| 规格 | 价格 | 库存 | 数量 |
|---|---|---|---|
| 1mg |
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| Other Sizes |
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| 靶点 |
β adrenergic receptor
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|---|---|
| 体外研究 (In Vitro) |
Bufuralol (Ro 3-4787) 盐酸盐是 CYP2D6 底物特异的，具有芳香环和碱性氮，经常用于评估 CYP2D6 活性 [3]。
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| 体内研究 (In Vivo) |
NADPH 介导的盐酸丁呋洛尔 (Ro 3-4787) 的代谢显示出双相动力学，其效率低于在猴子肠道和存在氢过氧化异丙苯 (CuOOH) 的猴子中观察到的代谢动力学，这与肝脏中的代谢一致。观察结果与[4]一致。
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| 酶活实验 |
细胞色素P450 2D6（CYP2D6）是一种高度多态性的酶，代谢大量治疗药物。迄今为止，已经报道了100多种CYP2D6等位基因变异。在这些变异中，我们最近在中国人群中发现了22种新的变异。本研究的目的是在体外对这些变体的酶活性进行功能表征。杆状病毒介导的表达系统用于高水平表达野生型CYP2D6.1和其他变体（CYP2D6.2、CYP2D6.10和22种新型CYP2D6变体）。然后，将含有表达的CYP2D6蛋白的昆虫微粒体分别与Bufuralol或右美沙芬在37°C下孵育20或25分钟。终止后，提取代谢物并用于高效液相色谱检测。在测试的24个CYP2D6变体中，发现两个变体（CYP2D6.92和CYP2D6.96）没有催化活性。其余22个变体对Bufuralol1'-羟基化的内在清除值显著降低，20个变体对右美沙芬O-去甲基化的内在清理值显著低于野生型CYP2D6.1。我们的体外结果表明，与野生型相比，大多数变体的催化活性显著降低，这些数据为中国和其他亚洲人群的个性化医疗提供了有价值的信息。[1]
代谢表型可能受到多种因素的影响，包括等位基因变异和与抑制剂的相互作用。人类CYP2D6负责大约20%的细胞色素P450介导的药物代谢，但由100多种已知变体组成；人群中常见几种变体，而其他变体则相当罕见。表达、纯化了四种CYP2D6等位基因变体，其中三种在活性位点远端具有一系列突变（*34、*17-2、*17-3），一种在活性部位附近具有突变的超代谢者（*53），以及参考*1和活性位点突变*1（Thr309Ala），并研究了它们与典型底物右美沙芬和Bufuralol以及灭活剂SCH 66712的相互作用。我们发现*34、*17-2和*17-3在产生与*1相同的代谢产物时，酶活性和NADPH偶联降低，这表明Arg296可能在NADPH偶联中发挥作用。高活性变体*53显示出与*1类似的NADPH偶联，但不易被SCH 66712灭活。Thr309Ala突变体显示出与*1相似的活性，但NADPH偶联大大减少。总体而言，这些结果表明，需要对个体CYP2D6变异进行动力学和代谢分析，以了解它们对可变药物反应的可能贡献以及个性化医疗的复杂性。[2] |
| 动物实验 |
Observations were made in eight subjects who exercised before and at 1, 2, 4, 6, 8 and 24 h after the double-blind oral administration of placebo, bufuralol 7.5, 15, 30, 60 and 120 mg and propranolol 40 and 160 mg. The exercise heart rate remained constant after placebo. Bufuralol 7.5 mg and propranolol 40 mg reduced exercise heart rate up to 6 and 8 h respectively after dosing but bufuralol 15, 30, 60 and 120 mg and propranolol 160 mg were still active at 24 h. The lowest exercise heart rate occurred at 2 h after all active treatments. Bufuralol 60 and 120 mg produced similar reduction in exercise tachycardia as propranolol 40 mg but less than propranolol 160 mg. Plasma levels of bufuralol and its two major metabolites were measured. The peak plasma concentrations of bufuralol occurred at 1.5 h after 7.5 mg and at 2 h after the other doses of bufuralol. In six subjects the plasma elimination half-life of bufuralol was 2.61 +/- 0.18 h and in the other three subjects 4.85 +/- 0.35 h. There was a corresponding longer time to peak concentration and plasma elimination half-life of the two metabolites in these three subjects. These findings show that bufuralol is a potent beta-adrenoceptor antagonist with partial agonist activity. It has a long duration of action and there is bimodal metabolism of the drug in man
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| 药代性质 (ADME/PK) |
Metabolites/Metabolites: Known metabolites of ibuprofen include 1',2'-vinylbuprofen, 4-hydroxybuprofen, and 6-hydroxybuprofen. Eight subjects were observed exercising 1, 2, 4, 6, 8, and 24 hours after receiving a double-blind oral dose of placebo, ibuprofen 7.5, 15, 30, 60, and 120 mg, and propranolol 40 and 160 mg. Exercise heart rate remained stable after placebo administration. Ibuprofen 7.5 mg and propranolol 40 mg reduced exercise heart rate at 6 and 8 hours after administration, respectively, but ibuprofen 15, 30, 60, and 120 mg and propranolol 160 mg remained effective at 24 hours. Exercise heart rate reached its lowest value 2 hours after all active treatments. Ibuprofen 60 mg and 120 mg were similar to propranolol 40 mg in reducing exercise-induced tachycardia, but less effective than propranolol 160 mg. The plasma concentrations of ibuprofen and its two major metabolites were determined. Peak plasma concentrations of ibuprofen 7.5 mg were reached 1.5 hours after administration, while peak plasma concentrations of other doses were reached 2 hours after administration. The plasma elimination half-life of ibuprofen was 2.61 ± 0.18 hours in 6 subjects and 4.85 ± 0.35 hours in 3 other subjects. The peak concentration times and plasma elimination half-lives of the two metabolites were also prolonged in these 3 subjects. These results suggest that ibuprofen is a potent β-adrenergic receptor antagonist with partial agonist activity. It has a long duration of action and exhibits bimodal metabolism in humans. [1]
|
| 毒性/毒理 (Toxicokinetics/TK) |
The oral LD50 in rats was 750 mg/kg. Behavioral effects included: seizures or impact on the epilepsy threshold; ataxia; and respiratory depression in the lungs, pleura, or respiration. (Drug Research, 27(1410), 1977 [PMID:20114]). The subcutaneous LD50 in rats was 1400 mg/kg. Behavioral effects included: seizures or impact on the epilepsy threshold; ataxia; and respiratory depression in the lungs, pleura, or respiration. Drug Research, 27(1410), 1977 [PMID:20114]
Oral LD50 in mice: 177 mg/kg. Behavioral studies: seizures or impact on the epilepsy threshold; ataxia; lung, pleural, or respiratory: respiratory depression. Arzneimittel-Forschung. Drug Research, 27(1410), 1977 [PMID:20114] Intraperitoneal LD50 in mice: 88 mg/kg. Behavioral studies: seizures or impact on the epilepsy threshold; ataxia; lung, pleural, or respiratory: respiratory depression. Arzneimittel-Forschung. Drug Research, 27(1410), 1977 [PMID:20114] Intravenous LD50 in mice: 29700 ug/kg Behavior: seizures or effects on the epileptic threshold; Behavior: ataxia; Lungs, pleura, or respiration: respiratory depression. Arzneimittel-Forschung. Drug Research, 27(1410), 1977 [PMID:20114] |
| 参考文献 |
|
| 分子式 |
C16H24CLNO2
|
|---|---|
| 分子量 |
297.82
|
| 精确质量 |
297.15
|
| 元素分析 |
C, 64.53; H, 8.12; Cl, 11.90; N, 4.70; O, 10.74
|
| CAS号 |
60398-91-6
|
| 相关CAS号 |
Bufuralol;54340-62-4; 59652-29-8 (HCl); 60398-91-6 (racemic HCl)
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| PubChem CID |
151573
|
| 外观&性状 |
Off-white to light brown solid powder
|
| 沸点 |
393.2ºC at 760 mmHg
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| 熔点 |
143-146ºC
|
| 闪点 |
191.6ºC
|
| LogP |
4.609
|
| tPSA |
45.4
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| 氢键供体(HBD)数目 |
3
|
| 氢键受体(HBA)数目 |
3
|
| 可旋转键数目(RBC) |
5
|
| 重原子数目 |
20
|
| 分子复杂度/Complexity |
287
|
| 定义原子立体中心数目 |
0
|
| InChi Key |
KJBONRGCLLBWCJ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C16H23NO2.ClH/c1-5-11-7-6-8-12-9-14(19-15(11)12)13(18)10-17-16(2,3)4;/h6-9,13,17-18H,5,10H2,1-4H3;1H
|
| 化学名 |
2-(tert-butylamino)-1-(7-ethyl-1-benzofuran-2-yl)ethanol;hydrochloride
|
| 别名 |
Bufuralol hydrochloride; 60398-91-6; Bufuralol HCl; 59652-29-8; Angium; bufuralol, hydrochloride; Bufuralol (hydrochloride); Bufurolol hydrochloride;
|
| 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 注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。 |
| 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) |
Ethanol: 15 mg/mL (50.37 mM)
DMSO: 10 mg/mL (33.58 mM) |
|---|---|
| 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 | 3.3577 mL | 16.7887 mL | 33.5773 mL | |
| 5 mM | 0.6715 mL | 3.3577 mL | 6.7155 mL | |
| 10 mM | 0.3358 mL | 1.6789 mL | 3.3577 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) 。
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