(3R,5R)-7-[(1S,2S,8S,8aR)-2-methyl-8-{[(2S)-2-methylbutanoyl]oxy}-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoic acid

• ChemBase编号: 4431
• 分子式: C23H36O6
• 平均质量: 408.52834
• 单一同位素质量: 408.25118887
• SMILES: O=C(O)C[C@H](O)C[C@H](O)CC[C@H]1[C@H](C=CC2=CCC[C@H](OC(=O)[C@H](CC)C)[C@H]12)C
• Canonical SMILES: CC[C@@H](C(=O)O[C@H]1CCC=C2[C@H]1[C@@H](CC[C@H](C[C@H](CC(=O)O)O)O)[C@H](C=C2)C)C
• InChI: InChI=1S/C23H36O6/c1-4-14(2)23(28)29-20-7-5-6-16-9-8-15(3)19(22(16)20)11-10-17(24)12-18(25)13-21(26)27/h6,8-9,14-15,17-20,22,24-25H,4-5,7,10-13H2,1-3H3,(H,26,27)/t14-,15-,17+,18+,19-,20-,22-/m0/s1
• InChIKey: BOZILQFLQYBIIY-INTXDZFKSA-N

名称和登记号

名称

• IUPAC标准名: (3R,5R)-7-[(1S,2S,8S,8aR)-2-methyl-8-{[(2S)-2-methylbutanoyl]oxy}-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoic acid
• IUPAC传统名: (3R,5R)-7-[(1S,2S,8S,8aR)-2-methyl-8-{[(2S)-2-methylbutanoyl]oxy}-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoic acid
• 别名: Compactin; Mevastatin

登记号

• CAS号: 73573-88-3
• PubChem SID: 160967863; 99443247
• PubChem CID: 446154

理论计算性质

JChem

• Acid pKa: 4.212299
• 质子受体: 5
• 质子供体: 3
• LogD (pH = 5.5): 1.643644
• LogD (pH = 7.4): -0.07435383
• Log P: 2.9506967
• 摩尔折射率: 112.126 cm^3
• 极化性: 43.689632 Å^3
• 极化表面积: 104.06 Å^2
• 可自由旋转的化学键: 11
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 4.03
• LOG S: -3.71
• 溶解度: 7.98e-02 g/l

详细说明

DrugBank - DB06693

• Drug Groups: experimental
• Description: Mevastatin or compactin is a cholesterol-lowering agent isolated from Penicillium citinium. It was the first discovered agent belonging to the class of cholesterol-lowering medications known as statins. During a search for antibiotic compounds produced by fungi in 1971, Akira Endo at Sankyo Co. (Japan) discovered a class of compounds that appeared to lower plasma cholesterol levels. Two years later, the research group isolated a compound structurally similar to hydroxymethylglutarate (HMG) that inhibited the incorporation of acetate. The compound was proposed to bind to the reductase enzyme and was named compactin. Mevastatin is a competitive inhibitor of HMG-Coenzyme A (HMG-CoA) reductase with a binding affinity 10,000 times greater than the HMG-CoA substrate itself. Mevastatin is a pro-drug that is activated by in vivo hydrolysis of the lactone ring. It has served as one of the lead compounds for the development of the synthetic compounds used today.
• Indication: Not used therapeutically due to its many side effects.
• Pharmacology: The primary cause of cardiovascular disease is atherosclerotic plaque formation. Sustained elevations of cholesterol in the blood increase the risk of cardiovascular disease. Mevastatin lowers hepatic production of cholesterol by competitively inhibiting HMG-CoA reductase, the enzyme that catalyzes the rate-limiting step in the cholesterol biosynthesis pathway via the mevalonic acid pathway. Decreased hepatic cholesterol levels causes increased uptake of low density lipoprotein (LDL) cholesterol and reduces cholesterol levels in the circulation.
• Toxicity: Side effects include those of other statins, such as myalgias, abdominal pain, nausea. It also has a higher chance of giving more severe side effects related to myotoxicity (myopathy, myositis, rhabdomyolysis), and hepatotoxicity, than other statins. Due to these major side effects and their enhanced rate of occurance, Mevastatin is not given therapeutically.
• Affected Organisms: Humans and other mammals
• References: [Chemspider]
• External Links: Wikipedia

参考文献

• Pubchem
• Chemspider
• Chemspider