BULAQUINE

Details

Stereochemistry	RACEMIC
Molecular Formula	C21H27N3O3
Molecular Weight	369.4574
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC(NC(C)CCCN\C(C)=C2\CCOC2=O)=C3N=CC=CC3=C1

InChI

InChIKey=ADCOUXIGWFEYJP-SDXDJHTJSA-N

InChI=1S/C21H27N3O3/c1-14(6-4-9-22-15(2)18-8-11-27-21(18)25)24-19-13-17(26-3)12-16-7-5-10-23-20(16)19/h5,7,10,12-14,22,24H,4,6,8-9,11H2,1-3H3/b18-15-

HIDE SMILES / InChI

Molecular Formula	C21H27N3O3
Molecular Weight	369.4574
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	1
Optical Activity	( + / - )

Description
Sources: http://www.cdri.res.in/Bulaquin.aspx | http://www.insa.nic.in/writereaddata/UpLoadedFiles/PINSA/Vol69B_2003_6_Art02.pdfhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2008/008316s017lbl.pdf

Primaquine is a oral medication used to treat and prevent malaria and to treat Pneumocystis pneumonia. Specifically it is used for malaria due to Plasmodium vivax and Plasmodium ovale along with other medications and for prevention if other options cannot be used. Primaquine is an alternative treatment for Pneumocystis pneumonia together with clindamycin. Primaquine is lethal to P. vivax and P. ovale in the liver stage, and also to P. vivax in the blood stage through its ability to do oxidative damage to the cell. However, the exact mechanism of action is not fully understood. Primaquine is well-absorbed in the gut and extensively distributed in the body without accumulating in red blood cells. Administration of primaquine with food or grapefruit juice increases its oral bioavailibity. In blood, about 20% of circulating primaquine is protein-bound, with preferential binding to the acute phase protein orosomucoid. With a half-life on the order of 6 hours, it is quickly metabolized by liver enzymes to carboxyprimaquine, which does not have anti-malarial activity. Common side effects of primaquine administration include nausea, vomiting, and stomach cramps. Primaquine phosphate is recommended only for the radical cure of vivax malaria, the prevention of relapse in vivax malaria, or following the termination of chloroquine phosphate suppressive therapy in an area where vivax malaria is endemic. Patients suffering from an attack of vivax malaria or having parasitized red blood cells should receive a course of chloroquine phosphate, which quickly destroys the erythrocytic parasites and terminates the paroxysm. Primaquine phosphate should be administered concurrently in order to eradicate the exoerythrocytic parasites in a dosage of 1 tablet (equivalent to 15 mg base) daily for 14 days.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Quinone reductase 2 12 Target ID: CHEMBL3959 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21074425	Inhibitor 8504		7.5 µM [IC50]
Chloroquine resistance transporter 3 Target ID: CHEMBL1795182 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24900883	Inhibitor 8504		68.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Plasmodium vivax malaria 6 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16969059	Curative		Approved 8583	AABLAQUIN Approved Use Treatment and prevention of p. vivax. Launch Date 2000
Plasmodium vivax malaria 6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/008316s017lbl.pdf	Curative		Approved 8583	PRIMAQUINE Approved Use Primaquine phosphate is indicated for the radical cure (prevention of relapse) of vivax malaria. Launch Date 1952

C_max

Value	Dose	Analyte	Population
53 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027117/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
104 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027117/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
65 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027118/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
66 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027118/	15 mg 1 times / day multiple, oral dose: 15 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
0.5 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027117/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027117/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
468 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027118/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
443 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027118/	15 mg 1 times / day multiple, oral dose: 15 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
5.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027117/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027117/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027118/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027118/	15 mg 1 times / day multiple, oral dose: 15 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
30 mg 1 times / day steady, oral Highest studied dose Dose: 30 mg, 1 times / day Route: oral Route: steady Dose: 30 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26366319/	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/26366319/	Other AEs: Malaise, Headache... Other AEs: Malaise (1 patient) Headache (2 patients) Nausea (1 patient) Pyrexia (1 patient) Vomiting (1 patient) Dizziness (1 patient) Asthenia (1 patient) Pruritus (1 patient) Haemoglobin decreased (1 patient) Dyspepsia (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/26366319/
0.6 mg/kg 1 times / day multiple, oral Highest studied dose Dose: 0.6 mg/kg, 1 times / day Route: oral Route: multiple Dose: 0.6 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12932090/	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: https://pubmed.ncbi.nlm.nih.gov/12932090/	Disc. AE: Hematocrit decreased... AEs leading to discontinuation/dose reduction: Hematocrit decreased (4 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/12932090/
15 mg 1 times / day steady, oral Recommended Dose: 15 mg, 1 times / day Route: oral Route: steady Dose: 15 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26366319/	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/26366319/	Other AEs: Malaise, Headache... Other AEs: Malaise (3 patients) Headache (1 patient) Nausea (2 patients) Pyrexia (1 patient) Vomiting (1 patient) Myalgia (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/26366319/
15 mg 1 times / day steady, oral Recommended Dose: 15 mg, 1 times / day Route: oral Route: steady Dose: 15 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26366319/	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/26366319/	Other AEs: Malaise, Headache... Other AEs: Malaise (4 patients) Headache (2 patients) Nausea (1 patient) Decreased appetite (3 patients) Pyrexia (1 patient) Vomiting (1 patient) Dizziness (1 patient) Asthenia (1 patient) Arthralgia (1 patient) Muscle spasms (1 patient) Dyspnoea exertional (1 patient) Diarrhoea (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/26366319/
75 mg single, oral Highest studied dose Dose: 75 mg Route: oral Route: single Dose: 75 mg Sources: https://pubmed.ncbi.nlm.nih.gov/16448575/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/16448575/	Sources: https://pubmed.ncbi.nlm.nih.gov/16448575/
25 mg 1 times / day multiple, oral Studied dose Dose: 25 mg, 1 times / day Route: oral Route: multiple Dose: 25 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16969059/	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/16969059/	Other AEs: Nausea, Dizziness... Other AEs: Nausea (4.3%) Dizziness (8.5%) Headache (4.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/16969059/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP3A4/5 296 P-gp 1741 OATP1A2 43 OATP1B1 1079	CYP2C19 1119 CYP1A2 1197	CYP1A2 832

Drug as perpetrator

Target	Modality	Activity
CYP3A4/5 357	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_2800AMX00403000_I100_1.pdf#page=32 Page: (PMDA_I100_1 in Japanese) 32	yes [IC50 19.4 uM]
OATP1A2 43	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_22800AMX00403000_A100_1.pdf#page=16 Page: (PMDA_A100_1 in Japanese) 16	yes [IC50 5.6 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_2800AMX00403000_I100_1.pdf#page=32 Page: (PMDA_I100_1 in Japanese) 32, 36	yes [Ki 0.22 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_2800AMX00403000_I100_1.pdf#page=32 Page: (PMDA_I100_1 in Japanese) 32	yes [Ki 23 uM]
CYP1A2 2333	inducer 1966 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_2800AMX00403000_I100_1.pdf#page=32 Page: (PMDA_I100_1 in Japanese) 32, 36	yes
OATP1B1 1095	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_22800AMX00403000_A100_1.pdf#page=16 Page: (PMDA_A100_1 in Japanese) 16	yes
P-gp 1932	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_2800AMX00403000_I100_1.pdf#page=32 Page: (PMDA_I100_1 in Japanese) 32	yes

Drug as victim

Target	Modality	Activity
CYP3A4 1946	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_2800AMX00403000_I100_1.pdf#page=30 Page: (PMDA_I100_1 in Japanese) 29-30	minor [Km 37000 uM]
CYP2C19 1119	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_2800AMX00403000_I100_1.pdf#page=30 Page: (PMDA_I100_1 in Japanese) 29-30	minor [Km 52000 uM]
CYP2C9 1193	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_2800AMX00403000_I100_1.pdf#page=30 Page: (PMDA_I100_1 in Japanese) 29-30	no
CYP2D6 1388	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_2800AMX00403000_I100_1.pdf#page=30 Page: (PMDA_I100_1 in Japanese) 29-30	weak [Km 37000 uM]
CYP1A2 1197	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_2800AMX00403000_I100_1.pdf#page=30 Page: (PMDA_I100_1 in Japanese) 29-30	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_22800AMX00403000_A100_1.pdf#page=10, https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/008316s023lbl.pdf#page=3 Page: (PMDA_A100_1 in Japanese) 10, (FDA label) 3

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:8405	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:8405
ChemicalBook	CB0875785	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0875785
eMolecules	1077024	https://www.emolecules.com/cgi-bin/more?vid=1077024
MolPort	MolPort-001-794-628	https://www.molport.com/shop/molecule-link/MolPort-001-794-628

PubMed

Title	Date	PubMed
Potentiation of the curative action of primaquine in vivax malaria by quinine and chloroquine.	1955 Aug	13242948
The haemolytic effect of various regimens of primaquine with chloroquine in American Negroes with G6PD deficiency and the lack of an effect of various antimalarial suppressive agents on erythrocyte metabolism.	1967	4864652
Methemoglobinemia provoked by malarial chemoprophylaxis in Vietnam.	1968 Nov 21	5686480
Simultaneous drug reactions in the same patient. Chloroquine-Primaquine sensitivity.	1970 Apr 27	5467364
The treatment of malaria in glucose-6-phosphate dehydrogenase deficient patients in Sabah.	1981 Dec	7325735
Pharmacokinetics of primaquine in man. I. Studies of the absolute bioavailability and effects of dose size.	1985 Jun	4027117
[Hemolytic reaction due to administration of primaquine].	1986 Apr	3742573
Drug- and chemical-induced methaemoglobinaemia. Clinical features and management.	1986 Jul-Aug	3537620
Activity of clindamycin with primaquine against Pneumocystis carinii in vitro and in vivo.	1988 Jun	3261959
Primaquine induced hemolysis in a Thai soldier.	1989 Dec	2639511
Immunogenicity of amodiaquine in the rat.	1990	2210868
Causal prophylactic activity of a new 8-aminoquinoline derivative against Plasmodium cynomolgi B in rhesus monkeys.	1990 May	2397941
Effect of anti-relapse antimalarial compound CDRI 80/53 and primaquine on hepatic mixed function oxidase system of rhesus monkey.	1990 Nov-Dec	2075158
Detection of antidrug IgG antibodies in patients with adverse drug reactions to amodiaquine.	1991	1959977
Acute intravascular haemolysis in Vanuatu following a single dose of primaquine in individuals with glucose-6-phosphate dehydrogenase deficiency.	1992 Oct	1404560
Effect of the antimalarial agents primaquine and (N'-3-acetyl-4-5-dihydro-2-furanyl)-N4-(6-methoxy-8-quinolinyl)1,4-pent ane-diamine on oxidative stress and antioxidant defences in mice.	1993 Nov 17	8250972
Prediction of aryl hydrocarbon receptor-mediated enzyme induction of drugs and chemicals by mRNA quantification.	1998 Dec	9860486
Time-dependent transcriptional induction of CYP1A1, CYP1A2 and CYP1B1 mRNAs by H+/K+ -ATPase inhibitors and other xenobiotics.	2003 Feb	12623754
cAMP-dependent exocytosis and vesicle traffic regulate CFTR and fluid transport in rat jejunum in vivo.	2003 Feb	12529251
Conductometric and indirect AAS determination of antimalarials.	2003 Mar 26	12644205
Real-time investigation of the interaction between primaquine phosphate and bovine serum albumin (BSA) by piezoelectric quartz crystal impedance analysis.	2003 Oct 9	14511914
Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data.	2003 Sep	12920490
Different structural requirements of the ligand binding domain of the aryl hydrocarbon receptor for high- and low-affinity ligand binding and receptor activation.	2004 Feb	14742684
Preparation and in vitro evaluation of primaquine-conjugated gum arabic microspheres.	2004 Jul-Aug	15244469
Feline babesiosis in South Africa: a review.	2004 Oct	15604490
Piperaquine: a resurgent antimalarial drug.	2005	15610051
Glucose-6-phosphate dehydrogenase deficiency in two returning Operation Iraqi Freedom soldiers who developed hemolytic anemia while receiving primaquine prophylaxis for malaria.	2005 Apr	15916292
Primaquine-induced hemolytic anemia: role of membrane lipid peroxidation and cytoskeletal protein alterations in the hemotoxicity of 5-hydroxyprimaquine.	2005 Aug	15840764
Exotic diseases of dogs and cats at risk of importation to Ireland.	2005 May 1	21851670
In Vitro and In Vivo pharmacokinetic studies of bulaquine (analogue of primaquine), a novel antirelapse antimalarial, in rat, rabbit and monkey--highlighting species similarities and differences.	2007 Jul	17410524
Formulation and evaluation of taste masked oral reconstitutable suspension of primaquine phosphate.	2008	18770047
Identification of differentially expressed genes after acute exposure to bulaquine (CDRI 80/53) in mice liver.	2008 Dec	18684221
Formulation and evaluation of primaquine phosphate taste-masked rapidly disintegrating tablet.	2008 Oct	18812020
Diverse chemicals including aryl hydrocarbon receptor ligands modulate transcriptional activity of the 3'immunoglobulin heavy chain regulatory region.	2009 Jun 30	19447539
Cytochrome P(450)-dependent toxic effects of primaquine on human erythrocytes.	2009 Nov 15	19616568
Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development.	2010 Dec	20829430
Feline babesiosis.	2010 Feb	20230438
The Summary Index of Malaria Surveillance (SIMS): a stable index of malaria within India.	2010 Feb 11	20181218
An open-label, randomised study of dihydroartemisinin-piperaquine versus artesunate-mefloquine for falciparum malaria in Asia.	2010 Jul 30	20689583
Monitoring for Plasmodium falciparum drug resistance to artemisinin and artesunate in Binh Phuoc Province, Vietnam: 1998-2009.	2010 Jun 24	20573274
Blockade of hERG K(+) channel by antimalarial drug, primaquine.	2010 May	20512476
In Tanzania, hemolysis after a single dose of primaquine coadministered with an artemisinin is not restricted to glucose-6-phosphate dehydrogenase-deficient (G6PD A-) individuals.	2010 May	20194698
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011 Jul 14	21599003
Novel potent metallocenes against liver stage malaria.	2012 Mar	22155838
Understanding the mechanisms for metabolism-linked hemolytic toxicity of primaquine against glucose 6-phosphate dehydrogenase deficient human erythrocytes: evaluation of eryptotic pathway.	2012 Mar 29	22330256
Characterization of Plasmodium liver stage inhibition by halofuginone.	2012 May	22438279
N-cinnamoylated chloroquine analogues as dual-stage antimalarial leads.	2013 Jan 24	23273038
Quinolin-4(1H)-imines are potent antiplasmodial drugs targeting the liver stage of malaria.	2013 Jun 13	23701465
Primaquine or other 8-aminoquinoline for reducing Plasmodium falciparum transmission.	2015 Feb 19	25693791
Development of HepG2-derived cells expressing cytochrome P450s for assessing metabolism-associated drug-induced liver toxicity.	2016 Aug 5	26477383

Patents

Sample Use Guides

In Vivo Use Guide

Patients recieved 25 mg once daily for 7 days.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Wed Apr 02 08:49:50 GMT 2025` Edited by `admin` on `Wed Apr 02 08:49:50 GMT 2025`
Record UNII	TSQ6U39Q3G
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AABLAQUINE

Preferred Name

English

BULAQUINE

Official Name

English

Bulaquine [WHO-DD]

Common Name

English

bulaquine [INN]

Common Name

English

DIHYDRO-3-(1-((4-((6-METHOXY-8-QUINOLYL)AMINO)PENTYL)AMINO)ETHYLIDENE)-2(3H)-FURANONE

Systematic Name

English

ELUBAQUINE

Common Name

English

CDRI 80/53

Code

English

2(3H)-FURANONE, DIHYDRO-3-(1-((4-((6-METHOXY-8-QUINOLINYL)AMINO)PENTYL)AMINO)ETHYLIDENE)-

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C271