N-羟基-2-(n-异丙氧基联苯-4-磺酰胺)乙酰胺 | 704888-90-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-羟基-2-(n-异丙氧基联苯-4-磺酰胺)乙酰胺
• 英文名称: 2-[([1,1'-biphenyl]-4-ylsulfonyl)(1-methylethoxy)amino]-N-hydroxyacetamide
• 英文别名: ARP 100；ARP-100；ARP100；N-hydroxy-2-(N-isopropoxybiphenyl-4-ylsulfonamido)acetamide；N-hydroxy-2-[(4-phenylphenyl)sulfonyl-propan-2-yloxyamino]acetamide
• CAS: 704888-90-4
• 化学式: C₁₇H₂₀N₂O₅S
• 分子量: 364.422
• InChiKey: PHGLPDURIUEELR-UHFFFAOYSA-N

物化性质

• 溶解度：
  在 DMSO 中溶解度为 100mM

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 海关编码：
  2935009090
• 危险性防范说明：
  P302+P352,P337+P313,P304+P340,P312,P280,P332+P313
• 危险性描述：
  H315,H319,H335

制备方法与用途

用途

ARP 100 是一种有效的 MMP-12/MMP-13 双重抑制剂。MMP-12 和 MMP-13 是锌依赖性内肽酶家族成员，它们在细胞外基质（ECM）分解障碍中起关键作用，特别是在类风湿性关节炎（RA）和骨关节炎（OA）这两种主要形式的关节炎中。

生物活性

ARP-100 作为一种有效的选择性基质金属蛋白酶 MMP-2 抑制剂 (IC50=12 nM)，能够与 MMP-2 的 S1’ 口袋相互作用，并在体外对基质胶的侵袭模型中显示抗侵袭特性。然而，它对其他一些 MMP 的抑制活性较小，具体如下：

• MMP-1: >50 μM (IC50)
• MMP-3: 4.5 μM (IC50)
• MMP-7: >50 μM (IC50)
• MMP-9: 0.2 μM (IC50)

靶点

MMP 类型	IC50 值
MMP-2	12 nM
MMP-9	0.2 μM
MMP-3	4.5 μM
MMP-1	>50 μM
MMP-7	>50 μM

体外研究

在体外研究中，ARP-100（50 nM）显著减少了侵袭性延长的总数。

反应信息

• 作为产物：
  描述：

  [(isopropoxy)(1,1'-biphenyl-4-ylsulfonyl)amino]acetic acid 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 25.0h， 生成 N-羟基-2-(n-异丙氧基联苯-4-磺酰胺)乙酰胺
  参考文献：
  名称：

  New N-arylsulfonyl-N-alkoxyaminoacetohydroxamic acids as selective inhibitors of gelatinase A (MMP-2)

  摘要：

  New N-arylsulfonyl-substituted alkoxyaminoaceto hydroxamic acid derivatives of types 8 and 10 designed as oxa-analogues of known sulfonamide-based MMPi of types 2 and 7 were synthesized and tested for their inhibitory activities on some matrix metalloproteinases. The combination of a biphenylsulfonamide group with oxyamino oxygen in the pharmacophoric central skeleton of sulfonamide-based MMPi obtained in the new sulfonamides 10 seems to be able to give selectivity for MMP-2 over MMP-1. The most potent derivative of this type, 10a, shows similar anti-invasive properties to the analogue reference drug CGS27023A, 2, in an in vitro model of invasion on matrigel, carried out on cellular lines of fibrosarcoma HT1080 (tumoural cells over-expressing MMP-2 and MMP-9). (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.01.047

文献信息

• Methods for treating diseases related to mitochondrial stress
  申请人：712 NORTH, INC.

  公开号：US10906931B2

  公开（公告）日：2021-02-02

  Means and methods for therapeutic intervention of mitochondrial disorders or diseases, and in particular to a method for the treatment, prevention and/or amelioration of a disorder or disease correlated with mitochondrial stress or dysfunction, a mitochondrial disorder or disease, or a disorder or disease characterized by OPA1 alterations are disclosed. Thereby, a pharmaceutically active amount of a compound capable of modulating the activity of OMA1 and/or an oligomeric complex comprising OMA1 is administered to a patient in need of medical intervention. Methods of screening for a compound capable of modulating the activity of OMA1 and/or an oligomeric complex comprising OMA1 are disclosed. Methods for determining the susceptibility for, predisposition for, or the presence of such a disorder or disease and whether a person in need will benefit from the therapeutic intervention, i.e. personalized medicine are also disclosed.

  本发明公开了治疗干预线粒体紊乱或疾病的手段和方法，特别是治疗、预防和/或改善与线粒体应激或功能障碍相关的紊乱或疾病、线粒体紊乱或疾病或以OPA1改变为特征的紊乱或疾病的方法。因此，能够调节 OMA1 和/或包含 OMA1 的低聚物复合物活性的化合物的药用活性量被施用给需要医疗干预的患者。本发明公开了筛选能够调节 OMA1 和/或包含 OMA1 的低聚物复合物活性的化合物的方法。此外，还公开了用于确定此类失调或疾病的易感性、易患性或存在性，以及有需要的人是否将从治疗干预（即个性化医疗）中获益的方法。
• METHOD OF TREATING A SUBJECT SUFFERING FROM DEGENERATIVE DISC DISEASE USING A MATRIX METALLOPROTEASE INHIBITOR
  申请人：Discogen, LLC

  公开号：EP1986657A2

  公开（公告）日：2008-11-05
• METALLOPROTEINASE 9 AND METALLOPROTEINASE 2 BINDING PROTEINS
  申请人：Dyax Corp.

  公开号：EP2262840A2

  公开（公告）日：2010-12-22
• METHODS FOR TREATING DISEASES RELATED TO MITOCHONDRIAL STRESS
  申请人：Alavi Khorassani Moghadam, Marcel Victor

  公开号：EP3548039A1

  公开（公告）日：2019-10-09
• Method of treating a subject suffering from degenerative disc disease using a matrix metalloprotease inhibitor
  申请人：Zahos Peter A.

  公开号：US20070190149A1

  公开（公告）日：2007-08-16

  The present invention provides a method for treating a vertebrate subject suffering from a degenerative disc disease by administering an inhibitor of a matrix metalloprotease (MMP) to the subject in an amount effective to treat the subject.