3-Furan-2-yl-2-[(4-methoxybenzenesulfonyl)-pyridin-3-ylmethylamino]-5-methyl-benzoic acid methyl ester | 206548-58-5

• 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-Furan-2-yl-2-[(4-methoxybenzenesulfonyl)-pyridin-3-ylmethylamino]-5-methyl-benzoic acid methyl ester
• 英文别名: Methyl 3-(furan-2-yl)-2-[(4-methoxyphenyl)sulfonyl-(pyridin-3-ylmethyl)amino]-5-methylbenzoate
• CAS: 206548-58-5
• 化学式: C₂₆H₂₄N₂O₆S
• 分子量: 492.552
• InChiKey: QNSZMMWYMFCNGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  107
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-Furan-2-yl-2-[(4-methoxybenzenesulfonyl)-pyridin-3-ylmethylamino]-5-methyl-benzoic acid methyl ester 在 sodium hydroxide 作用下， 生成 3-Furan-2-yl-2-[(4-methoxy-benzenesulfonyl)-pyridin-3-ylmethyl-amino]-5-methyl-benzoic acid
  参考文献：
  名称：

  The discovery of anthranilic acid-Based MMP inhibitors. Part 2: SAR of the 5-position and P11 groups

  摘要：

  A novel series of anthranilic acid-based inhibitors of MMP-1. MMP-9, MMP-13. and TACE was prepared and evaluated. Selective inhibitors of MMP-9, MMP-13, and TACE were identified, including the potent, orally active MMP-13 inhibitor 4p. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00419-x
• 作为产物：
  描述：

  3-Bromo-2-(4-methoxy-benzenesulfonylamino)-5-methyl-benzoic acid methyl ester 在 sodium hydride 作用下， 生成 3-Furan-2-yl-2-[(4-methoxybenzenesulfonyl)-pyridin-3-ylmethylamino]-5-methyl-benzoic acid methyl ester
  参考文献：
  名称：

  The discovery of anthranilic acid-Based MMP inhibitors. Part 2: SAR of the 5-position and P11 groups

  摘要：

  A novel series of anthranilic acid-based inhibitors of MMP-1. MMP-9, MMP-13. and TACE was prepared and evaluated. Selective inhibitors of MMP-9, MMP-13, and TACE were identified, including the potent, orally active MMP-13 inhibitor 4p. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00419-x

文献信息

• Preparation and use of ortho-sulfonamido aryl hydroxamic acids as matrix
  申请人：American Cyanamid Company

  公开号：US05929097A1

  公开（公告）日：1999-07-27

  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.

  本发明涉及新发现的低分子量、非肽类基质金属蛋白酶（例如明胶酶、溶基质素和胶原酶）和肿瘤坏死因子α转化酶（TACE，肿瘤坏死因子α转化酶）的抑制剂，这些抑制剂用于治疗与这些酶相关的疾病，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、关节创伤后的退行性软骨损失、神经系统脱髓鞘疾病、移植物排斥、恶病质、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、与年龄相关的黄斑变性、糖尿病视网膜病变、增生性玻璃体视网膜病变、早产儿视网膜病变、眼内炎症、圆锥角膜、干燥综合症、近视、眼内肿瘤、眼内血管生成/新生血管。本发明的TACE和MMP抑制的邻磺酰胺基芳基羟肟酸由下式表示：##STR1##，其中羟肟酸基团和磺酰胺基团通过相邻的碳原子与A组连接。
• THE PREPARATION AND USE OF ORTHO-SULFONAMIDO ARYL HYDROXAMIC ACIDS AS MATRIX METALLOPROTEINASE AND TACE INHIBITORS
  申请人：American Cyanamid Company

  公开号：EP0938471B1

  公开（公告）日：2001-12-12
• US5929097A
  申请人：——

  公开号：US5929097A

  公开（公告）日：1999-07-27
• [EN] THE PREPARATION AND USE OF ORTHO-SULFONAMIDO ARYL HYDROXAMIC ACIDS AS MATRIX METALLOPROTEINASE AND TACE INHIBITORS<br/>[FR] PREPARATION D'ACIDES ORTHO-SULFONAMIDO-ARYL HYDROXAMIQUES ET LEUR UTILISATION COMME METALLOPROTEINASES MATRICIELLES OU INHIBITEURS DE TACE
  申请人：——

  公开号：WO1998016503A2

  公开（公告）日：1998-04-23

  [EN] 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 formula (I) where the hydroxamic acid moiety and the sulfonamido moiety are bonded to adjacent carbons on group A where: A is phenyl or naphthyl, optionally substituted by R<1>, R<2>, R<3> and R<4>; Z is aryl, heteroaryl, or heteroaryl fused to a phenyl, where aryl is phenyl or naphthyl optionally substituted by R<1>, R<2>, R<3> and R<4>; heteroaryl is a 5-6 membered heteroaromatic ring having from 1 to 3 heteroatoms independently selected from N, O and S, and optionally substituted by R<1>, R<2>, R<3> and R<4>; and when heteroaryl is fused to phenyl, either or both of the rings can be optionally substituted by R<1>, R<2>, R<3> and R<4>; and 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.
  [FR] La présente invention concerne la découverte de nouveaux inhibiteurs non peptidiques et de faible poids moléculaire de métalloprotéinases matricielles (gélatinases, stromélysines et collagénases, par exemple) et un enzyme de transformation du TNF-alpha (enzyme de transformation du facteur alpha de nécrose des tumeurs, TACE) utiles pour le traitement de maladies dans lesquelles lesdits enzymes sont impliqués, dont, l'arthrite, la croissance tumorale et la métastase, l'angiogenèse, l'ulcération tissulaire, la cicatrisation anormale, la parodontopathie, la maladie osseuse, la protéinurie, l'anévrisme aortique, la perte cartilagineuse dégénérative consécutive à une lésion articulaire traumatique, les troubles de démyélinisation du système nerveux, le rejet de greffon, la cachexie, l'anorexie, l'inflammation, la fièvre, la résistance insulinique, le choc septique, l'insuffisance cardiaque globale, l'affection inflammatoire du système nerveux central, la maladie intestinale inflammatoire, l'infection à VIH, la dégénérescence maculaire liée à l'âge, la rétinopathie diabétique, la vitréorétinopathie proliférante, la rétinopathie de prématurité, l'inflammation oculaire, le kératocône, le syndrome de Sjogren, la myopie, les tumeurs oculaires, l'angiogenèse/néovascularisation oculaire. L'invention concerne des acides ortho-sulfonamido-aryl hydroxamiques de la formule (I) inhibant TACE et MMP, les sels pharmaceutiquement acceptables et les isomères et diastéréomères optiques desdits acides. Dans ladite formule, la fraction acide hydroxamique et la fraction sulfonamido sont liées à des carbones adjacents du groupe A. Dans ledit groupe, A est phényle ou naphtyle éventuellement substitué par R<1>, R<2>, R<3> et R<4>; Z est aryle, hétéroaryle ou hétéroaryle fusionné avec phényle, aryle étant phényle ou naphtyle éventuellement substitué par R<1>, R<2>, R<3> et R<4>; hétéroaryle est un noyau hétéroaromatique à 5 à 6 chaînons ayant 1 à 3 hétéroatomes indépendamment choisis dans le groupe constitué par N, O et S et éventuellement substitués par R<1>, R<2>, R<3> et R<4>; et si hétéroaryle est fusionné avec phényle, l'un ou l'autre noyau, ou les deux, peuvent être éventuellement substitués par R<1>, R<2>, R<3> et R<4>; R<1>, R<2>, R<3>, R<4>, R<5>, R<6> R<7>, R<8> et R<9> sont définis dans le descriptif.
• The discovery of anthranilic acid-Based MMP inhibitors. Part 2: SAR of the 5-position and P11 groups
  作者：J.I. Levin、J. Chen、M. Du、M. Hogan、S. Kincaid、F.C. Nelson、A.M. Venkatesan、T. Wehr、A. Zask、J. DiJoseph、L.M. Killar、S. Skala、A. Sung、M. Sharr、C. Roth、G. Jin、R. Cowling、K.M. Mohler、R.A. Black、C.J. March、J.S. Skotnicki

  DOI：10.1016/s0960-894x(01)00419-x

  日期：2001.8

  A novel series of anthranilic acid-based inhibitors of MMP-1. MMP-9, MMP-13. and TACE was prepared and evaluated. Selective inhibitors of MMP-9, MMP-13, and TACE were identified, including the potent, orally active MMP-13 inhibitor 4p. (C) 2001 Elsevier Science Ltd. All rights reserved.