(Z)-5-(benzo[d]thiazol-6-ylmethylene)-2-thioxoimidazolidin-4-one

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (Z)-5-(benzo[d]thiazol-6-ylmethylene)-2-thioxoimidazolidin-4-one
• 英文别名: (5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-sulfanylideneimidazolidin-4-one
• 化学式: C₁₁H₇N₃OS₂
• 分子量: 261.328
• InChiKey: KVKWXEDCCDYLBI-BAQGIRSFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (Z)-5-(benzo[d]thiazol-6-ylmethylene)-2-thioxoimidazolidin-4-one 在 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.5h， 生成 (±)-(4Z)-4-(1,3-benzothiazol-6-ylmethylene)-2-[(2-hydroxy-2-phenylethyl)amino]-1H-imidazol-5-one
  参考文献：
  名称：

  NEW IMIDAZOLONE DERIVATIVES AS INHIBITORS OF PROTEIN KINASES IN PARTICULAR DYRK1A, CLK1 AND/OR CLK4

  摘要：

  本发明涉及一种化合物，其化学式为（I），其中R1代表（C1-C6）烷基基团，螺环（C5-C11）双环环，融合苯基团，取代苯基团，R'-L-基团，其中L是一个单键或（Ci-C3）烷二基基团，而R'代表（C3-C8）环烷基团，桥接（C6-C10）环烷基团，（C3-C8）杂环烷基团，或（C3-C8）杂芳基团，或者R'-L-基团，其中L是一个（Ci-C3）烷二基基团，而R'是一个可选择取代的苯基团或其任何药用盐。本发明还涉及包含化合物（I）的组合物，以及制造所述化合物的方法以及其合成中间体。它还涉及所述化合物用作药物，特别是用于治疗和/或预防与唐氏综合症、阿尔茨海默病、痴呆症、tau蛋白病、帕金森病、CDKL5缺陷症、菲兰-麦克德米德综合症、自闭症、糖尿病、叶酸和蛋氨酸代谢调节、骨关节炎、杜兴氏肌营养不良、多种癌症、神经炎症、贫血和感染以及体温调节相关的认知缺陷。

  公开号：

  EP3904354A1
• 作为产物：
  描述：

  2-硫代乙内酰脲 、 6-苯并噻唑甲醛 在 哌啶 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 以88 %的产率得到(Z)-5-(benzo[d]thiazol-6-ylmethylene)-2-thioxoimidazolidin-4-one
  参考文献：
  名称：

  Leucettinibs，一类 DYRK/CLK 激酶抑制剂，灵感源自海洋海绵天然产物 Leucetamine B

  摘要：

  双特异性酪氨酸磷酸化调节激酶 (DYRK) 和 cdc2 样激酶 (CLK) 最近因其在各种病理学中的重要参与而引起了人们的关注。我们在此描述了一系列源自亮氨酰胺和海洋天然产物亮氨酰胺 B 的 DYRK/CLK 抑制剂。合成了 45 种带有融合的 [6 + 5]-杂芳基亚甲基的N 2-官能化 2-氨基咪唑啉-4-酮。苯并噻唑-6-基亚甲基被选为 15 个不同杂芳基亚甲基中最有效的残基。合成并广泛表征了186 个带有苯并噻唑-6-基亚甲基的N 2-取代 2-氨基咪唑啉-4-酮，统称为 Leucettinib。鉴定出亚纳摩尔 IC 50 （DYRK1A 为 0.5-20 nM）抑制剂，并在 DYRK1A 中对一种 Leucettinib 进行建模，并与 CLK1 和较弱抑制的脱靶 CSNK2A1 共结晶。合成了 Leucettinib 的激酶失活异构体（DYRK1A 上 >3–10 μM），称为

  DOI：

  10.1021/acs.jmedchem.3c00884

文献信息

• Systematic diversification of benzylidene heterocycles yields novel inhibitor scaffolds selective for Dyrk1A, Clk1 and CK2
  作者：Marica Mariano、Rolf W. Hartmann、Matthias Engel

  DOI：10.1016/j.ejmech.2016.02.017

  日期：2016.4

  The dual-specificity tyrosine-regulated kinase 1A (Dyrk1A) has gathered much interest as a pharmacological target in Alzheimer's disease (AD), but it plays a role in malignant brain tumors as well. As both diseases are multi-factorial, further protein kinases, such as Clk1 and CK2, were proposed to contribute to the pathogenesis. We designed a new class of α-benzylidene–γ-butyrolactone inhibitors that

  双特异性酪氨酸调节激酶​​1A（Dyrk1A）作为阿尔茨海默氏病（AD）的药理靶标引起了广泛兴趣，但它在恶性脑肿瘤中也起着重要作用。由于两种疾病都是多因素的，因此提出了进一步的蛋白激酶，例如Clk1和CK2，来促进发病机理。我们设计了一类新型的α-亚苄基-γ-丁内酯抑制剂，该抑制剂对Dyrk1A和/或Clk1的微摩尔浓度低，并且在最常报道的脱靶激酶中具有良好的选择性。杂环部分的系统取代使人们能够以有趣的选择性分布获得更多抑制剂类别，这表明亚苄基杂环为开发CMGC激酶家族成员Dyr1A / 1B，Clk1 / 4和CK2的抑制剂提供了多功能的工具箱。在基于细胞的测定中证明了抑制Dyrk1A介导的tau磷酸化的功效。还获得了多靶点但非非特异性激酶抑制剂，其共抑制了脂质激酶PI3Kα/γ。这些化合物显示出在低微摩尔范围内抑制U87MG细胞的增殖。基于分子特性，此处描述的抑制剂有望实现CNS活性。
• [EN] NOVEL HETEROCYCLIC DERIVATIVES WITH CARDIOMYOCYTE PROLIFERATION ACTIVITY FOR TREATMENT OF HEART DISEASES<br/>[FR] NOUVEAUX DÉRIVÉS HÉTÉROCYCLIQUES AYANT UNE ACTIVITÉ DE PROLIFÉRATION DE CARDIOMYOCYTES POUR LE TRAITEMENT DE MALADIES CARDIAQUES
  申请人：UNIV TONGJI

  公开号：WO2021115489A1

  公开（公告）日：2021-06-17

  Provided are novel heterocyclic derivatives with cardiomyocyte proliferation activity for treatment of heart diseases. Specifically, provided are the compounds of formula (I) or pharmaceutically acceptable salts, stereoisomers, solvates or prodrugs, preparation method thereof, application thereof and pharmaceutical composition useful for treatment of heart diseases.

  提供了具有心肌细胞增殖活性的新型杂环衍生物，用于治疗心脏疾病。具体提供了式（I）的化合物或药用盐、立体异构体、溶剂合物或前药，其制备方法、应用以及用于治疗心脏疾病的药物组合物。
• [EN] NOVEL HETEROCYCLIC DERIVATIVES WITH CARDIOMYOCYTE PROLIFERATION ACTIVITY FOR TREATMENT OF HEART DISEASES<br/>[FR] NOUVEAUX DÉRIVÉS HÉTÉROCYCLIQUES À ACTIVITÉ DE PROLIFÉRATION DE CARDIOMYOCYTES POUR LE TRAITEMENT DE MALADIES CARDIAQUES
  申请人：UNIV TONGJI

  公开号：WO2021114314A1

  公开（公告）日：2021-06-17

  Provided herein are novel heterocyclic derivatives with cardiomyocyte proliferation activity for treatment of heart diseases. Specifically, it provides the compounds of formula (I) or pharmaceutically acceptable salts, stereoisomers, solvates or prodrugs, preparation method therefor and application thereof. It also provides pharmaceutical composition useful for treatment of heart diseases.
• [EN] NEW IMIDAZOLONE DERIVATIVES AS INHIBITORS OF PROTEIN KINASES IN PARTICULAR DYRK1A, CLK1 AND/OR CLK4<br/>[FR] NOUVEAUX DÉRIVÉS D'IMIDAZOLONE EN TANT QU'INHIBITEURS DE PROTÉINE KINASES, EN PARTICULIER DYRK1A, CLK1 ET/OU CLK4
  申请人：PERHA PHARMACEUTICALS

  公开号：WO2021219828A1

  公开（公告）日：2021-11-04

  The present invention relates to a compound of formula (I) wherein R1 represents a (C1-C6)alkyl group, a spiro(C5-C11)bicyclic ring, a fused phenyl group, a substituted phenyl group, a R'-L- group, wherein L is either a single bond or a (C1-C3)alkanediyl group, and R' represents a (C3-C8)cycloalkyl group, a bridged (C6- C10)cycloalkyl group, a (C3-C8)heterocycloalkyl group, or a (C3-C8)heteroaryl group, or a R'-L- group wherein L is a (C1-C3)alkanediyl group, and R' is an optionally substituted phenyl group, and wherein R2 represents a hydrogen atom or a (C1-C3)alkyl group or any of its pharmaceutically acceptable salt. The present invention further relates to a composition comprising a compound of formula (I) and a process for manufacturing said compound as well as its synthesis intermediates. It also relates to said compound for use as a medicament, in particular in the treatment and/or prevention of cognitive deficits associated with Down syndrome; Alzheimer's disease; dementia; tauopathies; Parkinson's disease; CDKL5 Deficiency Disorder; Phelan- McDermid syndrome; autism; type 1 and type 2 diabetes; abnormal folate and methionine metabolism; osteoarthritis; Duchenne muscular dystrophy; several cancers; neuroinflammation, anemia and viral and unicellular infections and for regulating body temperature.
• NEW IMIDAZOLONE DERIVATIVES AS INHIBITORS OF PROTEIN KINASES IN PARTICULAR DYRK1A, CLK1 AND/OR CLK4
  申请人：Perha Pharmaceuticals

  公开号：EP3904354A1

  公开（公告）日：2021-11-03

  The present invention relates to a compound of formula (I) wherein R1 represents a (C1-C6)alkyl group, a spiro(C5-C11)bicyclic ring, a fused phenyl group, a substituted phenyl group, a R'-L- group, wherein L is either a single bond or a (Ci-C3)alkanediyl group, and R' represents a (C3-C8)cycloalkyl group, a bridged (C6-C10)cycloalkyl group, a (C3-C8)heterocycloalkyl group, or a (C3-C8)heteroaryl group, or a R'-L- group wherein L is a (Ci-C3)alkanediyl group, and R' is a an optionally substituted phenyl group or any of its pharmaceutically acceptable salt. The present invention further relates to a composition comprising a compound of formula (I) and a process for manufacturing said compound as well as its synthesis intermediates. It also relates to said compound for use as a medicament, in particular in the treatment and/or prevention of cognitive deficits associated with Down syndrome; Alzheimer's disease; dementia; tauopathies; Parkinson's disease; CDKL5 Deficiency Disorder; Phelan-McDermid syndrome; autism; diabetes; regulation of folate and methionine metabolism; osteoarthritis; Duchenne muscular dystrophy; several cancers; neuroinflammation, anemia and infections and for regulating body temperature.

  本发明涉及一种化合物，其化学式为（I），其中R1代表（C1-C6）烷基基团，螺环（C5-C11）双环环，融合苯基团，取代苯基团，R'-L-基团，其中L是一个单键或（Ci-C3）烷二基基团，而R'代表（C3-C8）环烷基团，桥接（C6-C10）环烷基团，（C3-C8）杂环烷基团，或（C3-C8）杂芳基团，或者R'-L-基团，其中L是一个（Ci-C3）烷二基基团，而R'是一个可选择取代的苯基团或其任何药用盐。本发明还涉及包含化合物（I）的组合物，以及制造所述化合物的方法以及其合成中间体。它还涉及所述化合物用作药物，特别是用于治疗和/或预防与唐氏综合症、阿尔茨海默病、痴呆症、tau蛋白病、帕金森病、CDKL5缺陷症、菲兰-麦克德米德综合症、自闭症、糖尿病、叶酸和蛋氨酸代谢调节、骨关节炎、杜兴氏肌营养不良、多种癌症、神经炎症、贫血和感染以及体温调节相关的认知缺陷。