(naphthalen-2-ylsulfonyl)-L-serine | 115241-92-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (naphthalen-2-ylsulfonyl)-L-serine
• 英文别名: N-(naphthalene-sulfonyl-(2))-L-serine；N-(Naphthalin-sulfonyl-(2))-L-serin；N-(2-Naphthalenylsulfonyl)-L-serine；(2S)-3-hydroxy-2-[(2-naphthalenylsulfonyl)amino]propanoic acid；(2S)-3-hydroxy-2-(naphthalen-2-ylsulfonylamino)propanoic acid
• CAS: 115241-92-4
• 化学式: C₁₃H₁₃NO₅S
• 分子量: 295.316
• InChiKey: DQSMOLGWAJNYHM-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (naphthalen-2-ylsulfonyl)-L-serine 在 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成
  参考文献：
  名称：

  Discovery of O-(3-carbamimidoylphenyl)-l-serine amides as matriptase inhibitors using a fragment-linking approach

  摘要：

  Matriptase is a cell-surface trypsin-like serine protease of epithelial origin, which cleaves and activates proteins including hepatocyte growth factor/scatter factor and proteases such as uPA, which are involved in the progression of various cancers. Here we report a fragment-linking approach, which led to the discovery of O-(3-carbamimidoylphenyl)-L-serine amides as potent matriptase inhibitors. The co-crystal structure of one of the potent inhibitors, 6 in complex with matriptase catalytic domain validated the working hypothesis guiding the development of this congeneric series and revealed the structural basis for matriptase inhibition. Replacement of a naphthyl group in 6 with 2,4,6-tri-isopropyl phenyl resulted in 10 with improved matriptase inhibition, which exhibited significant primary tumor growth inhibition in a mouse model of prostate cancer. Compounds such as 10, identified using a fragment-linking approach, can be explored further to understand the role of matriptase as a drug target in cancer and inflammation. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.12.008
• 作为产物：
  描述：

  methyl (naphthalen-2-ylsulfonyl)-L-serinate 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以75%的产率得到(naphthalen-2-ylsulfonyl)-L-serine
  参考文献：
  名称：

  Discovery of O-(3-carbamimidoylphenyl)-l-serine amides as matriptase inhibitors using a fragment-linking approach

  摘要：

  Matriptase is a cell-surface trypsin-like serine protease of epithelial origin, which cleaves and activates proteins including hepatocyte growth factor/scatter factor and proteases such as uPA, which are involved in the progression of various cancers. Here we report a fragment-linking approach, which led to the discovery of O-(3-carbamimidoylphenyl)-L-serine amides as potent matriptase inhibitors. The co-crystal structure of one of the potent inhibitors, 6 in complex with matriptase catalytic domain validated the working hypothesis guiding the development of this congeneric series and revealed the structural basis for matriptase inhibition. Replacement of a naphthyl group in 6 with 2,4,6-tri-isopropyl phenyl resulted in 10 with improved matriptase inhibition, which exhibited significant primary tumor growth inhibition in a mouse model of prostate cancer. Compounds such as 10, identified using a fragment-linking approach, can be explored further to understand the role of matriptase as a drug target in cancer and inflammation. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.12.008

文献信息

• [EN] HETEROCYCLIC DERIVATIVES AND THEIR USE AS ANTITHROMBOTIC AGENTS<br/>[FR] DERIVES HETEROCYCLIQUES ET LEUR UTILISATION EN TANT QU'AGENTS ANTITHROMBOTIQUES
  申请人：AKZO NOBEL N.V.

  公开号：WO1998047876A1

  公开（公告）日：1998-10-29

  (EN) The present invention relates to antithrombotic compounds comprising the group Q, Q having formula (I), wherein the substructure (i) is a structure selected from (a, b and c), wherein X is O or S; X' being independently CH or N; and m is 0, 1, 2 or 3; wherein the group Q is bound through an oxygen atom or an optionally substituted nitrogen or carbon atom, or a pharmaceutically acceptable salt thereof or a prodrug thereof. The compounds of the invention are therapeutically active and in particular are antithrombotic agents.(FR) La présente invention concerne des composé antithrombotiques comprenant le groupe Q correspondant à la formule (I) dans laquelle la sous-structure (i) est une structure choisie parmi (a), (b) ou (c) où X représente O ou S, X' représente indépendamment CH ou N, et m vaut 0, 1, 2 ou 3, le groupe Q étant fixé au moyen d'un atome d'oxygène ou d'un atome de carbone ou d'azote éventuellement substitué. L'invention concerne également un sel ou un promédicament de ces composés, acceptable sur le plan pharmacologique. Les compositions de l'invention sont actives sur le plan thérapeutique et constituent notamment des agents antithrombotiques.

  该发明涉及抗血栓化合物，包括具有公式（I）的Q基团，其中亚结构（i）是从（a）、（b）和（c）中选择的结构，其中X为O或S；X'独立地为CH或N；m为0、1、2或3；其中Q基团通过氧原子或可选择的取代氮或碳原子结合，或其药学可接受的盐或前药。该发明的化合物具有治疗活性，特别是抗血栓剂。
• Heterocyclic derivatives and their use as antithrombotic agents
  申请人：——

  公开号：US20030130270A1

  公开（公告）日：2003-07-10

  The present invention relates to antithrombotic compounds comprising the group Q, Q having formula (I), wherein the substructure (i) is a structure selected from (a, b and c), wherein X is 0 or S; X′ being independently CH or N; and m is 0, 1, 2 or 3; wherein the group Q is bound through an oxygen atom or an optionally substituted nitrogen or carbon atom, or a pharmaceutically acceptable salt thereof or a prodrug thereof. The compounds of the invention are therapeutically active and in particular are antithrombotic agents. 1

  本发明涉及抗血栓化合物，包括具有公式（I）的Q基团，其中亚结构（i）是从（a、b和c）中选择的结构，其中X为0或S；X'独立地为CH或N；m为0、1、2或3；其中Q基团通过氧原子或可选择取代的氮或碳原子结合，或其药学上可接受的盐或前药。本发明的化合物具有治疗活性，特别是抗血栓剂。
• Guanidinyl- or amidinyl-substituted heterocyclic thrombin inhibitors
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP0623595A1

  公开（公告）日：1994-11-09

  Guanidinyl- or amidinyl-substituted heterocyclic thrombin inhibitors are provided which have the structure wherein n is 0, l or 2;    X is S, SO, SO₂ or O;    R¹ is -A-R², where A is an alkyl, alkenyl, or alkynyl chain of 2 to 6 carbon atoms and R² is guanidine, amidine, or amino; or    R¹ is -(CH₂)p-A'-R2' where R2' is amidine and A' is an azacycloalkyl ring of 4 to 8 atoms, optionally substituted by alkyl, CO or halo; or    R¹ is -(CH₂)p-A''-R2'',    wherein R2'' is guanidine, amidine or aminomethyl, and A'' is aryl or cycloalkyl;    and p, R³, R⁴, R⁵ and R⁶ are as defined herein.

  提供了具有以下结构的胍基或脒基取代的杂环凝血酶抑制剂 其中 n 是 0、l 或 2； X是S、SO、SO₂或O； R¹ 是-A-R²，其中 A 是 2 至 6 个碳原子的烷基、烯基或炔基链，R² 是胍基、脒基或氨基；或 R¹ 是-(CH₂)p-A'-R2'，其中 R2'是脒，A'是 4 至 8 个原子的偶氮环烷基，可选择被烷基、CO 或卤代取代；或 R¹ 是-(CH₂)p-A''-R2''、 其中 R2''是胍基、脒基或氨甲基，A''是芳基或环烷基； p、R³、R⁴、R⁵ 和 R⁶ 如本文所定义。
• Chargaff; Ziff, Journal of Biological Chemistry, 1941, vol. 140, p. 928
  作者：Chargaff、Ziff

  DOI：——

  日期：——
• BERNAT, ANDRE;DELEBASSEE, DENIS;FREHEL, DANIEL;MAFFRAND, JEAN-PIERRE;VALL+
  作者：BERNAT, ANDRE、DELEBASSEE, DENIS、FREHEL, DANIEL、MAFFRAND, JEAN-PIERRE、VALL+

  DOI：——

  日期：——