tert-butyl (2-(1-(2,6-bis(4-(N'-hydroxycarbamimidoyl)phenoxy)isonicotinoyl)piperidin-4-yl)ethyl)carbamate | 1256591-32-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: tert-butyl (2-(1-(2,6-bis(4-(N'-hydroxycarbamimidoyl)phenoxy)isonicotinoyl)piperidin-4-yl)ethyl)carbamate
• 英文别名: tert-butyl N-[2-[1-[2,6-bis[4-(N'-hydroxycarbamimidoyl)phenoxy]pyridine-4-carbonyl]piperidin-4-yl]ethyl]carbamate
• CAS: 1256591-32-8
• 化学式: C₃₂H₃₉N₇O₇
• 分子量: 633.704
• InChiKey: ZYDKWHSTJMGFDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  46
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  207
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  tert-butyl (2-(1-(2,6-bis(4-(N'-hydroxycarbamimidoyl)phenoxy)isonicotinoyl)piperidin-4-yl)ethyl)carbamate 在 溶剂黄146 、 锌 作用下， 反应 4.0h， 生成 tert-butyl (2-(1-(2,6-bis(4-carbamimidoylphenoxy)isonicotinoyl)piperidin-4-yl)ethyl)carbamate
  参考文献：
  名称：

  Discovery of Pyridyl Bis(oxy)dibenzimidamide Derivatives as Selective Matriptase Inhibitors

  摘要：

  Matriptase belongs to trypsin-like serine proteases involved in matrix remodeling/degradation, growth regulation, survival, motility, and cell morphogenesis. Herein, we report a structure-based approach, which led to the discovery of sulfonamide and amide derivatives of pyridyl bis(oxy)benzamidine as potent and selective matriptase inhibitors. Co-crystal structures of selected compounds in complex with matriptase supported compound designing. Additionally, WaterMap analyses indicated the possibility of occupying a distinct pocket within the catalytic domain, exploration of which resulted in >100-fold improvement in potency. Co-crystal structure of 10 with matriptase revealed critical interactions leading to potent target inhibition and selectivity against other senile proteases.

  DOI：

  10.1021/ml400213v
• 作为产物：
  描述：

  2,6-二氯异烟酸乙酯 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 羟胺 、 potassium carbonate 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.34h， 生成 tert-butyl (2-(1-(2,6-bis(4-(N'-hydroxycarbamimidoyl)phenoxy)isonicotinoyl)piperidin-4-yl)ethyl)carbamate
  参考文献：
  名称：

  Discovery of Pyridyl Bis(oxy)dibenzimidamide Derivatives as Selective Matriptase Inhibitors

  摘要：

  Matriptase belongs to trypsin-like serine proteases involved in matrix remodeling/degradation, growth regulation, survival, motility, and cell morphogenesis. Herein, we report a structure-based approach, which led to the discovery of sulfonamide and amide derivatives of pyridyl bis(oxy)benzamidine as potent and selective matriptase inhibitors. Co-crystal structures of selected compounds in complex with matriptase supported compound designing. Additionally, WaterMap analyses indicated the possibility of occupying a distinct pocket within the catalytic domain, exploration of which resulted in >100-fold improvement in potency. Co-crystal structure of 10 with matriptase revealed critical interactions leading to potent target inhibition and selectivity against other senile proteases.

  DOI：

  10.1021/ml400213v

文献信息

• PROTEASE INHIBITORS
  申请人：Goswami Rajeev

  公开号：US20120136002A1

  公开（公告）日：2012-05-31

  A compound of formula (I) wherein R 1 to R 15 , P 1 , P 2 , A, B and Q are as defined in the claims and pharmaceutically acceptable salts and esters thereof, are disclosed. The compounds of formula (I) possess utility as matriptase inhibitors and are useful in the treatment of matriptase dependent conditions, particularly cancer.

  公式（I）的化合物中，其中R1至R15、P1、P2、A、B和Q的定义如索赔中所述，并披露其药用盐和酯。公式（I）的化合物具有作为matriptase抑制剂的效用，并在治疗matriptase依赖性疾病，特别是癌症方面是有用的。
• US8722930B2
  申请人：——

  公开号：US8722930B2

  公开（公告）日：2014-05-13
• [EN] PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE PROTÉASE
  申请人：ORION CORP

  公开号：WO2010133748A1

  公开（公告）日：2010-11-25

  A compound of formula (I) wherein R1 to R15, P1, P2, A, B and Q are as defined in the claims and pharmaceutically acceptable salts and esters thereof, are disclosed. The compounds of formula (I) possess utility as matriptase inhibitors and are useful in the treatment of matriptase dependent conditions, particularly cancer.
• Discovery of Pyridyl Bis(oxy)dibenzimidamide Derivatives as Selective Matriptase Inhibitors
  作者：Rajeev Goswami、Subhendu Mukherjee、Gerd Wohlfahrt、Chakshusmathi Ghadiyaram、Jwala Nagaraj、Beeram Ravi Chandra、Ramesh K. Sistla、Leena K. Satyam、Dodheri S. Samiulla、Anu Moilanen、Hosahalli S. Subramanya、Murali Ramachandra

  DOI：10.1021/ml400213v

  日期：2013.12.12

  Matriptase belongs to trypsin-like serine proteases involved in matrix remodeling/degradation, growth regulation, survival, motility, and cell morphogenesis. Herein, we report a structure-based approach, which led to the discovery of sulfonamide and amide derivatives of pyridyl bis(oxy)benzamidine as potent and selective matriptase inhibitors. Co-crystal structures of selected compounds in complex with matriptase supported compound designing. Additionally, WaterMap analyses indicated the possibility of occupying a distinct pocket within the catalytic domain, exploration of which resulted in >100-fold improvement in potency. Co-crystal structure of 10 with matriptase revealed critical interactions leading to potent target inhibition and selectivity against other senile proteases.