(+)-顺-地尔硫卓盐酸盐：钙通道拮抗驱动的多学科科研突破

中文名称 ：(+)-顺-地尔硫卓盐酸盐.

中文别名：盐酸地尔硫卓;顺-(+)-5-[(2-二甲氨基)乙基]-2-(4-甲氧基苯基)-3-乙酰氧基-2,3-二氢-1,5-苯并硫氮杂卓-4(5H)-酮盐酸盐;地尔硫;地尔硫卓;硫氮卓酮;恬尔心;硫氮酮;硫氮卓酮盐酸盐;顺-(+)-5-[(2-二甲氨基)乙基]-2-(4-甲氧基苯基)-3-乙酰氧基-2,3-二氢-1,5-苯并硫氮杂卓-4(5H)酮盐酸盐;盐酸地尔硫草;(+)-顺-地尔硫卓盐酸盐;(+)-cis-Diltiazem Hydrochloride (+)-顺-地尔硫卓盐酸盐;地尔硫卓-D5盐酸;地尔硫卓系统适应性 EP标准品;地尔硫卓盐酸盐;地尔硫卓杂质;盐酸地尔硫;盐酸地尔硫卓 EP标准品;盐酸地尔硫卓 USP标准品;盐酸地尔硫卓 标准品;盐酸硫氮卓酮;盐酸盐地尔硫卓 标准品;(+)-顺式盐酸地尔硫

英文名称：(+)-cis-Diltiazem Hydrochloride

英文别名：Dilthiazem hydrochloride;BENZOTHIAZEPIN-4(5H)-ONE HYDROCHLORIDE;(2S,3S)-(+)-CIS-3-(ACETOXY)-5-(2-DIMETHYLAMINOETHYL)-2,3-DIHYDRO-2-(4-METHOXYPHENYL)-1,5-BENZOTHIAZEPIN-4(5H)-ONE, HCL;(2S-CIS)-3-(ACETYLOXY)-5-[2-(DIMETHYLAMINO)ETHYL]-2,3-DIHYDRO-2-(4-METHOXYPHENYL)-1,5-BENZOTHIAZEPIN-4(5H)-ONE HYDROCHLORIDE;CIS-(+)-3-(ACETYLOXY)-5-[2-(DIMETHYLAMINO)ETHYL]-2,3-DIHYDRO-2-(4-METHOXY-PHENYL)-1,5-BENZOTHIAZEPIN-4(5H)-ONE HYDROCHLORIDE;CRD-401;DILTIAZEM-D3 HCL;DILTIAZEM HCL;DILTIAZEM HYDROCHLORIDE;L-CIS-DILTIAZEM HCL;1,5-benzothiazepin-4(5h)-one,2,3-dihydro-3-(acetyloxy)-5-(2-(dimethylamino)eth;2,3-dihydro-3-(acetyloxy)-5-(2-(dimethylamino)ethyl)-2-(4-methoxyphenyl)-5-benzothiazepin-4(5h)-one;altiazem;anginyl;angizem;britiazim;bruzem;calcicard;cardizem;dilpral;(+)-cis-Diltiazem Hydrochloride;(2S,3S)-(+)-3-Acetoxy-2,3-Dihydro-5-[2-(DimEthylamino)Ethyl]-2-(4-Methoxyphenyl)-1,5-Benzothiazepin-4(5H)-One Hydrochloride;Diltiazem · HCl;Diltiazem hydrochloride solution;Adizem;Cohlen;Cormax;Diltiazem (hydrochloride);Diltiazem hydrochloride s;dilzem;Kardil;masdil;Tiazac;Zilde;Zilden;(2S,3S)-(+)-cis-3-Acetoxy-5-(2-dimethylaminoethyl)-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one hydrochloride;(+)-cis-3-(Acetyloxy)-5-(2-(dimethylamino)ethyl)-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)one monohydrochloride

Cas No.：33286-22-5

分子式：C22H26N2O4S.HCl

分子量：450.98

包装储存：

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

生物活性 ：Diltiazem hydrochloride is a Ca influx inhibitor (slow channel blocker or calcium antagonist).

性状：Solid

体外研究(In Vitro)：

Benzothiazepine Ca antagonist diltiazem hydrochloride interacts with transmembrane segments IIIS6 and IVS6 in the α1 subunit of L-type Ca channels. Diltiazem causes a dose-dependent inhibiton of contractions as well as Ca influx stimulated by alpha adrenoceptor activation and high-K depolarization. Diltiazem is roughly equally potent in inhibiting contractions induced by high-K and a low concentration of norepinephrine (NE). Diltiazem also inhibits the Na-dependent Ca-efflux from heart mitochondria. Both the (+)-optical isomers of the cis- and trans-forms of diltiazem inhibit Na-Ca exchange activity with comparable potency (IC50 of 10-20 μM).

Medlife has not independently confirmed the accuracy of these methods. They are for reference only.

体内研究(In Vivo)：

Diltiazem produces a noncompetitive inhibition of Ca-induced contractions of depolarized rabbit aorta. Furthermore, there is a lack of parallelism between the smooth muscle effects of removal of [Ca]ex and of addition of diltiazem. Diltiazem improves the cardiac microcirculation and function in an experimental model of hyperthyroidism in rats. The treatment of hyperthyroid rats with losartan diltiazem (4.7±0.7%; P < 0.001) significantly reduces the percentage of fibrosis areas in the left ventricle . In conscious spontaneously hypertensive rats (SHR), diltiazem dose-dependently decreases the blood pressure and increases the heart rate after intravenous administration (0.03--1 mg/kg). Oral administration of diltiazem (100 mg/kg) also reduces the blood pressure of SHR.

Medlife has not independently confirmed the accuracy of these methods. They are for reference only.

运输条件：Room temperature or refrigerated transportation.

参考文献：

[1]. Kraus RL, et al. Molecular mechanism of diltiazem interaction with L-type Ca2+ channels. J Biol Chem. 1998 Oct 16;273(42):27205-12.  [Information]

[2]. van Breemen C, et al. The mechanism of inhibitory action of diltiazem on vascular smooth muscle contractility. J Pharmacol Exp Ther. 1981 Aug;218(2):459-63.  [Information]

[3]. Chiesi M, et al. Stereospecific action of diltiazem on the mitochondrial Na-Ca exchange system and on sarcolemmal Ca-channels. Biochem Pharmacol. 1987 Sep 1;36(17):2735-40.  [Information]

[4]. Freitas F, et al. Cardiac microvascular rarefaction in hyperthyroid rats is reversed by losartan, diltiazem, and propranolol. Fundam Clin Pharmacol. 2015 Feb;29(1):31-40.  [Information]

[5]. Sato M, et al. Hypotensive effects of diltiazem hydrochloride in the normotensive, spontaneously hypertensive and renal hypertensive rats (authors transl). Nihon Yakurigaku Zasshi. 1979 Mar;75(2):99-106.  [Information]

一、科研应用领域

心血管疾病模型研究

· 抗心律失常与抗心绞痛：作为钙离子通道阻滞剂，通过抑制L型钙通道减少心肌细胞钙内流，降低心肌收缩力和心率，用于模拟及治疗室上性心律失常、心绞痛等疾病。

· 高血压与心肌缺血保护：通过扩张血管平滑肌降低外周阻力和血压，改善心肌供血，用于高血压及缺血再灌注损伤的机制研究。

· 肥厚性心肌病治疗：探索其通过钙离子拮抗作用逆转心肌肥厚的分子机制。

药物代谢与药效学分析

· 药代动力学研究：分析其口服吸收率（>90%）、肝脏首过效应（生物利用度约45%）及代谢产物活性，优化给药方案。

· 毒理学评估：研究长期给药对肝肾功能、电解质平衡的影响，建立安全用药指南。

新型剂型开发与递送系统

· 缓释与控释制剂：通过优化制剂工艺（如缓释片、静脉注射剂）提高生物利用度，减少给药频率。

· 纳米载药系统：探索脂质体或聚合物载体增强靶向性，降低胃肠道副作用。

分析化学与标准品应用

· 色谱与质谱分析：作为高纯度标准品（纯度≥98%），用于液相色谱（HPLC）、质谱（UPLC-MS/MS）等定量检测方法开发。

· 法医学检测：在可卡因等违禁药物样本中检测地尔硫卓作为掺杂物，支持法医毒理学研究。

二、研究目标与前沿方向

分子机制与靶点优化

· 结构-活性关系研究：通过X射线晶体学或冷冻电镜解析其与钙通道的结合模式，指导药物结构修饰以增强选择性。

· 耐药性机制：探索细菌或肿瘤细胞对钙通道阻滞的适应性机制，开发联合用药策略（如与外排泵抑制剂联用）。

绿色合成与工艺改进

· 不对称合成法优化：开发高效环保的合成路径（如Darznes缩合反应），减少副产物并提高产率。

· 生物催化技术：利用工程菌株（如链霉菌）实现生物合成，降低原料成本及环境污染。

多学科交叉应用拓展

· 抗肿瘤研究：初步发现其通过线粒体功能障碍诱导肿瘤细胞凋亡，需进一步验证在食管癌等模型中的疗效。

· 免疫调节作用：研究其对巨噬细胞极化（M1/M2）的影响，探索在类风湿关节炎等免疫性疾病中的潜力。

精准医疗与个体化治疗

· 基因多态性分析：结合CYP3A4/3A5基因变异数据，制定个体化剂量调整方案。

· 生物标志物筛选：通过代谢组学筛选与疗效或毒性相关的标志物（如细胞色素P450酶活性标志物）。

三、总结与展望

(+)-顺-地尔硫卓盐酸盐凭借其钙通道拮抗活性和多效性药理作用，已成为心血管疾病、药物代谢及分析化学研究的重要工具。未来研究将聚焦于：

 靶向递送系统：结合AI与纳米技术实现精准治疗；

耐药性突破：开发新型衍生物及联合疗法；

临床转化加速：推动其在抗肿瘤、免疫调节等新适应症中的应用验证；

绿色生产工艺：推动合成生物学与环保技术的深度融合。

如需具体实验方案或产品参数，可参考供应商技术文档（如创赛科技、Medlife）。

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