3-[Benzyl-(4-methoxy-benzenesulfonyl)-amino]-4-methyl-thiophene-2-carboxylic acid hydroxyamide

• 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: 3-[Benzyl-(4-methoxy-benzenesulfonyl)-amino]-4-methyl-thiophene-2-carboxylic acid hydroxyamide
• 英文别名: 3-[benzyl-(4-methoxyphenyl)sulfonylamino]-N-hydroxy-4-methylthiophene-2-carboxamide
• 化学式: C₂₀H₂₀N₂O₅S₂
• 分子量: 432.521
• InChiKey: ZXJIVLSCJKOYTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  133
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  methyl 3-((4-methoxyphenyl)sulfonamido)-4-methylthiophene-2-carboxylate 在 sodium hydroxide 、 草酰氯 、 羟胺 、 sodium hydride 作用下， 生成 3-[Benzyl-(4-methoxy-benzenesulfonyl)-amino]-4-methyl-thiophene-2-carboxylic acid hydroxyamide
  参考文献：
  名称：

  Heteroaryl and cycloalkyl sulfonamide hydroxamic acid inhibitors of matrix metalloproteinases

  摘要：

  Heteroaryl and cycloalkyl sulfonamide-hydroxamic acid MMP inhibitors were investigated. Of these, the pyridyl analogue 2 is the most potent and selective inhibitor of MMP-9 and MMP-13 in vitro. (C) 2001 Elsevier Science Ltd. hll rights reserved.

  DOI：

  10.1016/s0960-894x(00)00644-2

文献信息

• Preparation and use of ortho-sulfonamido heteroaryl hydroxamic acids as matrix metalloproteinase and TACE inhibitors
  申请人：——

  公开号：US20010051614A1

  公开（公告）日：2001-12-13

  The present invention relates to the discovery of novel, low molecular weight, non-peptide inhibitors of matrix metalloproteinases (e.g. gelatinases, stromelysins and collagenases) and TNF-&agr; converting enzyme (TACE, tumor necrosis factor-&agr; converting enzyme) which are useful for the treatment of diseases in which these enzymes are implicated such as arthritis, tumor growth and metastasis, angiogenesis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, proteinuria, aneurysmal aortic disease, degenerative cartilage loss following traumatic joint injury, demyelinating diseases of the nervous system, graft rejection, cachexia, anorexia, inflammation, fever, insulin resistance, septic shock, congestive heart failure, inflammatory disease of the central nervous system, inflammatory bowel disease, HIV infection, age related macular degeneration, diabetic retinopathy, proliferative vitreoretinopathy, retinopathy of prematurity, ocular inflammation, keratoconus, Sjogren's syndrome, myopia, ocular tumors, ocular angiogenesis/neovascularization. The TACE and MMP inhibiting ortho-sulfonamido aryl hydroxamic acids of the present invention are represented by the formula 1 where the hydroxamic acid moiety and the sulfonamido moiety are bonded to adjacent carbons on group A where A is defined as: a 5-6 membered heteroaryl having from 1 to 3 heteroatoms independently selected from N, O, and S and optionally substituted by R 1 , R 2 and R 3 ; and Z, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are described in the specification, and the pharmaceutically acceptable salts thereof and the optical isomers and diastereomers thereof.

  本发明涉及发现了新型的低分子量非肽基基质金属蛋白酶（如明胶酶、基质金属蛋白酶和胶原酶）及TNF-α转化酶（TACE，肿瘤坏死因子-α转化酶）抑制剂，可用于治疗这些酶涉及的疾病，如关节炎、肿瘤生长和转移、血管生成、组织溃疡、异常伤口愈合、牙周病、骨病、蛋白尿、动脉瘤性主动脉病、创伤性关节损伤后退行性软骨丢失、神经系统脱髓鞘疾病、移植排斥、消瘦、厌食、炎症、发热、胰岛素抵抗、感染性休克、充血性心力衰竭、中枢神经系统炎症性疾病、炎症性肠病、HIV感染、年龄相关性黄斑变性、糖尿病视网膜病变、增殖性玻璃体视网膜病变、早产儿视网膜病变、眼部炎症、角膜圆锥、干燥综合症、近视、眼部肿瘤、眼部血管生成/新生。本发明的TACE和MMP抑制的邻磺酰胺基芳基羟肟酸的化合物由公式1表示，其中羟肟酸基和磺酰胺基与A基上相邻的碳原子结合，A定义为：一个5-6成员杂环，其中有1-3个杂原子，独立选择自N、O和S，并且可由R1、R2和R3取代；Z、R1、R2、R3、R4、R5、R6、R7、R8和R9在说明书中描述，以及其药学上可接受的盐、光学异构体和对映异构体。
• THE PREPARATION AND USE OF ORTHO-SULFONAMIDO HETEROARYL HYDROXAMIC ACIDS AS MATRIX METALLOPROTEINASE AND TACE INHIBITORS
  申请人：American Cyanamid Company

  公开号：EP0934300B1

  公开（公告）日：2002-12-18
• US6162821A
  申请人：——

  公开号：US6162821A

  公开（公告）日：2000-12-19
• US6162814A
  申请人：——

  公开号：US6162814A

  公开（公告）日：2000-12-19
• US6197795B1
  申请人：——

  公开号：US6197795B1

  公开（公告）日：2001-03-06