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)...

General Information

Structure

Molecular Formula

C₂₂H₁₉ClO₃

Molecular Mass

366.83746

Exact Mass

366.10227215

Charge

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

Calculated Properties

JChem

Acid pKa

8.233868

H Acceptors

H Donor

LogD (pH = 5.5)

4.9968457

LogD (pH = 7.4)

4.9382534

Log P

4.9976463

Molar Refractivity

103.1065

Polarizability

39.141586

Polar Surface Area

54.37

Rotatable Bonds

Lipinski's Rule of Five

true

ALOGPS 2.1

Log P

4.74

LOG S

-5.66

Solubility (Water)

7.96e-04 g/l

Data Source

Names and Identifiers

IUPAC name

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

Synonyms

Atovaquonetrans-2-[4-(4-Chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthalenedioneMepronAtovaquoneMalarone

Brand Name

Malarone PediatricMalaroneMepron

IUPAC Traditional name

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

Names and Identifiers

Registration numbers

CAS Number

PubChem CID

PubChem SID

CHEMBL

Medline Plus

Chemspider ID

DrugBank ID

CHEBI ID

Wikipedia Title

ATC CODE

Unique Ingredient Identifier

Y883P1Z2LT

KEGG ID

D00236

Registration numbers

Properties

Physical Property

Solubility

Practically insoluble

DMSO: >10 mg/mL

Hydrophobicity(logP)

5.8

Apperance

yellow powder

Pharmacology Properties

Admin Routes

oral only

Half Life

2.2 to 3.2 days

Legal Status

PoM (UK), Rx [US]

Mechanism of Action

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

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

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

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

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

Product Information

Purity

≥98% (HPLC)

Empirical Formula (Hill Notation)

C22H19ClO3

Application(s)

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

Properties

Related Proteins

No Data Available

Click here to submit data

Molecular Spectra

No Data Available

Click here to submit data

Molecule Details

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.

Molecule Details

References

PubChem Literature

From Data Sources

• 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)

References

Bioactivity

PubChem BioAssay

Bioactivity

Names and Identifiers

IUPAC name

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

Synonyms

Atovaquonetrans-2-[4-(4-Chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthalenedioneMepronAtovaquoneMalarone

Brand Name

Malarone PediatricMalaroneMepron

IUPAC Traditional name

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

Registration numbers

CAS Number

PubChem CID

PubChem SID

CHEMBL

Medline Plus

Chemspider ID

DrugBank ID

CHEBI ID

Wikipedia Title

ATC CODE

Unique Ingredient Identifier

Y883P1Z2LT

KEGG ID

D00236

Molecule Details

DrugBank

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

References

PubChem Literature

From Data Sources

• 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)

Bioactivity

PubChem BioAssay

Properties

Physical Property

Solubility

Practically insoluble

DMSO: >10 mg/mL

Hydrophobicity(logP)

5.8

Apperance

yellow powder

Pharmacology Properties

Admin Routes

oral only

Half Life

2.2 to 3.2 days

Legal Status

PoM (UK), Rx [US]

Mechanism of Action

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

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

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

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

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

Product Information

Purity

≥98% (HPLC)

Empirical Formula (Hill Notation)

C22H19ClO3

Application(s)

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

Molecule

ID:988