盐酸尼卡地平 | 69441-18-5

• 物质功能分类: 原料药 - 循环系统用药 - 防治心绞痛药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 盐酸尼卡地平
• 中文别名: 盐酸诺拉替坦；2,6-二甲基-4-(3-硝基苯基)-1,4-二氢-3,5-吡啶二羧酸2-[甲基(苄基)氨基]乙基甲基酯盐酸盐
• 英文名称: nicardipine hydrochloride
• 英文别名: Loxen；5-O-[2-[benzyl(methyl)amino]ethyl] 3-O-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate;hydron;chloride
• CAS: 69441-18-5；54527-84-3
• 化学式: C₂₆H₂₉N₃O₆*ClH
• mdl: MFCD00057327
• 分子量: 515.994
• InChiKey: AIKVCUNQWYTVTO-UHFFFAOYSA-N

物化性质

• 熔点：
  176-1780C
• 溶解度：
  二甲基亚砜：~1 mg/mL
• 碰撞截面：
  211.9 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

计算性质

• 辛醇/水分配系数(LogP)：
  3.56
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.307
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  8

安全信息

• 危险等级：
  6.1(b)

制备方法与用途

性质

本品为淡黄色粉末或黄色结晶性粉末；无臭，几乎无味。

用途

主要用于治疗：

1. 高血压，单独应用或与其他药物合并应用；
2. 心绞痛，单独应用或与其他药物合并应用。

化学成分

主要成分为盐酸尼卡地平，其化学名称为：2,6-二甲基-4-(3-硝基苯基)-1,4-二氢吡啶-3,5-二羧酸，3-[β-(N-苄基-N-甲氨基)]乙酯-5-甲酯盐酸盐。分子式：C₂₆H₂₉N₃O₆·HCl 分子量：515.99

药理作用： 本品为钙拮抗剂、血管扩张药，抑制心肌与血管平滑肌的跨膜钙离子内流而不改变血钙浓度。对血管的选择性较强，在动物实验中显示可扩张冠状血管平滑肌，并且在产生此作用时未见对心肌产生负性肌力作用。人体试验表明本品能够降低周围血管阻力，尤其是在高血压患者大于正常血压者中降压时伴有反射性心率加快。此外，本品还可使心脏射血分数及心排血量增多而左室舒张末压改变不多，并能增加冠状血流。

药物相互作用

1. 与β阻滞剂同用耐受良好；
2. 与西咪替丁同用可使本品血药浓度增高；
3. 与地高辛合用未见地高辛血药浓度增高，但需测定地高辛血药浓度；
4. 与环孢素合用时环孢素血药浓度增高；
5. 在体外治疗浓度的呋塞米、普萘洛尔、双嘧达莫、华法林、奎尼丁、萘普生加于人体血浆中不改变本品的蛋白结合率。

不良反应

1. 较常见者有脚肿、头晕、头痛、脸红。均为血管扩张的结果。
2. 较少见者有心悸、心动过速、心绞痛加重，通常是反射性心动过速所致；减小剂量或加用β-阻滞药可以纠正。
3. 少见者有恶心、口干、便秘、乏力、皮疹等。

禁忌症： 对本品有过敏反应者；重度主动脉瓣狭窄、颅内出血尚未完全止血者、脑中风等颅压患者。

储存

置棕色玻璃瓶中，密闭保存。

参考资料

血管扩张药 用途

反应信息

• 作为反应物：
  描述：

  盐酸尼卡地平 在 盐酸 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 6.0h， 以37%的产率得到N-nitroso-nicardipine
  参考文献：
  名称：

  Formation of DNA-damaging N-nitroso compounds from the interaction of calcium-channel blockers with nitrite

  摘要：

  A large number of drugs have been shown to react with nitrite to give genotoxic-carcinogenic N-nitroso compounds (NOC). However, the majority of drugs remain to be examined in this respect, among which calcium-channel blockers, all theoretically nitrosatable and widely used in the therapy of hypertension and other cardiovascular diseases. In this preliminary investigation, seven calcium-channel blockers have been examined either for their in vitro nitrosation according to the procedure recommended by the WHO, or for occurrence of liver DNA fragmentation, as detected by the Comet assay, in rats given by gavage 1/2 LD50 of the drug and 80 mg/kg of sodium nitrite. After 6 h incubation the yields of NOC formed in vitro from nicardipine, nifedipine, nimodipine and nitrendipine ranged from 37 to 45% of the theoretical one, whereas the yields of NOC formed from diltiazem, gallopamil and verapamil ranged from 2 to 5%. In vivo, as compared with the effect of the same dose of the drug alone, a significant increase of both tail length and tail moment, indicative of an increased frequency of DNA single-strand breaks and alkali-labile sites, was produced in rat liver DNA by the administration with nitrite of gallopamil, nifedipine, nimodipine and nitrendipine, the ratio [tail length of drug + NaNO2/tail length of drug alone] being 3.2 for nimodipine, 3.1 for gallopamil 2.2 for nifedipine, and 2.1 for nitrendipine. Even if present, the increase in the degree of DNA fragmentation did not reach the statistical significance in rats given with nitrite nicardipine, diltiazem and verapamil. Further studies should be performed to investigate the formation of NOC in conditions Simulating those occurring in the stomach of humans treated with a therapeutic dose, and to quantitate their genotoxic potency. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

  DOI：

  10.1016/j.tox.2007.06.001
• 作为产物：
  描述：

  2-hydroxyethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate 在 盐酸 、 水 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 9.5h， 生成 盐酸尼卡地平
  参考文献：
  名称：

  Synthesis of asymmetric 4-aryl-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylates with vasodilating and antihypertensive activities.

  摘要：

  合成了非对称的4-芳基-1,4-二氢-2,6-二甲基-3,5-吡啶二羧酸酯，其中含有2-乙烯二氧丙基、2-氧丙基或环丙基甲基作为酯基，以及相关衍生物，并进行了在麻醉开放胸腔犬中的扩血管活性及在意识清醒的自发性高血压大鼠中的抗高血压活性测试。环丙基甲基甲基1,4-二氢-2,6-二甲基-4-(3-硝基苯基)-3,5-吡啶二羧酸酯（5f，MPC-2101）和甲基2-氧丙基1,4-二氢-2,6-二甲基-4-(2-硝基苯基)-3,5-吡啶二羧酸酯（8i，MPC-1304）分别表现出强效的脑扩血管和抗高血压活性。在3.0 μg/kg的静脉给药后，5f对脊椎血流的最大增加为221.4%，而硝苯地平和尼卡地平氯化物分别为187.0%和166.3%。8i在0.3和1.0 mg/kg口服给药后的收缩压最大下降分别为42.2和54.0 mmHg，而硝苯地平、尼卡地平和肼苯噻啶氯化物在3.0 mg/kg时的最大下降分别为23.3、16.8和24.5 mmHg。5f和8i的显著扩血管和抗高血压效果持续时间比硝苯地平和尼卡地平更长。

  DOI：

  10.1248/cpb.34.1589

文献信息

• [EN] HETEROCYCLIC COMPOUNDS FOR THE TREATMENT OF STRESS-RELATED CONDITIONS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES POUR LE TRAITEMENT D'ÉTATS LIÉS AU STRESS
  申请人：OTSUKA PHARMA CO LTD

  公开号：WO2010137738A1

  公开（公告）日：2010-12-02

  The present invention provides a novel heterocyclic compound. A heterocyclic compound represented by general formula (1) wherein, R1 and R2, each independently represent hydrogen; a phenyl lower alkyl group that may have a substituent(s) selected from the group consisting of a lower alkyl group and the like on a benzene ring and/or a lower alkyl group; or a cyclo C3-C8 alkyl lower alkyl group; or the like; R3 represents a lower alkynyl group or the like; R4 represents a phenyl group that may have a substituent(s) selected from the group consisting of a 1,3,4-oxadiazolyl group that may have e.g., halogen or a heterocyclic group selected from pyridyl group and the like; the heterocyclic group may have at least one substituent(s) selected from a lower alkoxy group and the like or a salt thereof.

  本发明提供了一种新颖的杂环化合物。一种由通式（1）表示的杂环化合物，其中，R1和R2分别独立表示氢；苯基较低烷基基团，可能在苯环和/或较低烷基基团上具有从较低烷基基团等组成的取代基；或环C3-C8烷基较低烷基基团；或类似物；R3表示较低炔基基团或类似物；R4表示可能具有从1,3,4-噁二唑基团（例如，卤素）或从吡啶基团等组成的取代基的苯基团；所述杂环基可能具有至少一个从较低烷氧基等选择的取代基或其盐。
• Dibenzylamine compound and medicinal use thereof
  申请人：Maeda Kimiya

  公开号：US20050059810A1

  公开（公告）日：2005-03-17

  A dibenzylamine compound represented by the formula (1) wherein R 1 and R 2 are each a C 1-6 alkyl group optionally substituted by halogen atoms and the like; R 3 , R 4 and R 5 are each a hydrogen atom, a halogen atom and the like, or R 3 and R 4 may form, together with carbon atoms bonded thereto, a homocyclic or heterocyclic ring optionally having substituent(s); A is —N(R 7 ) (R 8 ) and the like; ring B is an aryl group or a heterocyclic residue; R 6 is a hydrogen atom, a halogen atom, a nitro group, a C 1-6 alkyl group and the like; n is an integer of 1 to 3, a prodrug thereof and a pharmaceutically acceptable salt thereof show selective and potent CETP inhibitory activity, and therefore, they can be provided as therapeutic or prophylactic agents for hyperlipidemia or arteriosclerosis and the like.

  一种二苄胺化合物，其化学式如下： 其中，R1和R2分别是C1-6烷基基团，可选择性地被卤原子等取代；R3、R4和R5分别是氢原子、卤原子等，或者R3和R4可以与与之相结合的碳原子一起形成一个具有取代基的同环或异环环；A是-N(R7)(R8)等；环B是芳基或杂环残基；R6是氢原子、卤原子、硝基、C1-6烷基基团等；n是1到3的整数，其前体和药学上可接受的盐表现出选择性和强效的CETP抑制活性，因此，它们可以作为治疗或预防高脂血症或动脉硬化等疾病的药物。
• Piperidine derivatives
  申请人：——

  公开号：US20040142956A1

  公开（公告）日：2004-07-22

  Compounds, compositions and methods are provided that are useful in the treatment or prevention of conditions or disorders associated with a neuropeptide receptor. The subject methods are particularly useful in the treatment and/or prevention of endocrine, metabolic, cardiovascular, neurologic, psychiatric, gastrointestinal, genitourinary and other disorders.

  提供了在治疗或预防与神经肽受体相关的疾病或疾病的化合物、组合物和方法。这些方法特别适用于治疗和/或预防内分泌、代谢、心血管、神经、精神、消化、泌尿生殖和其他疾病。
• Nitrogen-containing fused ring compounds and use thereof
  申请人：Hirata Kazuyuki

  公开号：US20070010670A1

  公开（公告）日：2007-01-11

  A URAT1 activity inhibitor containing a nitrogen-containing fused ring compound represented by the following formula [1]: wherein each symbol is as defined in the description. The present invention is useful for the prophylaxis or treatment of pathology showing involvement of uric acid, such as hyperuricemia, gouty tophus, acute gouty arthritis, chronic gouty arthritis, gouty kidney, urolithiasis, renal function disorder, coronary artery disease, ischemic heart disease and the like.

  一种包含氮含有融合环化合物的URAT1活性抑制剂，其化学式如下所示[1]： 其中每个符号如描述中所定义。本发明对于预防或治疗显示尿酸参与的病理学，如高尿酸血症、痛风石、急性痛风性关节炎、慢性痛风性关节炎、痛风性肾脏、尿路结石、肾功能障碍、冠状动脉疾病、缺血性心脏病等方面具有用处。
• Ester derivatives and medicinal use thereof
  申请人：Hagiwara Atsushi

  公开号：US20060089392A1

  公开（公告）日：2006-04-27

  The present invention relates to an ester represented by the formula [1]: or its pharmaceutically acceptable salt, or use of the same. The compound represented by the formula [1] or its pharmaceutically acceptable salt is useful as an agent for the treatment or prophylaxis of hyperlipidemia or the like, since it disappears very rapidly in the living body and has an excellent MTP inhibitory activity.

  本发明涉及如下公式[1]所示的酯： 或其药用可接受的盐，或其使用。由于公式[1]所示的化合物或其药用可接受的盐在生物体内消失得非常快，并且具有出色的MTP抑制活性，因此它可用作治疗或预防高脂血症等的药物。

表征谱图