drotaverine | 14009-24-6

• 物质功能分类: 原料药 - 消化系统用药 - 胃肠解痉药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: drotaverine
• 英文别名: Drotaverin；(1Z)-1-[(3,4-diethoxyphenyl)methylene]-6,7-diethoxy-3,4-dihydro-2H-isoquinoline；dotraverine；(1Z)-1-[(3,4-diethoxyphenyl)methylidene]-6,7-diethoxy-3,4-dihydro-2H-isoquinoline
• CAS: 14009-24-6
• 化学式: C₂₄H₃₁NO₄
• 分子量: 397.514
• InChiKey: OMFNSKIUKYOYRG-MOSHPQCFSA-N

物化性质

• 沸点：
  520.94°C (rough estimate)
• 密度：
  1.1507 (rough estimate)
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  49
• 氢给体数：
  1
• 氢受体数：
  5

ADMET

代谢

度罗泰韦林据报道会经历广泛的肝脏代谢，这是其主要消除途径。它也可能通过胆汁排泄形成结合型代谢物。提出的代谢途径和代谢物基于有限的动物研究：在大鼠中，度罗泰韦林的主要识别代谢物是4'-去乙酰度罗泰韦林、6-去乙酰度罗泰韦林、度罗泰瓦林和4'-去乙酰度罗泰瓦林，所有这些都在胆汁中与葡萄糖醛酸结合。4'-去乙酰度罗泰瓦林是排入胆汁中最主要的代谢物。

Drotaverine is reported to undergo extensive hepatic metabolism, which is its main route of elimination. It may also undergo biliary excretion to form conjugated metabolites. Proposed metabolic pathways and metabolites are based on limited animal studies: in rats, the major identified metabolites of drotaverine are 4'-desethyl-drotaverine, 6-desethyl-drotaverine, drotaveraldine, and 4'-desethyl-drotaveraldine, all of which are glucuronidated in the bile. 4'-desethyl-drotaveraldine was the most predominant metabolite eliminated into the bile.

来源:DrugBank

毒理性

• 蛋白质结合

没有可用的信息。

There is no information available.

来源:DrugBank

吸收、分配和排泄

• 吸收

度冷丁在口服给药后不完全被吸收，其生物利用度变异很大。单次口服80毫克剂量后，绝对生物利用度在24.5%至91%之间，平均为58.2 ± 18.2%。平均Cmax为292 ± 88 ng/mL。平均AUC为3251 ± 950 ng*h/mL。平均Tmax为1.9 ± 0.54小时。

Drotaverine is not completely absorbed following oral administration and its bioavailability is highly variable. Following oral administration of a single 80 mg dose, the absolute bioavailability ranged between 24.5 and 91 % with a mean of 58.2 ± 18.2%. Mean Cmax was 292 ± 88 ng/mL. Mean AUC was 3251 ± 950 ng*h/mL. Mean Tmax was 1.9 ± 0.54 hours.

来源:DrugBank

吸收、分配和排泄

• 消除途径

度冷丁主要通过肝脏代谢消除。约67%的药物在粪便中找到，20%的药物随尿液排出。

Drotaverine is mainly eliminated via hepatic metabolism. About 67% of the drug is found in feces and 20% of the drug was eliminated with urine.

来源:DrugBank

吸收、分配和排泄

• 分布容积

口服单一80毫克剂量后，平均分布体积为193 ± 48升。静脉注射80毫克剂量后，平均分布体积为195 ± 48升。

Following oral administration of a single 80 mg dose, the mean volume of distribution was 193 ± 48 L. Following an intravenous dose of 80 mg, the mean volume of distribution was 195 ± 48 L.

来源:DrugBank

吸收、分配和排泄

• 清除

口服单一80毫克剂量后，平均肾清除率为0.59 ± 0.18毫升/分钟。静脉注射80毫克剂量后，平均肾清除率为0.73 ± 0.29毫升/分钟。

Following oral administration of a single 80 mg dose, the mean renal clearance was 0.59 ± 0.18 mL/min. Following an intravenous dose of 80 mg, the mean renal clearance was 0.73 ± 0.29 mL/min.

来源:DrugBank

安全信息

• 海关编码：
  2933990090

制备方法与用途

解痉药：盐酸屈他维林

盐酸屈他维林有片剂和针剂两种形式。每支（2ml）针剂和诺仕帕中的每片含40mg盐酸屈他维林，直接作用于内脏平滑肌，用于解除或预防各种类型平滑肌痉挛发作，无论是功能性还是神经性痉挛。其解痉效果远强于罂粟碱，并且持续时间更长。该药物仅作用于平滑肌而不影响自主神经系统，因此被用作抗胆碱类解痉药。

适用范围：

• 胃肠道痉挛
• 胆绞痛（如胆囊炎、胆结石）
• 肾绞痛（如肾结石、输尿管结石、肾盂肾炎）
• 膀胱炎
• 痛经

用法与用量： 口服，每次40～80mg，每日3次；6岁以下儿童每次20～40mg，每日3次；6岁以上儿童及成人每次40mg，每日3次。也可皮下注射或肌注，每次40～80mg；必要时可于6～8小时后重复注射。若疼痛持续不缓解，也可以用40～80mg缓慢静脉注射。

不良反应与注意事项：

• 偶见恶心、心悸、头痛、头晕及低血压等。
• 青光眼患者禁用；对本药过敏者禁用；卟啉症患者禁用；前列腺增生患者禁用；严重的心脏病、肝脏疾病或肾脏疾病的病人也应避免使用。
• 妊娠与哺乳期应尽量避免服用。

反应信息

• 作为反应物：
  描述：

  drotaverine 、 2,4'-二溴苯乙酮 在 sodium carbonate 作用下， 以 异丙醇 为溶剂， 以68%的产率得到2-(4-bromophenyl)-1-(3',4'-diethoxyphenyl)-8,9-diethoxy-5,6-dihydropyrrolo[2,1-a]isoquinoline
  参考文献：
  名称：

  Enamines of the 1,2,3,4-tetrahydroiso-quinoline series in the Chichibabin synthesis of pyrrolo[2,1-a]isoquinolines and in reaction with oxalyl chloride

  摘要：

  DOI：

  10.1007/s10593-007-0142-6

文献信息

• 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。
• [EN] TRIAZOLOBENZAZEPINES AS VASOPRESSIN V1A RECEPTOR ANTAGONISTS<br/>[FR] TRIAZOLOBENZAZÉPINES UTILISÉES EN TANT QU'ANTAGONISTES DU RÉCEPTEUR DE LA VASOPRESSINE V1A
  申请人：RICHTER GEDEON NYRT

  公开号：WO2019116324A1

  公开（公告）日：2019-06-20

  The present invention relates to 5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepine derivatives of general formula (I) and/or salts thereof and/or geometric isomers thereof and/or stereoisomers thereof and/or enantiomers thereof and/or racemates thereof and/or diastereomers thereof and/or biologically active metabolites thereof and/or prodrugs thereof and/or solvates thereof and/or hydrates thereof and/or polymorphs thereof which are centrally and/or peripherally acting V1a receptor modulators, particularly V1a receptor antagonists. Additional subject of the present invention is the process for the preparation of the compounds and the intermediates of the preparation process as well. The invention also relates to the pharmaceutical compositions containing the compounds or together with one or more other active substances, as well as to the use in the treatment and/or prophylaxis of a disease or condition associated with V1a receptor function.

  本发明涉及一般式(I)的5,6-二氢-4H-[1,2,4]三唑并[4,3-a][1]苯并蒽啉衍生物和/或其盐和/或其几何异构体和/或其立体异构体和/或其对映异构体和/或其消旋体和/或其非对映异构体和/或其生物活性代谢物和/或其前药和/或其溶剂化合物和/或其水合物和/或其多晶形式，这些化合物是中枢和/或外周作用的V1a受体调节剂，特别是V1a受体拮抗剂。本发明的另一个主题是制备这些化合物的过程以及制备过程的中间体。该发明还涉及含有这些化合物或与一个或多个其他活性物质一起的药物组合物，以及在治疗和/或预防与V1a受体功能相关的疾病或症状中的用途。
• Multi-functional ionic liquid compositions for overcoming polymorphism and imparting improved properties for active pharmaceutical, biological, nutritional, and energetic ingredients
  申请人：Rogers D. Robin

  公开号：US20070093462A1

  公开（公告）日：2007-04-26

  Disclosed are ionic liquids and methods of preparing ionic liquid compositions of active pharmaceutical, biological, nutritional, and energetic ingredients. Also disclosed are methods of using the compositions described herein to overcome polymorphism, overcome solubility and delivery problems, to control release rates, add functionality, enhance efficacy (synergy), and improve ease of use and manufacture.

  揭示了离子液体及制备活性药物、生物、营养和能量成分的离子液体组合物的方法。还揭示了利用本文描述的组合物的方法，以克服多型性、克服溶解度和输送问题、控制释放速率、增加功能性、增强功效（协同作用）以及改善易用性和制造工艺。
• Dendrimers as molecular translocators
  申请人：Goodman Murray

  公开号：US20060216265A1

  公开（公告）日：2006-09-28

  Transport molecules include a dendrimer and a biologically active molecule. The dendrimer of such transport molecules includes at least one guanidine group, at least one protonated guanidine group, at least one protected guanidine group, at least one amidine group, at least one protonated amidine group, at least one protected amidine group, at least one ureido group, at least one protonated ureido group, at least one protected ureido group, at least one thioureido group, at least one protonated thioureido group, or at least one protected thioureido group. The biologically active molecule is bonded to the dendrimer. A method of increasing the bioavailability of a drug includes bonding the drug to a dendrimer of the invention.

  转运分子包括一种树枝状聚合物和一种生物活性分子。这些转运分子的树枝状聚合物包括至少一个胍基团、至少一个质子化的胍基团、至少一个保护的胍基团、至少一个酰胺基团、至少一个质子化的酰胺基团、至少一个保护的酰胺基团、至少一个脲基团、至少一个质子化的脲基团、至少一个保护的脲基团、至少一个硫脲基团、至少一个质子化的硫脲基团，或至少一个保护的硫脲基团。生物活性分子与树枝状聚合物结合。一种增加药物生物利用度的方法包括将药物与本发明的树枝状聚合物结合。
• [EN] CCL2 INHIBITORS<br/>[FR] INHIBITEURS DE CCL2
  申请人：AFECTA PHARMACEUTICALS INC

  公开号：WO2018231795A1

  公开（公告）日：2018-12-20

  Compounds, pharmaceutically acceptable salts, and pharmaceutical compositions thereof are disclosed that are useful for inhibition of the biological activity of CCL2, as well as methods of treatment for diseases involving the biological activity of CCL2.

  本文揭示了化合物、药用可接受盐及其药物组合物，这些化合物对于抑制CCL2的生物活性是有用的，以及涉及CCL2生物活性的疾病治疗方法。