Cycloguanil is a dihydrofolate reductase inhibitor, and is a metabolite of the antimalarial drug

proguanil Proguanil, also known as chlorguanide and chloroguanide, is a medication used to treat and prevent malaria. It is often used together with chloroquine or atovaquone. When used with chloroquine the combination will treat mild chloroquine resistan ...

; its formation in vivo has been thought to be primarily responsible for the antimalarial activity of proguanil. However, more recent work has indicated that, while proguanil is synergistic with the drug

atovaquone Atovaquone, sold under the brand name Mepron, is an antimicrobial medication for the prevention and treatment of ''Pneumocystis jirovecii'' pneumonia (PCP). Atovaquone is a chemical compound that belongs to the class of naphthoquinones. Atovaq ...

(as in the combination

Malarone Atovaquone/proguanil, sold under the brand name Malarone among others, is a fixed-dose combination medication used to treat and prevent malaria, including chloroquine-resistant malaria. It contains atovaquone and proguanil. It is not recommended f ...

), cycloguanil is in fact antagonistic to the effects of atovaquone, suggesting that, unlike cycloguanil, proguanil may have an alternative mechanism of antimalarial action besides dihydrofolate reductase inhibition. Although cycloguanil is not currently in general use as an antimalarial, the continuing development of resistance to current antimalarial drugs has led to renewed interest in studying the use of cycloguanil in combination with other drugs.

Synthesis

The reaction between 4-chloroaniline 06-47-8(1) and dicyandiamide (aka 2-cyanoguanidine) 61-58-5 (2) gives 4-chlorophenylbiguanide

304-59-6 3 (three) is a number, numeral and digit. It is the natural number following 2 and preceding 4, and is the smallest odd prime number and the only prime preceding a square number. It has religious or cultural significance in many societies ...

(3). The condensation of this immediately with acetone to form the aminal cycloguanil (4).

References

Antimalarial agents Triazines Guanidines Chlorobenzenes {{antiinfective-drug-stub