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Identification
NameProguanil
Accession NumberDB01131  (APRD00188)
TypeSmall Molecule
GroupsApproved
DescriptionProguanil is a prophylactic antimalarial drug, which works by stopping the malaria parasite, Plasmodium falciparum and Plasmodium vivax, from reproducing once it is in the red blood cells. It does this by inhibiting the enzyme, dihydrofolate reductase, which is involved in the reproduction of the parasite.
Structure
Thumb
Synonyms
N-(4-Chlorophenyl)-n'-(isopropyl)-imidodicarbonimidic diamide
1-(P-Chlorophenyl)-5-isopropylbiguanide
Chlorguanide
Chloroguanide
N-(4-Chlorophenyl)-n'-(isopropyl)-imidodicarbonimidic diamide
Proguanilum
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Paludrine Tab 0.1gmTablet100 mgOralAyerst Laboratories1974-12-311997-08-15Canada
Paludrine Tab 100mgTablet100 mgOralWyeth Ayerst Canada Inc.1996-10-252005-02-28Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
ChloroguanideNot Available
PaludrineNot Available
Brand mixtures
NameLabellerIngredients
Atovaquone and Proguanil HClPd Rx Pharmaceuticals, Inc.
Atovaquone and Proguanil HydrochlorideMylan Pharmaceuticals Inc.
Atovaquone and Proguanil Hydrochloride PediatricGlenmark Pharmaceuticals Inc.,Usa
Atovaquone ProguanilSanis Health Inc
MalaronePd Rx Pharmaceuticals, Inc.
Malarone PediatricGlaxosmithkline Inc
Mylan-atovaquone/proguanilMylan Pharmaceuticals Ulc
Teva-atovaquone ProguanilTeva Canada Limited
Salts
Name/CASStructureProperties
Proguanil hydrochloride
ThumbNot applicableDBSALT001187
Categories
UNIIS61K3P7B2V
CAS number500-92-5
WeightAverage: 253.731
Monoisotopic: 253.109423244
Chemical FormulaC11H16ClN5
InChI KeySSOLNOMRVKKSON-UHFFFAOYSA-N
InChI
InChI=1S/C11H16ClN5/c1-7(2)15-10(13)17-11(14)16-9-5-3-8(12)4-6-9/h3-7H,1-2H3,(H5,13,14,15,16,17)
IUPAC Name
(E)-1-({amino[(4-chlorophenyl)amino]methylidene}amino)-N'-(propan-2-yl)methenimidamide
SMILES
CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1
Pharmacology
IndicationFor the causal prevention and suppression of malaria caused by susceptible strains of P. falciparum and other species of Plasmodium found in some geographical areas of the world.
Structured Indications
PharmacodynamicsProguanil is a biguanide derivative that is converted to an active metabolite called cycloguanil. It exerts its antimalarial action by inhibiting parasitic dihydrofolate reductase enzyme. It has causal prophylactic and suppressive activity against P. falciparum and cures the acute infection. It is also effective in suppressing the clinical attacks of vivax malaria. However it is slower compared to 4-aminoquinolines.
Mechanism of actionProguanil inhibits the dihydrofolate reductase of plasmodia and thereby blocks the biosynthesis of purines and pyrimidines, which are essential for DNA synthesis and cell multiplication. This leads to failure of nuclear division at the time of schizont formation in erythrocytes and liver.
TargetKindPharmacological actionActionsOrganismUniProt ID
Bifunctional dihydrofolate reductase-thymidylate synthaseProteinunknown
inhibitor
Plasmodium falciparum (isolate K1 / Thailand)P13922 details
Dihydrofolate reductaseProteinyes
inhibitor
HumanP00374 details
Related Articles
AbsorptionRapidly and well absorbed in humans following oral doses ranging from 50 to 500 mg.
Volume of distributionNot Available
Protein bindingApproximately 75%
Metabolism

Variably metabolized in the liver by cytochrome P450 isoenzymes to the active triazine metabolite, cycloguanil. This variable metabolism of proguanil may have profound clinical importance in poor metabolizers such as the Asian and African populations at risk for malaria infection. Prophylaxis with proguanil may not be effective in these persons because they may not achieve adequate therapeutic levels of the active compound, cycloguanil, even after multiple doses.

SubstrateEnzymesProduct
Proguanil
cycloguanilDetails
Route of eliminationNot Available
Half lifeApproximately 20 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Plasmodium
PathwaysNot Available
SNP Mediated Effects
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeEffectReference(s)
Cytochrome P450 2C19
Gene symbol: CYP2C19
UniProt: P33261
rs4244285 CYP2C19*2A Allele, homozygotePoor metabolizer, lower dose requirement13680037
Cytochrome P450 2C19
Gene symbol: CYP2C19
UniProt: P33261
rs4986893 CYP2C19*3A Allele, homozygotePoor metabolizer, lower dose requirement13680037
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Proguanil can be increased when it is combined with Abiraterone.Approved
AcepromazineThe serum concentration of Acepromazine can be increased when it is combined with Proguanil.Approved, Vet Approved
AceprometazineThe serum concentration of Aceprometazine can be increased when it is combined with Proguanil.Approved
AlimemazineThe serum concentration of Alimemazine can be increased when it is combined with Proguanil.Approved, Vet Approved
AmiodaroneThe metabolism of Proguanil can be decreased when combined with Amiodarone.Approved, Investigational
AprepitantThe serum concentration of Proguanil can be increased when it is combined with Aprepitant.Approved, Investigational
ArmodafinilThe metabolism of Proguanil can be decreased when combined with Armodafinil.Approved, Investigational
ArtemetherThe risk or severity of adverse effects can be increased when Artemether is combined with Proguanil.Approved
AtazanavirThe metabolism of Proguanil can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Proguanil can be decreased when combined with Atomoxetine.Approved
AzithromycinThe metabolism of Proguanil can be decreased when combined with Azithromycin.Approved
BexaroteneThe serum concentration of Proguanil can be decreased when it is combined with Bexarotene.Approved, Investigational
BL-1020The serum concentration of BL-1020 can be increased when it is combined with Proguanil.Investigational
BoceprevirThe metabolism of Proguanil can be decreased when combined with Boceprevir.Approved
BortezomibThe metabolism of Proguanil can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Proguanil can be decreased when it is combined with Bosentan.Approved, Investigational
CaffeineThe metabolism of Proguanil can be decreased when combined with Caffeine.Approved
CapecitabineThe metabolism of Proguanil can be decreased when combined with Capecitabine.Approved, Investigational
CarbamazepineThe metabolism of Proguanil can be increased when combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Proguanil can be increased when it is combined with Ceritinib.Approved
ChloramphenicolThe metabolism of Proguanil can be decreased when combined with Chloramphenicol.Approved, Vet Approved
ChlorpromazineThe serum concentration of Chlorpromazine can be increased when it is combined with Proguanil.Approved, Vet Approved
CholecalciferolThe metabolism of Proguanil can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Proguanil can be decreased when combined with Cimetidine.Approved
CitalopramThe metabolism of Proguanil can be decreased when combined with Citalopram.Approved
ClarithromycinThe metabolism of Proguanil can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Proguanil can be decreased when combined with Clemastine.Approved
ClotrimazoleThe metabolism of Proguanil can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe metabolism of Proguanil can be decreased when combined with Cobicistat.Approved
ConivaptanThe serum concentration of Proguanil can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Proguanil can be decreased when combined with Crizotinib.Approved
CyclosporineThe metabolism of Proguanil can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
Cyproterone acetateThe serum concentration of Proguanil can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
DabrafenibThe serum concentration of Proguanil can be decreased when it is combined with Dabrafenib.Approved
DapsoneThe risk or severity of adverse effects can be increased when Proguanil is combined with Dapsone.Approved, Investigational
DarunavirThe metabolism of Proguanil can be decreased when combined with Darunavir.Approved
DasatinibThe serum concentration of Proguanil can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Proguanil can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Proguanil can be decreased when combined with Delavirdine.Approved
DexamethasoneThe serum concentration of Proguanil can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DihydroergotamineThe metabolism of Proguanil can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Proguanil can be decreased when combined with Diltiazem.Approved
DisulfiramThe metabolism of Proguanil can be decreased when combined with Disulfiram.Approved
DoxycyclineThe metabolism of Proguanil can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Proguanil can be decreased when combined with Dronedarone.Approved
EfavirenzThe serum concentration of Proguanil can be decreased when it is combined with Efavirenz.Approved, Investigational
EnzalutamideThe serum concentration of Proguanil can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Proguanil can be decreased when combined with Erythromycin.Approved, Vet Approved
Eslicarbazepine acetateThe serum concentration of Proguanil can be decreased when it is combined with Eslicarbazepine acetate.Approved
EsomeprazoleThe metabolism of Proguanil can be decreased when combined with Esomeprazole.Approved, Investigational
EtravirineThe serum concentration of Proguanil can be decreased when it is combined with Etravirine.Approved
FesoterodineThe serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Proguanil.Approved
FloxuridineThe metabolism of Proguanil can be decreased when combined with Floxuridine.Approved
FluconazoleThe metabolism of Proguanil can be decreased when combined with Fluconazole.Approved
FluorouracilThe metabolism of Proguanil can be decreased when combined with Fluorouracil.Approved
FluoxetineThe metabolism of Proguanil can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluphenazineThe serum concentration of Fluphenazine can be increased when it is combined with Proguanil.Approved
FluvastatinThe metabolism of Proguanil can be decreased when combined with Fluvastatin.Approved
FluvoxamineThe metabolism of Proguanil can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Proguanil can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Proguanil can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Proguanil can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Proguanil can be increased when it is combined with Fusidic Acid.Approved
GemfibrozilThe metabolism of Proguanil can be decreased when combined with Gemfibrozil.Approved
IdelalisibThe serum concentration of Proguanil can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Proguanil can be decreased when combined with Imatinib.Approved
IndinavirThe metabolism of Proguanil can be decreased when combined with Indinavir.Approved
IrbesartanThe metabolism of Proguanil can be decreased when combined with Irbesartan.Approved, Investigational
IsavuconazoniumThe metabolism of Proguanil can be decreased when combined with Isavuconazonium.Approved, Investigational
IsoniazidThe metabolism of Proguanil can be decreased when combined with Isoniazid.Approved
IsradipineThe metabolism of Proguanil can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Proguanil can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Proguanil can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Proguanil can be decreased when combined with Ketoconazole.Approved, Investigational
LeflunomideThe metabolism of Proguanil can be decreased when combined with Leflunomide.Approved, Investigational
LidocaineThe metabolism of Proguanil can be decreased when combined with Lidocaine.Approved, Vet Approved
LopinavirThe metabolism of Proguanil can be decreased when combined with Lopinavir.Approved
LosartanThe metabolism of Proguanil can be decreased when combined with Losartan.Approved
LovastatinThe metabolism of Proguanil can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Proguanil can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Proguanil can be decreased when it is combined with Lumacaftor.Approved
LumefantrineThe risk or severity of adverse effects can be increased when Proguanil is combined with Lumefantrine.Approved
MesoridazineThe serum concentration of Mesoridazine can be increased when it is combined with Proguanil.Approved
MethotrimeprazineThe serum concentration of Methotrimeprazine can be increased when it is combined with Proguanil.Approved
Methylene blueThe serum concentration of Methylene blue can be increased when it is combined with Proguanil.Investigational
MetoprololThe serum concentration of Metoprolol can be increased when it is combined with Proguanil.Approved, Investigational
MexiletineThe metabolism of Proguanil can be decreased when combined with Mexiletine.Approved
MifepristoneThe serum concentration of Proguanil can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Proguanil can be decreased when it is combined with Mitotane.Approved
MoclobemideThe metabolism of Proguanil can be decreased when combined with Moclobemide.Approved
ModafinilThe serum concentration of Proguanil can be decreased when it is combined with Modafinil.Approved, Investigational
MoricizineThe serum concentration of Moricizine can be increased when it is combined with Proguanil.Approved, Withdrawn
NafcillinThe serum concentration of Proguanil can be decreased when it is combined with Nafcillin.Approved
NefazodoneThe metabolism of Proguanil can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Proguanil can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Proguanil can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Proguanil can be increased when combined with Nevirapine.Approved
NicardipineThe metabolism of Proguanil can be decreased when combined with Nicardipine.Approved
NicotineThe metabolism of Proguanil can be decreased when combined with Nicotine.Approved
NilotinibThe metabolism of Proguanil can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Proguanil can be decreased when combined with Olaparib.Approved
OmeprazoleThe metabolism of Proguanil can be decreased when combined with Omeprazole.Approved, Investigational, Vet Approved
OsimertinibThe serum concentration of Proguanil can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Proguanil can be increased when it is combined with Palbociclib.Approved
PantoprazoleThe metabolism of Proguanil can be decreased when combined with Pantoprazole.Approved
Peginterferon alfa-2bThe serum concentration of Proguanil can be increased when it is combined with Peginterferon alfa-2b.Approved
PentobarbitalThe metabolism of Proguanil can be increased when combined with Pentobarbital.Approved, Vet Approved
PerazineThe serum concentration of Perazine can be increased when it is combined with Proguanil.Investigational
PerphenazineThe serum concentration of Perphenazine can be increased when it is combined with Proguanil.Approved
PhenobarbitalThe metabolism of Proguanil can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Proguanil can be increased when combined with Phenytoin.Approved, Vet Approved
PosaconazoleThe metabolism of Proguanil can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Proguanil can be increased when combined with Primidone.Approved, Vet Approved
ProchlorperazineThe serum concentration of Prochlorperazine can be increased when it is combined with Proguanil.Approved, Vet Approved
PromazineThe serum concentration of Promazine can be increased when it is combined with Proguanil.Approved, Vet Approved
PromethazineThe serum concentration of Promethazine can be increased when it is combined with Proguanil.Approved
PropiopromazineThe serum concentration of Propiopromazine can be increased when it is combined with Proguanil.Vet Approved
PyrimethamineThe metabolism of Proguanil can be decreased when combined with Pyrimethamine.Approved, Vet Approved
QuinineThe metabolism of Proguanil can be decreased when combined with Quinine.Approved
RanolazineThe metabolism of Proguanil can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Proguanil can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Proguanil can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Proguanil can be increased when combined with Rifapentine.Approved
RitonavirThe serum concentration of Proguanil can be decreased when it is combined with Ritonavir.Approved, Investigational
RopiniroleThe metabolism of Proguanil can be decreased when combined with Ropinirole.Approved, Investigational
SaquinavirThe metabolism of Proguanil can be decreased when combined with Saquinavir.Approved, Investigational
SecobarbitalThe metabolism of Proguanil can be increased when combined with Secobarbital.Approved, Vet Approved
SertralineThe metabolism of Proguanil can be decreased when combined with Sertraline.Approved
SildenafilThe metabolism of Proguanil can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Proguanil can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Proguanil can be increased when it is combined with Simeprevir.Approved
SorafenibThe metabolism of Proguanil can be decreased when combined with Sorafenib.Approved, Investigational
St. John's WortThe serum concentration of Proguanil can be decreased when it is combined with St. John's Wort.Nutraceutical
StiripentolThe serum concentration of Proguanil can be increased when it is combined with Stiripentol.Approved
SulfadiazineThe metabolism of Proguanil can be decreased when combined with Sulfadiazine.Approved, Vet Approved
SulfamethoxazoleThe metabolism of Proguanil can be decreased when combined with Sulfamethoxazole.Approved
SulfisoxazoleThe metabolism of Proguanil can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe metabolism of Proguanil can be decreased when combined with Telaprevir.Approved
TelithromycinThe metabolism of Proguanil can be decreased when combined with Telithromycin.Approved
TenofovirThe metabolism of Proguanil can be decreased when combined with Tenofovir.Approved, Investigational
TeriflunomideThe serum concentration of Proguanil can be decreased when it is combined with Teriflunomide.Approved
TheophyllineThe metabolism of Proguanil can be decreased when combined with Theophylline.Approved
ThiethylperazineThe serum concentration of Thiethylperazine can be increased when it is combined with Proguanil.Withdrawn
ThioridazineThe serum concentration of Thioridazine can be increased when it is combined with Proguanil.Approved
TicagrelorThe metabolism of Proguanil can be decreased when combined with Ticagrelor.Approved
TiclopidineThe metabolism of Proguanil can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Proguanil can be decreased when it is combined with Tocilizumab.Approved
TolbutamideThe metabolism of Proguanil can be decreased when combined with Tolbutamide.Approved
TopiramateThe metabolism of Proguanil can be decreased when combined with Topiramate.Approved
TranylcypromineThe metabolism of Proguanil can be decreased when combined with Tranylcypromine.Approved
TrifluoperazineThe serum concentration of Trifluoperazine can be increased when it is combined with Proguanil.Approved
TriflupromazineThe serum concentration of Triflupromazine can be increased when it is combined with Proguanil.Approved, Vet Approved
TrimethoprimThe metabolism of Proguanil can be decreased when combined with Trimethoprim.Approved, Vet Approved
Valproic AcidThe metabolism of Proguanil can be decreased when combined with Valproic Acid.Approved, Investigational
ValsartanThe metabolism of Proguanil can be decreased when combined with Valsartan.Approved, Investigational
VemurafenibThe serum concentration of Proguanil can be increased when it is combined with Vemurafenib.Approved
VenlafaxineThe metabolism of Proguanil can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Proguanil can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Proguanil can be decreased when combined with Voriconazole.Approved, Investigational
WarfarinProguanil may increase the anticoagulant activities of Warfarin.Approved
ZafirlukastThe metabolism of Proguanil can be decreased when combined with Zafirlukast.Approved, Investigational
ZiprasidoneThe metabolism of Proguanil can be decreased when combined with Ziprasidone.Approved
Food Interactions
  • Take with food.
References
Synthesis Reference

Dhananjay Govind Sathe, Harish Kashinath Mondkar, Tanaji Shamrao Jadhav, Nitin Nivrutti Hagavane, “Process of Preparation of Proguanil.” U.S. Patent US20110263901, issued October 27, 2011.

US20110263901
General ReferencesNot Available
External Links
ATC CodesP01BB51P01BB01
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9544
Blood Brain Barrier+0.728
Caco-2 permeable+0.5
P-glycoprotein substrateNon-substrate0.7
P-glycoprotein inhibitor INon-inhibitor0.9482
P-glycoprotein inhibitor IINon-inhibitor0.8511
Renal organic cation transporterNon-inhibitor0.7381
CYP450 2C9 substrateNon-substrate0.7646
CYP450 2D6 substrateNon-substrate0.9115
CYP450 3A4 substrateNon-substrate0.6085
CYP450 1A2 substrateInhibitor0.8751
CYP450 2C9 inhibitorNon-inhibitor0.9591
CYP450 2D6 inhibitorInhibitor0.6507
CYP450 2C19 inhibitorNon-inhibitor0.9405
CYP450 3A4 inhibitorNon-inhibitor0.9109
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8774
Ames testNon AMES toxic0.5887
CarcinogenicityNon-carcinogens0.616
BiodegradationNot ready biodegradable0.9939
Rat acute toxicity2.6787 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9701
hERG inhibition (predictor II)Non-inhibitor0.9265
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
TabletOral
Tablet, film coatedOral
TabletOral100 mg
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point129 °CPhysProp
water solubility156 mg/LNot Available
logP2.53SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.286 mg/mLALOGPS
logP1.9ALOGPS
logP1.89ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)19.77ChemAxon
pKa (Strongest Basic)10.12ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area88.79 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity71.07 m3·mol-1ChemAxon
Polarizability26.84 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as chlorobenzenes. These are compounds containing one or more chlorine atoms attached to a benzene moiety.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassHalobenzenes
Direct ParentChlorobenzenes
Alternative Parents
Substituents
  • Chlorobenzene
  • Biguanide
  • Aryl halide
  • Aryl chloride
  • Guanidine
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboximidamide
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Imine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Plasmodium falciparum (isolate K1 / Thailand)
Pharmacological action
unknown
Actions
inhibitor
General Function:
Thymidylate synthase activity
Specific Function:
Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, DNA precursor synthesis, and for the conversion of dUMP to dTMP.
Gene Name:
Not Available
Uniprot ID:
P13922
Molecular Weight:
71816.775 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Nadph binding
Specific Function:
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.
Gene Name:
DHFR
Uniprot ID:
P00374
Molecular Weight:
21452.61 Da
References
  1. Kaneko A, Bergqvist Y, Takechi M, Kalkoa M, Kaneko O, Kobayakawa T, Ishizaki T, Bjorkman A: Intrinsic efficacy of proguanil against falciparum and vivax malaria independent of the metabolite cycloguanil. J Infect Dis. 1999 Apr;179(4):974-9. [PubMed:10068594 ]
  2. Vasconcelos KF, Plowe CV, Fontes CJ, Kyle D, Wirth DF, Pereira da Silva LH, Zalis MG: Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase of isolates from the Amazon region of Brazil. Mem Inst Oswaldo Cruz. 2000 Sep-Oct;95(5):721-8. [PubMed:10998224 ]
  3. Tahar R, de Pecoulas PE, Basco LK, Chiadmi M, Mazabraud A: Kinetic properties of dihydrofolate reductase from wild-type and mutant Plasmodium vivax expressed in Escherichia coli. Mol Biochem Parasitol. 2001 Apr 6;113(2):241-9. [PubMed:11295178 ]
  4. Durand R, Jafari S, Bouchaud O, Ralaimazava P, Keundjian A, Le Bras J: Plasmodium falciparum: pfcrt and DHFR mutations are associated with failure of chloroquine plus proguanil prophylaxis in travelers. J Infect Dis. 2001 Dec 15;184(12):1633-4. [PubMed:11740746 ]
  5. Le Bras J, Durand R: The mechanisms of resistance to antimalarial drugs in Plasmodium falciparum. Fundam Clin Pharmacol. 2003 Apr;17(2):147-53. [PubMed:12667224 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
References
  1. Lu AH, Shu Y, Huang SL, Wang W, Ou-Yang DS, Zhou HH: In vitro proguanil activation to cycloguanil is mediated by CYP2C19 and CYP3A4 in adult Chinese liver microsomes. Acta Pharmacol Sin. 2000 Aug;21(8):747-52. [PubMed:11501186 ]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms.
Gene Name:
CYP2E1
Uniprot ID:
P05181
Molecular Weight:
56848.42 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23