4-Chlorophenyl 3-(2,4-difluorophenyl)-3-oxopropanimidothioate | 764645-61-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-Chlorophenyl 3-(2,4-difluorophenyl)-3-oxopropanimidothioate
• 英文别名: (4-chlorophenyl) 3-(2,4-difluorophenyl)-3-oxopropanimidothioate
• CAS: 764645-61-6
• 化学式: C₁₅H₁₀ClF₂NOS
• 分子量: 325.766
• InChiKey: SJYNIFXHYBFZOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  66.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-Chlorophenyl 3-(2,4-difluorophenyl)-3-oxopropanimidothioate 以 四氢呋喃 、 溶剂黄146 为溶剂， 反应 3.0h， 生成 2-{4-[6-amino-5-(2,4-difluorobenzoyl)-2-oxopyridin-1(2H)-yl]phenyl}ethyl acetate
  参考文献：
  名称：

  [EN] INHIBITORS OF P38 MAP KINASE
  [FR] INHIBITEURS DE LA P38 MAP KINASE

  摘要：

  式(I)的化合物是p38 MAP激酶抑制剂，用于治疗自身免疫和炎症性疾病：其中：G为-N=或-CH=；D为一个可选择取代的二价单环或双环芳基或杂环芳基基团，具有5-13个环成员；R6为氢或可选择取代的CrC3烷基；P代表氢，U代表式(IA)的基团；或U代表氢，P代表式(IA)的基团；其中A代表一个可选择取代的二价单环或双环碳环或杂环基团，具有5-13个环成员；z为O或1；-X1-L1-Y-是一个连接基团或键；R1为一个羧酸基(-COOH)，或者是可由一个或多个细胞内酯酶水解为羧酸基的酯基团；R2和R3如权利要求中所定义。

  公开号：

  WO2009106844A1

文献信息

• ENZYME AND RECEPTOR MODULATION
  申请人：Davidson Alan Hornsby

  公开号：US20100317865A1

  公开（公告）日：2010-12-16

  Covalent conjugates of an α,α-disubstituted glycine ester and a modulator of the activity of a target intracellular enzyme or receptor, wherein the ester group of the conjugate is hydrolysable by one or more intracellular carboxylesterase enzymes to the corresponding acid and the α,α-disubstituted glycine ester is conjugated to the modulator at a position remote from the binding interface between the inhibitor and the target enzyme or receptor pass into cells and the active acid hydrolysis product accumulates within the cells.

  一种α，α-二取代甘氨酸酯和靶细胞内酶或受体活性调节剂的共价结合物，其中共轭物的酯基可被一个或多个细胞内羧酯酶水解为相应的酸，α，α-二取代甘氨酸酯与调节剂结合在远离抑制剂与靶酶或受体之间结合界面的位置，进入细胞并使活性酸水解产物在细胞内积累。
• [EN] COMBINATION OF P38 INHIBITORS AND ANOTHER ANTICANCER AGENTS<br/>[FR] COMBINAISON D'INHIBITEURS DE P38 ET D'AUTRES AGENTS ANTICANCÉREUX
  申请人：CHROMA THERAPEUTICS LTD

  公开号：WO2014170677A1

  公开（公告）日：2014-10-23

  The present invention provides an amino acid ester of formula (I), or a pharmaceutically acceptable salt, hydrate or solvate thereof, for use in combination with a cytotoxic agent: (Formula (I)). The combination is useful in the treatment of cancer.

  本发明提供了式（I）的氨基酸酯，或其药用可接受的盐、水合物或溶剂化合物，用于与细胞毒性药物结合使用：（式（I））。该组合物在癌症治疗中很有用。
• [EN] TREATMENT OF CANCER BY STIMULATION OF IL-12 PRODUCTION<br/>[FR] TRAITEMENT DU CANCER PAR STIMULATION DE LA PRODUCTION D'IL-12
  申请人：MACROPHAGE PHARMA LTD

  公开号：WO2019043389A1

  公开（公告）日：2019-03-07

  The present invention relates to a compound and composition for use in the stimulation of IL-12 production and IFN-γ production, which compound is selected from: tert-butyl N-[2-4-[6-amino-5-(2,4-difluorobenzoyl)-2-oxopyridin-1(2H)-yl]-3,5- difluorophenyl}ethyl)-L-alaninate, or a pharmaceutically acceptable salt, hydrate or solvate thereof; and N-[2-4-[6-amino-5-(2,4-difluorobenzoyl)-2-oxopyridin-1(2H)-yl]-3,5- difluorophenyl}ethyl)-L-alanine.

  该发明涉及一种化合物和组合物，用于刺激IL-12和IFN-γ的产生，所述化合物选自：叔丁基N-[2-4-[6-氨基-5-(2,4-二氟苯甲酰)-2-氧代吡啶-1(2H)-基]-3,5-二氟苯基}乙基)-L-丙氨酸酯，或其药用可接受的盐、水合物或溶剂和N-[2-4-[6-氨基-5-(2,4-二氟苯甲酰)-2-氧代吡啶-1(2H)-基]-3,5-二氟苯基}乙基)-L-丙氨酸。
• [EN] TERT-BUTYL N-[2-{4-[6-AMINO-5-(2,4-DIFLUOROBENZOYL)-2-OXOPYRIDIN-1(2H)-YL]-3,5- DIFLUOROPHENYL}ETHYL]-L-ALANINATE OR A SALT, HYDRATE OR SOLVATE THEREOF<br/>[FR] TERT-BUTYL N-[2-{4-[6-AMINO-5-(2,4-DIFLUOROBENZOYL)-2-OXOPYRIDIN-1(2H)-YL]-3,5-DIFLUOROPHÉNYL}ÉTHYL)-L-ALANINATE OU UN SEL, HYDRATE OU SOLVATE DE CELUI-CI
  申请人：CHROMA THERAPEUTICS LTD

  公开号：WO2014060742A1

  公开（公告）日：2014-04-24

  The present invention provides a compound which is: tert-butyl N-[2-4-[6-amino-5- (2,4-difluorobenzoyl)-2-oxopyridin-1(2H)-yl]-3,5-difluorophenyl}ethyl)-L-alaninate or a salt, hydrate or solvate thereof. The present invention also provides a pharmaceutical composition comprising the compound together with one or more pharmaceutically acceptable carriers and/or excipients. The compound and composition are useful for inhibiting the activity of a p38 MAP kinase enzyme. As such they may be used in the treatment of a autoimmune or inflammatory disease, or a cell proliferative disease. In addition, the invention provides an acid produced by hydrolysis of the ester group of the compound of the invention. The acid is N-[2-4-[6-amino-5-(2,4-difluorobenzoyl)-2- oxopyridin-1(2H)-yl]-3,5-difluorophenyl}ethyl)-L-alanine.

  本发明提供一种化合物，即：叔丁基N-[2-4-[6-氨基-5-(2,4-二氟苯甲酰)-2-氧代吡啶-1(2H)-基]-3,5-二氟苯基}乙基)-L-丙氨酸酯或其盐、水合物或溶剂合物。本发明还提供了包括该化合物及一种或多种药用可接受的载体和/或赋形剂的药物组合物。该化合物和组合物可用于抑制p38 MAP激酶酶的活性。因此，它们可用于治疗自身免疫或炎症性疾病，或细胞增殖性疾病。此外，该发明提供了通过水解该化合物的酯基而产生的酸。该酸为N-[2-4-[6-氨基-5-(2,4-二氟苯甲酰)-2-氧代吡啶-1(2H)-基]-3,5-二氟苯基}乙基)-L-丙氨酸。
• [EN] P38 MAP KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA MAP KINASE P38
  申请人：CHROMA THERAPEUTICS LTD

  公开号：WO2009060160A1

  公开（公告）日：2009-05-14

  Compounds of formula (I) are inhibitors of p38 MAP kinase, and are therefore of utility in the treatment of, inter alia, inflammatory conditions including rheumatoid arthritis and COPD: formula (I) wherein: G is -N= or -CH=; D is an optionally substituted divalent mono- or bi-cyclic aryl or heteroaryl radical having 5 - 13 ring members; R6 is hydrogen or optionally substituted C1-C3 alkyl; P represents hydrogen and U represents a radical of formula (IA); or U represents hydrogen and P represents a radical of formula -A-(CH2)z-X1-L1 -Y-NH-CHR1R2 wherein A represents an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5 - 13 ring members; z, Y, L1, and X1 are as defined in the specification; R1 is a carboxylic acid group (-COOH), or an ester group which is hydrolysable by one or more intracellular esterase enzymes to a carboxylic acid group; and R2 is the side chain of a natural or non-natural alpha amino acid.

  公式（I）的化合物是p38 MAP激酶的抑制剂，因此在治疗炎症性疾病包括类风湿性关节炎和COPD方面具有效用：公式（I）其中：G是-N =或-CH =; D是具有5-13个环成员的可选取代的二价单环或双环芳基或杂芳基基团; R6是氢或可选取代的C1-C3烷基; P代表氢，U代表公式（IA）的基团;或U代表氢，P代表公式-A-（CH2）z-X1-L1-Y-NH-CHR1R2的基团，其中A代表具有5-13个环成员的可选取代的二价单环或双环碳环或杂环基团; z，Y，L1和X1如规范中定义; R1是羧酸基（-COOH）或可由一个或多个细胞内酯酶酶水解为羧酸基的酯基;而R2是天然或非天然α氨基酸的侧链。