ロバスタチン

ロバスタチン · (2S)-2-メチルブタン酸=(1S,3R,7S,8S,8aR)-8-[2-((2R,4R)-4-ヒドロキシ-6-オキソテトラヒドロ-2H-ピラン-2-イル)エチル]-3,7-ジメチル-1,2,3,7,8,8a-ヘキサヒドロ-1-ナフチル · (2R)-2α,6β-ジメチル-2,3,4,4aβ,5,6-ヘキサヒドロ-4α-[[(2S)-2-メチルブチリル]オキシ]-5β-[2-[(2R)-4β-ヒドロキシ-6-オキソテトラヒドロ-2H-ピラン-2α-イル]エチル]ナフタレン · (S)-2-メチルブタン酸(1S)-1,2,3,7,8,8aα-ヘキサヒドロ-3β,7α-ジメチル-8α-[2-[(2R,4R)-テトラヒドロ-4-ヒドロキシ-6-オキソ-2H-ピラン-2-イル]エチル]ナフタレン-1β-イル · メビノリン · (+)-メビノリン · モナコリンKラクトン · (2S)-2-メチルブタン酸(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-ヒドロキシ-6-オキソテトラヒドロ-2H-ピラン-2-イル]エチル]-3,7-ジメチル-1,2,3,7,8,8a-ヘキサヒドロナフタレン-1-イル

https://huagongshe.com/ja/chemical/53232

識別子と物理属性

CAS No.	75330-75-5
分子式	C24H36O5
平均分子量	404.5 g/mol
単同位体質量	404.25627425 g/mol
SMILES	CC[C@H](C)C(=O)O[C@H]1C[C@@H](C)C=C2C=C[C@H](C)[C@H](CC[C@@H]3C[C@@H](O)CC(=O)O3)[C@H]21
InChIKey	PCZOHLXUXFIOCF-BXMDZJJMSA-N
PubChem CID	53232
ChEMBL	CHEMBL152032
ChEBI	CHEBI:40303
EC No.	616-212-7
DTXSID	DTXSID5020784
現地名	ロバスタチン

化学・物理的性質

XLogP	4.3
極性表面積	72.8
水素結合供与体数	1
水素結合受容体数	5
回転可能結合数	7
重原子数	29
形式電荷	0
複雑度	666
医薬品	Pharmaceuticals -> AntilipidemicsPharmaceuticals -> StatinsPharmaceuticals -> Listed in ZINC15
LogP（分配係数）	log Kow = 4.264.54.04
Color/Form	White crystalsWhite crystals from acetone aqueousA white, non-hygroscopic crystalline powder
溶解度	In water, 0.4X10-3 mg/mL at 25 °CInsoluble in waterSolubility at 25 °C (mg/mL): acetone 47, acetonitrile 28, n-butanol 7, iso-butanol 14, chloroform 350, N,N-dimethylformamide 90, ethanol 16, methanol 28, n-octanol 2, n-propanol 11, iso-propanol 20Practically insoluble in hexaneVery soluble in chloroformsoluble in dimethyl formamideslightly soluble in acetone, ethanolエタノール：可溶9.80～10.20mg/mL、透明、無色～微黄色25℃で0.0004mg/mL
Human Drugs	Breast FeedingLactationMilk, HumanAnticholesteremic AgentsHydroxymethylglutaryl-CoA Reductase InhibitorsHypolipidemic AgentsFDA approved drugs -> Active ingredientLipid-lowering agents
Endocrine Disruptors	Potential endocrine disrupting compound
融点	179 °CMP: 174.5 °C (under nitrogen)175°C
Optical Rotation	Specific optical rotation at 25 °C for D (sodium) line: +323 deg (c = 0.5 g in 100 ml acetonitrile)
Physical Description	Solid
Stability/Shelf Life	Stable under recommended storage conditions.Lovastatin tablets should be stored in well-closed, light-resistant containers at 5-30 °C. When stored under these conditions, the tablets are stable for 24 months after the date of manufacture. Lovastatin is sensitive to light. Following exposure to extreme light conditions, the drug is stable for 24 hours or 1 month when exposed to UV (approximately 3230 lux) or fluorescent (approximately 10,764 lux) light, respectively, at 28 °C in air.
Dissociation Constants	13.49
比旋光度	D25 +323° (c = 0.5 g in 100 ml acetonitrile)
沸点	559.2±50.0 °C(Predicted)
密度	1.12±0.1 g/cm3(Predicted)
蒸気圧	0Pa at 25℃
屈折率	320 ° (C=0.5, CH3CN)
貯蔵条件	-20°C
外観・状態	白色からオフホワイトの粉末
pKa（酸解離定数）	13.49±0.40(Predicted)
色	白い
Merck	14,5586
BCS Class	2
安定性	購入日から2年間安定です。この DMSO またはエタノール溶液は、-20°C で 2 か月間保存できます。
InChIKey	PCZOHLXUXFIOCF-BXMDZJJMSA-N
SMILES	[H][C@]12[C@H](C[C@@H](C)C=C1C=C[C@H](C)[C@@H]2CC[C@@H]3C[C@@H](O)CC(=O)O3)OC(=O)[C@@H](C)CC
LogP（分配係数）	4.260
CAS データベース	75330-75-5(CAS DataBase Reference)
EPAの化学物質情報	Lovastatin (75330-75-5)

化学的特性

White Solid

安全性と法規制

GHS 分類	This chemical does not meet GHS hazard criteria for 0.4% (1 of 247) of reports.DangerH302 (19%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P260, P261, P264, P270, P272, P280, P301+P317, P302+P352, P318, P319, P321, P330, P333+P317, P362+P364, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 247 reports by companies from 18 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
規制情報	Hazard Traits - Developmental ToxicityRegulation (EC) No 178/2002 (amended)Status: Active Update: 03-09-2012 https://echa.europa.eu/registration-dossier/-/registered-dossier/10864Butanoic acid, 2-methyl-, (1S,3R,7S,8S,8aR)-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-2-(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-ylethyl-1-naphthalenyl ester, (2S)-: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.
FDA 要件	The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including lovastatin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
Toxic Combustion Products	Special hazards arising from the substance or mixture: Carbon oxides.
Hazard Classes and Categories	Acute Tox. 4 (19%)Acute Tox. 4 (100%)
Hazardous Reactivities and Incompatibilities	Incompatible materials: Strong oxidizing agents.
消火手順	Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.
保管条件	Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature: 2 - 8 °C.Store at 20 deg to 25 °C (68 deg to 77 °F). Lovastatin Tablets USP must be protected from light.

用途

病理研究用、昆虫神経ペプチド類の作用機構の研究用。

説明

Lovastatin is an orally-active hypocholesterolemic useful in the treatment of familial hypercholesterolemia. The drug acts by inhibiting the HMG-CoA reductase-catalyzed rate limiting step of cholesterol biosynthesis. While treatment with lovastatin leads to significant reductions in total and LDL cholesterol, its effect on atherosclerosis or coronary heart disease has not been established.

来歴

Statins are the most extensively used class of lipid-lowering medication. Lovastatin is the second statin discovered by scientists.Later, the official name lovastatin was established. The activity of lovastatin is much better than compactin.In July 1982, lovastatin showed dramatic effects on lowering LDL cholesterol in patients with severe hypercholesterolemia who were unresponsive to the existedmedicines, with very few adverse reactions .

使用

Lovastatin (mevinolin) is a metabolite first isolated from Monascus ruber and later found in several other fungal species. Lovastatin is a potent inhibitor of HMG-CoA. HMG-CoA reductase is the rate-controlling enzyme of the mevalonate pathway, responsible for the biosynthesis of cholesterol. Lovastatin was developed as a drug as a hypolipemic agent.

一般的な説明

Lovastatin, 2-methylbutanoic acid 1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy6-oxo-2H-pyran-2-yl)ethyl]-1-naphthalenyl ester, mevinolin,MK-803 (Mevacor) (formerly called mevinolin), is a potentinhibitor of HMG-CoA. The drug was obtained originallyfrom the fermentation products of the fungi Aspergillus terreusand Monascus ruber. Lovastatin was one of two originalHMG-CoA reductase inhibitors. The other drug, mevastatin(formerly called compactin), was isolated from cultures ofPenicillium cillium citrum. Mevastatin was withdrawn fromclinical trials because it altered intestinal morphology in dogs.This effect was not observed with lovastatin. For inhibitoryeffects on HMG-CoA reductase, the lactone ring must be hydrolyzedto the open-ring heptanoic acid.