CYCLOGUANIL PAMOATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H16O6.2C11H14ClN5
Molecular Weight	891.8
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.CC3(C)N=C(N)N=C(N)N3C4=CC=C(Cl)C=C4.OC(=O)C5=CC6=C(C=CC=C6)C(CC7=C8C=CC=CC8=CC(C(O)=O)=C7O)=C5O

InChI

InChIKey=LUNRMKZYOGNOTR-UHFFFAOYSA-N

InChI=1S/C23H16O6.2C11H14ClN5/c24-20-16(14-7-3-1-5-12(14)9-18(20)22(26)27)11-17-15-8-4-2-6-13(15)10-19(21(17)25)23(28)29;2*1-11(2)16-9(13)15-10(14)17(11)8-5-3-7(12)4-6-8/h1-10,24-25H,11H2,(H,26,27)(H,28,29);2*3-6H,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

Molecular Formula	C23H16O6
Molecular Weight	388.3695
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
Kinetic properties of dihydrofolate reductase from wild-type and mutant Plasmodium vivax expressed in Escherichia coli.	2001 Apr 6	11295178
A search for sources of drug resistance by the 4D-QSAR analysis of a set of antimalarial dihydrofolate reductase inhibitors.	2001 Jan	11217916
Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s.	2001 Jan	11124226
Homology modeling of wild type and pyrimethamine/cycloguanil-cross resistant mutant type Plasmodium falciparum dihydrofolate reductase. A model for antimalarial chemotherapy resistance.	2001 Jul 24	11551441
Molecular epidemiology of malaria in Cameroon. XII. In vitro drug assays and molecular surveillance of chloroquine and proguanil resistance.	2002 Oct	12455495
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
Pregnancy and use of oral contraceptives reduces the biotransformation of proguanil to cycloguanil.	2003 Oct	12955370
The chemotherapy of rodent malaria. LXII. Drug combinations to impede the selection of drug resistance, part 5: rates of development of resistance to some inhibitors of folate metabolism and to artesunate.	2004 Dec	15667710
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
Inhibitors of multiple mutants of Plasmodium falciparum dihydrofolate reductase and their antimalarial activities.	2004 Jan 29	14736247
Translational up-regulation of antifolate drug targets in the human malaria parasite Plasmodium falciparum upon challenge with inhibitors.	2004 Jul	15138068
Determination of paraldehyde by gas chromatography in whole blood from children.	2004 Jun 15	15135115
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
Syntheses of 2,4,6-trisubstituted triazines as antimalarial agents.	2005 Feb 1	15664807
In vitro recrudescence of Plasmodium falciparum parasites suppressed to dormant state by atovaquone alone and in combination with proguanil.	2005 Jan	15550263
Shikimate and folate pathways in the protozoan parasite, Perkinsus olseni.	2005 Jul	15907564
Stoichiometric selection of tight-binding inhibitors by wild-type and mutant forms of malarial (Plasmodium falciparum) dihydrofolate reductase.	2005 Mar 1	15732900
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
Multiple synergistic interactions between atovaquone and antifolates against Plasmodium falciparum in vitro: a rational basis for combination therapy.	2006 Mar	16457769
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 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
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
Multiple origins and regional dispersal of resistant dhps in African Plasmodium falciparum malaria.	2009 Apr 14	19365539
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

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:43:56 GMT 2023` Edited by `admin` on `Sat Dec 16 17:43:56 GMT 2023`
Record UNII	TCO0SY4N3D
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CYCLOGUANIL PAMOATE

Official Name

English

CI-501

Code

English

CN-14329-23A

Code

English

cycloguanil embonate [INN]

Common Name

English

CYCLOGUANIL EMBONATE

Official Name

English

NSC-77830

Code

English

2-NAPHTHALENECARBOXYLIC ACID, 4,4'-METHYLENEBIS(3-HYDROXY-, COMPD. WITH 1-(4-CHLOROPHENYL)-1,6-DIHYDRO-6,6-DIMETHYL-1,3,5-TRIAZINE-2,4-DIAMINE (1:2)

Common Name

English

CN-14,329-23A

Code

English

CYCLOGUANIL PAMOATE [USAN]

Common Name

English

Cycloguanil embonate [WHO-DD]

Common Name

English

4,6-DIAMINO-1-(P-CHLOROPHENYL)-1,2-DIHYDRO-2,2-DIMETHYL-S-TRIAZINE COMPOUND (2:1) WITH 4,4'-METHYLENEBIS(3-HYDROXY-2-NAPHTHOIC ACID)

Common Name

English

CYCLOGUANIL PAMOATE [MI]

Common Name

English

PAM-MR-807-23A

Code

English

Classification Tree Code System Code

WHO-ATC

P01BB02