2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)thio)benzo[d]thiazole | 104499-49-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)thio)benzo[d]thiazole
• 英文别名: 2-{[(4-Methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfanyl}-1,3-benzothiazole；2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfanyl]-1,3-benzothiazole
• CAS: 104499-49-2
• 化学式: C₁₆H₁₆N₂OS₂
• 分子量: 316.448
• InChiKey: QZMVWAOUDXZPTO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  88.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)thio)benzo[d]thiazole 生成 2-[(4-Methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-1,3-benzothiazole
  参考文献：
  名称：

  摘要：

  DOI：
• 作为产物：
  描述：

  4-甲氧基-3,5-二甲基-2-羟甲基吡啶 在 氯化亚砜 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.5h， 生成 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)thio)benzo[d]thiazole
  参考文献：
  名称：

  Proton pump inhibitors selectively suppress MLL rearranged leukemia cells via disrupting MLL1-WDR5 protein-protein interaction

  摘要：

  Genetic rearrangements of the mixed lineage leukemia (MLL) leading to oncogenic MLL-fusion proteins (MLL-FPs). MLL-FPs occur in about 10% of acute leukemias and are associated with dismal prognosis and treatment outcomes which emphasized the need for new therapeutic strategies. In present study, by a cell-based screening in-house compound collection, we disclosed that Rabeprazole specially inhibited the proliferation of leukemia cells harboring MLL-FPs with little toxicity to non-MLL cells. Mechanism study showed Rabeprazole down-regulated the transcription of MLL-FPs related Hox and Meis1 genes and effectively inhibited MLL1 H3K4 methyltransferase (HMT) activity in MV4-11 cells bearing MLL-AF4 fusion protein. Displacement of MLL1 probe from WDR5 protein suggested that Rabeprazole may inhibit MLL1 HMT activity through disturbing MLL1-WDR5 protein-protein interaction. Moreover, other proton pump inhibitors (PPIs) also indicated the inhibition activity of MLL1-WDR5. Preliminary SARs showed the structural characteristics of PPIs were also essential for the activities of MLL1-WDR5 inhibition. Our results indicated the drug reposition of PPIs for MLL-rearranged leukemias and provided new insight for further optimization of targeting MLL1 methyltransferase activity, the MLL1-WDR5 interaction or WDR5. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.112027

文献信息

• Benzimidazoles, and their production formulation and use as gastric acid secretion inhibitors
  申请人：FISONS plc

  公开号：EP0174717A1

  公开（公告）日：1986-03-19

  There are described compounds of formula I, in which Rc is a nucleophilic nitrogen, oxygen or sulphur separated from the SO group by 1, 2, 3, 4 or 5 other atoms, R1, R1,R3 and R4, which may be the same or different, are each hydrogen, halogen, alkoxy, alkyl, fluoroalkyl, alkanoyl, RS(O)n-, -NO2, -N(R)2, -NHCOR, or -COOH or an ester or amide thereof, or an adjacent pair of R1, R2, R3 and R4 may in addition to the values given above, together form a chain -(CH2)x- or, together with the carbon atoms to which they are attached, form a 6 membered unsaturated carboxylic or nitrogen heterocyclic ring, x is 3, 4 or 5, n is 0, 1 or 2, X is 0, S or NR15, R15 is hydrogen, -COR, -COOR or alkyl which latter is optionally substituted by -OCOR, R is phenyl, or alkyl optionally substituted by phenyl, the phenyl groups in turn optionally being substituted by alkyl, provided that i) Rc is not -CH2CH2-morpholino, ii) that when Rc is a nitrogen nucleophile carried on an aryl or heteroaryl group R,5 is not a group -COR in which R is unsubstituted alkyl, iii) when X is NR15 Rc does not comprise an unsaturated nitrogen heterocyclic ring other than such a ring substituted by a either a) a substituted or unsubstituted amino group, or b) an N-oxido group, and iv) when X is NR15 Rc does not comprise an alkyl group substituted by an optionally alkyl or halo substitute piperidino group, and pharmaceutically acceptable salts thereof. There are also described processes for making the compounds, and their formulation and use as pharmaceuticals, e.g. to treat gastric acid secretion.

  所述化合物为式 I、 其中 Rc 是亲核的氮、氧或硫，与 SO 基团之间隔着 1、2、3、4 或 5 个原子、 R1、R1、R3 和 R4（可以相同或不同）各自为氢、卤素、烷氧基、烷基、氟烷基、烷酰基、RS(O)n-、-NO2、-N(R)2、-NHCOR 或 -COOH 或其酯或酰胺、 或相邻的一对 R1、R2、R3 和 R4 除上述数值外，还可共同形成链-(CH2)x-，或与它们所连接的碳原子一起形成一个 6 个成员的不饱和羧基或氮杂环、 x 是 3、4 或 5、 n 是 0、1 或 2、 X 是 0、S 或 NR15、 R15 是氢、-COR、-COR 或烷基，后者任选被-OCOR 取代、 R 是苯基，或任选被苯基取代的烷基，苯基又任选被烷基取代、 条件是 i) Rc 不是- -吗啉基，ii) 当 Rc 是芳基或杂芳基上携带的亲氮核物时，R,5 不是基团-COR，其中 R 是未取代的烷基、iii) 当 X 为 NR15 时，Rc 不包括不饱和氮杂环，但被 a）取代或未取代的氨基或 b）N-氧代基团取代的环除外；以及 iv) 当 X 为 NR15 时，Rc 不包括被任选烷基或卤代哌啶基取代的烷基、 及其药学上可接受的盐类。 此外，还描述了制造这些化合物的工艺，以及它们作为药物的配制和使用，例如用于治疗胃酸分泌。
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