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

• ChemBase编号: 60
• 分子式: C23H36O7
• 平均质量: 424.52774
• 单一同位素质量: 424.24610349
• SMILES: O([C@@H]1[C@@H]2[C@H]([C@H](C=CC2=C[C@@H](O)C1)C)CC[C@@H](O)C[C@@H](O)CC(=O)O)C(=O)[C@H](CC)C
• Canonical SMILES: CC[C@@H](C(=O)O[C@H]1C[C@H](O)C=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/C23H36O7/c1-4-13(2)23(29)30-20-11-17(25)9-15-6-5-14(3)19(22(15)20)8-7-16(24)10-18(26)12-21(27)28/h5-6,9,13-14,16-20,22,24-26H,4,7-8,10-12H2,1-3H3,(H,27,28)/t13-,14-,16+,17+,18+,19-,20-,22-/m0/s1
• InChIKey: TUZYXOIXSAXUGO-PZAWKZKUSA-N

名称和登记号

名称

• IUPAC标准名: (3R,5R)-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2-methyl-8-{[(2S)-2-methylbutanoyl]oxy}-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoic acid
• IUPAC传统名: pravastatin
• 商标名: Elisor; Lipostat; Mevalotin; Mevinolin; Oliprevin; Pravachol; Pravaselect; Selectin; Selipran; Vasten
• 别名: Pravastatina [Spanish]; Pravastatin Sodium; Pravastatine [French]; Pravastatinum [Latin]; Pravastatin; (βR,δR,1S,2S,6S,8S,8aR)-1,2,6,7,8,8a-Hexahydro-β,δ,6-trihydroxy-2-methyl-8-[(2S)-2-methyl-1-oxobutoxy]-1-naphthaleneheptanoic Acid-3H; Pravastatin-3H

登记号

• CAS号: 81093-37-0
• PubChem SID: 160963523; 46504851
• PubChem CID: 54687

理论计算性质

JChem

• Acid pKa: 4.212299
• 质子受体: 6
• 质子供体: 4
• LogD (pH = 5.5): 0.34003893
• LogD (pH = 7.4): -1.3779589
• Log P: 1.6470916
• 摩尔折射率: 113.5979 cm^3
• 极化性: 44.338123 Å^3
• 极化表面积: 124.29 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: 2.23
• LOG S: -3.24
• 溶解度: 2.42e-01 g/l

分子性质

理化性质

• 溶解度: 2464mg/L
• 疏水性(logP): 2.2

详细说明

DrugBank - DB00175

• Drug Groups: approved
• Description: Pravastatin is a cholesterol-lowering agent that belongs to a class of medications known as statins. It was derived from microbial transformation of mevastatin, the first statin discovered. It is a ring-opened dihydroxyacid with a 6’-hydroxyl group that does not require in vivo activation. Pravastatin is one of the lower potency statins; however, its increased hydrophilicity is thought to confer advantages such as minimal penetration through lipophilic membranes of peripheral cells, increased selectivity for hepatic tissues, and a reduction in side effects compared with lovastatin and simvastatin.
• Indication: For the treatment of hypercholesterolemia and to reduce the risk of cardiovascular disease.
• Pharmacology: The primary cause of cardiovascular (CV) disease is atherosclerotic plaque formation and sustained elevation of cholesterol in the blood increases the risk of CV disease. Pravastatin 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. Pravastatin also inhibits hepatic synthesis if VLDL. At therapeutic doses, pravastatin lowers LDL cholesterol by 20-30%, increase high density lipoprotein (HDL) cholesterol by 3-10%, and decrease plasma triglycerides by 19-34%. HDL cholesterol is thought to confer protective effects against CV disease, whereas high LDL and triglyceride levels are associated with higher risk of disease.
• Toxicity: Side effects include diarrhea, nausea, constipation, gas abdominal pain, myopathy, myositis, rhabdomyolysis, and hepatotoxicity. LD₅₀=mg/kg (orally in rat)
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic, there is a small amount of metabolism by P450 enzymes, but this effect is so minimal that inhibitory pharmacokinetic drug interactions have no real effect on its overall activity and elimination. An in vitro study which found moderate affinity for P450 2C9 (major), 2D6 and 3A4.
• Absorption: Average oral absorption of pravastatin is 34% and absolute bioavailability is 17%.
• Half Life: 77 hours
• Protein Binding: 50%
• Elimination: Approximately 20% of a radiolabeled oral dose is excreted in urine and 70% in the feces.
• External Links: Wikipedia; RxList; Drugs.com

Toronto Research Chemicals - P702003

Radiolabelled Pravastatin (P702000). A competitive inhibitor of HMG-CoA reductase. Bioactive metabolite of Mevastatin.

参考文献

• Watanabe, M., et al.: Bioorg. Med. Chem., 5, 437 (1997)
• Lee, E., et al.: Clin. Pharmacol. Ther., 78, 330 (1997)
• Ferdinand, K.C., et al.: Am. J. Cardiol., 97, 229 (1997)