tert-butyl 2-amino-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡喃类
• 英文名称: tert-butyl 2-amino-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carboxylate
• 英文别名: 2-Amino-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester
• 化学式: C₁₂H₁₇NO₃S
• mdl: MFCD25731481
• 分子量: 255.338
• InChiKey: KBYPTTZAZWQVQQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.583
• 拓扑面积：
  89.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-amino-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carboxylate 在 calcium carbonate 作用下， 以 吡啶 、 二氯甲烷 、 水 为溶剂， 反应 3.0h， 生成 (S)-tert-butyl 2-(3-(1-phenylethyl)thioureido)-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carboxylate
  参考文献：
  名称：

  Discovery, structure-activity relationship study and biological evaluation of 2-thioureidothiophene-3-carboxylates as a novel class of C-X-C chemokine receptor 2 (CXCR2) antagonists

  摘要：

  The C-X-C motif ligand 8 and C-X-C chemokine receptor 2 (CXCL8-CXCR2) axis is involved in pathogenesis of various diseases including inflammation and cancers. Various CXCR2 antagonists are under development for several diseases. Our previous high-throughput cell-based assay specific for CXCR2 has identified a pyrimidine-based compound CX797 acting on CXCR2 down-stream signaling. A lead optimization campaign through scaffold-hopping strategy led to a series of 2-thioureidothiophene-3-carboxylates (TUTP) as novel CXCR2 antagonists. Structure-activity relationship study of TUTPs led to the identification of compound 52 that significantly inhibited CXCR2-mediated beta-arrestin recruitment signaling (IC50 = 1.1 +/- 0.01 mu M) with negligible effect on CXCL8-mediated cAMP signaling and calcium flux. Similar to the known CXCR2 antagonist SB265610, compound 52 inhibited CXCL8-CXCR2 induced phosphorylation of ERK1/2. TUTP compounds also inhibited CXCL8-mediated cell migration and showed synergy with doxorubicin in ovarian cancer cells, thereby supporting TUTPs as promising compounds for cancer treatment. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112387
• 作为产物：
  描述：

  四氢吡喃酮 、 氰乙酸叔丁酯 在 吗啉 、 sulfur 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以86%的产率得到tert-butyl 2-amino-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carboxylate
  参考文献：
  名称：

  三环1,3-恶嗪-4-酮的合成及胆固醇酯酶和乙酰胆碱酯酶抑制的动力学分析。

  摘要：

  合成了一系列噻吩并[1,3]恶嗪-4-酮和噻吩并[1,3]噻嗪-4-酮，并研究了它们作为α/β水解酶胆固醇酯酶（CEase）和乙酰胆碱酯酶（AChE）的抑制剂。在噻吩上稠合的脂环族五或六元环的引入有利于抑制CEase。这类化合物被分析为真正的替代底物抑制剂。6,7-二氢-2-（二甲基氨基）-4H，5H-环戊[4,5]噻吩并[2,3-d] [1,3]恶嗪-4-酮（33）的K（i）值630 nM的样品对CEase催化降解的敏感性低。化合物33及其类似物不抑制AChE。在碱性氮原子上带有大的疏水取代基的四氢​​吡啶环的引入提供了对Chase完全无活性的AChE抑制剂。7-苄基5,6,7,8-四氢-2-（N-3，4-二甲氧基苄基-N-甲基氨基）-4H-吡啶基[4'，3'：4,5]噻吩并[2,3-d] [1,3]恶嗪-4-酮（21）的IC（50）抑制AChE的值为330 nM。得出了在无限抑制剂浓度

  DOI：

  10.1021/jm0508639

文献信息

• Synthesis of Tricyclic 1,3-Oxazin-4-ones and Kinetic Analysis of Cholesterol Esterase and Acetylcholinesterase Inhibition
  作者：Markus Pietsch、Michael Gütschow

  DOI：10.1021/jm0508639

  日期：2005.12.1

  3]oxazin-4-ones and thieno[1,3]thiazin-4-ones were synthesized and investigated as inhibitors of the alpha/beta hydrolases cholesterol esterase (CEase) and acetylcholinesterase (AChE). The introduction of a cycloaliphatic five- or six-membered ring fused at the thiophene was favorable for CEase inhibition. Such compounds were analyzed as true alternate substrate inhibitors. 6,7-Dihydro-2-(dimethylamino)-4H,5H-cyclopenta[4

  合成了一系列噻吩并[1,3]恶嗪-4-酮和噻吩并[1,3]噻嗪-4-酮，并研究了它们作为α/β水解酶胆固醇酯酶（CEase）和乙酰胆碱酯酶（AChE）的抑制剂。在噻吩上稠合的脂环族五或六元环的引入有利于抑制CEase。这类化合物被分析为真正的替代底物抑制剂。6,7-二氢-2-（二甲基氨基）-4H，5H-环戊[4,5]噻吩并[2,3-d] [1,3]恶嗪-4-酮（33）的K（i）值630 nM的样品对CEase催化降解的敏感性低。化合物33及其类似物不抑制AChE。在碱性氮原子上带有大的疏水取代基的四氢​​吡啶环的引入提供了对Chase完全无活性的AChE抑制剂。7-苄基5,6,7,8-四氢-2-（N-3，4-二甲氧基苄基-N-甲基氨基）-4H-吡啶基[4'，3'：4,5]噻吩并[2,3-d] [1,3]恶嗪-4-酮（21）的IC（50）抑制AChE的值为330 nM。得出了在无限抑制剂浓度
• Rab7 GTPase inhibitors and related methods of treatment
  申请人：Wandinger-Ness Angela

  公开号：US08765803B1

  公开（公告）日：2014-07-01

  This invention relates to compounds and their use as inhibitors or activators of Rab7 GTPase to treat or prevent the onset of Rab 7 GTPase-associated disorders such as neuropathies, cancer, metabolic diseases of bone and lipid storage. The invention is also applicable to infectious diseases where Rab7 is inactivated or its protein-protein interactions are modulated to facilitate intracellular survival of pathogens. The compound described acts as a competitive inhibitor of nucleotide binding and as such also has utility as a scaffold for targeting other small GTPases. In one aspect, methods of treatment of the invention are used to treat or prevent the onset of hereditary sensory neuropathies such as Charcot-Marie-Tooth type 2B disease. Related pharmaceutical compositions, assays, and drug screens are also provided.

  这项发明涉及化合物及其作为Rab7 GTP酶的抑制剂或激活剂的用途，用于治疗或预防Rab 7 GTP酶相关疾病的发作，如神经病变、癌症、骨代谢疾病和脂质储存疾病。该发明还适用于Rab7被灭活或其蛋白质-蛋白质相互作用被调节以促进病原体细胞内存活的传染病。所描述的化合物作为核苷酸结合的竞争性抑制剂，因此还可作为靶向其他小GTP酶的支架。在一个方面，该发明的治疗方法被用于治疗或预防遗传性感觉神经病变，如沙尔科-玛丽-图特2B型疾病的发作。还提供相关的药物组合物、分析和药物筛选。
• [EN] MODULATORS OF PROTEIN TYROSINE PHOSPHATASES<br/>[FR] MODULATEURS DE PROTEINE-TYROSINE-PHOSPHATASES
  申请人：NOVO NORDISK A/S

  公开号：WO1999046237A1

  公开（公告）日：1999-09-16

  (EN) The present invention provides novel compounds, novel compositions, methods of their use, and methods of their manufacture, where such compounds are pharmacologically useful inhibitors of Protein Tyrosine Phosphatases (PTPases, PTPs) such as PTP1B, TC-PTP, CD45, SHP-1, SHP-2, PTP$g(a), PTP$g(e), PTP$g(m), PTP$g(d), PTP$g(s), PTP$g(z), PTP$g(b), PTPD1, PTPD2, PTPH1, PTP-MEG1, PTP-LAR, and HePTP. These compounds are indicated in the management or treatment of a broad range of diseases such as autoimmune diseases, acute and chronic inflammation, osteoporosis, various forms of cancer and malignant diseases, and type I diabetes and type II diabetes.(FR) Cette invention se rapporte à de nouveaux composés, à de nouvelles compositions, à des procédés pour leur utilisation et à des procédés pour leur fabrication, ces composés constituant des inhibiteurs pharmacologiquement utiles des protéine-tyrosine-phosphatases (PTPases, PTP) telles que PTP1B, TC-PTP, CD45, SHP-1, SHP-2, PTP$g(a), PTP$g(e), PTP$g(m), PTP$g(d), PTP$g(s), PTP$g(z), PTP$g(b), PTPD1, PTPD2, PTPH1, PTP-MEG1, PTP-LAR ET HePTP. Ces composés sont indiqués dans la prise en charge ou le traitement d'une large gamme de maladies, telles que les maladies auto-immunes, les inflammations aiguës et chroniques, l'ostéoporose, diverses formes de cancer et d'affections malignes, ainsi que le diabète de type I et le diabète de type II.

  本发明提供了新型化合物、新型组合物、它们的使用方法和制造方法，这些化合物是药理学上有用的蛋白酪氨酸磷酸酶（PTPases，PTPs）抑制剂，如PTP1B、TC-PTP、CD45、SHP-1、SHP-2、PTP $g（a）、PTP $g（e）、PTP $g（m）、PTP $g（d）、PTP $g（s）、PTP $g（z）、PTP $g（b）、PTPD1、PTPD2、PTPH1、PTP-MEG1、PTP-LAR和HePTP。这些化合物适用于治疗广泛的疾病，如自身免疫疾病、急性和慢性炎症、骨质疏松症、各种癌症和恶性疾病，以及1型和2型糖尿病的管理或治疗。
• [EN] MODULATORS OF PROTEIN TYROSINE PHOSPHATASES (PTPASES)<br/>[FR] MODULATEURS DE PROTEINE TYROSINE PHOSPHATASES (PTPASES)
  申请人：NOVO NORDISK A/S

  公开号：WO1999046267A1

  公开（公告）日：1999-09-16

  (EN) The present invention provides novel compounds, novel compositions, methods of their use, and methods of their manufacture, where such compounds are pharmacologically useful inhibitors of Protein Tyrosine Phosphatases (PTPases) such as PTP1B, CD45, SHP-1, SHP-2, PTP$g(a), LAR and HePTP or the like. The compounds are useful in the treatment of type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance, obesity, immune dysfunctions including autoimmunity diseases with dysfunctions of the coagulation system, allergic diseases including asthma, osteoporosis, proliferative disorders including cancer and psoriasis, diseases with decreased or increased synthesis or effects of growth hormone, diseases with decreased or increased synthesis of hormones or cytokines that regulate the release of/or response to growth hormone, diseases of the brain including Alzheimer's disease and schizophrenia, and infectious diseases.(FR) L'invention concerne de nouveaux composés, de nouvelles compositions, des méthodes d'utilisation et des méthodes de fabrication associées. Lesdits composés sont des inhibiteurs de protéine tyrosine phosphatases (PTPases) pharmacologiquement utiles, tels que PTP1B, CD45, SHP-1, SHP-2, PTP$g(a), LAR et HePTP ou analogues. Ces composés sont utiles dans le traitement du diabète du type I, du diabète du type II, de l'intolérance au glucose, de la résistance insulinique, de l'obésité, des dysfonctionnements immunitaires parmi lesquels les maladies auto-immunes entraînant un dysfonctionnement du système de coagulation, des maladies allergiques parmi lesquelles l'asthme, de l'ostéoporose, des troubles proliférants parmi lesquels le cancer et le psoriasis, des maladies entraînant une baisse ou une augmentation de la synthèse ou des effets des hormones de croissance, des maladies entraînant une baisse ou une augmentation de la synthèse des hormones ou cytokines qui régulent la libération d'hormones de croissance ou la réaction à ces hormones, des maladies cérébrales parmi lesquelles la maladie d'Alzheimer et la schizophrénie, et des maladies infectieuses.

  该发明提供了新型化合物、新型组合物、它们的使用方法和制备方法，其中这些化合物是药理学上有用的蛋白酪氨酸磷酸酶（PTPases）抑制剂，如PTP1B、CD45、SHP-1、SHP-2、PTP$g(a)、LAR和HePTP等。这些化合物在治疗I型糖尿病、II型糖尿病、糖耐量受损、胰岛素抵抗、肥胖症、免疫功能障碍包括自身免疫疾病与凝血系统功能障碍、包括哮喘等过敏性疾病、骨质疏松症、增生性疾病包括癌症和银屑病、生长激素合成或效应减少或增加的疾病、调节生长激素释放或响应的激素或细胞因子合成减少或增加的疾病、包括阿尔茨海默病和精神分裂症的大脑疾病以及传染性疾病中具有用处。
• Modulators of protein tyrosine phosphatases (PTPases)
  申请人：——

  公开号：US20030069267A1

  公开（公告）日：2003-04-10

  The present invention provides novel compounds, novel compositions, methods of their use, and methods of their manufacture, where such compounds are pharmacologically useful inhibitors of Protein Tyrosine Phosphatases (PTPase's) such as PTP1B, CD45, SHP-1, SHP-2, PTP&agr;, LAR and HePTP or the like. The compounds are useful in the treatment of type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance, obesity, immune dysfunctions including autoimmunity diseases with dysfunctions of the coagulation system, allergic diseases including asthma, osteoporosis, proliferative disorders including cancer and psoriasis, diseases with decreased or increased synthesis or effects of growth hormone, diseases with decreased or increased synthesis of hormones or cytokines that regulate the release of/or response to growth hormone, diseases of the brain including Alzheimer's disease and schizophrenia, and infectious diseases.

  本发明提供了新型化合物、新型组合物、它们的使用方法和制造方法，其中这些化合物是药理学上有用的蛋白酪氨酸磷酸酶（PTPase's）抑制剂，如PTP1B、CD45、SHP-1、SHP-2、PTP&agr;、LAR和HePTP等。这些化合物可用于治疗I型糖尿病、II型糖尿病、糖耐量受损、胰岛素抵抗、肥胖症、免疫功能障碍，包括凝血系统功能障碍的自身免疫性疾病、包括哮喘在内的过敏性疾病、骨质疏松症、增生性疾病，包括癌症和银屑病、合成减少或增加或对生长激素释放或响应调节的激素或细胞因子的疾病，包括阿尔茨海默病和精神分裂症的脑部疾病以及传染病。