4-chloro-2-ethylthieno[3,2-d]pyrimidine

• 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: 4-chloro-2-ethylthieno[3,2-d]pyrimidine
• 化学式: C₈H₇ClN₂S
• 分子量: 198.676
• InChiKey: MMMNKOCOCDWGIE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-甲基噻唑 、 4-chloro-2-ethylthieno[3,2-d]pyrimidine 在 四(三苯基膦)钯 正丁基锂 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 17.25h， 生成 2-ethyl-4-(4-methyl-2-thiazolyl)thieno[3,2-d]pyrimidine
  参考文献：
  名称：

  Antagonists of the human adenosine A2A receptor. Part 2: Design and synthesis of 4-arylthieno[3,2-d]pyrimidine derivatives

  摘要：

  We describe herein the discovery and development of a series of 4-arylthieno[3,2-d]pyrimidines which are potent adenosine A(2A) receptor antagonists. These novel compounds show high degrees of selectivity against the human A(1), A(2B) and A(3) receptor sub-types. Moreover, a number of these compounds show promising activity in vivo, suggesting potential utility in the treatment of Parkinson's disease. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.03.076
• 作为产物：
  描述：

  3-氨基噻吩-2-甲酰胺 在 sodium hydroxide 、 三氯氧磷 作用下， 反应 1.83h， 生成 4-chloro-2-ethylthieno[3,2-d]pyrimidine
  参考文献：
  名称：

  Design, Synthesis, and Biological Activities of New Thieno[3,2-d]pyrimidines as Selective Type 4 Phosphodiesterase Inhibitors

  摘要：

  A common pharmacophore for compounds structurally related to nitraquazone has been derived. Using this pharmacophore, new structures have been designed, synthesized, and evaluated for their inhibitory potencies against cyclic adenosine 5'-monophosphate (cAMP) specific phosphodiesterase (PDE 4). From these compounds, 4-benzylamino-2-butylthieno[3,2-d]-pyrimidine (4) was selected for optimization. The effects of changes to the lipophilic groups and the amino linkage on the PDE 4 activity have been investigated. As a result, some potent PDE 4 inhibitors, selective with respect to PDE 3, have been identified. A selected group of compounds have been further evaluated for their ability to displace [H-3]rolipram from its binding site and also to potentiate isoprenaline-induced cAMP accumulation in isolated guinea pig eosinophils. Of these, 2-butyl-4-cyclohexylaminothieno[3,2-d]pyrimidine (33) has an interesting profile, with an important improvement in PDE 4/[H-3]rolipram ratio with respect to reference drugs, and good activity in cAMP potentiation, consistent with efficient cell penetration.

  DOI：

  10.1021/jm981012m

文献信息

• Microwave-assisted synthesis of potent PDE7 inhibitors containing a thienopyrimidin-4-amine scaffold
  作者：Ana I. Sánchez、Ricardo Meneses、José M. Mínguez、Araceli Núñez、Rafael R. Castillo、Fabiana Filace、Carolina Burgos、Juan J. Vaquero、Julio Álvarez-Builla、Alvaro Cortés-Cabrera、Federico Gago、Emma Terricabras、Víctor Segarra

  DOI：10.1039/c4ob00175c

  日期：——

  Thienopyrimidin-4-amines have been synthesized, evaluated and modelled as phosphodiesterase inhibitors.

  噻唑嘧啶-4-胺已被合成、评估并建模为磷酸二酯酶抑制剂。
• Antagonists of the human adenosine A2A receptor. Part 1: Discovery and synthesis of thieno[3,2-d]pyrimidine-4-methanone derivatives
  作者：Roger J. Gillespie、David R. Adams、David Bebbington、Karen Benwell、Ian A. Cliffe、Claire E. Dawson、Colin T. Dourish、Allan Fletcher、Suneel Gaur、Paul R. Giles、Allan M. Jordan、Antony R. Knight、Lars J.S. Knutsen、Anthony Lawrence、Joanne Lerpiniere、Anil Misra、Richard H.P. Porter、Robert M. Pratt、Robin Shepherd、Rebecca Upton、Simon E. Ward、Scott M. Weiss、Douglas S. Williamson

  DOI：10.1016/j.bmcl.2008.03.075

  日期：2008.5

  The (-)-(11R,2'S)-enantiomer of the antimalarial drug mefloquine has been found to be a reasonably potent and moderately selective adenosine A(2A) receptor antagonist. Further investigation of this compound has led to the discovery of a series of keto-aryl thieno[3,2-d]pyrimidine derivatives, which are potent and selective antagonists of the adenosine A(2A) receptor. These derivatives show selectivity

  已经发现抗疟药甲氟喹的（-）-（11R，2'S）-对映异构体是一种有效的，中等选择性的腺苷A（2A）受体拮抗剂。对该化合物的进一步研究导致发现了一系列酮基-芳基噻吩并[3,2-d]嘧啶衍生物，它们是腺苷A（2A）受体的有效和选择性拮抗剂。这些衍生物显示出对A（1）受体的选择性。此外，这些化合物中的一些已显示在常用模型中具有体内活性，这提示了治疗帕金森氏病的潜力。
• Piperazinylpyrimidines as .beta.-adrenergic receptor blockers
  申请人：Merck & Co., Inc.

  公开号：US04994464A1

  公开（公告）日：1991-02-19

  Certain piperazinylpyrimidines have pronounced .beta.-adrenergic blocking properties and some of the compounds are particularly useful in the treatment of elevated intraocular pressure and glaucoma.

  某些哌嗪基嘧啶具有明显的β-肾上腺素能阻滞作用，其中一些化合物在治疗眼压升高和青光眼方面特别有用。
• 7,8-dihydro-4-(1-pierazinyl)-6H-thiopyrano-[3,2-d] pyrimidines as
  申请人：Merck & Co., Inc.

  公开号：US04889856A1

  公开（公告）日：1989-12-26

  7,8-Dihydro-4-(1-piperazinyl)-6H-thiopyranopyrimidines have .beta.-adrenergic blocking properties and are thus useful in the treatment of cardiovascular ailments known to be amenable to .beta.-blocker therapy. Certain of the compounds are useful in the treatment of elevated intraocular pressure by topical ocular administration.

  7,8-二氢-4-(1-哌嗪基)-6H-硫代吡咯烷嘧啶具有β-肾上腺素受体阻滞作用，因此在治疗已知适用于β-受体阻滞剂治疗的心血管疾病方面非常有用。其中某些化合物通过局部眼用可用于治疗眼内压升高。
• Thieno(3,2-d)pyrimidines and furano(3,2-d)pyramidines and their use as purinergic receptor antagonists
  申请人：Gillespie Roger John

  公开号：US20080153820A1

  公开（公告）日：2008-06-26

  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 5 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 3 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.

  化合物的化学式为(I)，其中X为S或O; R1选自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、CONR5R7、CONR5NR6R7、NR6R7、NR5CONR6R7、NR5COR6、NR5CO2R8和NR5SO2R8; R2选自通过不饱和碳原子连接的芳基; R3选自H、烷基、羟基、烷氧基、卤素、CN和NO2; R3选自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分别选自H、烷基和芳基，或者其中R6和R7在(NR6R7)基团中，R6和R7可以连接形成杂环基团，或者其中R5、R6和R7在(CONR5NR6R7)基团中，R5和R6可以连接形成杂环基团; R8选自烷基和芳基，或其药学上可接受的盐或前药，以及在治疗和治疗阻断嘌呤受体，特别是腺苷受体，尤其是A2A受体可能有益的紊乱的使用，特别是其中该紊乱是运动紊乱，如帕金森病或该紊乱是抑郁症、认知或记忆障碍、急性或慢性疼痛、ADHD或嗜睡症，或者其中该药物是用于对受试者进行神经保护。