methyl 3-(4-methoxy-benzenesulfonylamino)-2,6-dimethoxy-isonicotinate | 206192-70-3

• 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: methyl 3-(4-methoxy-benzenesulfonylamino)-2,6-dimethoxy-isonicotinate
• 英文别名: methyl 2,6-dimethoxy-3-[(4-methoxyphenyl)sulfonylamino]pyridine-4-carboxylate
• CAS: 206192-70-3
• 化学式: C₁₆H₁₈N₂O₇S
• 分子量: 382.394
• InChiKey: NJPCPJHSVVIMPG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  methyl 3-(4-methoxy-benzenesulfonylamino)-2,6-dimethoxy-isonicotinate 在 lithium hydroxide 、 草酰氯 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成
  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
• 作为产物：
  描述：

  3-(tert-butoxycarbonylamino)-2,6-dimethoxypyridine 在 正丁基锂 、 四甲基乙二胺 、 TEA 、 对甲苯磺酸 作用下， 生成 methyl 3-(4-methoxy-benzenesulfonylamino)-2,6-dimethoxy-isonicotinate
  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

• Heteroaryl acetylenic sulfonamide and phosphinic acid amide hydroxamic acid tace inhibitors
  申请人：American Cyanamid Company

  公开号：US06200996B1

  公开（公告）日：2001-03-13

  Compounds of the formula: are useful in treating disease conditions mediated by TNF-&agr; such as rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease and degenerative cartilage loss.

  该式化合物在治疗由TNF-α介导的疾病条件中具有用处，如类风湿性关节炎、骨关节炎、败血症、艾滋病、溃疡性结肠炎、多发性硬化症、克罗恩病和软骨退行性损失。
• Preparation and use of ortho-sulfonamido heteroaryl hydroxamic acids as
  申请人：American Cyanamid Company

  公开号：US05962481A1

  公开（公告）日：1999-10-05

  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-.alpha. converting enzyme (TACE, tumor necrosis factor-.alpha. 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 ##STR1## 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.sup.1, R.sup.2 and R.sup.3 ; and Z, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are described in the specification, and the pharmaceutically acceptable salts thereof and the optical isomers and diastereomers thereof.

  本发明涉及新型、低分子量、非肽类基质金属蛋白酶抑制剂（例如明胶酶、基质金属蛋白酶和胶原酶）以及TNF-α转化酶（TACE，肿瘤坏死因子-α转化酶）的发现，这些抑制剂对于治疗这些酶涉及的疾病非常有用，例如关节炎、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、动脉瘤性主动脉疾病、创伤性关节损伤后的退行性软骨丢失、神经系统的脱髓鞘疾病、移植排斥、消瘦、厌食、炎症、发热、胰岛素抵抗、脓毒性休克、充血性心力衰竭、中枢神经系统的炎症性疾病、炎症性肠病、艾滋病毒感染、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、Sjogren综合征、近视、眼部肿瘤、眼部血管生成/新生。 本发明的TACE和MMP抑制的ortho-磺酰胺基芳基羟肟酸由以下公式表示：##STR1##其中，羟肟酸基团和磺酰胺基团与A组上相邻的碳键合，其中A被定义为：具有1至3个异构原子（独立选择自N、O和S）的5-6成员杂环，可选地被R1、R2和R3取代；Z、R1、R2、R3、R4、R5、R6、R7、R8和R9在规范中描述，以及其药学上可接受的盐和其光学异构体和对映异构体。
• Heteroaryl acetylenic sulfonamide and phosphinic acid amide hydroxamic acid TACE inhibitors
  申请人：——

  公开号：US20020188132A1

  公开（公告）日：2002-12-12

  Compounds of the formula: 1 are useful in treating disease conditions mediated by TNF-&agr; such as rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease and degenerative cartilage loss.

  公式为1的化合物在治疗由TNF-α介导的疾病条件方面非常有用，例如类风湿性关节炎、骨关节炎、败血症、艾滋病、溃疡性结肠炎、多发性硬化症、克隆氏病和软骨退行性损失。
• 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。
• Preparation and use of ortho-sulfonamide heteroarly hydroxamic acids as
  申请人：American Home Products Corporation

  公开号：US06162821A1

  公开（公告）日：2000-12-19

  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-.alpha. converting enzyme (TACE, tumor necrosis factor-.alpha. 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 ##STR1## 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.sup.1, R.sup.2 and R.sup.3 ; and Z, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are described in the specification, and the pharmaceutically acceptable salts thereof and the optical isomers and diastereomers thereof.

  本发明涉及发现了一种新型的、低分子量的、非肽类的基质金属蛋白酶（如明胶酶、基质金属蛋白酶和胶原酶）和TNF-α转化酶（TACE，肿瘤坏死因子-α转化酶）抑制剂，用于治疗这些酶所涉及的疾病，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、动脉瘤性主动脉疾病、创伤性关节损伤后的退行性软骨丢失、神经系统的脱髓鞘疾病、移植排斥反应、消耗症、厌食症、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、Sjogren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结构式为##STR1##其中，羟肟酸基团和磺酰胺基团与A基上的相邻碳原子键合，其中A定义为：一种由1到3个独立选择的N、O和S异原子组成的5-6元杂环，可选地被R.sup.1、R.sup.2和R.sup.3取代；Z、R.sup.1、R.sup.2、R.sup.3、R.sup.4、R.sup.5、R.sup.6、R.sup.7、R.sup.8和R.sup.9在说明书中描述，以及其药学上可接受的盐和其光学异构体和对映异构体。