3-(6-Benzylamino-2-methylsulfanyl-5-nitro-pyrimidin-4-yloxy)-N,N-dimethyl-benzamide | 203925-95-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(6-Benzylamino-2-methylsulfanyl-5-nitro-pyrimidin-4-yloxy)-N,N-dimethyl-benzamide
• 英文别名: 2-Methylthio-4-(benzyl)amino-5-nitro-6-(3-dimethylaminocarbonylphenoxy)pyrimidine；3-[6-(benzylamino)-2-methylsulfanyl-5-nitropyrimidin-4-yl]oxy-N,N-dimethylbenzamide
• CAS: 203925-95-5
• 化学式: C₂₁H₂₁N₅O₄S
• 分子量: 439.495
• InChiKey: XHMKZFKAMGRQCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  139
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-(6-Benzylamino-2-methylsulfanyl-5-nitro-pyrimidin-4-yloxy)-N,N-dimethyl-benzamide 在 盐酸 、 oxone 、 caesium carbonate 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙腈 为溶剂， 190.0 ℃ 、66.66 Pa 条件下， 反应 0.5h， 生成 3-[9-Benzyl-2-(2-benzyloxy-5-cyano-phenoxy)-8-methyl-9H-purin-6-yloxy]-N,N-dimethyl-benzamide
  参考文献：
  名称：

  Design, synthesis, and biological activity of novel purine and bicyclic pyrimidine factor Xa inhibitors

  摘要：

  The synthesis of amidinoaryloxy 9-benzyl-8-methyl-9H-purine, 7,8-dihydropteridine-6(5H)-one and 5,7-dihydropyrimido[4,5-b][1,4]oxazine-6-one inhibitors of Factor Xa is described. These compounds show nanomolar potency against FXa and maintain high selectivity over thrombin and trypsin. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00386-2
• 作为产物：
  描述：

  2-甲硫基-4,6-二氯-5-硝基嘧啶 在 caesium carbonate 作用下， 以 乙腈 为溶剂， 反应 4.0h， 生成 3-(6-Benzylamino-2-methylsulfanyl-5-nitro-pyrimidin-4-yloxy)-N,N-dimethyl-benzamide
  参考文献：
  名称：

  Design, synthesis, and biological activity of novel purine and bicyclic pyrimidine factor Xa inhibitors

  摘要：

  The synthesis of amidinoaryloxy 9-benzyl-8-methyl-9H-purine, 7,8-dihydropteridine-6(5H)-one and 5,7-dihydropyrimido[4,5-b][1,4]oxazine-6-one inhibitors of Factor Xa is described. These compounds show nanomolar potency against FXa and maintain high selectivity over thrombin and trypsin. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00386-2

文献信息

• Purine derivatives and their use as anti-coagulants
  申请人：Berlex Laboratories, Inc.

  公开号：US05753635A1

  公开（公告）日：1998-05-19

  This invention is directed to purine derivatives of the following formulae: ##STR1## wherein Z.sup.1 is --O--, --N(R.sup.10)-- or --CH.sub.2 O--; Z.sup.2 is --O--, --N(R.sup.10)-- or --OCH.sub.2 --; R.sup.1 and R.sup.4 are each independently hydrogen, halo, alkyl, --OR.sup.10, --C(O)OR.sup.10, --C(O)N(R.sup.10)R.sup.11, --N(R.sup.10)R.sup.11, --N(R.sup.10)C(O)R.sup.10, or --N(H)S(O).sub.2 R.sup.13 ; R.sup.2 is --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.10, --C(NH)N(H)C(O)OR.sup.13, --C(NH)N(H)C(O)R.sup.10, --C(NH)N(H)S(O).sub.2 R.sup.13, or --C(NH)N(H)C(O)N(H)R.sup.10 ; R.sup.3 is halo, alkyl, haloalkyl, haloalkoxy, ureido, cyano, guanidino, --OR.sup.10, --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.10, --C(O)N(R.sup.10)R.sup.11, --R.sup.12 --C(O)N(R.sup.10)R.sup.11, --CH(OH)C(O)N(R.sup.10)R.sup.11, --N(R.sup.10)R.sup.11, --R.sup.12 --N(R.sup.10)R.sup.11, --C(O)OR.sup.10, --R.sup.12 --C(O)OR.sup.10, --N(R.sup.10)C(O)R.sup.10, (1,2)-tetrahydropyrimidinyl (optionally substituted by alkyl), (1,2)-imidazolyl (optionally substituted by alkyl), or (1,2)-imidazolinyl (optionally substituted by alkyl); R.sup.5 is hydrogen, halo, alkyl, cycloalkyl, haloakyl, aryl, aralkyl, alkylthio, hydroxy, mercapto, alkoxy, or --N(R.sup.10)R.sup.11 ; and R.sup.6 is defined herein. These compounds are useful as anti-coagulants. This invention is also directed to pharmaceutical compositions containing the compounds of the invention, and methods of using the compounds to treat disease-states characterized by thrombotic activity.

  本发明涉及以下式的嘌呤衍生物：##STR1## 其中，Z.sup.1为--O--，--N(R.sup.10)--或--CH.sub.2 O--；Z.sup.2为--O--，--N(R.sup.10)--或--OCH.sub.2--；R.sup.1和R.sup.4各自独立地为氢、卤、烷基、--OR.sup.10、--C(O)OR.sup.10、--C(O)N(R.sup.10)R.sup.11、--N(R.sup.10)R.sup.11、--N(R.sup.10)C(O)R.sup.10或--N(H)S(O).sub.2R.sup.13；R.sup.2为--C(NH)NH.sub.2、--C(NH)N(H)OR.sup.10、--C(NH)N(H)C(O)OR.sup.13、--C(NH)N(H)C(O)R.sup.10、--C(NH)N(H)S(O).sub.2R.sup.13或--C(NH)N(H)C(O)N(H)R.sup.10；R.sup.3为卤、烷基、卤代烷基、卤代烷氧基、脲基、氰基、胍基、--OR.sup.10、--C(NH)NH.sub.2、--C(NH)N(H)OR.sup.10、--C(O)N(R.sup.10)R.sup.11、--R.sup.12--C(O)N(R.sup.10)R.sup.11、--CH(OH)C(O)N(R.sup.10)R.sup.11、--N(R.sup.10)R.sup.11、--R.sup.12--N(R.sup.10)R.sup.11、--C(O)OR.sup.10、--R.sup.12--C(O)OR.sup.10、--N(R.sup.10)C(O)R.sup.10、（1,2）-四氢嘧啶基（可选地被烷基取代）、（1,2）-咪唑基（可选地被烷基取代）或（1,2）-咪唑啉基（可选地被烷基取代）；R.sup.5为氢、卤、烷基、环烷基、卤代烷基、芳基、芳基烷基、烷硫基、羟基、巯基、烷氧基或--N(R.sup.10)R.sup.11；R.sup.6在此定义。这些化合物可用作抗凝剂。本发明还涉及含有该发明化合物的药物组合物以及使用该化合物治疗由血栓活动所特征的疾病状态的方法。
• PURINE DERIVATIVES AND THEIR USE AS ANTI-COAGULANTS
  申请人：SCHERING AKTIENGESELLSCHAFT

  公开号：EP0920430A1

  公开（公告）日：1999-06-09
• US5753635A
  申请人：——

  公开号：US5753635A

  公开（公告）日：1998-05-19
• [EN] PURINE DERIVATIVES AND THEIR USE AS ANTI-COAGULANTS<br/>[FR] DERIVES DE LA PURINE ET LEUR UTILISATION COMME ANTICOAGULANTS
  申请人：SCHERING AKTIENGESELLSCHAFT

  公开号：WO1998007725A1

  公开（公告）日：1998-02-26

  (EN) This invention is directed to purine derivatives which are useful as anti-coagulants. This invention is also directed to pharmaceutical compositions containing the compounds of the invention, and methods of using the compounds to treat disease-states characterized by thrombotic activity.(FR) L'invention concerne des dérivés de la purine qui peuvent être utilisés comme anticoagulants. L'invention traite aussi de compositions pharmaceutiques contenant les composés selon l'invention, et des procédés pour utiliser ces composés pour traiter les maladies caractérisées par l'activité thrombotique.
• Design, synthesis, and biological activity of novel purine and bicyclic pyrimidine factor Xa inhibitors
  作者：Brad O. Buckman、Raju Mohan、Sunil Koovakkat、Amy Liang、Lan Trinh、Michael M. Morrissey

  DOI：10.1016/s0960-894x(98)00386-2

  日期：1998.8

  The synthesis of amidinoaryloxy 9-benzyl-8-methyl-9H-purine, 7,8-dihydropteridine-6(5H)-one and 5,7-dihydropyrimido[4,5-b][1,4]oxazine-6-one inhibitors of Factor Xa is described. These compounds show nanomolar potency against FXa and maintain high selectivity over thrombin and trypsin. (C) 1998 Elsevier Science Ltd. All rights reserved.