Proguanil

Bezeichnung:Proguanil

CAS-Nr500-92-5

Englisch Name:N-(4-CHLOROPHENYL)-N'-(ISOPROPYL)-IMIDODICARBONIMIDIC DIAMIDE

CBNumberCB7455742

SummenformelC11H16ClN5

Molgewicht253.73

MOL-Datei500-92-5.mol

Synonyma

Proguanil

Proguanil physikalisch-chemischer Eigenschaften

Schmelzpunkt	129°
Siedepunkt	399.65°C (rough estimate)
Dichte	1.2039 (rough estimate)
Brechungsindex	1.6110 (estimate)
storage temp.	Store at -20°C, protect from light
Löslichkeit	DMF: 2mg/mL; DMSO: 3mg/mL; DMSO:PBS (pH 7.2) (1:10): 0.09mg/mL; Ethanol: 1mg/mL
Aggregatzustand	A solid
pka	11.15±0.10(Predicted)
Farbe	White to off-white

Gefahreninformationscode (GHS)

N-(4-CHLOROPHENYL)-N'-(ISOPROPYL)-IMIDODICARBONIMIDIC DIAMIDE Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
Chloroguanide is active with respect to exoerythrocyte and erythrocyte forms of plasmodia. It is most beneficial for suppressive therapy. It is used for preventing malaria, and it should be started 2 weeks before entering a malarial zone and should be taken for 8 weeks. Synonyms of this drug are biguanide, bigunal, paludrine, proguanil, and others.
Verwenden
Proguanil is medicaments; used in preparation of pyrrolecarboxamide derivatives as anti-malarial agents.
Indications
Chloroguanide hydrochloride (Paludrine) is activated to a triazine metabolite, cycloguanil, which also interferes with parasite folic acid synthesis. It is a dihydrofolate reductase inhibitor that is used for the prophylaxis of malaria caused by all susceptible strains of plasmodia. Chloroguanide is rapidly absorbed from the gastrointestinal tract. Peak plasma levels occur 2 to 4 hours after oral administration, and the drug is excreted in the urine with an elimination half-life of 12 to 21 hours. Its side effects and spectrum of antimalarial activity are quite similar to those of pyrimethamine.The conversion of chloroguanide to the active metabolite is decreased in pregnancy and also as a result of genetic polymorphism in 3% of whites and Africans and 20% of Asians.
Definition
ChEBI: A biguanide compound which has isopropyl and p-chlorophenyl substituents on the terminal N atoms. A prophylactic antimalarial drug, it works by inhibiting the enzyme dihydrofolate reductase, which is involved in the reproduction of the malaria parasites Plasmodium falciparum and P. vivax within the red blood cells.
Trademarks
Paludrine (Zeneca).
Antimicrobial activity
Proguanil has low antiplasmodial action, but useful activity is attributable to the metabolite cycloguanil, which inhibits the early erythrocytic stages of all four Plasmodium spp. that cause human malaria and the primary hepatic stage of P. falciparum. Proguanil acts synergistically with atovaquone and probably enhances its effect on mitochondrial membrane charge.
Acquired resistance
Resistance of P. falciparum associated with point mutations of dihydrofolate reductase has been reported worldwide. Resistance in P. vivax and P. malariae has been reported in South East Asia. Cross-resistance with pyrimethamine is not absolute, because differential resistance can arise from different point mutations on the dihydrofolate reductase gene.
Pharmazeutische Anwendungen
A synthetic arylbiguanide, formulated as the hydrochloride for oral use. It is slightly soluble in water.
Pharmakokinetik
Oral absorption: >90%
C_max 100 mg oral: 0.4 mg/L after 2–4 h
Plasma half-life: 10 h
Plasma protein binding: 75%
Oral absorption is slow. It is 75% protein bound and is concentrated 10- to 15-fold by erythrocytes. About 20% of the drug is metabolized to dihydrotriazene derivatives, most importantly cycloguanil,by hepatic cytochrome P₄₅₀ processes. Cycloguanil is detectable 2 h after administration of proguanil. High proportions of ‘non-metabolizers’ have been identified in Japan and Kenya, indicating another source of resistance. About 60% of the dose is excreted in the urine.
Clinical Use
Antimalarial prophylaxis (usually in combination with chloroquine)
Treatment and prophylaxis for drug-resistant falciparum malaria (in combination with atovaquone)
Nebenwirkungen
It is well tolerated at recommended doses. Gastrointestinal and renal effects have been reported at doses exceeding 600 mg per day.
Sicherheitsprofil
Poison by ingestion, intravenous, and intraperitoneal routes. Experimental reproductive effects. When heated to decomposition it emits toxic fumes of Cland NOx.
Synthese
Chloroguanide, N1 -(4-chlorophenyl)-N5 -isopropylbiguanide (37.1.3.2), is made from 4-chloroaniline and sodium dicyanoamide, the interaction of which results in the formation of (4-chlorophenyl)dicyanodiamide (37.1.3.1). Reacting this with isopropylamine gives the desired chloroguanide.

In in vitro conditions, chloroguanide is not active, although in the organism it transforms to an active dihydrotriazine compound.

N-(4-CHLOROPHENYL)-N'-(ISOPROPYL)-IMIDODICARBONIMIDIC DIAMIDE Upstream-Materialien And Downstream Produkte

Proguanil Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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