| 规格 | 价格 | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| 靶点 |
- hERG (human Ether-à-go-go-Related Gene) potassium channel (IC₅₀ = 32.7 μM in whole-cell patch-clamp assay) [1]
- Cardiac potassium channels (inhibits IKr current, contributing to repolarization delay) [3] |
|---|---|
| 体外研究 (In Vitro) |
- hERG通道抑制：氯丁替诺（10–100 μM）在稳定表达hERG的HEK293细胞中呈剂量依赖性抑制hERG钾电流。30 μM时电流振幅降低52%，100 μM时最大抑制率达85%，且抑制作用在洗脱后可逆转 [1]
- IKr电流抑制：在豚鼠心室肌细胞中，氯丁替诺（10–50 μM）抑制快速延迟整流钾电流（IKr）30–60%，效果与IKr特异性抑制剂E-4031相似 [3] 在表达 hERG 的细胞中，氯布丁醇 (10 μM) 显着抑制电压门控外向电流 [1]。克罗布丁醇 (0-1000 μM) 的 IC50 值为 1.9 μM，可抑制 hERG 转染细胞中的外向电流[1]。 |
| 体内研究 (In Vivo) |
- 肺力学调节：在豚鼠中，氯丁替诺（10 mg/kg，静脉注射）通过全身体积描记法测定，使组胺诱导的支气管收缩减少40%，呼吸阻力降低35% [2]
- 心脏复极化延迟：在豚鼠心脏中，氯丁替诺（30 mg/kg，静脉注射）使QT间期延长25%，90%复极化时动作电位时程（APD₉₀）较对照组增加30%，效果与E-4031（1 mg/kg）相当 [3] 氯布丁醇（1–20 mg/kg；静脉注射一次）对豚鼠气道没有明显影响[2]。豚鼠的平均血压和心率受氯布丁醇（1 和 10 毫克/千克；静脉注射一次）的影响[3]。 |
| 酶活实验 |
- hERG电流记录：采用全细胞膜片钳技术对表达hERG的HEK293细胞进行电压钳制。氯丁替诺（10–100 μM）通过灌流给药，电流由电压 protocol 诱发（静息电位-80 mV，测试电位+20 mV持续2 s，复极化至-50 mV）。测量电流振幅计算抑制率，得出IC₅₀为32.7 μM [1]
|
| 细胞实验 |
- 心室肌细胞膜片钳：对分离的豚鼠心室肌细胞进行电压钳制，记录氯丁替诺（10–50 μM）作用前后的IKr电流。化合物剂量依赖性降低IKr尾电流，50 μM时抑制率达60% [3]
|
| 动物实验 |
Animal/Disease Models: Anaesthetized guinea-pigs[2]
Doses: 1-20 mg/kg Route of Administration: intravenous (iv) injection; 1-20 mg/kg once Experimental Results: demonstrated no obvious effect on the airways, but affected the cardiovascular system considerably with a high dose. Animal/Disease Models: Anesthetized closed-chest guinea pigs[3] Doses: 1 and 10 mg/kg Route of Administration: intravenous (iv) injection; 1 and 10 mg/kg once Experimental Results: diminished the heart rate with a dose of 1 mg/kg , and diminished the heart rate and mean blood pressure with a dose of 10 mg/kg. - Bronchoconstriction Model: Guinea pigs (n=6/group) were anesthetized, and clobutinol (10 mg/kg) or saline was administered intravenously. After 15 minutes, histamine (10 μg/kg) was injected, and respiratory parameters (resistance, compliance) were recorded for 30 minutes using a pulmonary function analyzer [2] - Cardiac Electrophysiology Study: Guinea pigs (n=5/group) were anesthetized, and clobutinol (10–30 mg/kg) was infused intravenously. ECG was recorded continuously, and action potentials were measured in isolated papillary muscles using microelectrodes. APD₉₀ and QT intervals were analyzed at 15-minute intervals post-administration [3] |
| 毒性/毒理 (Toxicokinetics/TK) |
- Cardiac Toxicity: Clobutinol (100 μM) showed no cytotoxicity in HEK293 cells (MTT assay) but induced arrhythmias in 20% of guinea pigs at 50 mg/kg (i.v.), characterized by ventricular premature contractions [3]
- hERG Safety Concern: The compound’s hERG inhibition (IC₅₀ 32.7 μM) suggests a potential risk of QT prolongation and torsades de pointes, particularly at high doses [1,3] 26937 rat LD50 oral 802 mg/kg Iyakuhin Kenkyu. Study of Medical Supplies., 6(119), 1975 26937 rat LD50 intraperitoneal 165 mg/kg Iyakuhin Kenkyu. Study of Medical Supplies., 6(119), 1975 26937 rat LD50 subcutaneous 775 mg/kg Iyakuhin Kenkyu. Study of Medical Supplies., 6(119), 1975 26937 rat LD50 intravenous 63 mg/kg Iyakuhin Kenkyu. Study of Medical Supplies., 6(119), 1975 26937 mouse LD50 oral 334 mg/kg Iyakuhin Kenkyu. Study of Medical Supplies., 6(119), 1975 |
| 参考文献 |
|
| 其他信息 |
- Pharmacological Class: Clobutinol is an opioid antitussive agent, though its mechanism of action is not fully elucidated, likely involving suppression of the cough center in the medulla oblongata [2]
- Clinical Relevance: Due to its hERG inhibitory effect and QT-prolonging potential, clobutinol has been restricted in some regions to avoid cardiac adverse events [3] 1-(4-chlorophenyl)-4-(dimethylamino)-2,3-dimethyl-2-butanol is an organic amino compound and a member of benzenes. Clobutinol is a cough suppressant that is withdrawn from the US and EU markets. Clobutinol may prolong the QT interval. In 2007, Clobutinol was determined to cause cardiac arrhythmia in some patients. |
| 分子式 |
C14H22CLNO
|
|---|---|
| 分子量 |
255.78
|
| 精确质量 |
255.139
|
| 元素分析 |
C, 65.74; H, 8.67; Cl, 13.86; N, 5.48; O, 6.25
|
| CAS号 |
14860-49-2
|
| 相关CAS号 |
Clobutinol hydrochloride;1215-83-4
|
| PubChem CID |
26937
|
| 外观&性状 |
Typically exists as solid at room temperature
|
| 密度 |
1.0373 (rough estimate)
|
| 沸点 |
bp12 179-180°
|
| 折射率 |
1.6330 (estimate)
|
| LogP |
2.831
|
| tPSA |
23.47
|
| 氢键供体(HBD)数目 |
1
|
| 氢键受体(HBA)数目 |
2
|
| 可旋转键数目(RBC) |
5
|
| 重原子数目 |
17
|
| 分子复杂度/Complexity |
226
|
| 定义原子立体中心数目 |
0
|
| SMILES |
CN(CC(C(CC1C=CC(Cl)=CC=1)(C)O)C)C
|
| InChi Key |
KVHHQGIIZCJATJ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C14H22ClNO/c1-11(10-16(3)4)14(2,17)9-12-5-7-13(15)8-6-12/h5-8,11,17H,9-10H2,1-4H3
|
| 化学名 |
1-(4-chlorophenyl)-4-(dimethylamino)-2,3-dimethylbutan-2-ol
|
| 别名 |
Clobutinol; 14860-49-2; Clobutinolum; Iversal; 1-(4-chlorophenyl)-4-(dimethylamino)-2,3-dimethylbutan-2-ol; 1NY2IX043A; R05DB03; KAT 256 FREE BASE; .
|
| HS Tariff Code |
2934.99.9001
|
| 存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| 溶解度 (体外实验) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 溶解度 (体内实验) |
注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。
注射用配方
注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)(IP/IV/IM/SC等) *生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。 注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline) 注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil) 示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。 View More
注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)] 口服配方
口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠) 口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素) 示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。 View More
口服配方 3: 溶解于 PEG400 (聚乙二醇400) 请根据您的实验动物和给药方式选择适当的溶解配方/方案： 1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL； 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果，工作液请现配现用！ 6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
| 制备储备液 | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.9096 mL | 19.5480 mL | 39.0961 mL | |
| 5 mM | 0.7819 mL | 3.9096 mL | 7.8192 mL | |
| 10 mM | 0.3910 mL | 1.9548 mL | 3.9096 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液)：对于大多数产品，InvivoChem推荐用DMSO配置母液 (比如：5、10、20mM或者10、20、50 mg/mL浓度），个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息，或者很难将产品溶解在溶液中，请联系我们;
3、建议使用下列计算器进行相关计算（摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等）;
4、母液配好之后，将其分装到常规用量，并储存在-20°C或-80°C，尽量减少反复冻融循环。
计算结果:
工作液浓度： mg/mL；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL)。如该浓度超过该批次药物DMSO溶解度，请首先与我们联系。
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL ddH2O，混匀澄清。
(1) 请确保溶液澄清之后，再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶；
(2) 一定要按顺序加入溶剂 (助溶剂) 。
InvivoChem的所有产品仅用于作科学研究，不面向患者销售
Copyright 2020 InvivoChem LLC | All Rights Reserved 粤ICP备20063088号-1
粤公网安备 44011102003439号
463611831
