Cycloguanil is a

dihydrofolate reductase inhibitor A dihydrofolate reductase inhibitor (DHFR inhibitor) is a molecule that inhibits the function of dihydrofolate reductase, and is a type of antifolate. Since folate is needed by rapidly dividing cells to make thymine, this effect may be used to th ...

, and is a metabolite of the

antimalarial drug Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young c ...

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 resist ...

; 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. Atova ...

(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 ...

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

References

{{Antimalarials Antimalarial agents Triazines Guanidines 4-Chlorophenyl compounds