N-2-Naphtalenesulfonyl-S-4-monomethoxytrityl-(L)-cysteine | 244606-15-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: N-2-Naphtalenesulfonyl-S-4-monomethoxytrityl-(L)-cysteine
• 英文别名: (2R)-3-[(4-methoxyphenyl)-diphenylmethyl]sulfanyl-2-(naphthalen-2-ylsulfonylamino)propanoic acid
• CAS: 244606-15-3
• 化学式: C₃₃H₂₉NO₅S₂
• 分子量: 583.729
• InChiKey: JDUUFHDURMALTC-HKBQPEDESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  126
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-2-Naphtalenesulfonyl-S-4-monomethoxytrityl-(L)-cysteine 在 三异丙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.33h， 生成 (R)-3-Mercapto-2-(naphthalene-2-sulfonylamino)-propionic acid
  参考文献：
  名称：

  Design and synthesis of a novel synthetic NAPAP-penta-saccharide conjugate displaying a dual antithrombotic action

  摘要：

  The synthesis of a novel antithrombotic consisting of a heparin pentasaccharide conjugated to the active site inhibitor N-(2-naphtalenesulfonyl)-glycyl-(D)-4-aminophenyl-alanyl-piperidine(NAPAP) (i.e. compound I) is reported. This conjugate shows a unique pharmacological profile both in vitro and in vivo having direct anti-thrombin and ATIII-mediated anti-Xa activity. Furthermore, conjugate I has a prolonged in vivo half-life compared to NAPAP (1.5 h vs 9 min.), (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00320-0
• 作为产物：
  描述：

  S-<4-monomethoxytrityl>-(L)-cysteine 、 2-萘磺酰氯 在 sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 以76%的产率得到N-2-Naphtalenesulfonyl-S-4-monomethoxytrityl-(L)-cysteine
  参考文献：
  名称：

  Design and synthesis of a novel synthetic NAPAP-penta-saccharide conjugate displaying a dual antithrombotic action

  摘要：

  The synthesis of a novel antithrombotic consisting of a heparin pentasaccharide conjugated to the active site inhibitor N-(2-naphtalenesulfonyl)-glycyl-(D)-4-aminophenyl-alanyl-piperidine(NAPAP) (i.e. compound I) is reported. This conjugate shows a unique pharmacological profile both in vitro and in vivo having direct anti-thrombin and ATIII-mediated anti-Xa activity. Furthermore, conjugate I has a prolonged in vivo half-life compared to NAPAP (1.5 h vs 9 min.), (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00320-0

文献信息

• [EN] ANTITHROMBOTIC COMPOUNDS<br/>[FR] COMPOSES ANTITHROMBOTIQUES
  申请人：AKZO NOBEL N.V.

  公开号：WO1999065934A1

  公开（公告）日：1999-12-23

  (EN) The present invention relates to compounds of formula (I), wherein R1 is phenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, (iso)quinolinyl, tetrahydro(iso)quinolinyl, 3,4-dihydro-1H-isoquinolinyl, chromanyl or the camphor group, which groups may optionally be substituted with one or more substitutents selected from (1-8C)alkyl or (1-8C)alkoxy; R2 and R3 are independently H or (1-8C)alkyl; R4 is (1-8C)alkyl or (3-8C)cycloalkyl; or R3 and R4 together with the nitrogen atom to which they are bonded are a nonaromatic (4-8)membered ring optionally containing another heteroatom, the ring optionally being substituted with (1-8C)alkyl or SO2-(1-8C)alkyl; Q is a spacer having a chain length of 10 to 70 atoms; and Z is a negatively charged oligosaccharide residue comprising two to six monosaccharide units, the charge being compensated by positively charged counterions; or a pharmaceutically acceptable salt thereof or a prodrug thereof. The compounds of the invention have antithrombotic activity an can be used in treating or preventing thrombin-related diseases.(FR) La présente invention concerne des composés de formule (I), dans laquelle R1 représente un groupe phényle, naphtyle, 1,2,3,4-tétrahydronaphtyle, (iso)quinolinyle, tétrahydro(iso)quinolinyle, 3,4-dihydro-1H-isoquinolinyle, chromanyle, ou camphre, ces groupes étant éventuellement substitués avec un ou plusieurs substituants choisis parmi alkyle(1-8C) ou alcoxy(1-8C); R2 et R3 représentent indépendamment H ou alkyle(1-8C); R4 représente alkyle(1-8C) ou cycloalkyle(3-8C); ou R3 et R4 forment avec l'atome d'azote auquel ils sont liés un cycle non aromatique de 4 à 8 chaînons contenant un autre hétéroatome, ce cycle étant éventuellement substitué avec alkyle(1-8C) ou alkyle(1-8C)-SO2; Q représente un bras espaceur présentant une longueur de chaîne variant entre 10 et 70 atomes; et Z représente un reste d'oligosaccharide chargé négativement, comprenant deux à six unités de monosaccharide, la charge étant compensée par des ions complémentaires chargés positivement. L'invention concerne également un sel pharmaceutiquement acceptable ou un promédicament de ces composés. Les composés de cette invention, qui présentent une activité antithrombotique, peuvent notamment être utilisés pour traiter ou prévenir les maladies liées à la thrombine.

  本发明涉及式（I）的化合物，其中R1表示苯基，萘基，1,2,3,4-四氢萘基，（异）喹啉基，四氢（异）喹啉基，3,4-二氢-1H-异喹啉基，色基或藿香酮基，这些基团可能被一个或多个取代基选自（1-8C）烷基或（1-8C）烷氧基；R2和R3独立地表示H或（1-8C）烷基；R4表示（1-8C）烷基或（3-8C）环烷基；或R3和R4与它们所连接的氮原子一起形成一个非芳香性的（4-8）环，该环可以选择地包含另一个杂原子，该环可以被（1-8C）烷基或SO2-（1-8C）烷基取代；Q是具有10到70个原子的链长度的间隔物；Z是由两到六个单糖单位组成的带负电荷的寡糖残基，该电荷由正电荷的对离子补偿；或其药学上可接受的盐或前药。本发明的化合物具有抗血栓活性，可用于治疗或预防与凝血酶相关的疾病。
• Antithrombotic compounds
  申请人：Akzo Nobel N.V.

  公开号：US06486129B1

  公开（公告）日：2002-11-26

  The present invention relates to compounds of formula (1), wherein R1 is phenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, (iso)quinolinyl, tetrahydro(iso)quinolinyl, 3,4-dihydro-1H-isoquinolinyl, chromanyl or the camphor group, which groups may optionally be substituted with one or more substitutents selected from (1-8C)alkyl or (1-8C)alkoxy; R2 and R3 are independently H or (1-8C)alkyl; R4 is (1-8C)alkyl or (3-8C)cycloalkyl; or R3 and R4 together with the nitrogen atom to which they are bonded are a nonaromatic (4-8)membered ring optionally containing another heteroatom, the ring optionally being substituted with (1-8C)alkyl or SO2-(1-8C)alkyl; Q is a spacer having a chain length of 10 to 70 atoms; and Z is a negatively charged oligosaccharide residue comprising two to six monosaccharide units, the charge being compensated by positively charged counterions; or a pharmaceutically acceptable salt thereof or a prodrug thereof. The compounds of the invention have antithrombotic activity an can be used in treating or preventing thrombin-related diseases.

  本发明涉及式（1）的化合物，其中R1为苯基、萘基、1,2,3,4-四氢萘基、（异）喹啉基、四氢（异）喹啉基、3,4-二氢-1H-异喹啉基、香豆素基或腈酮基，这些基团可以选择性地被一个或多个取代基（选择自（1-8C）烷基或（1-8C）烷氧基）所取代；R2和R3独立地为H或（1-8C）烷基；R4为（1-8C）烷基或（3-8C）环烷基；或者R3和R4与它们所连接的氮原子一起形成一个非芳香性（4-8）成员环，该环可以选择性地含有另一种杂原子，并且该环可以被（1-8C）烷基或SO2-（1-8C）烷基所取代；Q为具有10至70个原子的链长度的间隔物；Z为由两到六个单糖单位组成的带负电荷的寡糖残基，该电荷由正电荷的对离子所补偿；或其药学上可接受的盐或前药。该发明的化合物具有抗血栓活性，可用于治疗或预防与凝血酶相关的疾病。
• ANTITHROMBOTIC COMPOUNDS
  申请人：Akzo Nobel N.V.

  公开号：EP1087992A1

  公开（公告）日：2001-04-04
• Design and synthesis of a novel synthetic NAPAP-penta-saccharide conjugate displaying a dual antithrombotic action
  作者：Rogier C. Buijsman、Jan E.M. Basten、Theo G. van Dinther、Gijsbert A. van der Marel、Constant A.A. van Boeckel、Jacques H. van Boom

  DOI：10.1016/s0960-894x(99)00320-0

  日期：1999.7

  The synthesis of a novel antithrombotic consisting of a heparin pentasaccharide conjugated to the active site inhibitor N-(2-naphtalenesulfonyl)-glycyl-(D)-4-aminophenyl-alanyl-piperidine(NAPAP) (i.e. compound I) is reported. This conjugate shows a unique pharmacological profile both in vitro and in vivo having direct anti-thrombin and ATIII-mediated anti-Xa activity. Furthermore, conjugate I has a prolonged in vivo half-life compared to NAPAP (1.5 h vs 9 min.), (C) 1999 Elsevier Science Ltd. All rights reserved.