CAS 95233-18-4|CAS 94015-53-9|2-hydroxy-3-[(1r,4r)-4-(4-chlorophenyl)cyclohexyl]-1,4-dihydronaphthalene-1,4-dione|Atovaquone|Malarone Pediatric|atovaquone|Malarone|Mepron|trans-2-[4-(4-Chlorophenyl)...

基本信息

化学结构

分子式

C₂₂H₁₉ClO₃

分子量

366.83746

精确质量

366.10227215

电荷

InChI

InChI=1S/C22H19ClO3/c23-16-11-9-14(10-12-16)13-5-7-15(8-6-13)19-20(24)17-3-1-2-4-18(17)21(25)22(19)26/h1-4,9-13,15,26H,5-8H2/t13-,15-

InChIKey

KUCQYCKVKVOKAY-CTYIDZIISA-N

Canonic Smiles

Clc1ccc(cc1)[C@@H]1CC[C@H](CC1)C1=C(O)C(=O)c2c(C1=O)cccc2

Isomeric Smiles

C1(=C(C(=O)c2c(C1=O)cccc2)O)[C@@H]1CC[C@H](CC1)c1ccc(cc1)Cl

计算属性

JChem

Acid pKa

8.233868

质子受体

质子供体

LogD (pH = 5.5)

4.9968457

LogD (pH = 7.4)

4.9382534

Log P

4.9976463

摩尔折射率

103.1065

极化性

39.141586

极化表面积

54.37

可自由旋转的化学键

里宾斯基五规则

true

ALOGPS 2.1

Log P

4.74

LOG S

-5.66

溶解度

7.96e-04 g/l

数据来源

名称和标识

商标名

Malarone PediatricMalaroneMepron

IUPAC标准名

2-hydroxy-3-[(1r,4r)-4-(4-chlorophenyl)cyclohexyl]-1,4-dihydronaphthalene-1,4-dione

IUPAC传统名

atovaquone 2-hydroxy-3-[(1r,4r)-4-(4-chlorophenyl)cyclohexyl]-1,4-dihydronaphthalene-1,4-dione

别名

AtovaquoneAtovaquonetrans-2-[4-(4-Chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthalenedioneMepronMalarone

名称和标识

数据登录号

CAS号

PubChem CID

PubChem SID

CHEMBL

Medline Plus

Chemspider ID

DrugBank ID

CHEBI ID

维基百科标题

ATC码

美国药典/FDA物质标识码

KEGG ID

数据登录号

化合物性质

理化性质

疏水性(logP)

5.8

溶解度

Practically insoluble

DMSO: >10 mg/mL

外观

yellow powder

药理学性质

半衰期

2.2 to 3.2 days

给药途径

oral only

法定药品分级

PoM (UK), Rx [US]

生物活性机理

Inhibition of electron transport by atovaquone will result in indirect inhibition of these enzymes.

The ultimate metabolic effects of such blockade may include inhibition of nucleic acid and ATP synthesis.

In Plasmodium species, the site of action appears to be the cytochrome bc1 complex (Complex III).

Several metabolic enzymes are linked to the mitochondrial electron transport chain via ubiquinone.

The mechanism of action against Pneumocystis carinii has not been fully elucidated

产品相关信息

Empirical Formula (Hill Notation)

C22H19ClO3

纯度

≥98% (HPLC)

应用领域

Antiprotozoal

Orally active antiprotozoal used for treatment of AIDS-associated pneumonia

Antiparasitic agent

Active (in animals and in vitro) against Pneumocystis carinii, Plasmodia, and tachyzoite and cyst forms of Toxoplasma gondii

化合物性质

分子相关蛋白质

暂无数据

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分子图谱

暂无数据

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描述信息

DrugBank

DB01117

Drug Groups

approved

Description

A hydroxynaphthoquinone that has antimicrobial activity and is being used in antimalarial protocols. [PubChem]

Indication

For the treatment or prevention of Pneumocystis carinii pneumonia in patients who are intolerant to trimethoprim-sulfamethoxazole (TMP-SMX). Also indicated for the acute oral treatment of mild to moderate PCP in patients who are intolerant to TMP-SMX.

Pharmacology

Atovaquone is a highly lipophilic drug that closely resembles the structure ubiquinone. Its inhibitory effect being comparable to ubiquinone, in sensitive parasites atovaquone can act by selectively affecting mitochondrial electron transport and parallel processes such as ATP and pyrimidine biosynthesis. For illustration, cytochrome bc1 complex (complex III) seems to serve as a highly discriminating molecular target for atovaquone in Plasmodia
atovaquone has the advantage of not causing myelosuppression, which is an important issue in patients who have undergone bone marrow transplantation.

Toxicity

The median lethal dose is higher than the maximum oral dose tested in mice and rats (1825 mg/kg per day). Overdoses up to 31,500 mg of atovaquone have been reported. In one such patient who also took an unspecified dose of dapsone, methemoglobinemia occurred. Rash has also been reported after overdose.

Affected Organisms

Plasmodium

Biotransformation

Some evidence suggests limited metabolism (although no metabolites have been identified).

Absorption

The bioavailability of atovaquone is low and variable and is highly dependent on formulation and diet. Bioavailability of the suspension increases two-fold when administered with meals. When administered with food, bioavailability is approximately 47%. Without food, the bioavailability is 23%.

Half Life

2.2 to 3.2 days

Protein Binding

Atovaquone is extensively bound to plasma proteins (99.9%) over the concentration range of 1 to 90 µg/mL.

Elimination

The half-life of atovaquone is long due to presumed enterohepatic cycling and eventual fecal elimination. There was little or no excretion of atovaquone in the urine (less than 0.6%).

Distribution

* 0.60 ± 0.17 L/kg

Clearance

* 10.4 +/- 5.5 ml/min [HIV-infected patients receiving IV administration]

External Links

• [Wikipedia]

• [RxList]

• [Drugs.com]

Wikipedia

Atovaquone

Sigma Aldrich

A7986

Application
Atovaquone inhibits the cytochrome bc(1) complex via interactions with the Rieske iron-sulfur protein and cytochrome b in the ubiquinol oxidation pocket. In addition to its use as a treatment for toxoplasmosis, atovaquone has antimalarial properties and prevents pneumocystis pneumonia post-renal transplant.
Biochem/physiol Actions
Atovaquone is an anti-protozoal mitochondrial electron transport inhibitor; Antimalarial; Antipneumocystic, and has also been used to treat toxoplasmosis. It is an analog of protozoan mitochondrial protein ubiquinone, and acts by inhibiting the cytochrome bc(1) complex via interactions with the Rieske iron-sulfur protein and cytochrome b in the ubiquinol oxidation pocket.

描述信息

参考文献

PubChem文献

数据源提供

• Falloon, J. et al., N. Engl. J. Med., 1991, 325, 1534, (use)

• DeAngelis, D.V. et al., J. Chromatogr., 1994, 652, 211, (hplc)

• Haile, L.G. et al., Ann. Pharmacother., 1993, 27, 1488, (rev)

• Eur. Pat., 1984, Wellcome, 123 238; CA, 102, 113082w, (synth, pharmacol)

• Martindale, The Extra Pharmacopoeia, 30th edn., Pharmaceutical Press, 1993, 510

• Hudson, A.T., Parasitol. Today, 1993, 9, 66, (rev)

• Hughes, W.T. et al., Antimicrob. Agents Chemother., 1990, 34, 225, (pharmacol)

• Aranjo, F.G. et al., Antimicrob. Agents Chemother., 1991, 35, 293, (pharmacol)

• Drugs of Today (Barcelona), 1993, 29, 243, (rev)

参考文献

生物活性

PubChem BioAssay

生物活性

名称和标识

商标名

Malarone PediatricMalaroneMepron

IUPAC标准名

2-hydroxy-3-[(1r,4r)-4-(4-chlorophenyl)cyclohexyl]-1,4-dihydronaphthalene-1,4-dione

IUPAC传统名

atovaquone 2-hydroxy-3-[(1r,4r)-4-(4-chlorophenyl)cyclohexyl]-1,4-dihydronaphthalene-1,4-dione

别名

AtovaquoneAtovaquonetrans-2-[4-(4-Chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthalenedioneMepronMalarone

数据登录号

CAS号

PubChem CID

PubChem SID

CHEMBL

Medline Plus

Chemspider ID

DrugBank ID

CHEBI ID

维基百科标题

ATC码

美国药典/FDA物质标识码

KEGG ID

描述信息

DB01117

Drug Groups

approved

Description

A hydroxynaphthoquinone that has antimicrobial activity and is being used in antimalarial protocols. [PubChem]

Indication

Pharmacology

Toxicity

Affected Organisms

Plasmodium

Biotransformation

Some evidence suggests limited metabolism (although no metabolites have been identified).

Absorption

Half Life

2.2 to 3.2 days

Protein Binding

Atovaquone is extensively bound to plasma proteins (99.9%) over the concentration range of 1 to 90 µg/mL.

Elimination

The half-life of atovaquone is long due to presumed enterohepatic cycling and eventual fecal elimination. There was little or no excretion of atovaquone in the urine (less than 0.6%).

Distribution

* 0.60 ± 0.17 L/kg

Clearance

* 10.4 +/- 5.5 ml/min [HIV-infected patients receiving IV administration]

External Links

• [Wikipedia]

• [RxList]

• [Drugs.com]

Wikipedia

Atovaquone

Sigma Aldrich

A7986

参考文献

PubChem文献

数据源提供

• Falloon, J. et al., N. Engl. J. Med., 1991, 325, 1534, (use)

• DeAngelis, D.V. et al., J. Chromatogr., 1994, 652, 211, (hplc)

• Haile, L.G. et al., Ann. Pharmacother., 1993, 27, 1488, (rev)

• Eur. Pat., 1984, Wellcome, 123 238; CA, 102, 113082w, (synth, pharmacol)

• Martindale, The Extra Pharmacopoeia, 30th edn., Pharmaceutical Press, 1993, 510

• Hudson, A.T., Parasitol. Today, 1993, 9, 66, (rev)

• Hughes, W.T. et al., Antimicrob. Agents Chemother., 1990, 34, 225, (pharmacol)

• Aranjo, F.G. et al., Antimicrob. Agents Chemother., 1991, 35, 293, (pharmacol)

• Drugs of Today (Barcelona), 1993, 29, 243, (rev)

生物活性

PubChem BioAssay

化合物性质

理化性质

疏水性(logP)

5.8

溶解度

Practically insoluble

DMSO: >10 mg/mL

外观

yellow powder

药理学性质

半衰期

2.2 to 3.2 days

给药途径

oral only

法定药品分级

PoM (UK), Rx [US]

生物活性机理

Inhibition of electron transport by atovaquone will result in indirect inhibition of these enzymes.

The ultimate metabolic effects of such blockade may include inhibition of nucleic acid and ATP synthesis.

In Plasmodium species, the site of action appears to be the cytochrome bc1 complex (Complex III).

Several metabolic enzymes are linked to the mitochondrial electron transport chain via ubiquinone.

The mechanism of action against Pneumocystis carinii has not been fully elucidated

产品相关信息

Empirical Formula (Hill Notation)

C22H19ClO3

纯度

≥98% (HPLC)

应用领域

Antiprotozoal

Orally active antiprotozoal used for treatment of AIDS-associated pneumonia

Antiparasitic agent

Active (in animals and in vitro) against Pneumocystis carinii, Plasmodia, and tachyzoite and cyst forms of Toxoplasma gondii

化合物信息

ID:988