2-pyridyl 6-chloromethyl-2-oxo-2H-1-benzopyran-3-carboxylate

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 2-pyridyl 6-chloromethyl-2-oxo-2H-1-benzopyran-3-carboxylate
• 英文别名: Pyridin-2-yl 6-(chloromethyl)-2-oxochromene-3-carboxylate
• 化学式: C₁₆H₁₀ClNO₄
• 分子量: 315.713
• InChiKey: SCFXEDNQUIBVKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  65.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-羟基-5-(羟基甲基)苯甲醛 在 哌啶 、 吡啶 、 盐酸 、 氯化亚砜 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 25.0h， 生成 2-pyridyl 6-chloromethyl-2-oxo-2H-1-benzopyran-3-carboxylate
  参考文献：
  名称：

  3,6-Disubstituted Coumarins as Mechanism-Based Inhibitors of Thrombin and Factor Xa

  摘要：

  In this work, coumarins were screened on thrombin (THR) and factor Xa (FXa), two of the most promising targets for the development of anticoagulant drugs. This allowed us to highlight compound 30, characterized by a 2,5-dichlorophenyl ester in the 3-position and a chloromethyl moiety in the 6-position, as a very potent THR inhibitor (k(i)/K-I, = 37 000 M-1 s(-1)). Moreover, this compound exhibits good selectivity over FXa (168-fold) and trypsin (54-fold). The mechanism of inactivation was investigated in this series and significantly differs from that previously observed with (x-chymotrypsin. Indeed, the addition of hydrazine on the THR-inhibitor complex promotes a partial induced THR reactivation. This reactivation, confirmed by LC/MS, showed the resurgence of the native THR and a new dihydrazide complex. Docking experiments were then efficiently used to explain the trends observed in the enzymatic assays as well as to corroborate the postulated inhibition mechanism. Finally, the cell permeability of our derivatives was estimated using a computational approach.

  DOI：

  10.1021/jm050448g

文献信息

• 6-Substituted 2-Oxo-2<i>H</i>-1-benzopyran-3-carboxylic Acid as a Core Structure for Specific Inhibitors of Human Leukocyte Elastase
  作者：Caroline Doucet、Lionel Pochet、Nicole Thierry、Bernard Pirotte、Jacques Delarge、Michèle Reboud-Ravaux

  DOI：10.1021/jm990070k

  日期：1999.10.1

  (k(i)/K(I) = 107 000 M(-1). s(-1) for 4c) and thrombin (k(i)/K(I) = 7 200 M(-1).s(-1) for 3b) as demonstrated by spontaneous or hydroxylamine-accelerated reactivation, irrespective of the nature of the substituent at the 6-position. Conversely, alpha-chymotrypsin was irreversibly inhibited by 6-chloromethyl derivatives (k(i)/K(I) = 107 400 M(-1). s(-1) for 3b). The presence of a latent alkylating function

  设计了6-取代的2-氧代-2H-1-苯并吡喃-3-羧酸的吡啶酯作为基于机制的人白细胞弹性蛋白酶抑制剂。系列4的化合物特异性抑制该酶。几种被测化合物（系列2和3）是人白细胞弹性蛋白酶和α-胰凝乳蛋白酶的有力的时间依赖性抑制剂。这些系列的某些化合物可抑制凝血酶。胰蛋白酶不受抑制。观察到人类白细胞弹性蛋白酶（k（i）/ K（I）= 107 000 M（-1）。s（-1）对于4c）和凝血酶（k（i）/ K（I）= 7）暂时失活200 m（-1）.s（-1）对于3b），通过自发或羟胺加速的再活化来证明，而与6位取代基的性质无关。相反，α-胰凝乳蛋白酶被6-氯甲基衍生物不可逆地抑制（k（i）/ K（I）= 107400 M（-1）。s（-1）for 3b）。导致这种失活需要在6-位（氯甲基）存在潜在的烷基化功能。在没有这种烷基化功能的情况下（系列4），人类白细胞弹性蛋白酶被特异性抑制，这表明该新系列的
• Use of coumarin derivatives for the preparation of drugs for treating skin diseases
  申请人：Université Pierre et Marie Curie - Paris 6

  公开号：EP2545916A1

  公开（公告）日：2013-01-16

  The invention relates to a compound of formula (I) wherein n equals 0 or 1, and wherein, if n=1, Z represents O or S, R1 represents at least one group chosen among the group consisting of hydrogen, a linear or branched, saturated or not, C1-C7 alkyl, substituted, or not, by a halogen, a group -CH2-O-CO-R5 wherein R5 is chosen among a hydrogen atom, and a linear or branched, saturated or not, C1-C7 alkyl, substituted or not by at least one halogen, and an amine, and R2 is chosen among the group consisting of a linear or branched, saturated or not C1-C7 alkyl, a C3-C6 cycloalkyl, an aryl group, and an heteroaryl group for its use for the treatment of pathologies involving an excess of activity of at least one member of the kallikrein family.

  该发明涉及一种具有公式（I）的化合物，其中n等于0或1，如果n=1，则Z代表O或S，R1代表至少选择自氢、一种线性或支链、饱和或非饱和的C1-C7烷基中的一种，该烷基可以被卤素取代或不取代，一个基团-CH2-O-CO-R5，其中R5选择自氢原子，以及一种线性或支链、饱和或非饱和的C1-C7烷基，该烷基可以被至少一个卤素取代或不取代，以及一种胺，R2选择自线性或支链、饱和或非饱和的C1-C7烷基中的一种，C3-C6环烷基，芳基和杂环芳基，用于治疗涉及至少一种卡利克雷因家族成员活性过高的病理的用途。
• USE OF COUMARIN DERIVATIVES FOR THE PREPARATION OF DRUGS FOR TREATING SKIN DISEASES
  申请人：UNIVERSITE PIERRE ET MARIE CURIE (PARIS 6)

  公开号：US20140148480A1

  公开（公告）日：2014-05-29

  A compound of formula (I-1) wherein n equals 0 or 1, Z represents O or S, R1 represents one group chosen among the group consisting of hydrogen, C1-C7 alkyl, substituted, or not, by a halogen, a hydroxyl or a —O—R12 group, wherein R12 is a C1-C7 alkyl, a group —CH 2 —O—CO—R5 wherein R5 is chosen among a hydrogen atom and a C1-C7 alkyl, substituted or not by at least one halogen, a group —O—R13, wherein R13 is chosen among hydrogen and a C1-C7 alkyl, an amine or a —CH 2 — amine, R′1 represents a group chosen among hydrogen and —O—R14, wherein R14 is chosen among hydrogen and a C1-C7 alkyl, and R2 is chosen among the group consisting of a C1-C7 alkyl, a C3-C6 cycloalkyl, an aryl group, and an heteroaryl group for the treatment of pathologies involving excess activity of at least one member of the kallikrein family.

  化合物的公式（I-1），其中n等于0或1，Z代表O或S，R1代表从以下组中选择的一组基团，该组基团由氢，C1-C7烷基组成，被卤素，羟基或—O—R12基团取代或未取代，其中R12是C1-C7烷基，一个基团—CH2—O—CO—R5，其中R5选择氢原子和C1-C7烷基，被至少一个卤素取代或未取代，一个基团—O—R13，其中R13选择氢和C1-C7烷基，胺或—CH2—胺，R'1代表选择氢和—O—R14之一的基团，其中R14选择氢和C1-C7烷基，而R2选择在由C1-C7烷基，C3-C6环烷基，芳基和杂芳基组成的一组中，用于治疗涉及至少一种卡利克雷因家族成员过度活性的病理情况。
• US6355658B1
  申请人：——

  公开号：US6355658B1

  公开（公告）日：2002-03-12
• US9006466B2
  申请人：——

  公开号：US9006466B2

  公开（公告）日：2015-04-14