

  公开号：WO2004065394A1

  公开（公告）日：2004-08-05

  The invention relates to thienopyrimidinediones of formula (1) wherein R1 and R2 each independently represent a C1-6akyl, C3-6alkyl, C3-6alkenyl, C3-5cycloalkylC1-3alkyl or C3-6cycloalkyl; each of which may be optionally substituted by 1 to 3 halogen atoms R3 is a group CO-G or SO2-G where G is a 5- or 6-membered ring containing a nitrogen atom and a second heteroatom selected from oxygen and sulphur adjacent to the nitrogen; the ring being substituted by at least one group as defined in the specification, Q is CR4R5 where R4 is hydrogen, fluorine or C1-6 alkyl and R5 is hydrogen, fluorine or hydroxy; and Ar is a 5-10-membered aromatic ring system wherein up to 4 ring atoms may be heteroatoms independently selected from nitrogen, oxygen and sulphur, the ring system being optionally substituted by one or more groups defined in the specification; as well as pharmaceutically acceptable salts and solvates thereof. Processes for their preparation of the compounds, pharmaceutical compositions containing them and their use in therapy, in particular in immunosuppression therapy are also described.

  该发明涉及式（1）的噻吩嘧啶二酮，其中R1和R2分别独立表示C1-6烷基，C3-6烷基，C3-6烯基，C3-5环烷基C1-3烷基或C3-6环烷基；每个基可能被1至3个卤原子取代，R3是一个基CO-G或SO2-G，其中G是一个含有氮原子和氮旁边选择的氧和硫的5-或6-成员环；该环被至少一个如规范中定义的基所取代，Q是CR4R5，其中R4是氢，氟或C1-6烷基，R5是氢，氟或羟基；Ar是一个5-10成员芳香环系统，其中最多4个环原子可以是独立选择的氮、氧和硫的杂原子，该环系统可以被一个或多个如规范中定义的基取代；以及其药学上可接受的盐和溶剂。还描述了制备这些化合物的方法，含有它们的药物组合物以及它们在疗法中的使用，特别是在免疫抑制疗法中的使用。
• Thienopyrimidinediones and their use in the modulation of autoimmune disease
  申请人：——

  公开号：US20040254198A1

  公开（公告）日：2004-12-16

  The invention relates to a compound of formula (1); wherein: R 1 and R 2 each independently represent a C 1-6 alkyl, C 3-6 alkenyl, C 3-6 cycloalkyl C 1-3 alkyl or C 3-6 cycloalkyl; each of which may be optionally substituted by 1 to 3 halogen atoms; R 3 is isoxyzolidin-2-ylcarbonyl or tetrahydroisoxazin-2-ylcarbonyl wherein each ring is optionally substituted by one hydroxy group; Q is CO— or C(R 4 )(R 5 )—(wherein R 4 is a hydrogen atom or C 1-4 alkyl and R 5 is a hydrogen atom or hydroxy group); Ar is a 5- to 10-membered aromatic ring system wherein up to 4 ring atoms may be heteroatoms independently selected from nitrogen, oxygen and sulphur, the ring system being optionally substituted by one or more substituents as defined in the specification. It also relates to methods of preparing, pharmaceutical compositions containing and methods of using the compound of the formula (1), particularly in the modulation of autoimmune disease. 1

  本发明涉及一种式子(1)的化合物; 其中：R1和R2各自独立地表示C1-6烷基，C3-6烯基，C3-6环烷基，C1-3烷基或C3-6环烷基; 每个基团可能被1至3个卤素原子取代; R3是异噁唑啉-2-基甲酰基或四氢异噁唑啉-2-基甲酰基，其中每个环可能被一个羟基取代; Q是CO-或C（R4）（R5）-（其中R4是氢原子或C1-4烷基，R5是氢原子或羟基）; Ar是一个5-至10-成员的芳香环系统，其中最多4个环原子可以独立地选自氮，氧和硫，该环系统可能被一个或多个定义在说明书中的取代基取代。它还涉及制备，含有该式（1）化合物的制药组合物以及使用该化合物的方法，特别是在自身免疫性疾病的调节中使用。
• Thienopyriminediones and their use in the modulation of autoimmune disease
  申请人：Guile David Simon

  公开号：US20060052400A1

  公开（公告）日：2006-03-09

  The invention relates to thienopyrimidinediones of formula (1) wherein R 1 and R 2 each independently represent a C 1-6 akyl, C 3-6 alkyl, C 3-6 alkenyl, C 3-5 cycloalkylC 1-3 alkyl or C 3-6 cycloalkyl; each of which may be optionally substituted by 1 to 3 halogen atoms R 3 is a group CO-G or SO 2 -G where G is a 5- or 6-membered ring containing a nitrogen atom and a second heteroatom selected from oxygen and sulphur adjacent to the nitrogen; the ring being substituted by at least one group as defined in the specification, Q is CR 4 R 5 where R 4 is hydrogen, fluorine or C 1-6 alkyl and R 5 is hydrogen, fluorine or hydroxy; and Ar is a 5-10-membered aromatic ring system wherein up to 4 ring atoms may be heteroatoms independently selected from nitrogen, oxygen and sulphur, the ring system being optionally substituted by one or more groups defined in the specification; as well as pharmaccutically acceptable salts and solvates thereof. Processes for their preparation of the compounds, pharmaceutical compositions containing them and their use in therapy, in particular in immunosuppressive therapy are also described.

  本发明涉及公式（1）的噻唑嘧啶二酮，其中R1和R2各自独立地表示C1-6烷基，C3-6烷基，C3-6烯基，C3-5环烷基C1-3烷基或C3-6环烷基；每个基团可以选择性地被1至3个卤素原子取代。R3是一个CO-G或SO2-G基团，其中G是一个5或6元环，包含一个氮原子和一个紧邻氮原子的第二个杂原子，可以选择性地被规范中定义的至少一个基团取代。Q是CR4R5，其中R4是氢，氟或C1-6烷基，R5是氢，氟或羟基；Ar是一个5-10元芳香环系统，其中最多4个环原子可以独立选择为氮，氧和硫杂原子，该环系统可以选择性地被规范中定义的一个或多个基团取代；以及其药学上可接受的盐和溶剂化合物。还描述了制备这些化合物的方法，包含它们的药物组成物以及它们在治疗中的应用，特别是在免疫抑制治疗中的应用。
• THIENOPYRIMIDINEDIONES AND THEIR USE IN THE MODULATION OF AUTOIMMUNE DISEASE
  申请人：Guile Simon David

  公开号：US20080214579A1

  公开（公告）日：2008-09-04

  The invention relates to thienopyrimidinediones of formula (1): in which R 1 , R 2 , R 3 , Q, and Ar are defined in the specification. The invention also relates to processes for the preparation of the compounds of formula (1), pharmaceutical compositions containing these compounds, and use of these compounds in therapy, in particular in immunosuppression therapy.

  本发明涉及公式（1）的噻唑嘧啶二酮： 其中R1、R2、R3、Q和Ar在说明书中有定义。本发明还涉及制备公式（1）化合物的过程，含有这些化合物的制药组合物，以及这些化合物在治疗中的使用，特别是在免疫抑制治疗中的使用。
• Chemical Compounds
  申请人：Reynolds Rachel Heulwen

  公开号：US20080153855A1

  公开（公告）日：2008-06-26

  The invention relates to a compound of formula (1) in which Q is —CO— or —C(R 4 )(R 5 )—, where R 4 is a hydrogen atom or C 1-4 alkyl and R 5 is a hydrogen atom or hydroxy group; and Ar is a 5- to 10-membered aromatic ring system where up to 4 ring atoms may be heteroatoms independently selected from nitrogen, oxygen and sulphur, the ring system being optionally substituted by one or more substituents as defined in the specification. It also relates to methods of preparing, pharmaceutical compositions containing and methods of using the compound of the formula (1), particularly in the modulation of autoimmune disease.

  本发明涉及一种化合物，其化学式为（1），其中Q为—CO—或—C（R4）（R5）—，其中R4为氢原子或C1-4烷基，R5为氢原子或羟基；Ar为一个5-到10-成员的芳香环系，其中最多4个环原子可以是氮、氧和硫的杂原子，该环系可以被定义在规范中的一个或多个取代基所取代。本发明还涉及制备方法、含有该化合物的药物组合物以及使用该化合物的方法，特别是在自身免疫性疾病的调节方面。