1-(tert-butoxycarbonyl)-4-[[5(6)-chlorobenzimidazol-2-yl]sulfonyl]piperazine | 859140-24-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 1-(tert-butoxycarbonyl)-4-[[5(6)-chlorobenzimidazol-2-yl]sulfonyl]piperazine
• 英文别名: 1-(5-chlorobenzimidazol-2-ylsulphonyl)-4-(t-butyloxycarbonyl)piperazine；1-(5-chlorobenzimidazol-2-ylsulfonyl)-4-(t-butyloxycarbonyl)piperazine；tert-butyl 4-[(6-chloro-1H-benzimidazol-2-yl)sulfonyl]piperazine-1-carboxylate
• CAS: 859140-24-2
• 化学式: C₁₆H₂₁ClN₄O₄S
• 分子量: 400.886
• InChiKey: RNESNOGOPVBUIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(tert-butoxycarbonyl)-4-[[5(6)-chlorobenzimidazol-2-yl]sulfonyl]piperazine 、 4-吡啶-4-基苯甲酸 在 盐酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 、 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 4.0h， 生成 1-[[5(6)-chlorobenzoimidazol-2-yl]sulfonyl]-4-[4-(4-pyridyl)benzoyl]piperazine
  参考文献：
  名称：

  Heterocyclic derivatives which inhibit factor Xa

  摘要：

  本发明涉及式(I)的杂环衍生物或其药学上可接受的盐，其具有抗血栓和抗凝血性质，因此在人类或动物的治疗方法中有用。本发明还涉及制备这些杂环衍生物的过程，含有它们的制药组合物以及它们在制造用于产生抗血栓或抗凝血效应的药物中的使用。

  公开号：

  US06753331B1
• 作为产物：
  描述：

  5-氯苯并咪唑-2-硫醇 在 氯 、 溶剂黄146 作用下， 以 水 、 丙酮 为溶剂， 反应 21.17h， 生成 1-(tert-butoxycarbonyl)-4-[[5(6)-chlorobenzimidazol-2-yl]sulfonyl]piperazine
  参考文献：
  名称：

  Design, synthesis, and biological activity of non-basic compounds as factor Xa inhibitors: SAR study of S1 and aryl binding sites

  摘要：

  Compound 7 was identified as the active metabolite of 6 by HPLC and mass spectral analysis. Modification of lead compound 7 by transformation of its N-oxide 6-6 biaryl ring system and fused aromatics produced a series of non-basic fxa inhibitors with excellent potency in anti-fXa and anticoagulant assays. The optimized compounds 73b and 75b showed sub to one digit micromolar anticoagulant activity (PTCT2). Particularly, anti-fXa activity was detected in plasma of rats orally administered with 1 mg/kg of compound 75b. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.04.006

文献信息

• Heterocyclic derivatives which inhibit factor Xa
  申请人：AstraZeneca AB

  公开号：US06753331B1

  公开（公告）日：2004-06-22

  The invention relates to heterocyclic derivatives of formula (I), or pharmaceutically-acceptable salts thereof, which possess antithrombotic and anticoagulant properties and are accordingly useful in methods of treatment of humans or animals. The invention also relates to processes for the preparation of the heterocyclic derivatives, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments for use in the production of an antithrombotic or anticoagulant effect.

  本发明涉及式(I)的杂环衍生物或其药学上可接受的盐，其具有抗血栓和抗凝血性质，因此在人类或动物的治疗方法中有用。本发明还涉及制备这些杂环衍生物的过程，含有它们的制药组合物以及它们在制造用于产生抗血栓或抗凝血效应的药物中的使用。
• HETEROCYCLIC DERIVATIVES WHICH INHIBIT FACTOR XA
  申请人：AstraZeneca AB

  公开号：EP1082321B1

  公开（公告）日：2004-11-17
• US6753331B1
  申请人：——

  公开号：US6753331B1

  公开（公告）日：2004-06-22
• [EN] HETEROCYCLIC DERIVATIVES WHICH INHIBIT FACTOR XA<br/>[FR] DERIVES HETEROCYCLIQUES INHIBANT LE FACTEUR XA
  申请人：ASTRAZENECA AB

  公开号：WO1999057113A1

  公开（公告）日：1999-11-11

  (EN) The invention relates to heterocyclic derivatives of formula (I), or pharmaceutically-acceptable salts thereof, which possess antithrombotic and anticoagulant properties and are accordingly useful in methods of treatment of humans or animals. The invention also relates to processes for the preparation of the heterocyclic derivatives, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments for use in the production of an antithrombotic or anticoagulant effect.(FR) Cette invention concerne des dérivés hétérocycliques de formule (I) ou bien leurs sels pharmaceutiquement acceptables qui possèdent des propriétés antithrombotique et anticoagulante et qui, par conséquent, sont utiles dans des procédés de traitement destiné à l'homme ou aux animaux. Cette invention concerne également des procédés de préparation des dérivés hétérocycliques, des compositions pharmaceutiques contenant ces derniers ainsi que leur utilisation dans la fabrication de médicaments destinés à produire un effet antithrombotique ou anticoagulant.
• Design, synthesis, and biological activity of non-basic compounds as factor Xa inhibitors: SAR study of S1 and aryl binding sites
  作者：Satoshi Komoriya、Noriyasu Haginoya、Shozo Kobayashi、Tsutomu Nagata、Akiyoshi Mochizuki、Masanori Suzuki、Toshiharu Yoshino、Haruhiko Horino、Takayasu Nagahara、Makoto Suzuki、Yumiko Isobe、Taketoshi Furugoori

  DOI：10.1016/j.bmc.2005.04.006

  日期：2005.6

  Compound 7 was identified as the active metabolite of 6 by HPLC and mass spectral analysis. Modification of lead compound 7 by transformation of its N-oxide 6-6 biaryl ring system and fused aromatics produced a series of non-basic fxa inhibitors with excellent potency in anti-fXa and anticoagulant assays. The optimized compounds 73b and 75b showed sub to one digit micromolar anticoagulant activity (PTCT2). Particularly, anti-fXa activity was detected in plasma of rats orally administered with 1 mg/kg of compound 75b. (c) 2005 Elsevier Ltd. All rights reserved.