N-(((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-10-(3-(naphthalen-1-yl)ureido)-6-oxo-3,4,5,6-tetrahydro-2H-benzo[b][1,5]oxazocin-2-yl)methyl)-4-methoxy-N-methylbenzenesulfonamide | 1314268-71-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-(((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-10-(3-(naphthalen-1-yl)ureido)-6-oxo-3,4,5,6-tetrahydro-2H-benzo[b][1,5]oxazocin-2-yl)methyl)-4-methoxy-N-methylbenzenesulfonamide
• 英文别名: N-{[(2R,3R)-5-[(S)-1-hydroxypropan-2-yl]-3-methyl-10-[3-(naphthalen-1-yl)ureido]-6-oxo-3,4,5,6-tetrahydro-1H-benzo[b][1,5]oxazocin-2-yl]methyl}-4-methoxy-N-methylbenzenesulfonamide；1-[(2R,3R)-5-[(2S)-1-hydroxypropan-2-yl]-2-[[(4-methoxyphenyl)sulfonyl-methylamino]methyl]-3-methyl-6-oxo-3,4-dihydro-2H-1,5-benzoxazocin-10-yl]-3-(1-naphthalenyl)urea；1-[(2R,3R)-5-[(2S)-1-hydroxypropan-2-yl]-2-[[(4-methoxyphenyl)sulfonyl-methylamino]methyl]-3-methyl-6-oxo-3,4-dihydro-2H-1,5-benzoxazocin-10-yl]-3-naphthalen-1-ylurea
• CAS: 1314268-71-7
• 化学式: C₃₄H₃₈N₄O₇S
• 分子量: 646.764
• InChiKey: FXIXTIXYCSOXIT-UDKTZTBJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  46
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  146
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  在 pyridine hydrofluoride 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 N-(((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-10-(3-(naphthalen-1-yl)ureido)-6-oxo-3,4,5,6-tetrahydro-2H-benzo[b][1,5]oxazocin-2-yl)methyl)-4-methoxy-N-methylbenzenesulfonamide
  参考文献：
  名称：

  Synthesis of a Novel Suppressor of β-Cell Apoptosis via Diversity-Oriented Synthesis

  摘要：

  The synthesis of a stereochemically diverse library of medium-sized rings accessible via a "build/couple/pair" strategy is described. Key aspects of the synthesis include SNAr cycloetherification of a linear amine template to afford eight stereoisomeric eight-membered lactams and subsequent solid-phase diversification of these scaffolds to yield a 6488-membered library. Screening of this compound collection in a cell-based assay for the suppression of cytokine-induced beta-cell apoptosis resulted in the identification of a small-molecule suppressor capable of restoring glucose-stimulated insulin secretion in a rat beta-cell line. The presence of all stereoisomers in the screening collection enabled preliminary determination of the structural and stereochemical requirements for cellular activity, while efficient follow-up chemistry afforded BRD0476 (probe ML187), which had an approximately 3-fold increase in activity. These results demonstrate the utility of diversity-oriented synthesis to probe discovery using cell-based screening and the importance of including stereochemical diversity in screening collections for the development of stereo/structure-activity relationships.

  DOI：

  10.1021/ml200120m

文献信息

• US8741905B2
  申请人：——

  公开号：US8741905B2

  公开（公告）日：2014-06-03
• [EN] COMPOUNDS AND METHODS FOR TREATING AUTOIMMUNE DISEASES<br/>[FR] COMPOSÉS ET PROCÉDÉS POUR TRAITER DES MALADIES AUTO-IMMUNES
  申请人：BROAD INST INC

  公开号：WO2012061754A2

  公开（公告）日：2012-05-10

  The invention relates to a compound of Formula I: