Benzyl 3-[3-[bis[(2-methylpropan-2-yl)oxycarbonylamino]methylideneamino]oxypropoxy]-5-chlorobenzoate | 245116-21-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Benzyl 3-[3-[bis[(2-methylpropan-2-yl)oxycarbonylamino]methylideneamino]oxypropoxy]-5-chlorobenzoate
• 英文别名: benzyl 3-[3-[bis[(2-methylpropan-2-yl)oxycarbonylamino]methylideneamino]oxypropoxy]-5-chlorobenzoate
• CAS: 245116-21-6
• 化学式: C₂₈H₃₆ClN₃O₈
• 分子量: 578.062
• InChiKey: WCDKRYCTTZHFSA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  40
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  134
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  Benzyl 3-[3-[bis[(2-methylpropan-2-yl)oxycarbonylamino]methylideneamino]oxypropoxy]-5-chlorobenzoate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 以70%的产率得到3-[3-[Bis[(2-methylpropan-2-yl)oxycarbonylamino]methylideneamino]oxypropoxy]-5-chlorobenzoic acid
  参考文献：
  名称：

  Oxyguanidines. Part 2: Discovery of a novel orally active thrombin inhibitor through structure-based drug design and parallel synthesis

  摘要：

  Through structure-based drug design and parallel synthesis, we have discovered a novel series of nonpeptidic phenyl-based thrombin inhibitors using oxyguanidines as guanidine bioisosteres. These compounds have been found to be highly potent, highly selective, and orally bioavailable. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.05.002
• 作为产物：
  描述：

  3,5-二氯苯酚 在 4-二甲氨基吡啶 、 草酰氯 、 四丁基氟化铵 、 caesium carbonate 、 magnesium 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 、 三苯基膦 、 甲胺 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 Benzyl 3-[3-[bis[(2-methylpropan-2-yl)oxycarbonylamino]methylideneamino]oxypropoxy]-5-chlorobenzoate
  参考文献：
  名称：

  Oxyguanidines. Part 2: Discovery of a novel orally active thrombin inhibitor through structure-based drug design and parallel synthesis

  摘要：

  Through structure-based drug design and parallel synthesis, we have discovered a novel series of nonpeptidic phenyl-based thrombin inhibitors using oxyguanidines as guanidine bioisosteres. These compounds have been found to be highly potent, highly selective, and orally bioavailable. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.05.002

文献信息

• Benzamide and sulfonamide substitued aminoguanidines and alkoxyguanidines as protese inhibitors
  申请人：——

  公开号：US20010031870A1

  公开（公告）日：2001-10-18

  The present invention is directed to aminoguanidine and alkoxyguanidine compounds, including compounds of Formula I: 1 wherein X is O or NH, L is —O— or —SO 2 —, and R 1 -R 4 , R 9 -R 19 , R a , R b , R c , Y, Z, n and m are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit proteolytic enzymes such as thrombin. Also described are methods for preparing the compounds of Formula I. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin, or are intermediates useful for forming compounds having antithrombotic activity. The invention includes a composition for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation in a mammal. Other uses of compounds of the invention are as anticoagulants either embedded in or physically linked to materials used in the manufacture of devices used in blood collection, blood circulation, and blood storage.

  本发明涉及氨基胍和烷氧基胍化合物，包括公式I的化合物：其中X为O或NH，L为—O—或—SO2—，R1-R4，R9-R19，Ra，Rb，Rc，Y，Z，n和m在规范中设置，以及其水合物，溶剂化物或药学上可接受的盐，可抑制蛋白酶酶如凝血酶。还描述了制备公式I化合物的方法。其中某些化合物通过直接选择性抑制凝血酶表现出抗血栓活性，或是用于形成具有抗血栓活性的化合物的中间体。本发明包括一种用于抑制哺乳动物中的血小板丢失、抑制血小板聚集、抑制纤维蛋白形成、抑制血栓形成和抑制栓塞形成的组合物。本发明化合物的其他用途是作为抗凝剂，嵌入或物理连接到用于血液采集、血液循环和血液储存的设备制造材料中。
• BENZAMIDE AND SULFONAMIDE SUBSTITUTED AMINOGUANIDINES AND ALKOXYGUANIDINES AS PROTEASE INHIBITORS
  申请人：3-DIMENSIONAL PHARMACEUTICALS, INC.

  公开号：EP1070049B1

  公开（公告）日：2004-06-30
• US6344486B1
  申请人：——

  公开号：US6344486B1

  公开（公告）日：2002-02-05
• [EN] BENZAMIDE AND SULFONAMIDE SUBSTITUTED AMINOGUANIDINES AND ALKOXYGUANIDINES AS PROTEASE INHIBITORS<br/>[FR] AMINOGUANIDINES SUBSTITUEES DE BENZAMIDE ET DE SULFONAMIDE ET ALKOXYGUANIDINES EN TANT QU'INHIBITEURS DE PROTEASE
  申请人：3-DIMENSIONAL PHARMACEUTICALS, INC.

  公开号：WO1999051571A1

  公开（公告）日：1999-10-14

  (EN) The present invention is directed to aminoguanidine and alkoxyguanidine compounds, including compounds of Formula (I), wherein X is O or NH, L is -O- or -SO2-, and R1-R4, R9-R19, Ra, Rb, Rc, Y, Z, n and m are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit proteolytic enzymes such as thrombin. Also described are methods for preparing the compounds of Formula (I). Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin, or are intermediates useful for forming compounds having antithrombotic activity. The invention includes a composition for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation in a mammal. Other uses of compounds of the invention are as anticoagulants either embedded in or physically linked to materials used in the manufacture of devices used in blood collection, blood circulation, and blood storage.(FR) L'invention concerne des composés d'aminoguanidine et d'alkoxyguanidine, y compris des composés représentés par la formule (I), dans laquelle X représente O ou NH, L représente -O- ou -SO2- et R1-R4, R9-R19, Ra, Rb, Rc, Y, Z, n et m sont définis dans le descriptif, ainsi que leurs hydrates, solvates ou sels acceptables sur le plan pharmaceutique, inhibant des enzymes protéolytiques, tels que thrombine. Elle concerne également des procédés servant à préparer ces composés représentés par la formule (I). Certains de ces composés exercent une activité antithrombotique par l'intermédiaire de l'inhibition directe sélective de thrombine ou sont des intermédiaires utiles pour produire des composés exerçant une activité antithrombotique. Elle concerne une composition servant à inhiber la perte des plaquettes sanguines, la formation d'agrégats de plaquettes sanguines, la formation de fibrine, la formation de thrombus et d'embolus chez un mammifère. Ces composés peuvent également être utilisés en tant qu'anticoagulants, soit noyés dans des matériaux mis en application afin de fabriquer des dispositifs servant au prélèvement sanguin, à la circulation sanguine ou à la conservation du sang, soit reliés physiquement à ces matériaux.
• Oxyguanidines. Part 2: Discovery of a novel orally active thrombin inhibitor through structure-based drug design and parallel synthesis
  作者：Tianbao Lu、Thomas Markotan、Frank Coppo、Bruce Tomczuk、Carl Crysler、Stephen Eisennagel、John Spurlino、Lisa Gremminger、Richard M Soll、Edward C Giardino、Roger Bone

  DOI：10.1016/j.bmcl.2004.05.002

  日期：2004.7

  Through structure-based drug design and parallel synthesis, we have discovered a novel series of nonpeptidic phenyl-based thrombin inhibitors using oxyguanidines as guanidine bioisosteres. These compounds have been found to be highly potent, highly selective, and orally bioavailable. (C) 2004 Elsevier Ltd. All rights reserved.