benzyl 2-[4-[(diaminomethylideneamino)methyl]cyclohexanecarbonyl]oxybenzoate,hydrochloride | 78718-25-9

• 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 2-[4-[(diaminomethylideneamino)methyl]cyclohexanecarbonyl]oxybenzoate,hydrochloride
• 英文别名: 2'-benzyloxycarbonylphenyl trans-4-guanidinomethylcyclohexanecarboxylate hydrochloride；benexate hydrochloride
• CAS: 78718-25-9
• 化学式: C₂₃H₂₇N₃O₄*ClH
• 分子量: 445.946
• InChiKey: ZNYYFCHDQJQKOK-AELULUIVSA-N

物化性质

• 熔点：
  83°

计算性质

• 辛醇/水分配系数(LogP)：
  3.66
• 重原子数：
  31.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  114.5
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  benzyl 2-[4-[(diaminomethylideneamino)methyl]cyclohexanecarbonyl]oxybenzoate,hydrochloride 在 palladium-carbon 作用下， 以 甲醇 、 溶剂黄146 为溶剂， 以91.3%的产率得到2'-Hydroxycarbonylphenyl trans-4-guanidinomethylcyclohexanecarboxylate hydrochloride
  参考文献：
  名称：

  Cyclohexane carboxylic acid derivatives

  摘要：

  化合物的式子为：##STR1## 其中，R1代表vanilyl，naphthyl，pyridyl或α-生育酚基团，或者是式子##STR2## 其中，R2代表氢原子，低烷氧基，甲酰基，低烷酰基或苯基团，或者是式子--(CH2)nCOOR3，其中，R3代表氢原子，低烷基，苯基，苄基，苯氧羰基甲基基团，n代表0到2的整数，或其药学上可接受的盐，可用作抗溃疡剂。

  公开号：

  US04348410A1
• 作为产物：
  描述：

  柳酸苄酯 、 TRANS-4-GUANIDINOMETHYLCYCLOHEXANECARBOXYLIC ACID HYDROCHLORIDE 在 N,N'-二环己基碳二亚胺 作用下， 以 吡啶 、 N,N-二甲基甲酰胺 为溶剂， 以89%的产率得到benzyl 2-[4-[(diaminomethylideneamino)methyl]cyclohexanecarbonyl]oxybenzoate,hydrochloride
  参考文献：
  名称：

  Medicinal chemical studies on synthetic protease inhibitors, trans-4-guanidinomethylcyclohexanecarboxylic acid aryl esters.

  摘要：

  合成了trans-4-氨基甲基环己甲酸(trans-GMCHA)的芳香酯，并测试了其对丝氨酸蛋白酶的抑制作用，包括胰蛋白酶、糜蛋白酶、纤溶酶、血浆激肽酶、胰腺激肽酶、尿激酶和凝血酶。总体而言，这些化合物对糜蛋白酶、胰腺激肽酶和尿激酶显示出强烈的抑制作用，但效果在很大程度上取决于苯核中的取代基。一些trans-GMCHA芳香酯显著抑制了化合物48/80诱导的肥大细胞组胺释放，其中对酚-tert-丁基酚酯的活性尤其强。

  DOI：

  10.1248/cpb.33.647

文献信息

• Prodrugs containing novel bio-cleavable linkers
  申请人：Satyam Apparao

  公开号：US20060046967A1

  公开（公告）日：2006-03-02

  The invention provides the compounds of formula (I) or pharmaceutically acceptable salts thereof. The invention also provides pharmaceutical compositions comprising one or more compounds of formula I or intermediates thereof and one more of pharmaceutically acceptable carriers, vehicles or diluents. The invention further provides methods of preparation and methods of use of prodrugs including NO-releasing prodrugs, double prodrugs and mutual prodrugs comprising the compounds of formula I.

  本发明提供了公式(I)的化合物或其药用可接受的盐。本发明还提供了包含一个或多个公式I的化合物或其中间体以及一个或多个药用可接受的载体、车辆或稀释剂的药物组合物。本发明进一步提供了包括制备方法和使用方法在内的前药，包括释放一氧化氮的前药、双前药和相互前药，由公式I的化合物组成。
• Hydroxylated nebivolol metabolites
  申请人：O'Donnell P. John

  公开号：US20070014733A1

  公开（公告）日：2007-01-18

  Hydroxylated nebivolol metabolites increase NO release from human endothelial cell preparations in a concentration dependent fashion following acute administration. In addition, hydroxylated nebivolol metabolites, including but not limited to 4-hydroxy-6,6′difluoro-, 4-hydroxy-5-phenol-6,6′difluoro-, and 4-hydroxy-8-pheno-6,6′difluoro-, have the ability to increase the capacity for NO release in human endothelial cells following chronic administration. This invention provides hydroxylated nebivolol metabolites and compositions comprising nebivolol and/or at least one hydroxylated metabolite of nebivolol and/or at least one additional compound used to treat cardiovascular diseases or a pharmaceutically acceptable salt thereof. In addition, this invention provides methods of treating and/or preventing vascular diseases by administering at least one hydroxylated metabolite of nebivolol that is capable of releasing a therapeutically effective amount of nitric oxide to a targeted site affected by the vascular disease. Also, this invention is directed to the treatment and/or prevention of migraine headaches administering at least one hydroxylated metabolite of nebivolol. This invention may also be used in conjunction with or as a single treatment of metabolic syndrome disorders.

  羟基化奈必洛尔代谢物在急性给药后以浓度依赖性方式增加人内皮细胞制剂的一氧化氮释放。此外，羟基化奈必洛尔代谢物，包括但不限于4-羟基-6,6'-二氟代-、4-羟基-5-苯酚-6,6'-二氟代-和4-羟基-8-苯并-6,6'-二氟代-，在慢性给药后能够增加人内皮细胞的一氧化氮释放能力。本发明提供了羟基化奈必洛尔代谢物和包含奈必洛尔和/或至少一种羟基化奈必洛尔代谢物和/或至少一种用于治疗心血管疾病的附加化合物的组合物，以及可药用的盐。此外，本发明还提供了通过给药至少一种能够释放治疗有效量的一氧化氮到受血管疾病影响的靶向部位的羟基化奈必洛尔代谢物来治疗和/或预防血管疾病的方法。本发明还涉及通过给药至少一种羟基化奈必洛尔代谢物来治疗和/或预防偏头痛。本发明还可以与治疗代谢综合征障碍的其他治疗联合使用，或作为单一治疗。
• Nitric Oxide Releasing Prodrugs of Therapeutic Agents
  申请人：SATYAM Apparao

  公开号：US20110263526A1

  公开（公告）日：2011-10-27

  The present invention relates to nitric oxide releasing prodrugs of known drugs or therapeutic agents which are represented herein as compounds of formula (I) wherein the drugs or therapeutic agents contain one or more functional groups independently selected from a carboxylic acid, an amino, a hydroxyl and a sulfhydryl group. The invention also relates to processes for the preparation of the nitric oxide releasing prodrugs (the compounds of formula (I)), to pharmaceutical compositions containing them and to methods of using the prodrugs.

  本发明涉及已知药物或治疗剂的一氧化氮释放前药，其在此处表示为式(I)的化合物，其中药物或治疗剂包含一个或多个功能基团，独立地选自羧酸、氨基、羟基和巯基。该发明还涉及制备一氧化氮释放前药（式(I)的化合物）的方法，含有它们的药物组合物以及使用这些前药的方法。
• Glucuronidated nebivolol metabolites
  申请人：O'Donnell P. John

  公开号：US20070014734A1

  公开（公告）日：2007-01-18

  This invention provides glucuronidated nebivolol metabolites and pharmaceutical compositions of glucuronidated nebivolol metabolites for treatment of cardiovascular diseases. In addition, this invention also provides compositions comprising nebivolol and/or at least one glucuronidated metabolite of nebivolol and/or at least one other active compound in a pharmaceutically acceptable carrier. This invention also provides methods of treating and/or preventing vascular diseases, by administering at least one glucuronidated metabolite of nebivolol that is capable of releasing a therapeutically effective amount of nitric oxide to a targeted site affected by the vascular disease. Also, this invention is directed to the treatment and/or prevention of migraine headaches administering at least one glucuronidated metabolite of nebivolol. This invention may also be used in conjunction with or as a single treatment of metabolic syndrome disorders.

  这项发明提供了葡萄糖醛酸化的尼布ivolol代谢物以及用于治疗心血管疾病的葡萄糖醛酸化的尼布ivolol代谢物的制药组合物。此外，该发明还提供了包含尼布ivolol和/或至少一种尼布ivolol的葡萄糖醛酸化代谢物和/或至少一种其他活性化合物的药用可接受载体的组合物。该发明还提供了通过向受影响血管疾病的靶位点投与至少一种能释放治疗有效量一氧化氮的尼布ivolol的葡萄糖醛酸化代谢物来治疗和/或预防血管疾病的方法。此外，该发明旨在通过投与至少一种尼布ivolol的葡萄糖醛酸化代谢物来治疗和/或预防偏头痛。该发明还可与代谢综合征紊乱的单一治疗或联合治疗一起使用。
• Methods for protection of stratified squamous epithelium against injury by noxious substances and novel agents for use therefor
  申请人：——

  公开号：US20020052408A1

  公开（公告）日：2002-05-02

  Novel sulfate ester agents and the use of those agents for treating gastroesophageal reflux disease (GERD) are described, exemplary agents being of the formula: 1 wherein X is —OCH 2 — or —CH 2 O—; Y is a group pendant from X comprising at least one —OSO 3 R 4 moiety, wherein R 4 is H or a pharmaceutically acceptable cation; n is an integer from 1-3; and R 1 and R 2 are each independently selected from the group consisting of —H, a halogen with an atomic number from 9 to 53, —SO 3 R 4 , —NCS, —NCO, —NH(CO)—OR 3 , —NH(CS)SR 3 , —NH(C═NH)OR 3 , —NHCOCH 2 Cl, —NHCOCH 2 Br, —NHCO—CH═CH 2 , —NHC(O)—CF 3 , wherein R 4 is H or a pharmaceutically acceptable cation.

  描述了新型硫酸酯类药剂以及利用这些药剂治疗胃食管反流病（GERD）的方法，示例药剂的结构如下：其中X为—O —或—CH2O—；Y是从X中悬挂的一个含有至少一个—OSO3R4基团的基团，其中R4为H或药用可接受的阳离子；n为1-3的整数；R1和R2各自独立地选择自—H、原子序数为9至53的卤素、—SO3R4、—NCS、—NCO、—NH(CO)—OR3、—NH(CS)SR3、—NH(C═NH)OR3、—NHCO Cl、—NHCO Br、—NHCO—CH═CH2、—NHC(O)—CF3的基团，其中R4为H或药用可接受的阳离子。