ARP101 | 849773-64-4

• 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: ARP101
• 英文别名: (2R)-N-hydroxy-3-methyl-2-[(4-phenylphenyl)sulfonyl-propan-2-yloxyamino]butanamide
• CAS: 849773-64-4
• 化学式: C₂₀H₂₆N₂O₅S
• 分子量: 406.503
• InChiKey: DGZZVIWCMGVHGV-LJQANCHMSA-N

物化性质

• 熔点：
  117-119 °C
• 密度：
  1.230±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：>20mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 危险品运输编号：
  UN 2811 6.1/PG 3
• 危险标志：
  GHS06
• 危险性描述：
  H301
• 危险性防范说明：
  P301 + P310

反应信息

• 作为产物：
  描述：

  (S)-ALPHA羟基异正戊酸叔丁酯 在 焦磷酸硫胺素 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 39.0h， 生成 ARP101
  参考文献：
  名称：

  N-i-Propoxy-N-biphenylsulfonylaminobutylhydroxamic acids as potent and selective inhibitors of MMP-2 and MT1-MMP

  摘要：

  Structural manipulation of the pharmacophoric model of type A selective MMP inhibitors (MMPi), obtained by the insertion of some alkyl substituents R-2 possessing an appropriate geometry, steric bulkiness and lipophilicity, is able to improve potency, in the subnanomolar range on MMP-2, and to give a good MMP inhibition on MMP-14 (MT1-MMP) in the designed MMPi of type C, while maintaining a good MMP-1/MMP-2 selectivity profile. The simultaneous inhibition of these two enzymes yields type C compounds, which are potent antiangiogenic agents, able to block a chemoinvasion model on HUVEC cells in the micromolar range. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.024

文献信息

• Amber force field implementation, molecular modelling study, synthesis and MMP-1/MMP-2 inhibition profile of (R)- and (S)-N-hydroxy-2-(N-isopropoxybiphenyl-4-ylsulfonamido)-3-methylbutanamides
  作者：Tiziano Tuccinardi、Adriano Martinelli、Elisa Nuti、Paolo Carelli、Federica Balzano、Gloria Uccello-Barretta、Gillian Murphy、Armando Rossello

  DOI：10.1016/j.bmc.2006.01.056

  日期：2006.6

  Ab initio calculations (B3LYP/Lan12DZ level of theory) were performed in this study to determine all the structural and catalytic zinc parameters required in order to study MMPs and their complexes with hydroxamate inhibitors by means of the AMBER force field. The parameters thus obtained were used in order to study the docking of some known MMPi (Batimastat, CGS 27023A and. Prinomastat) and our previously described inhibitor a which had shown an inhibitory activity for MMP-1, and -2, with the aim of explaining the different selectivity. On this basis the two enantiomers (R)-b and (S)-b were designed and synthesized, as more potent MMP-2 inhibitors than our previously described inhibitor a. Between these two enantiomers the eutomer (R)-b proved to be 24.7 times and 15.3 times more potent than CGS 27023A and the parent compound a on MMP-2, maintaining a higher index of MMP-2/MMP-1 selectivity compared with CGS 27023A and the more potent inhibitor Prinomastat. The hydroxamate (R)-b can be considered as a progenitor of a new class of biphenylsulfonamido-based inhibitors that differ from compound a in the presence of an alkyl side chain on the C alpha atom, and show different potency and selectivity profiles on the two MMPs considered. (c) 2006 Elsevier Ltd. All rights reserved.
• METHODS FOR IMAGING BONE PRECURSOR CELLS USING DUAL-LABELED IMAGING AGENTS TO DETECT MMP-9 POSITIVE CELLS
  申请人：Davis Elizabeth A.

  公开号：US20140178293A1

  公开（公告）日：2014-06-26

  The present invention includes embodiments for methods and compositions that identify the presence of or risk for developing heterotopic ossification, particularly prior to mineralization of the bone. In particular embodiments, MMP-9 and/or MMP-2 agents comprising dual imaging moieties are used to identify patterns of MMP-9 and/or MMP-2 localization, respectively, that is then predictive of heterotopic ossification.
• [EN] METHODS FOR IMAGING BONE PRECURSOR CELLS USING DUAL-LABELED IMAGING AGENTS TO DETECT MMP-9 POSITIVE CELLS<br/>[FR] PROCÉDÉS D'IMAGERIE DE CELLULES OSSEUSES PRÉCURSEURS AU MOYEN D'AGENTS D'IMAGERIE À DOUBLE MARQUAGE, POUR LA DÉTECTION DE CELLULES POSITIVES MMP-9
  申请人：BAYLOR COLLEGE MEDICINE

  公开号：WO2012154654A2

  公开（公告）日：2012-11-15

  The present invention includes embodiments for methods and compositions that identify the presence of or risk for developing heterotopic ossification, particularly prior to mineralization of the bone. In particular embodiments, MMP-9 and/or MMP-2 agents comprising dual imaging moieties are used to identify patterns of MMP-9 and/or MMP-2 localization, respectively, that is then predictive of heterotopic ossification.
• [EN] COMPOSITIONS AND MULTIPLEX ASSAYS FOR CHARACTERIZING ACTIVE PROTEASES AND THEIR INHIBITORS<br/>[FR] COMPOSITIONS ET DOSAGES MULTIPLEXES POUR CARACTÉRISER DES PROTÉASES ACTIVES ET LEURS INHIBITEURS
  申请人：MASSACHUSETTS INST TECHNOLOGY

  公开号：WO2019046288A1

  公开（公告）日：2019-03-07

  Proteases regulate a wide range of normal cellular functions where dysregulated activity is observed in various diseases. Compositions and methods use protease activity multiplexed bead-based immunoassays to profile protease activity. This platform technology integrates protease activity measurements with total protein quantification techniques. It represents a significant improvement over existing detection techniques by allowing for multiplexed, sensitive active protease measurements in complex biological samples. Exemplary multiplexed detections are realized in a single assay using a minute sample amount (e.g., 5 µl) for active recombinant MMP-1, -2, -3, -7, 9, and 12 and those same MMPs in cell culture supernatant, menstrual fluid effluent, and peritoneal aspirates. This multiplexed platform achieves high level of sensitivities equal to or better than existing leading single-plex detection strategies. It also allows for high throughput screening to identify inhibitors of proteases in complex, donor-derived samples.