| 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) |
Cardiotoxicity: Chlorobutanol (100 μM) did not show cytotoxicity in HEK293 cells (MTT test), but at a dose of 50 mg/kg (intravenous injection), 20% of guinea pigs developed arrhythmias characterized by premature ventricular contractions [3]. - hERG safety issues: The inhibitory effect of this compound on hERG (IC₅₀ 32.7 μM) suggests a potential risk of QT interval prolongation and torsades de pointes ventricular tachycardia, especially at high doses [1,3]. Oral LD50 of 26937 rats: 802 mg/kg Iyakuhin Kenkyu. Study of Medical Supplies., 6(119), 1975. Intraperitoneal LD50 of 26937 rats: 165 mg/kg Iyakuhin Kenkyu. Study of Medical Supplies. , 6(119), 1975
26937 Subcutaneous LD50 in rats: 775 mg/kg Iyakuhin Kenkyu. Medical Supplies Research. , 6(119), 1975 26937 Intravenous LD50 in rats: 63 mg/kg Iyakuhin Kenkyu. Medical Supplies Research. , 6(119), 1975 26937 Oral LD50 in mice: 334 mg/kg Iyakuhin Kenkyu. Medical Supplies Research, 6(119), 1975 |
| 参考文献 |
|
| 其他信息 |
Pharmacological classification: Chlorobutanol is an opioid antitussive, but its mechanism of action has not been fully elucidated, and it may be related to the inhibition of the medullary cough center [2]
- Clinical significance: Due to its hERG inhibitory effect and potential for QT interval prolongation, chlorobutanol has been restricted in some regions to avoid adverse cardiac events [3] 1-(4-chlorophenyl)-4-(dimethylamino)-2,3-dimethyl-2-butanol is an organic amino compound belonging to the benzene class of compounds. Chlorobutanol is an antitussive that has been withdrawn from the US and EU markets. Chlorobutanol may prolong the QT interval. In 2007, a study found that chlorobutanol could cause arrhythmias 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) 。
IDOR-1104-0086
Maxi-K modulator 1
VU6032735
VU6080824
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