cyclopentyl N-(2-{4-[6-amino-5-(4-fluorobenzoyl)-2-oxopyridin-1(2H)-yl]-3,5-difluorophenyl}ethyl)-L-leucinate | 1151804-64-6

• 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: cyclopentyl N-(2-{4-[6-amino-5-(4-fluorobenzoyl)-2-oxopyridin-1(2H)-yl]-3,5-difluorophenyl}ethyl)-L-leucinate
• 英文别名: cyclopentyl (2S)-2-[2-[4-[2-amino-3-(4-fluorobenzoyl)-6-oxopyridin-1-yl]-3,5-difluorophenyl]ethylamino]-4-methylpentanoate
• CAS: 1151804-64-6
• 化学式: C₃₁H₃₄F₃N₃O₄
• 分子量: 569.624
• InChiKey: UOGLSSUKEOBBGO-SANMLTNESA-N

物化性质

• 沸点：
  632.9±55.0 °C(predicted)
• 密度：
  1.30±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  41
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  cyclopentyl leucinate 、 2-{4-[6-amino-5-(4-fluorobenzoyl)-2-oxopyridin-1(2H)-yl]-3,5-difluorophenyl}ethyl methanesulfonate 在 potassium carbonate 、 sodium iodide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以11%的产率得到cyclopentyl N-(2-{4-[6-amino-5-(4-fluorobenzoyl)-2-oxopyridin-1(2H)-yl]-3,5-difluorophenyl}ethyl)-L-leucinate
  参考文献：
  名称：

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

  摘要：

  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。

  公开号：

  WO2009060160A1

文献信息

• P38 MAP KINASE INHIBITORS
  申请人：Moffat David Festus Charles

  公开号：US20100267774A1

  公开（公告）日：2010-10-21

  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; R 6 is hydrogen or optionally substituted C 1 -C 3 alkyl; P represents hydrogen and U represents a radical of formula (IA); or U represents hydrogen and P represents a radical of formula -A-(CH 2 ) z —X 1 -L 1 -Y—NH—CHR 1 R 2 wherein A represents an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5-13 ring members; z, Y, L 1 , and X 1 are as defined in the specification; R 1 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 R 2 is the side chain of a natural or non-natural alpha amino acid.

  式（I）的化合物是p38 MAP激酶的抑制剂，因此在治疗包括类风湿性关节炎和COPD等炎症疾病方面具有实用性：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代表式（IA）的基团; 或U代表氢，P代表式-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如规范中所定义; 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; R2是天然或非天然α氨基酸的侧链。
• TERT-BUTYL N-[2-ETHYL]-L-ALANINATE OR A SALT, HYDRATE OR SOLVATE THEREOF
  申请人：CHROMA THERAPEUTICS LTD

  公开号：US20150246883A1

  公开（公告）日：2015-09-03

  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tert-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-丙氨酸盐、水合物或溶剂化物。本发明还提供一种含有该化合物及一种或多种药学上可接受的载体和/或赋形剂的制药组合物。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，本发明提供了由本发明化合物的酯基水解产生的酸。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。
• N-[2-{4-[6-AMINO-5-(2,4-DIFLUOROBENZOYL)-2-OXOPYRIDIN-1(2H)-YL]-3,5-DIFLUOROPHENYL}ETHYL]-L-ALANINE
  申请人：MACROPHAGE PHARMA LIMITED

  公开号：EP3222616A1

  公开（公告）日：2017-09-27

  The present invention provides a metabolite produced by hydrolysis of the ester compound tert-butyl N-[2-4-[6-amino-5-(2,4-difluorobenzoyl)-2-oxopyridin-1(2H)-yl]-3,5-difluorophenyl}ethyl)-L-alaninate, which is useful for inhibiting the activity of a p38 MAP kinase enzyme.

  本发明提供了一种由酯类化合物 N-[2-4-[6-氨基-5-(2,4-二氟苯甲酰基)-2-氧代吡啶-1(2H)-基]-3,5-二氟苯基}乙基)-L-丙氨酸叔丁酯水解产生的代谢物，它可用于抑制 p38 MAP 激酶的活性。
• 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
  申请人：Macrophage Pharma Limited

  公开号：US10370332B2

  公开（公告）日：2019-08-06

  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.

  本发明提供了一种化合物：N-[2-4-[6-氨基-5-(2,4-二氟苯甲酰基)-2-氧代吡啶-1(2H)-基]-3,5-二氟苯基}乙基)-L-丙氨酸叔丁酯或其盐、水合物或溶液。本发明还提供了一种药物组合物，其中包含该化合物以及一种或多种药学上可接受的载体和/或赋形剂。本发明的化合物和组合物可用于抑制 p38 MAP 激酶的活性。因此，它们可用于治疗自身免疫性或炎症性疾病，或细胞增殖性疾病。此外，本发明还提供了一种通过水解本发明化合物的酯基而产生的酸。该酸为N-[2-4-[6-氨基-5-(2,4-二氟苯甲酰基)-2-氧代吡啶-1(2H)-基]-3,5-二氟苯基}乙基)-L-丙氨酸。
• 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
  申请人：MACROPHAGE PHARMA LIMITED

  公开号：EP2909175B1

  公开（公告）日：2017-06-07