CYCLOGUANIL HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C11H14ClN5.ClH
Molecular Weight	288.176
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=MOUAPRKJJUXEIE-UHFFFAOYSA-N

InChI=1S/C11H14ClN5.ClH/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);1H

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

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

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
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
The chemotherapy of rodent malaria. LXIII. Drug combinations to impede the selection of drug resistance, part 6: the potential value of chlorproguanil and dapsone in combination, and with the addition of artesunate.	2005 Jul	16004705
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
Plasmodium falciparum: interaction of shikimate analogues with antimalarial drugs.	2005 Nov	16140296
[Chemosusceptibility analysis of Plasmodium falciparum imported from Comoros to Marseilles, France in 2001-2003].	2005 Oct	16310329
Susceptibility studies of Malaysian Plasmodium falciparum clones to type II antifolate drugs after 3 years of continuous in vitro culture.	2005 Oct	16227695
A simple dual selection for functionally active mutants of Plasmodium falciparum dihydrofolate reductase with improved solubility.	2005 Oct	16120637
The pharmacokinetics and pharmacodynamics of atovaquone and proguanil for the treatment of uncomplicated falciparum malaria in third-trimester pregnant women.	2005 Sep	16041597
Sensitive method for the quantitative determination of proguanil and its metabolites in rat blood and plasma by liquid chromatography-mass spectrometry.	2006 Jan 18	16310420
Urban malaria in Dakar, Senegal: chemosusceptibility and genetic diversity of Plasmodium falciparum isolates.	2006 Jul	16837722
In vitro activity of iron-binding compounds against Senegalese isolates of Plasmodium falciparum.	2006 Jun	16595639
Population pharmacokinetic and pharmacodynamic modelling of the antimalarial chemotherapy chlorproguanil/dapsone.	2006 Mar	16487222
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
Amino acid mutations in Plasmodium vivax DHFR and DHPS from several geographical regions and susceptibility to antifolate drugs.	2006 Oct	17038682
Drug resistance to sulphadoxine-pyrimethamine in Plasmodium falciparum malaria in Mlimba, Tanzania.	2006 Oct 31	17076899
Effect of honey on CYP3A4, CYP2D6 and CYP2C19 enzyme activity in healthy human volunteers.	2007 Apr	17371531
A novel Plasmodium falciparum expression system for assessing antifolate resistance caused by mutant P. vivax dihydrofolate reductase-thymidylate synthase.	2007 Aug 1	17597462
Intermittent preventive treatment for malaria in pregnancy in Africa: what's new, what's needed?	2007 Feb 16	17306014
Simultaneous determination of monodesethylchloroquine, chloroquine, cycloguanil and proguanil on dried blood spots by reverse-phase liquid chromatography.	2007 Feb 19	17097257
Molecular surveillance of drug-resistance associated mutations of Plasmodium falciparum in south-west Tanzania.	2007 Jan 15	17224049
Rapid dissemination of Plasmodium falciparum drug resistance despite strictly controlled antimalarial use.	2007 Jan 3	17206274
The role of tryptophan-48 in catalysis and binding of inhibitors of Plasmodium falciparum dihydrofolate reductase.	2007 Jun	17320089
Analysis of sulphadoxine/pyrimethamine resistance-conferring mutations of Plasmodium falciparum from Mozambique reveals the absence of the dihydrofolate reductase 164L mutant.	2007 Mar 23	17378942
Prevalence of mutations associated with antimalarial drugs in Plasmodium falciparum isolates prior to the introduction of sulphadoxine-pyrimethamine as first-line treatment in Iran.	2007 Nov 13	17999755
Antimalarial drug susceptibility and point mutations associated with drug resistance in 248 Plasmodium falciparum isolates imported from Comoros to Marseille, France in 2004 2006.	2007 Sep	17827355
Modelling and informatics in the analysis of P. falciparum DHFR enzyme inhibitors.	2008	18673224
The usefulness of twenty-four molecular markers in predicting treatment outcome with combination therapy of amodiaquine plus sulphadoxine-pyrimethamine against falciparum malaria in Papua New Guinea.	2008 Apr 19	18423045
Synthesis and bioevaluation of hybrid 4-aminoquinoline triazines as a new class of antimalarial agents.	2008 Dec 15	18951791
Plasmodium falciparum malaria and atovaquone-proguanil treatment failure.	2008 Feb	18258131
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
Molecular epidemiology of drug-resistant malaria in western Kenya highlands.	2008 Jul 31	18671871
Novel triazine JPC-2067-B inhibits Toxoplasma gondii in vitro and in vivo.	2008 Mar 5	18320016
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
Prevalence of pfmdr1, pfcrt, pfdhfr and pfdhps mutations associated with drug resistance, in Luanda, Angola.	2008 Nov 17	19014684
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
Multiple origins and regional dispersal of resistant dhps in African Plasmodium falciparum malaria.	2009 Apr 14	19365539
Analysis of genetic mutations associated with anti-malarial drug resistance in Plasmodium falciparum from the Democratic Republic of East Timor.	2009 Apr 9	19358729
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
Structure-activity relationship and comparative docking studies for cycloguanil analogs as PfDHFR-TS inhibitors.	2009 Jul	19588935
WISDOM-II: screening against multiple targets implicated in malaria using computational grid infrastructures.	2009 May 1	19409081
A systematic review and meta-analysis of evidence for correlation between molecular markers of parasite resistance and treatment outcome in falciparum malaria.	2009 May 4	19413906
Catalytic and ligand-binding characteristics of Plasmodium falciparum serine hydroxymethyltransferase.	2009 Nov	19591883

Substance Class	Chemical Created by `admin` on `Fri Dec 15 19:39:44 GMT 2023` Edited by `admin` on `Fri Dec 15 19:39:44 GMT 2023`
Record UNII	5C8E0L7498
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CYCLOGUANIL HYDROCHLORIDE

Common Name

English

NSC-3074

Code

English

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

Common Name

English

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

Common Name

English

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

Common Name

English

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

Systematic Name

English

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

Systematic Name

English

BN-2410

Code

English

CHLOROGUANIDE TRIAZINE HYDROCHLORIDE

Common Name

English

Code System Code Type Description

EPA CompTox

DTXSID7049053