(S)-3-methyl-2-(8-(3-(trifluoromethyl)-1H-pyrazol-1-yl)dibenzo[b,d]furan-3-ylsulfonamido)butanoic acid | 1025717-80-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: (S)-3-methyl-2-(8-(3-(trifluoromethyl)-1H-pyrazol-1-yl)dibenzo[b,d]furan-3-ylsulfonamido)butanoic acid
• 英文别名: (2S)-3-methyl-2-[[8-[3-(trifluoromethyl)pyrazol-1-yl]dibenzofuran-3-yl]sulfonylamino]butanoic acid
• CAS: 1025717-80-9
• 化学式: C₂₁H₁₈F₃N₃O₅S
• 分子量: 481.452
• InChiKey: WOQIQKYKNMVGLZ-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  3-氨基二苯并呋喃 在 盐酸 、 二氧化硫 、 溴 、 氯 、 溶剂黄146 、 N,N-二异丙基乙胺 、 sodium butanolate 、 三(邻甲基苯基)磷 、 三氟乙酸 、 copper dichloride 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 、 sodium nitrite 作用下， 以 二氯甲烷 、 水 、 溶剂黄146 、 甲苯 为溶剂， 反应 76.0h， 生成 (S)-3-methyl-2-(8-(3-(trifluoromethyl)-1H-pyrazol-1-yl)dibenzo[b,d]furan-3-ylsulfonamido)butanoic acid
  参考文献：
  名称：

  Discovery of potent and selective matrix metalloprotease 12 inhibitors for the potential treatment of chronic obstructive pulmonary disease (COPD)

  摘要：

  Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease associated with irreversible progressive airflow limitation. Matrix metalloproteinase-12 (MMP-12) has been characterized to be one of the major proteolytic enzymes to induce airway remodeling, destruction of elastin and the aberrant remodeling of damaged alveoli in COPD and asthma. The goal of this project is to develop and identify an orally potent and selective small molecule inhibitor of MMP-12 for treatment of COPD and asthma. Syntheses and structure-activity relationship (SAR) studies of a series of dibenzofuran (DBF) sulfonamides as MMP-12 inhibitors are described. Potent inhibitors of MMP-12 with excellent selectivity against other MMPs were identified. Compound 26 (MMP118), which exhibits excellent oral efficacy in the MMP-12 induced ear-swelling inflammation and lung inflammation mouse models, had been successfully advanced into Development Track status. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.046

文献信息

• Cathepsin cysteine protease inhibitors
  申请人：Bayly Christopher

  公开号：US20090176859A1

  公开（公告）日：2009-07-09

  The present invention relates to a novel class of compounds mainly, leucinamide-amino-carboxylate derivatives of formula (I) wherein Y is CR 1 R 2 , O, S, —SO 2 , C=0 or NR 9 ; Z is CR 1 R 2 , O, S, —SO 2 , C═O or NR 9 and each G is independently a CR 1 CR 2 . Said compounds are cathepsin cysteine protease inhibitors, including but not limited to, inhibitors of cathepsin K, L, S and B and to pharmaceutical compositions thereof. These compounds are useful for treating and preventing cathepsin dependent conditions in which inhibition of bone resorption is indicated, such as osteoporosis.

  本发明涉及一种新型化合物类别，主要是公式（I）中的亮氨酰胺基-氨基-羧酸衍生物，其中Y为CR1R2，O，S，—SO2，C=0或NR9；Z为CR1R2，O，S，—SO2，C═O或NR9，每个G独立地为CR1CR2。所述化合物是半胱氨酸蛋白酶的卡特普西蛋白酶抑制剂，包括但不限于卡特普西蛋白酶K、L、S和B的抑制剂，以及其制药组合物。这些化合物对于治疗和预防卡特普西蛋白依赖性疾病，如骨质疏松症等需要抑制骨吸收的疾病是有用的。
• WO2008/57254
  申请人：——

  公开号：——

  公开（公告）日：——
• TRICYCLIC COMPOUNDS AS MATRIX METALLOPROTEINASE INHIBITORS
  申请人：Wyeth

  公开号：EP2074107A2

  公开（公告）日：2009-07-01
• [EN] TRICYCLIC COMPOUNDS AS MATRIX METALLOPROTEINASE INHIBITORS<br/>[FR] COMPOSÉS TRICYCLIQUES SERVANT D'INHIBITEURS DES MÉTALLOPROTÉASES MATRICIELLES
  申请人：WYETH CORP

  公开号：WO2008057254A2

  公开（公告）日：2008-05-15

  [EN] The present invention relates to compositions of the formula (I): and pharmaceutically acceptable salts, hydrates, or esters thereof, wherein R¹, R², R³, R⁴, R⁵, X, and Y are as defined herein. The present teachings also provide methods of making the compounds of formula I, and methods of treating pathologic conditions or disorders mediated wholly or in part by matrix metalloproteinases, such as asthma and chronic obstructive pulmonary disease, comprising administering a therapeutically effective amount of a compound of formula (I) to a mammal (e.g., a human) in need thereof.
  [FR] La présente invention concerne des composés de formule (I) : et des sels, hydrates ou esters acceptables du point de vue pharmaceutique de ceux-ci, R¹, R², R³, R⁴, R⁵, X et Y étant tels que définis ici. La présente invention concerne également des procédés de fabrication des composés de formule (I) et des procédés de traitement d'affections ou troubles pathologiques induits entièrement ou en partie par des métalloprotéases matricielles, tels que l'asthme et une bronchopneumopathie chronique obstructive, lesquels consistent à administrer une quantité efficace du point de vue thérapeutique d'un composé de formule (I) à un mammifère (par exemple à un humain) qui en a besoin.