4-氧代-3,4-二氢噻吩并[3,2-d]嘧啶-2-羧酸乙酯 | 319442-19-8

• 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
• 中文名称: 4-氧代-3,4-二氢噻吩并[3,2-d]嘧啶-2-羧酸乙酯
• 英文名称: ethyl 4-oxo-3,4-dihydrothieno[3,2-d]pyrimidine-2-carboxylate
• 英文别名: ethyl 4-oxo-3H,4H-thieno[3,2-d]pyrimidine-2-carboxylate；Ethyl 4-oxo-3,4-dihydrothieno[3,2-d]pyrimidine-2-carboxylate；ethyl 4-oxo-3H-thieno[3,2-d]pyrimidine-2-carboxylate
• CAS: 319442-19-8
• 化学式: C₉H₈N₂O₃S
• 分子量: 224.24
• InChiKey: MZMHHCYVZKHGQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  96
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  4-氧代-3,4-二氢噻吩并[3,2-d]嘧啶-2-羧酸乙酯 在 sodium tetrahydroborate 、 三溴化磷 、 N,N-二异丙基乙胺 、 potassium iodide 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 2-((4-fluorophenyl)(methoxy)methyl)-N-(5-methyl-1H-pyrazol-3-yl)thieno[3,2-d]pyrimidin-4-amine
  参考文献：
  名称：

  [EN] THIENOPYRIDINE AND THIENOPYRIMIDINE COMPOUNDS AND METHODS OF USE THEREOF
  [FR] COMPOSÉS THIÉNOPYRIDINES ET THIÉNOPYRIMIDINES ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  本文提供了用于治疗JAK激酶介导疾病的噻吩并噻嘧啶化合物的化学式（I），包括JAK2激酶、JAK3激酶或TYK2激酶介导的疾病。还提供了包含这些化合物的药物组合物以及使用这些化合物和组合物的方法。

  公开号：

  WO2012030894A1
• 作为产物：
  描述：

  3-氨基-2-噻吩甲酸 在 吡啶 、 ammonium acetate 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 4-氧代-3,4-二氢噻吩并[3,2-d]嘧啶-2-羧酸乙酯
  参考文献：
  名称：

  Thieno[2,3-d]pyrimidine-2-carboxamides bearing a carboxybenzene group at 5-position: Highly potent, selective, and orally available MMP-13 inhibitors interacting with the S1″ binding site

  摘要：

  On the basis of X-ray co-crystal structures of matrix metalloproteinase-13 (MMP-13) in complex with its inhibitors, our structure-based drug design (SBDD) strategy was directed to achieving high affinity through optimal protein-ligand interaction with the unique S1 '' hydrophobic specificity pocket. This report details the optimization of lead compound 44 to highly potent and selective MMP-13 inhibitors based on fused pyrimidine scaffolds represented by the thienopyrimidin-4-one 26c. Furthermore, we have examined the release of collagen fragments from bovine nasal cartilage in response to a combination of IL-1 and oncostatin M. (C) 2014 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2014.07.025

文献信息

• SUBSTITUTED 2- AMIDOQUINAZOL-4-ONES AS MATRIX METALLOPROTEINASE-13 INHIBITORS
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US20150329556A1

  公开（公告）日：2015-11-19

  The present invention provides a novel amide derivative having a matrix metalloproteinase inhibitory activity, and useful as a pharmaceutical agent, which is a compound represented by the formula (I) wherein ring A is an optionally substituted, nitrogen containing heterocycle, ring B is an optionally substituted monocyclic homocycle or an optionally substituted monocyclic heterocycle, Z is N or NR 1 (R 1 is a hydrogen atom or an optionally substituted hydrocarbon group), is a single bond or a double bond, R 2 is a hydrogen atom or an optionally substituted hydrocarbon group, X is an optionally substituted spacer having 1 to 6 atoms, ring C is (1) an optionally substituted homocycle or (2) an optionally substituted heterocycle other than a ring represented by (II) (X′ is S, O, SO, or CH 2 ), and at least one of ring B and ring C has substituent(s), provided that N-(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]2 hydroxypropyl}5,6 dimethyl 4 oxo 1,4 dihydrothieno[2,3-d]pyrimidine-2-carboxamide is excluded, or a salt thereof.

  本发明提供了一种新型酰胺衍生物，具有基质金属蛋白酶抑制活性，并且作为药用剂是有用的，该化合物由以下式(I)表示，其中环A是一个可选择取代的含氮杂环，环B是一个可选择取代的单环同核环或可选择取代的单环杂环，Z是N或NR1（R1是氢原子或可选择取代的碳氢基团），是一个单键或双键，R2是氢原子或可选择取代的碳氢基团，X是一个具有1到6个原子的可选择取代的间隔物，环C是（1）一个可选择取代的同核环或（2）一个除了由（II）表示的环之外的可选择取代的杂环（X′是S、O、SO或CH2），并且环B和环C中至少有一个有取代基，但不包括N-(1S,2R)-1-(3,5-二氟苄基)-3-[(3-乙基苄基)氨基]2-羟基丙基}5,6-二甲基-4-氧代-1,4-二氢噻唑并[2,3-d]嘧啶-2-羧酰胺，或其盐。
• ALKYNYL ALCOHOLS AND METHODS OF USE
  申请人：Genentech, Inc.

  公开号：US20150057260A1

  公开（公告）日：2015-02-26

  The invention relates to compounds of Formula (0): wherein A 1 -A 8 , R 4 and R 5 each has the meaning as described herein. Compounds of Formula (0) and pharmaceutical compositions thereof are useful in the treatment of diseases and disorders in which undesired or over-activation of NF-kB signaling is observed.

  该发明涉及具有以下结构的化合物（0）：其中A1-A8，R4和R5分别具有如本文所述的含义。 公式（0）的化合物及其药物组成物在治疗观察到NF-kB信号不受欢迎或过度激活的疾病和紊乱中是有用的。
• [EN] ALKYNYL ALCOHOLS AND METHODS OF USE<br/>[FR] ALCOOLS ALCYNYLIQUES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015025026A1

  公开（公告）日：2015-02-26

  The invention relates to compounds of Formula (0): wherein A1-A8, R4 and R5 each has the meaning as described herein. Compounds of Formula (0) and pharmaceutical compositions thereof are useful in the treatment of diseases and disorders in which undesired or over-activation of NF-kB signaling is observed.

  该发明涉及以下式的化合物（0）：其中A1-A8，R4和R5分别具有如本文所述的含义。该式（0）的化合物及其药物组合物在治疗观察到NF-kB信号不良或过度激活的疾病和紊乱中是有用的。
• Thieno-and furopyrimidine derivatives as A2A-receptor antagonists
  申请人：Vernalis Research Limited

  公开号：US06787541B1

  公开（公告）日：2004-09-07

  Compounds of formula (I): wherein X is S. Compounds can be used for treating a disorder in which the blocking of purine receptors is beneficial.

  式(I)的化合物：其中X为S。该化合物可用于治疗一种需要阻断嘌呤受体有益的疾病。
• Thieno(3,2-d)pyrimidines and furano(3,2-d)pyimidines and their use as purinergic receptor antagonists
  申请人：——

  公开号：US20040097524A1

  公开（公告）日：2004-05-20

  A compound of formula (I), wherein X is S or O; R 1 is selected from H, alkyl, aryl, hydroxy, alkoxy, aryloxy, thioalkyl, thioaryl, halogen, CN, COR 5 , CO 2 R 5 , CONR 6 R 7 , CONR 5 NR 6 R 7 , NR 6 R 7 , NR 5 CONR 6 R 7 , NR 5 COR 6 , NR 5 CO 2 R 8 , and NR 5 SO 2 R 8 ; R 2 is selected from aryl attached via an unsaturated carbon atom; R 3 is selected from H, alkyl, hydroxy, alkoxy, halogen, CN and NO 2 ; R 4 is selected from H, alkyl, aryl, hydroxy, alkoxy, aryloxy, thioalkyl, thioaryl, halogen, CN, NO 2 , COR 5 , CO 2 R 5 , CONR 6 R 7 , CONR 5 NR 6 R 7 , NR 6 R 7 , NR 5 CONR 6 R 7 , NR 5 COR 6 , NR 5 CO 2 R 8 and NR 5 SO 2 R 8 ; R 5 , R 6 and R 7 are independently selected from H, alkyl and aryl or where R 6 and R 7 are in an (NR 6 R 7 ) group, R 6 and R 7 may be linked to form a heterocyclic group, or where R 5 , R 6 and R 7 are in a (CONR 5 NR 6 R 7 ) group, R 5 and R 6 may be linked to form a heterocyclic group; and R 8 is selected from alkyl and aryl, or a pharmaceutically acceptable salt thereof or prodrug thereof, and the use thereof in therapy and in the treatment or prevention of a disorder in which the blocking of purine receptors, particularly adenosine receptors and more particularly A 2A receptors, may be beneficial, particularly wherein said disorder is a movement disorder such a Parkinson's disease or said disorder is depression, cognitive or memory impairment, acute or chronic pain, ADHD or narcolepsy, or wherein said medicament is for neuroprotection in a subject. 1

  式（I）的化合物，其中X为S或O；R1选择自H，烷基，芳基，羟基，烷氧基，芳氧基，硫代烷基，硫代芳基，卤素，CN，COR5，CO2R5，CONR6R7，CONR5NR6R7，NR6R7，NR5CONR6R7，NR5COR6，NR5CO2R8和NR5SO2R8；R2选择自通过不饱和碳原子连接的芳基；R3选择自H，烷基，羟基，烷氧基，卤素，CN和NO2；R4选择自H，烷基，芳基，羟基，烷氧基，芳氧基，硫代烷基，硫代芳基，卤素，CN，NO2，COR5，CO2R5，CONR6R7，CONR5NR6R7，NR6R7，NR5CONR6R7，NR5COR6，NR5CO2R8和NR5SO2R8；R5，R6和R7独立选择自H，烷基和芳基，或者当R6和R7在（NR6R7）基团中时，R6和R7可以连接形成杂环基团，或者当R5，R6和R7在（CONR5NR6R7）基团中时，R5和R6可以连接形成杂环基团；R8选择自烷基和芳基，或其在治疗中的药用盐或前药，以及其在治疗或预防阻断嘌呤受体，特别是腺苷受体，尤其是A2A受体可能有益的紊乱中的使用，特别是其中所述紊乱是帕金森病等运动障碍或所述紊乱是抑郁症、认知或记忆障碍、急性或慢性疼痛、ADHD或嗜睡症，或者其中所述药物是用于受试者的神经保护。