Desmethyl Carvedilol
(Synonyms: O-去甲卡维地洛) 目录号 : GC49866
An active metabolite of carvedilol
Cas No.:72956-44-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >90.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Desmethyl carvedilol is an active metabolite of the non-selective β-adrenergic receptor (β-AR) antagonist carvedilol .1,2,3 It is formed from carvedilol by the cytochrome P450 (CYP) isoform CYP2C9.1 Desmethyl carvedilol inhibits store-overload-induced calcium release in HEK293 cells expressing the ryanodine receptor 2 (RyR2) R4496C (RyR2R4496C) mutation (IC50 = 7.62 µM), a mutation that results in spontaneous calcium release from the endoplasmic reticulum.2 It reduces increases in heart rate and prevents decreases in diastolic blood pressure induced by isoproterenol in conscious rabbits (ED50s = 32 and 5 µg/kg, respectively).3
1.Oldham, H.G., and Clarke, S.E.In vitro identification of the human cytochrome P450 enzymes involved in the metabolism of R(+)- and S(-)-carvedilolDrug Metab. Dispos.25(8)970-977(1997) 2.Smith, C.D., Wang, A., Vembaiyan, K., et al.Novel carvedilol analogues that suppress store-overload-induced Ca2+ releaseJ. Med. Chem.56(21)8625-8655(2013) 3.Strein, K., Sponer, G., MÜller-Beckmann, B., et al.Pharmacological profile of carvedilol, a compound with β-blocking and vasodilating propertiesJ. Cardiovasc. Pharmacol.10(Suppl. 11)S33-S41(1987)
| Cas No. | 72956-44-6 | SDF | Download SDF |
| 别名 | O-去甲卡维地洛 | ||
| Canonical SMILES | OC1=C(OCCNCC(COC2=C(C(C=CC=C3)=C3N4)C4=CC=C2)O)C=CC=C1 | ||
| 分子式 | C23H24N2O4 | 分子量 | 392.5 |
| 溶解度 | DMSO: soluble | 储存条件 | -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 | 2.5478 mL | 12.7389 mL | 25.4777 mL |
| 5 mM | 0.5096 mL | 2.5478 mL | 5.0955 mL |
| 10 mM | 0.2548 mL | 1.2739 mL | 2.5478 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 | ||||||||||
| 计算重置 | ||||||||||
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。
UHPLC Enantiomer Resolution for the ɑ/β-Adrenoceptor Antagonist R/S-Carvedilol and Its Major Active Metabolites on Chiralpak IB N-5
Molecules 2022 Aug 5;27(15):4998.PMID:35956942DOI:10.3390/molecules27154998.
Carvedilol (CAR), a racemic lipophilic aryloxy propanolamine, acts as a selective α1-adrenoreceptor antagonist and a nonselective β-adrenoreceptor antagonist. CAR metabolism mainly produces three active metabolites: Desmethyl Carvedilol (DMC), 4'-hydroxy carvedilol (4'OHC) and 5'-hydroxy carvedilol (5'OHC). The oxidative S-(-)-metabolites contribute to the β-antagonistic effect, yet not to the α-antagonistic effect to be observed after drug dosage. Therefore, the three β-adrenoceptor blocking metabolites, which are structurally closely related to the parent CAR, are included into the development of a bioanalytical quantitative method for all major active species relevant with respect to adrenoceptor-blockade. Because of the given pharmacological profile, resolution of the enantiomers of carvedilol, of 4'- and 5'-hydroxy carvedilol as well as of DMC, is mandatory. The current study aims to determine the response surface for the enantiomer separation of the parent CAR as well as the major metabolites on a suitable chiral stationary phase. Design of experiment approach (DoE) was utilized in an initial screening phase followed by central-composite design for delimitation of the response surface for resolution of the four enantiomeric pairs in least run time. The impact of chromatographic variables (composition and percentage of organic modifier(s), buffer type, buffer pH, flow rate) on critical peaks resolution and adjusted retention time was evaluated, in order to select the most significant critical quality attributes. On this basis, a robust UHPLC-UV method was developed and optimized for the simultaneous, enantioselective determination of CAR along with its major active metabolites (4'OHC, 5'OHC, and DMC) on Chiralpak IBN-5. The optimized UHPLC-UV method (which includes metoprolol as the internal standard) was validated according to the ICH M10 guidelines for bioanalytical methods and proven to be linear, precise, accurate, and robust. The validated assay was applied to plasma samples from cardiovascular patients treated with rac-CAR (blood randomly drawn at different times after oral CAR intake). In order to provide more insight into the mechanism of the enantiomer separation of CAR and its metabolites on the CSP, docking experiments were performed. Molecular simulation studies suggest the chiral recognition to be mainly due to different binding poses of enantiomers of the same compound.