{(2S)-1-[(benzyloxy)carbonyl]pyrrolidin-2-yl}methyl 4-({[4-(4-cyano-2-methylphenyl)-3,6-dihydropyridin-1(2H)-yl]sulfonyl}methyl)-4-[(hydroxyamino)carbonyl]piperidine-1-carboxylate | 869189-47-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: {(2S)-1-[(benzyloxy)carbonyl]pyrrolidin-2-yl}methyl 4-({[4-(4-cyano-2-methylphenyl)-3,6-dihydropyridin-1(2H)-yl]sulfonyl}methyl)-4-[(hydroxyamino)carbonyl]piperidine-1-carboxylate
• 英文别名: [(2S)-1-phenylmethoxycarbonylpyrrolidin-2-yl]methyl 4-[[4-(4-cyano-2-methylphenyl)-3,6-dihydro-2H-pyridin-1-yl]sulfonylmethyl]-4-(hydroxycarbamoyl)piperidine-1-carboxylate
• CAS: 869189-47-9
• 化学式: C₃₄H₄₁N₅O₈S
• 分子量: 679.794
• InChiKey: IKHMVJSBPMTQTG-LJAQVGFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  48
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  178
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  {(2S)-1-[(benzyloxy)carbonyl]pyrrolidin-2-yl}methyl 4-({[4-(4-cyano-2-methylphenyl)-3,6-dihydropyridin-1(2H)-yl]sulfonyl}methyl)-4-[(hydroxyamino)carbonyl]piperidine-1-carboxylate 在 Pd-BaSO₄ 氢气 作用下， 生成 (2S)-pyrrolidin-2-ylmethyl 4-({[4-(4-cyano-2-methylphenyl)-3,6-dihydropyridin-1(2H)-yl]sulfonyl}methyl)-4-[(hydroxyamino)carbonyl]piperidine-1-carboxylate
  参考文献：
  名称：

  Conversion of an MMP-potent scaffold to an MMP-selective HER-2 sheddase inhibitor via scaffold hybridization and subtle permutations

  摘要：

  A series of beta-sulfonamide piperidine hydroxamates were prepared and shown to be potent inhibitors of the human epidermal growth factor receptor-2 (HER-2) sheddase with excellent selectivity against MMP-1, -2, -3, and -9. This was achieved by exploiting subtle differences within the otherwise highly conserved S-1' binding pocket of the active sites within the metalloprotease family. In addition, it was discovered that the introduction of polarity to the P-1 and P-1' groups reduced the projected human clearance. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2007.11.086
• 作为产物：
  描述：

  在 N-甲基吗啉 、 羟胺 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 {(2S)-1-[(benzyloxy)carbonyl]pyrrolidin-2-yl}methyl 4-({[4-(4-cyano-2-methylphenyl)-3,6-dihydropyridin-1(2H)-yl]sulfonyl}methyl)-4-[(hydroxyamino)carbonyl]piperidine-1-carboxylate
  参考文献：
  名称：

  Conversion of an MMP-potent scaffold to an MMP-selective HER-2 sheddase inhibitor via scaffold hybridization and subtle permutations

  摘要：

  A series of beta-sulfonamide piperidine hydroxamates were prepared and shown to be potent inhibitors of the human epidermal growth factor receptor-2 (HER-2) sheddase with excellent selectivity against MMP-1, -2, -3, and -9. This was achieved by exploiting subtle differences within the otherwise highly conserved S-1' binding pocket of the active sites within the metalloprotease family. In addition, it was discovered that the introduction of polarity to the P-1 and P-1' groups reduced the projected human clearance. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2007.11.086

文献信息

• Hydroxamic acid derivatives as metalloprotease inhibitors
  申请人：Burns M. David

  公开号：US20050250789A1

  公开（公告）日：2005-11-10

  The present invention provides compounds of Formula I or II: salt form or prodrug thereof, wherein variables are defined herein, that are modulators of metalloproteases such as matrix metalloproteases (MMPs) and ADAMs. The compounds or compositions described herein can be used to treat diseases associated with metalloprotease activity including, for example, arthritis, cancer, cardiovascular disorders, skin disorders, inflammation or allergic conditions.

  本发明提供了Formula I或II的化合物： 盐形式或其前药，其中变量在此处定义，这些化合物是金属蛋白酶调节剂，如基质金属蛋白酶（MMPs）和ADAMs。本文描述的化合物或组合物可用于治疗与金属蛋白酶活性相关的疾病，包括例如关节炎、癌症、心血管疾病、皮肤疾病、炎症或过敏症状。
• [EN] HYDROXAMIC ACID DERIVATIVES AS METALLOPROTEASE INHIBITORS<br/>[FR] DERIVES D'ACIDE HYDROXAMIQUE EN TANT QU'INHIBITEURS DE METALLOPROTEASES
  申请人：INCYTE CORP

  公开号：WO2005117882A9

  公开（公告）日：2007-03-01

  [EN] The present invention provides compounds of Formula (I ) or (II), salt form or prodrug thereof, wherein variables are defined herein, that are modulators of metalloproteases such as matrix metalloproteases (MMPs) and ADAMs. The compounds or compositions described herein can be used to treat diseases associated with metalloprotease activity including, for example, arthritis, cancer, cardiovascular disorders, skin disorders, inflammation or allergic conditions.
  [FR] L'invention concerne des analogues de 3-aryl pyridazines 5,6-disubstituées de formule (I) et de formule (II), dans lesquelles R₁, R₂, R₃, R₈, R₉, A et Ar sont tels que définis dans la description. Lesdits composées sont des ligands de récepteurs C5a. Les composés préférés de formule (I) et (II) se fixent aux récepteurs C5a avec une grande affinité et présentent une activité antagoniste neutre ou agoniste inverse au niveau des récepteurs C5a. La présente invention concerne également des compositions pharmaceutiques comprenant lesdits composés, ainsi que l'utilisation desdits composé dans le traitement d'une variété de troubles inflammatoires, cardiovasculaires et du système immunitaire. En outre, la présente invention concerne des 3-aryl pyridazines 5,6-disubstituées, utiles en tant que sondes pour la localisation de récepteurs C5a.