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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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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. | |
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.
| 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Excretion and metabolism of the antihypertensive agent, RWJ-26240 (McN-5691) in dogs
Drug Metab Dispos 1998 Feb;26(2):115-25.PMID:9456297doi
The excretion and metabolism of a 2-ethynylbenzenealkanamine analog, antihypertensive RWJ-26240 (McN-5691), in beagle dogs was investigated. Recoveries of total radioactivity in urine and feces in the 7 days after oral administration of 14C-RWJ-26240 (6 mg/kg dose) were 2.8% and 96.8% of the radioactive dose, respectively. Representative plasma, urine, and fecal samples were pooled and purified for metabolite profiling, isolation, and identification. Unchanged RWJ-26240 (<19% of the dose) plus 12 metabolites were isolated and identified from these samples using chromatography (TLC, HPLC), spectroscopy (NMR, MS), and derivatization techniques. Unchanged RWJ-26240 plus identified metabolites accounted for >75% of the sample radioactivity in plasma and feces. The formation of RWJ-26240 metabolites can be depicted by the following proposed pathways: 1) N-demethylation, 2) O-demethylation, 3) phenyl hydroxylation, and 4) N-dealkylation. The first three pathways appeared to be quantitatively important steps which led to the production of four major metabolites (each >5% of the sample radioactivity). RWJ-26240 was extensively metabolized in the dog, and fecal excretion was the major route of elimination of RWJ-26240 and its metabolites.
Recent advances in biotransformation of CNS and cardiovascular agents
Curr Drug Metab 2000 Nov;1(3):255-70.PMID:11465048DOI:10.2174/1389200003338965.
Compound biotransformation is a very important research area for drug discovery and development. In this review, publications from the metabolism studies of ten compounds, seven CNS and three cardiovascular agents, from the Johnson & Johnson Corp. were reviewed. The seven CNS compounds are: three antipsychotic agents, mazapertine (arypiperazine analog), RWJ-46344 (arypiperidine analog) and risperidone (aryisoxazole-piperidine analog), one antidepressant, etoperidone (arypiperazine analog), one anxiolytic agent, fenobam (aryimidazole urea analog), one muscle relaxant, xilobam (pyrrolidinylidene urea analog), and one antiepileptic agent, topiramate (fructopyranose sulfamate analog). The three cardiovascular agents are: two arylalkylamine calcium channel blockers, bepridil and RWJ-26240, and one thioindolaminidine antianginal agent, RWJ-34130. Other antipsychotic and antidepressant agents with similar analogs (ziprasidone, trazodone and nefazodone) as well as other similar analogs of calcium channel blockers (verapamil) are discussed. In this article, excretion and metabolism (in vitro, in vivo) of compounds are reviewed from the CNS agents to the cardiovascular agents, including structures of parent compounds, their metabolites, metabolic pathways, and methods for the isolation, profiling, quantification and structural identification of unchanged compounds and metabolites. Pharmacological activities of parent compounds and their metabolites are also briefly discussed.
Biotransformation of an antihypertensive arylalkylamine analogue in the rat
Xenobiotica 1998 Oct;28(10):957-72.PMID:9849643DOI:10.1080/004982598239029.
1. The excretion and metabolism of N-[2-(3,4-dimethoxyphenyl)ethyl]-5-methoxy-N,alpha-dimethyl-2-(phenyl ethynyl) benzenepropanamine (RWJ-26240) in the Wistar rat has been investigated after a single oral dose of 14C-RWJ-26240 (50 mg/kg free base). 2. Plasma samples were obtained for 24 h after dosing and urine and faecal samples were collected over 8 days, and they accounted for 0.9 and 96% of the dose, respectively. 3. Representative samples of plasma, urine and faecal samples were purified for metabolite isolation and identification using HPLC, tlc, mass spectra (CI and EI), 1H-NMR and derivatization. 4. Unchanged RWJ-26240 plus 11 metabolites were identified and accounted for > 80% of the sample radioactivity. 5. Four metabolic pathways for RWJ-26240 are proposed; namely (1) N-demethylation, (2) O-demethylation, (3) phenyl hydroxylation and (4) N-dealkylation. Pathways 1-3 appeared to be quantitatively more important.