乙溴替丁 | 100981-43-9

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 乙溴替丁
• 英文名称: Ebrocit
• 英文别名: N-[[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]ethyl]amino]methylene]-4-bromobenzenesulfonamide；Ebrotidine；N-(4-bromophenyl)sulfonyl-N'-[2-[[2-(diaminomethylideneamino)-1,3-thiazol-4-yl]methylsulfanyl]ethyl]methanimidamide
• CAS: 100981-43-9
• 化学式: C₁₄H₁₇BrN₆O₂S₃
• 分子量: 477.43
• InChiKey: ZQHFZHPUZXNPMF-UHFFFAOYSA-N

物化性质

• 熔点：
  142.5-146℃
• 沸点：
  633.0±65.0 °C(Predicted)
• 密度：
  1.73±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  198
• 氢给体数：
  3
• 氢受体数：
  7

ADMET

毒理性

• 药物性肝损伤

化合物：埃布罗替丁

Compound:ebrotidine

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

药物性肝损伤标注：最令人关注的药物性肝损伤

DILI Annotation:Most-DILI-Concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

严重程度等级：8

Severity Grade:8

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

已撤回

Label Section:Withdrawn

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 《FDA-批准的药物标签用于研究药物诱导的肝损伤》，药物发现今天，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007 M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: 人类药物诱导肝损伤风险最大的参考药物清单。药物发现今天 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007 M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

安全信息

• 海关编码：
  2942000000
• 储存条件：
  | 2-8℃ |

制备方法与用途

Ebrotidine（FI 3542）是一种竞争性H₂受体拮抗剂，其Ki值为127.5 nM，并具备抗分泌活性，适用于胃部保护。

反应信息

• 作为反应物：
  描述：

  乙溴替丁 在 双氧水 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以57%的产率得到N-(4-溴苯基)磺酰基-N'-[2-[[2-(二氨基亚甲基氨基)-1,3-噻唑-4-基]甲基磺酰基]乙基]甲脒
  参考文献：
  名称：

  尿液中一种新的H2受体拮抗剂ebrotidine的代谢产物。

  摘要：

  埃布罗替丁是一种新型的H2受体拮抗剂，对胃粘膜具有明显的保护作用。提出了该化合物的初步代谢途径，并合成了假设的代谢物。通过HPLC分离和FT-IR和1H NMR对收集的馏分进行光谱鉴定，证实了尿液中依替丁定及其代谢物依替丁定S-氧化物和4-溴苯磺酰胺的存在。依布替丁S，S-二氧化物已通过HPLC使用二极管阵列检测法进行了鉴定。

  DOI：

  10.1002/jps.2600830228
• 作为产物：
  描述：

  4-溴苯磺酰胺 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 反应 4.0h， 生成 乙溴替丁
  参考文献：
  名称：

  Inhibitors of gastric acid secretion: N-sulphonyl formamidines in a series of new histamine H2-receptor antagonists

  摘要：

  DOI：

  10.1016/0223-5234(88)90174-2

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。
• Sulfonamidines, process for the production thereof and pharmaceutical
  申请人：Ferrer Internacional S.A.

  公开号：US04728655A1

  公开（公告）日：1988-03-01

  Sulfonamidine is disclosed of the general formula (I): R--NH--CH.dbd.N--SO.sub.2 --R.sub.1 (I) wherein R is a group selected from 2-[[(5-methyl-1H-imidazole-4-yl)methyl]thio]ethyl], 2-[[[5-[(dimethylamino)methyl]-2-furanyl]methyl]thio]ethyl, 2-[[[2-[(aminoiminomethyl)amino]-4-thiazolyl]methyl]thio]ethyl] or 3-[3-(1-piperidinylmethyl)phenoxy] propyl and R.sub.1 is alkyl; or a phenyl group optionally substituted by alkyl, halogen, nitro, alkoxy, alkanoylamino, carboxylic acid, alkoxycarbonyl, dialkylamino, alkylsulphonyl, alkylsulphonylamino or alkylthio; or 1,3,4-thiadiazole-2-yl substituted by alkanoylamino, and the pharmaceutically acceptable salts thereof, as well as a process for preparing these compounds and pharmaceutical compositions containing the same. These compounds have antiulcer activity and can be used in the treatment of peptic ulcers and other pathologies caused or stimulated by gastric acidity.

  Sulfonamidine揭示了一般式(I)：R--NH--CH.dbd.N--SO.sub.2 --R.sub.1 (I)，其中R是从2-[[(5-甲基-1H-咪唑-4-基)甲基]硫基]乙基，2-[[[5-[(二甲氨基)甲基]-2-呋喃基]甲基]硫基]乙基，2-[[[2-[(氨基亚甲基)氨基]-4-噻唑基]甲基]硫基]乙基或3-[3-(1-哌啶基甲基)苯氧基]丙基中选择的基团，而R.sub.1是烷基；或者是苯基，可以选择地被烷基，卤素，硝基，烷氧基，烷酰胺基，羧酸，烷氧羰基，二烷基氨基，烷基磺酰基，烷基磺酰胺基或烷基硫基取代；或者是被烷酰胺基取代的1,3,4-噻二唑-2-基；以及其药学上可接受的盐，以及制备这些化合物的方法和含有这些化合物的药物组合物。这些化合物具有抗溃疡活性，可用于治疗消化性溃疡和其他由胃酸引起或刺激的病理。
• [EN] POLYMERIC HYPERBRANCHED CARRIER-LINKED PRODRUGS<br/>[FR] PROMÉDICAMENTS LIÉS À DES EXCIPIENTS POLYMÉRIQUES HYPERBRANCHÉS
  申请人：ASCENDIS PHARMA AS

  公开号：WO2013024048A1

  公开（公告）日：2013-02-21

  The present invention relates to water-soluble carrier-linked prodrugs of formula (I),wherein POL is a polymeric moiety,each Hyp is independently a hyperbranched moiety,each moiety SP is independently a spacer moiety, each L is independently a reversible prodrug linker moiety, m is 0 or 1, each n is independently an integer from 2 to 200 and each x is independently 0 or 1. It further relates to pharmaceutical compositions comprising said water- soluble carrier-linked prodrugs and methods of treatment.

  本发明涉及水溶性载体连接的前药，其化学式为（I），其中POL是聚合物基团，每个Hyp是独立的超支化基团，每个基团SP是独立的间隔基团，每个L是独立的可逆前药连接基团，m为0或1，每个n是独立的整数，范围从2到200，每个x是独立的0或1。此外，还涉及包含所述水溶性载体连接的前药的药物组合物和治疗方法。