phenyl 6-(hydroxymethyl)-2-oxo-2H-1-benzopyran-3-carboxylate | 1418001-49-6

• 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: phenyl 6-(hydroxymethyl)-2-oxo-2H-1-benzopyran-3-carboxylate
• 英文别名: Phenyl 6-(hydroxymethyl)-2-oxochromene-3-carboxylate；phenyl 6-(hydroxymethyl)-2-oxochromene-3-carboxylate
• CAS: 1418001-49-6
• 化学式: C₁₇H₁₂O₅
• 分子量: 296.279
• InChiKey: POULFORWHOQIFG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 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：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  phenyl 6-(hydroxymethyl)-2-oxo-2H-1-benzopyran-3-carboxylate 在 吡啶 、 二溴亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以15%的产率得到phenyl 6-(bromomethyl)-2-oxo-2H-1-benzopyran-3-carboxylate
  参考文献：
  名称：

  Toward the First Class of Suicide Inhibitors of Kallikreins Involved in Skin Diseases

  摘要：

  The inhibition of kallikreins 5 and 7, and possibly kallikrein 14 and matriptase, (that initiates the kallikrein proteolytic cascade) constitutes an innovative way to treat some skin diseases such as Netherton syndrome. We present here the inhibitory properties of coumarin-3-carboxylate derivatives against these enzymes. Our small collection of these versatile organic compounds was enriched by newly synthesized derivatives in order to obtain molecules selective against one, two, three enzymes or acting on the four ones. We evidenced a series of compounds with IC50 values in the nanomolar range. A suicide mechanism was observed against kallikrein 7 whereas the inactivation was either definitive (suicide type) or transient for kallikreins 5 and 14, and matriptase. Most of these potent inhibitors were devoid of cytotoxicity toward healthy human keratinocytes. In situ zymography investigations on skin sections from human kallikrein 5 transgenic mouse revealed significant reduction of the global proteolytic activity by several compounds.

  DOI：

  10.1021/jm500988d
• 作为产物：
  描述：

  苯酚 在 哌啶 、 溶剂黄146 、 三氯氧磷 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 生成 phenyl 6-(hydroxymethyl)-2-oxo-2H-1-benzopyran-3-carboxylate
  参考文献：
  名称：

  Toward the First Class of Suicide Inhibitors of Kallikreins Involved in Skin Diseases

  摘要：

  The inhibition of kallikreins 5 and 7, and possibly kallikrein 14 and matriptase, (that initiates the kallikrein proteolytic cascade) constitutes an innovative way to treat some skin diseases such as Netherton syndrome. We present here the inhibitory properties of coumarin-3-carboxylate derivatives against these enzymes. Our small collection of these versatile organic compounds was enriched by newly synthesized derivatives in order to obtain molecules selective against one, two, three enzymes or acting on the four ones. We evidenced a series of compounds with IC50 values in the nanomolar range. A suicide mechanism was observed against kallikrein 7 whereas the inactivation was either definitive (suicide type) or transient for kallikreins 5 and 14, and matriptase. Most of these potent inhibitors were devoid of cytotoxicity toward healthy human keratinocytes. In situ zymography investigations on skin sections from human kallikrein 5 transgenic mouse revealed significant reduction of the global proteolytic activity by several compounds.

  DOI：

  10.1021/jm500988d

文献信息

• [EN] USE OF COUMARIN DERIVATIVES FOR THE PREPARATION OF DRUGS FOR TREATING SKIN DISEASES<br/>[FR] UTILISATION DE DÉRIVÉS DE COUMARINE POUR LA PRÉPARATION DE MÉDICAMENTS POUR LE TRAITEMENT DE MALADIES DE LA PEAU
  申请人：UNIV PARIS CURIE

  公开号：WO2013010963A1

  公开（公告）日：2013-01-24

  The invention relates to 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 ofhydrogen, 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 CH2OCOR5 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 CH2-amine, R1 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 its use for the treatment of pathologies involving an excess of activity of at least one member of the kallikrein family.

  该发明涉及一种化合物，其化学式为（I-1），其中n等于0或1，Z代表O或S，R1代表在羟基、C1-C7烷基、经取代或未取代的氢、卤素、羟基或O-R12基团中选择的一种基团，其中R12是C1-C7烷基、CH2OCOR5基团中的一种，其中R5选择在氢原子和C1-C7烷基之间，经取代或未取代，至少含有一个卤素，O-R13基团中选择在氢和C1-C7烷基之间，胺或CH2-胺，R1代表在氢和O-R14之间选择的一种基团，其中R14选择在氢和C1-C7烷基之间，R2选择在C1-C7烷基、C3-C6环烷基、芳基和杂环芳基之间的一种基团，用于治疗涉及卡利克雷因家族至少一成员活性过量的病理。
• 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。
• US9006466B2
  申请人：——

  公开号：US9006466B2

  公开（公告）日：2015-04-14
• US9532973B2
  申请人：——

  公开号：US9532973B2

  公开（公告）日：2017-01-03
• US9814696B2
  申请人：——

  公开号：US9814696B2

  公开（公告）日：2017-11-14