CYCLOGUANIL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C11H14ClN5
Molecular Weight	251.715
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1(C)N=C(N)N=C(N)N1C2=CC=C(Cl)C=C2

InChI

InChIKey=QMNFFXRFOJIOKZ-UHFFFAOYSA-N

InChI=1S/C11H14ClN5/c1-11(2)16-9(13)15-10(14)17(11)8-5-3-7(12)4-6-8/h3-6H,1-2H3,(H4,13,14,15,16)

HIDE SMILES / InChI

Molecular Formula	C11H14ClN5
Molecular Weight	251.715
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/29061131 | https://www.ncbi.nlm.nih.gov/pubmed/29882324

Cycloguanil is a dihydrofolate reductase inhibitor and is a metabolite of the antimalarial drug proguanil. The parent drug proguanil was suggested to contribute to the antimalarial activity as well, but the mechanism of action is unknown. Proguanil is a prodrug that is metabolized to its main active metabolite, cycloguanil, mostly via CYP2C19. There is significant variation in proguanil pharmacokinetics.12 CYP2C19 is the predominant enzyme catalyzing the bioactivation of proguanil to cycloguanil. Cycloguanil is one of the few antimalarial drugs that act on both the erythrocytic and on the pre-erythrocytic (hepatic) forms of the malaria parasites. 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.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dihydrofolate reductase 57 Target ID: CHEMBL1939 Sources:

PubMed

Title	Date	PubMed
Molecular characterization of dihydrofolate reductase in relation to antifolate resistance in Plasmodium vivax.	2002 Jan	11755187
Monitoring the drug-sensitivity of Plasmodium falciparum in coastal towns in Madagascar by use of in vitro chemosensitivity and mutation detection tests.	2002 Sep	12375368
Synthesis of solution-phase combinatorial library of 4,6-diamino-1,2-dihydro-1,3,5-triazine and identification of new leads against A16V+S108T mutant dihydrofolate reductase of Plasmodium falciparum.	2003 Jan 17	12470716
DHFR and DHPS genotypes of Plasmodium falciparum isolates from Gabon correlate with in vitro activity of pyrimethamine and cycloguanil, but not with sulfadoxine-pyrimethamine treatment efficacy.	2003 Jul	12805261
Different mutation patterns of atovaquone resistance to Plasmodium falciparum in vitro and in vivo: rapid detection of codon 268 polymorphisms in the cytochrome b as potential in vivo resistance marker.	2003 Mar 19	12665429
Susceptibility of Plasmodium falciparum to the drugs used to treat severe malaria (quinine) and to prevent malaria (mefloquine, cycloguanil) in Comoros Union and Madagascar.	2004 Jan	14971233
Homology building as a means to define antigenic epitopes on dihydrofolate reductase (DHFR) from Plasmodium falciparum.	2004 Jun 12	15193156
Short communication: Prevalence of mutations associated with resistance to atovaquone and to the antifolate effect of proguanil in Plasmodium falciparum isolates from northern Ghana.	2004 Mar	14996365
In vitro metabolism of phenoxypropoxybiguanide analogues in human liver microsomes to potent antimalarial dihydrotriazines.	2005 Apr 21	15828818
Malaria epidemic and drug resistance, Djibouti.	2005 Feb	15752455
Shikimate and folate pathways in the protozoan parasite, Perkinsus olseni.	2005 Jul	15907564
Malarial (Plasmodium falciparum) dihydrofolate reductase-thymidylate synthase: structural basis for antifolate resistance and development of effective inhibitors.	2005 Mar	15796007
Multiple synergistic interactions between atovaquone and antifolates against Plasmodium falciparum in vitro: a rational basis for combination therapy.	2006 Mar	16457769
Integration and mining of malaria molecular, functional and pharmacological data: how far are we from a chemogenomic knowledge space?	2006 Nov 17	17112376
Intermittent preventive treatment for malaria in pregnancy in Africa: what's new, what's needed?	2007 Feb 16	17306014
Role of specific cytochrome P450 isoforms in the conversion of phenoxypropoxybiguanide analogs in human liver microsomes to potent antimalarial dihydrotriazines.	2008 Feb	18006651
Sulphadoxine/pyrimethamine versus amodiaquine for treating uncomplicated childhood malaria in Gabon: a randomized trial to guide national policy.	2008 Feb 12	18267042
Effect of folate derivatives on the activity of antifolate drugs used against malaria and cancer.	2008 May	18259776
Escalating Plasmodium falciparum antifolate drug resistance mutations in Macha, rural Zambia.	2008 May 21	18495008
Mutations in the Plasmodium falciparum cytochrome b gene are associated with delayed parasite recrudescence in malaria patients treated with atovaquone-proguanil.	2008 Nov 20	19021900
A novel in silico approach to drug discovery via computational intelligence.	2009 Apr	19348414
Interactions between cycloguanil derivatives and wild type and resistance-associated mutant Plasmodium falciparum dihydrofolate reductases.	2009 Apr	19156529
Indigenous evolution of Plasmodium falciparum pyrimethamine resistance multiple times in Africa.	2009 Feb	19036751
Molecular characterization of antifolates resistance-associated genes, (dhfr and dhps) in Plasmodium vivax isolates from the Middle East.	2009 Jan 28	19175936
WISDOM-II: screening against multiple targets implicated in malaria using computational grid infrastructures.	2009 May 1	19409081
Catalytic and ligand-binding characteristics of Plasmodium falciparum serine hydroxymethyltransferase.	2009 Nov	19591883

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:18:00 GMT 2023` Edited by `admin` on `Fri Dec 15 15:18:00 GMT 2023`
Record UNII	26RM326WVN
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CYCLOGUANIL

Common Name

English

1-(4-CHLOROPHENYL)-1,6-DIHYDRO-6,6-DIMETHYL-1,3,5-TRIAZINE-2,4-DIAMINE

Systematic Name

English

CYCLOGUANIL [MI]

Common Name

English

Cycloguanil [WHO-DD]

Common Name

English

4,6-DIAMINO-1-(P-CHLOROPHENYL)-1,2-DIHYDRO-2,2-DIMETHYL-S-TRIAZINE

Common Name

English

Classification Tree Code System Code

WHO-ATC

P01BB02