N-(2-naphthalenesulfonyl) D-valine

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-(2-naphthalenesulfonyl) D-valine
• 英文别名: N-(2-naphthalenesulfonyl)-D-valine；(2R)-3-methyl-2-(naphthalen-2-ylsulfonylamino)butanoic acid
• 化学式: C₁₅H₁₇NO₄S
• 分子量: 307.37
• InChiKey: GFCPZHIUZCLSNZ-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  91.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(2-naphthalenesulfonyl) D-valine 在 N-甲基吗啉 、 三乙基硅烷 、 2-Chloro-1,3-dimethylimidazolidinium hexafluorophosphate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 N-hydroxy-3-methyl-2-(naphthalene-2-sulfonylamino)-butyramide
  参考文献：
  名称：

  Potent and selective 2-naphthylsulfonamide substituted hydroxamic acid inhibitors of matrix metalloproteinase-13

  摘要：

  The matrix metalloproteinase enzyme MMP-13 plays a key role in the degradation of type II collagen in cartilage and bone in osteoarthritis (OA). An effective MMP-13 inhibitor would provide a disease modifying therapy for the treatment of arthritis, although this goal still continues to elude the pharmaceutical industry due to issues with safety. Our efforts have resulted in the discovery of a series of hydroxamic acid inhibitors of MMP-13 that do not significantly inhibit MMP-2 (gelatinase-1). MMP-2 has been implicated in the musculoskeletal side effects resulting from pan-MMP inhibition due to findings from spontaneously occurring human MMP-2 deletions. Analysis of the SAR of hundreds of previously prepared hydroxamate based MMP inhibitors lead us to 2-naphthylsulfonamide substituted hydroxamates which exhibited modest selectivity for MMP-13 versus MMP-2. This Letter describes the lead optimization of 1 and identification of inhibitors exhibiting >100-fold selectivity for MMP-13 over MMP-2 (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.087
• 作为产物：
  描述：

  D-valine t-butyl ester 在 盐酸 、 水 、 三乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 N-(2-naphthalenesulfonyl) D-valine
  参考文献：
  名称：

  Potent and selective 2-naphthylsulfonamide substituted hydroxamic acid inhibitors of matrix metalloproteinase-13

  摘要：

  The matrix metalloproteinase enzyme MMP-13 plays a key role in the degradation of type II collagen in cartilage and bone in osteoarthritis (OA). An effective MMP-13 inhibitor would provide a disease modifying therapy for the treatment of arthritis, although this goal still continues to elude the pharmaceutical industry due to issues with safety. Our efforts have resulted in the discovery of a series of hydroxamic acid inhibitors of MMP-13 that do not significantly inhibit MMP-2 (gelatinase-1). MMP-2 has been implicated in the musculoskeletal side effects resulting from pan-MMP inhibition due to findings from spontaneously occurring human MMP-2 deletions. Analysis of the SAR of hundreds of previously prepared hydroxamate based MMP inhibitors lead us to 2-naphthylsulfonamide substituted hydroxamates which exhibited modest selectivity for MMP-13 versus MMP-2. This Letter describes the lead optimization of 1 and identification of inhibitors exhibiting >100-fold selectivity for MMP-13 over MMP-2 (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.087
• 作为试剂：
  描述：

  4-苄氧基苯甲醛 、 [1,4-Dioxaspiro[4.5]decan-8-ylidene(ethoxy)methoxy]-trimethylsilane 在 硼烷四氢呋喃络合物 、 N-(2-naphthalenesulfonyl) D-valine 作用下， 以 various solvent(s) 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  A Catalytic Asymmetric Synthesis of a Spirofused Azetidinone as a Cholesterol Absorption Inhibitor

  摘要：

  DOI：

  10.1021/jo9704366

文献信息

• Catalytic enantioselective synthesis of a spriofused azetidinone
  申请人：Schering Corporation

  公开号：US05648484A1

  公开（公告）日：1997-07-15

  A process for producing a compound of the formula ##STR1## comprises the following sequence of steps: ##STR2## wherein the various radicals are as defined in the specification.

  一种生产化合物##STR1##的方法，包括以下步骤：##STR2##其中各种基团如规范中所定义。
• CATALIC ENANTIOSELECTIVE SYNTHESIS OF A SPIRO-FUSED AZETIDINONE
  申请人：SCHERING CORPORATION

  公开号：EP0827496A1

  公开（公告）日：1998-03-11
• US5648484A
  申请人：——

  公开号：US5648484A

  公开（公告）日：1997-07-15
• [EN] CATALIC ENANTIOSELECTIVE SYNTHESIS OF A SPIRO-FUSED AZETIDINONE<br/>[FR] SYNTHESE CATALYTIQUE ENANTIOSELECTIVE D'UNE AZETIDINONE A FUSION SPIRO
  申请人：SCHERING CORPORATION

  公开号：WO1996027587A1

  公开（公告）日：1996-09-12

  (EN) A process for producing a compound of formula (1.0) comprises the sequence of steps: (2.0), (3.0), (5.0) or (5.1), (8.0) or (8.1), (9.0) and (1.0); wherein the various radicals are as defined in the specification.(FR) L'invention porte un procédé permettant de produire un composé de la formule (1.0) comprenant la série des étapes suivantes: (2.0), (3.0), (5.0) ou (5.1), (8.0) ou (8.1), (9.0) et (1.0), dans lesquelles les différents radicaux correspondent à la définition donnée dans la description.
• A Catalytic Asymmetric Synthesis of a Spirofused Azetidinone as a Cholesterol Absorption Inhibitor
  作者：Guangzhong Wu、Wanda Tormos

  DOI：10.1021/jo9704366

  日期：1997.9.1