(Z)-5-((1H-indol-5-yl)methylene)thiazolidine-2,4-dione | 911714-37-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (Z)-5-((1H-indol-5-yl)methylene)thiazolidine-2,4-dione
• 英文别名: (5Z)-5-(1H-indol-5-ylmethylene)-1,3-thiazolidine-2,4-dione；(5Z)-5-(1H-indol-5-ylmethylidene)-1,3-thiazolidine-2,4-dione
• CAS: 911714-37-9
• 化学式: C₁₂H₈N₂O₂S
• 分子量: 244.274
• InChiKey: HMJGKIIGEUACRU-POHAHGRESA-N

物化性质

• 熔点：
  281-283 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 密度：
  1.551±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.49
• 重原子数：
  17.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  61.96
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  2,4-噻唑烷二酮 、 5-吲哚甲醛 在 哌啶 作用下， 以 乙醇 为溶剂， 以67%的产率得到(Z)-5-((1H-indol-5-yl)methylene)thiazolidine-2,4-dione
  参考文献：
  名称：

  5-Arylidenethioxothiazolidinones as Inhibitors of Tyrosyl–DNA Phosphodiesterase I

  摘要：

  Tyrosyl-DNA phosphodiesterase I (Tdp1) is a cellular enzyme that repairs the irreversible topoisomerase I (Top1)-DNA complexes and confers chemotherapeutic resistance to Top1 inhibitors. Inhibiting Tdp1 provides an attractive approach to potentiating clinically used Top1 inhibitors. However, despite recent efforts in studying Tdp1 as a therapeutic target, its inhibition remains poorly understood and largely underexplored. We describe herein the discovery of arylidene thioxothiazolidinone as a scaffold for potent Tdp1 inhibitors based on an initial tyrphostin lead compound 8. Through structure-activity relationship (SAR) studies we demonstrated that arylidene thioxothiazolidinones inhibit Tdp1 and identified compound 50 as a submicromolar inhibitor of Tdp1 (IC50 = 0.87 mu M). Molecular modeling provided insight into key interactions essential for observed activities. Some derivatives were also active against endogenous Tdp1 in whole cell extracts. These findings contribute to advancing the understanding on Tdp1 inhibition.

  DOI：

  10.1021/jm3008773

文献信息

• CHEMICAL COMPOUNDS 251
  申请人：Dakin Leslie

  公开号：US20110218182A1

  公开（公告）日：2011-09-08

  The invention relates to chemical compounds of formula (I), and salts thereof. In some embodiments, the invention relates to inhibitors or modulators of PIM-1 and/or PIM-2, and/or PIM-3 protein kinase activity or enzyme function. In still further embodiments, the invention relates to pharmaceutical compositions comprising compounds disclosed herein, and their use in the prevention and treatment of PIM kinase related conditions and diseases, preferably cancer.

  该发明涉及化学式(I)的化合物及其盐。在某些实施例中，该发明涉及PIM-1和/或PIM-2以及/或PIM-3蛋白激酶活性或酶功能的抑制剂或调节剂。在更进一步的实施例中，该发明涉及包含本文披露的化合物的药物组合物，以及它们在预防和治疗PIM激酶相关疾病和疾病，特别是癌症中的用途。
• Chemical Compounds 251
  申请人：AstraZeneca AB

  公开号：US20150051185A1

  公开（公告）日：2015-02-19

  The invention relates to chemical compounds of formula I, and salts thereof. In some embodiments, the invention relates to inhibitors or modulators of PIM-1 and/or PIM-2, and/or PIM-3 protein kinase activity or enzyme function. In still further embodiments, the invention relates to pharmaceutical compositions comprising compounds disclosed herein, and their use in the prevention and treatment of PIM kinase related conditions and diseases, preferably cancer.

  本发明涉及公式I的化合物及其盐。在某些实施例中，本发明涉及PIM-1和/或PIM-2，以及/或PIM-3蛋白激酶活性或酶功能的抑制剂或调节剂。在更进一步的实施例中，本发明涉及包含本文所披露的化合物的制药组合物，以及它们在预防和治疗PIM激酶相关的疾病和状况，尤其是癌症方面的应用。
• US8901307B2
  申请人：——

  公开号：US8901307B2

  公开（公告）日：2014-12-02
• [EN] THIAZOLIDINE AND OXAZOLIDINE INDOLES WITH HYPOCLYCEMIC ACTIVITY<br/>[FR] COMPOSES DE THIAZOLIDINE ET D'OXAZOLIDINE DE TYPE INDOLES AVEC ACTION HYPOGLYCEMIQUE
  申请人：NISSAN CHEMICAL INDUSTRIES, LTD.

  公开号：WO1996026207A1

  公开（公告）日：1996-08-29

  (EN) An indole type thiazolidine compound of formula (I) and its salt, wherein X1 is S or O; X2 is S, O or NH; Y is CR6R7 (R6 is a hydrogen atom or a C1-C7 alkyl group); R1 is a substituent at the 2-, 3-, 4-, 5-, 6- or 7- position of an indole ring and is a C1-C10 alkyl group, -Wk-V$i(l)-Z (Z is a C3-C10 cycloalkyl group, a C6-C14 aromatic group, a C1-C12 heterocyclic aromatic group, a C1-C6 heterocycloaliphatic group, etc., V is O, S, etc., W is a divalent C1-C6 saturated or C2-C6 unsaturated hydrocarbon group which may be substituted with at most 3 of hydroxyl, oxo and C1-C7 alkyl groups, and each of k and $i(l) is 0 or 1), -V-W-Z (V, W and Z are as defined above), -W-V-W-Z (V, W and Z are as defined above, and two W's may be the same or different), or R1 may be a hydrogen atom when Y is bonded to the 4-, 5-, 6- or 7-position of an indole ring; each of R2 and R3 is a substituent at the 2-, 3-, 4-, 5-, 6- or 7-position of an indole ring, and is independently a hydrogen atom, a C1-C7 alkyl group, or the like; R4 is a hydrogen atom or a C1-C7 alkyl group; R5 is a hydrogen atom or a carboxymethyl group; and Rn is a substituent at the 1-position of an indole ring, and is a hydrogen atom, a C1-C7 alkyl group, a C1-C7 alkoxy group, an alkylsulfonyl group, an arylsulfonyl group, or the like.(FR) Composé de thiazolidine de type indole, de formule (I) et son sel: où X1 est S ou O; X2 est S, O ou NH; Y est CR6R7 (R6 est un atome d'hydrogène ou un groupe alkyle C1-C7); R1 se substitue en position 2-, 3-, 4-, 5-, 6, ou 7- d'un noyau indole et consiste en un groupe alkyle C1-C10, -Wk-V$i(l)-Z (Z est un groupe cycloalkyle C3-C10, un groupe aromatique hétérocyclique C1-C12, un groupe hétérocycloaliphatique C1-C16, etc., V est O, S, etc., W est un groupe hydrocarbone divalent saturé C1-C6 ou insaturé C2-C6, qui peut comporter au plus 3 substitutions par des groupes hydroxyle, oxo et alkyle C1-C7, k et $i(l) étant égaux à 0 ou à 1), -V-W-Z (V, W et Z sont conformes aux définitions données plus haut), -W-V-W-Z (V, W et Z sont conformes aux définitions données plus haut, et les deux radicaux W peuvent être identiques ou différents), ou R1 peut être un atome d'hydrogène si Y est lié à la position 4-, 5- ou 7- d'un noyau indole; chacun des groupes R2 et R3 se substitue à la position 2-, 3-, 4-, 5-, 6-, ou 7- d'un noyau indole, et est constitué, de façon indépendante, d'un atome d'hydrogène, d'un groupe alkyle C1-C7 ou d'un groupe similaire; R4 est un atome d'hydrogène ou un groupe alkyle C1-C7; R5 est un atome d'hydrogène ou un groupe carboxyméthyle; et Rn se substitue à la position 1- d'un noyau indole, et est constitué d'un atome d'hydrogène, d'un groupe alkyle C1-C7, d'un groupe alkoxy, d'un group alkylsulfonyle, d'un groupe arylsulfonyle, ou d'un groupe similaire.
• [EN] CHEMICAL COMPOUNDS 251<br/>[FR] COMPOSÉS CHIMIQUES 251
  申请人：ASTRAZENECA AB

  公开号：WO2010001169A2

  公开（公告）日：2010-01-07

  The invention relates to chemical compounds of formula (I), and salts thereof. In some embodiments, the invention relates to inhibitors or modulators of PIM-1 and/or PIM-2, and/or PIM-3 protein kinase activity or enzyme function. In still further embodiments, the invention relates to pharmaceutical compositions comprising compounds disclosed herein, and their use in the prevention and treatment of PIM kinase related conditions and diseases, preferably cancer.