McN5691 (RWJ26240)
(Synonyms: RWJ26240) 目录号 : GC32636
McN5691 (RWJ26240) 是一种电压敏感型钙通道阻滞剂。
Cas No.:99254-95-2
Sample solution is provided at 25 µL, 10mM.
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McN5691 is a voltage-sensitive calcium channel blocker.
McN5691 (1 and 10 μM) prevents 60 mM KCl-induced contraction and calcium uptake and causes concentration-dependent relaxation (EC50=190 μM) of 30 mM KCl-contracted aortic rings. At or below 10 μM, McN5691 (McN-5691) has no effects on basal tone or calcium uptake (45Ca) in isolated rings of rabbit thoracic aorta. McN5691 causes complete high affinity inhibition (Kd=39.5 nM) of specific diltiazem binding to the benzothiazepine receptor on the voltage-sensitive calcium channel in skeletal muscle microsomal membranes. In contrast to diltiazem, McN5691 inhibits specific dihydropyridine receptor binding, but the effect is biphasic with high (Kd=4.7 nM) and low (Kd=919.8 nM) affinity components. McN5691 inhibits norepinephrine (NE)-induced contraction (10 μM) and calcium uptake (1 and 10 μM) and causes concentration-dependent relaxation (EC50=159 μM) of 1 μM NE-contracted rings of rabbit thoracic aorta[1].
The excretion and metabolism of a 2-ethynylbenzenealkanamine analog, antihypertensive McN5691 (RWJ-26240), in beagle dogs is investigated. A total of 96.8% and 2.8% of the radioactive dose are excreted in feces and urine, respectively, during the 7 days after oral administration of 14C-McN5691. Of the radioactive dose, 96.8% and 2.8% is recovered in feces and urine, respectively, in the 7 days after oral administration of 14C-McN5691. More than 87% of the dose is excreted in feces during the 48 hours. McN5691 is extensively metabolized in dogs. Unchanged McN5691 is found in less than 0.1% and 19% of the dose in the 0-24 hour urine and 0-48 hour fecal extract, respectively, and 36% of the sample in the 4 hour plasma[2]. In the McN5691 (McN-5691) study, vascular resistances tend to be higher in spontaneously hypertensive rat (SHR) than in Wistar-Kyoto (WKY) but the differences are statistically significant only in the cerebellum and the midbrain[3].
[1]. Flaim SF, et al. Structurally novel antihypertensive compound, McN-5691, is a calcium channel blocker in vascular smooth muscle. J Pharmacol Exp Ther. 1991 Jan;256(1):279-88. [2]. Wu WN, et al. Excretion and metabolism of the antihypertensive agent, RWJ-26240 (McN-5691) in dogs. Drug Metab Dispos. 1998 Feb;26(2):115-25. [3]. Flaim SF, et al. Effects of the novel calcium channel blocker, McN-5691, on cardiocirculatory dynamics and cardiac output distribution in conscious spontaneously hypertensive rat. J Cardiovasc Pharmacol. 1988 Apr;11(4):489-500.
Animal experiment: | Dogs[2]14C- McN5691 is administered by gavage to male and female beagle dogs (3 of each sex, weight 10.2-12.8 kg) as a single 6 mg/kg (as free base in corn oil) dose. Plasma samples are obtained for 24 hours after dosing. Urine and fecal samples are collected over a 7-day period. Each collected sample is assayed for total radioactivity and analyzed by TLC and HPLC.Rats[3]Studies are conducted in male SHR and control normotensive Wistar-Kyoto (WKY) rats. All animals are housed in constant temperature and environment facilities and given standard lab chow and water ad libitum. Four separate studies are conducted using conscious, age-matched animals:(a) SHR receiving McN5691 as a hydrochloride salt (McN5691) (n=8, body weight=361±7 g); (b) SHR receiving vehicle (VH) (n= 8, bodyweight=381±5g); (C) WKY receiving McN5691(n=9, body weight=355±7 g); and (d) WKY receiving VH (n=6, body weight=342±7g). McN5691 or VH alone is administered i.v. (right jugular vein) as a 15 min continuous infusion for each dose. Each animal receives three doses of McN5691 (0.3, 1.0 and 3.0 mg/kg) in a cumulative fashion or VH infused at an equal rate (0.0408 mL/min). |
References: [1]. Flaim SF, et al. Structurally novel antihypertensive compound, McN-5691, is a calcium channel blocker in vascular smooth muscle. J Pharmacol Exp Ther. 1991 Jan;256(1):279-88. | |
| Cas No. | 99254-95-2 | SDF | |
| 别名 | RWJ26240 | ||
| Canonical SMILES | COC1=C(OC)C=CC(CCN(C)C(C)CCC(C=C(OC)C=C2)=C2C#CC3=CC=CC=C3)=C1 | ||
| 分子式 | C30H35NO3 | 分子量 | 457.6 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1853 mL | 10.9266 mL | 21.8531 mL |
| 5 mM | 0.4371 mL | 2.1853 mL | 4.3706 mL |
| 10 mM | 0.2185 mL | 1.0927 mL | 2.1853 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
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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，
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 saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >98.00%
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