Details
Stereochemistry | ACHIRAL |
Molecular Formula | C21H33N3O.2ClH |
Molecular Weight | 416.428 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.Cl.CCN(CC)CCCCCCNC1=CC(OC)=CC2=C1N=CC=C2C
InChI
InChIKey=AFMFKGVIHLNIEO-UHFFFAOYSA-N
InChI=1S/C21H33N3O.2ClH/c1-5-24(6-2)14-10-8-7-9-12-22-20-16-18(25-4)15-19-17(3)11-13-23-21(19)20;;/h11,13,15-16,22H,5-10,12,14H2,1-4H3;2*1H
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/12431016Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16945323
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12431016
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16945323
Sitamaquine (WR-6026) is an orally active 8-aminoquinoline analog in development by the Walter Reed Army Institute, in collaboration with GlaxoSmithKline (formerly SmithKline Beecham), for the potential treatment of visceral leishmaniasis. Phase III trials for the treatment of visceral leishmaniasis had been initiated by March 2002, at which time GlaxoSmithKline hoped to file an MAA in 2003. By 1999, the compound had also undergone phase I trials in HIV-infected individuals for the treatment of Pneumocystis carinii infection. Preclinical studies have been conducted in primates and rodents for the potential treatment of Babesia microti infection.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL367 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21633025 |
29.2 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Curative | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
484.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10235511 |
150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SITAMAQUINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
577 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21633025 |
2 mg/kg single, oral dose: 2 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
SITAMAQUINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
451 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21633025 |
2 mg/kg 1 times / day multiple, oral dose: 2 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered: |
SITAMAQUINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
503 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21633025 |
2 mg/kg 1 times / day multiple, oral dose: 2 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered: |
SITAMAQUINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
639 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21633025 |
2 mg/kg 1 times / day single, oral dose: 2 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
SITAMAQUINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
6916 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10235511 |
150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SITAMAQUINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
7147 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21633025 |
2 mg/kg single, oral dose: 2 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
SITAMAQUINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
7723 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21633025 |
2 mg/kg 1 times / day multiple, oral dose: 2 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered: |
SITAMAQUINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
8350 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21633025 |
2 mg/kg 1 times / day multiple, oral dose: 2 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered: |
SITAMAQUINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
8574 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21633025 |
2 mg/kg 1 times / day single, oral dose: 2 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
SITAMAQUINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
19.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21633025 |
2 mg/kg 1 times / day multiple, oral dose: 2 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered: |
SITAMAQUINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
18.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21633025 |
2 mg/kg 1 times / day multiple, oral dose: 2 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered: |
SITAMAQUINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Doses
Dose | Population | Adverse events |
---|---|---|
120 mg 1 times / day multiple, oral MTD Dose: 120 mg, 1 times / day Route: oral Route: multiple Dose: 120 mg, 1 times / day Sources: Page: p.29 |
unhealthy, ADULT n = 18 Health Status: unhealthy Condition: HIV infection Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 18 Sources: Page: p.29 |
DLT: Elevated triglycerides... Disc. AE: Skin rash, Nausea... Dose limiting toxicities: Elevated triglycerides (5.6%) AEs leading todiscontinuation/dose reduction: Skin rash (11.1%) Sources: Page: p.29Nausea (5.6%) Vomiting (5.6%) Headache (5.6%) CPK increased (5.6%) LDH increased (5.6%) AST increased (5.6%) ALT increased (5.6%) |
150 mg 1 times / day multiple, oral Studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: Page: p.29 |
unhealthy, ADULT n = 8 Health Status: unhealthy Condition: HIV infection Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 8 Sources: Page: p.29 |
DLT: Methemoglobinemia, Methemoglobinemia... Disc. AE: Histoplasmosis, Fever... Dose limiting toxicities: Methemoglobinemia (12.5%) AEs leading toMethemoglobinemia (37.5%) Elevated triglycerides (12.5%) discontinuation/dose reduction: Histoplasmosis (12.5%) Sources: Page: p.29Fever (12.5%) Flushing (12.5%) Skin rash (12.5%) |
2.5 mg/kg 1 times / day multiple, oral Studied dose Dose: 2.5 mg/kg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg/kg, 1 times / day Sources: Page: p.1008 |
unhealthy, CHILD,ADULT n = 28 Health Status: unhealthy Condition: visceral leishmaniasis Age Group: CHILD,ADULT Sex: M+F Food Status: UNKNOWN Population Size: 28 Sources: Page: p.1008 |
Disc. AE: Bone marrow depression, Acute renal failure... AEs leading to discontinuation/dose reduction: Bone marrow depression (3.6%) Sources: Page: p.1008Acute renal failure (3.6%) Bone marrow depression (3.6%) Cardio-respiratory failure (grade 5, 3.6%) Nephrotic syndrome (7.2%) Glomerulonephritis (7.2%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Skin rash | 11.1% Disc. AE |
120 mg 1 times / day multiple, oral MTD Dose: 120 mg, 1 times / day Route: oral Route: multiple Dose: 120 mg, 1 times / day Sources: Page: p.29 |
unhealthy, ADULT n = 18 Health Status: unhealthy Condition: HIV infection Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 18 Sources: Page: p.29 |
Elevated triglycerides | 5.6% DLT |
120 mg 1 times / day multiple, oral MTD Dose: 120 mg, 1 times / day Route: oral Route: multiple Dose: 120 mg, 1 times / day Sources: Page: p.29 |
unhealthy, ADULT n = 18 Health Status: unhealthy Condition: HIV infection Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 18 Sources: Page: p.29 |
ALT increased | 5.6% Disc. AE |
120 mg 1 times / day multiple, oral MTD Dose: 120 mg, 1 times / day Route: oral Route: multiple Dose: 120 mg, 1 times / day Sources: Page: p.29 |
unhealthy, ADULT n = 18 Health Status: unhealthy Condition: HIV infection Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 18 Sources: Page: p.29 |
AST increased | 5.6% Disc. AE |
120 mg 1 times / day multiple, oral MTD Dose: 120 mg, 1 times / day Route: oral Route: multiple Dose: 120 mg, 1 times / day Sources: Page: p.29 |
unhealthy, ADULT n = 18 Health Status: unhealthy Condition: HIV infection Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 18 Sources: Page: p.29 |
CPK increased | 5.6% Disc. AE |
120 mg 1 times / day multiple, oral MTD Dose: 120 mg, 1 times / day Route: oral Route: multiple Dose: 120 mg, 1 times / day Sources: Page: p.29 |
unhealthy, ADULT n = 18 Health Status: unhealthy Condition: HIV infection Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 18 Sources: Page: p.29 |
Headache | 5.6% Disc. AE |
120 mg 1 times / day multiple, oral MTD Dose: 120 mg, 1 times / day Route: oral Route: multiple Dose: 120 mg, 1 times / day Sources: Page: p.29 |
unhealthy, ADULT n = 18 Health Status: unhealthy Condition: HIV infection Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 18 Sources: Page: p.29 |
LDH increased | 5.6% Disc. AE |
120 mg 1 times / day multiple, oral MTD Dose: 120 mg, 1 times / day Route: oral Route: multiple Dose: 120 mg, 1 times / day Sources: Page: p.29 |
unhealthy, ADULT n = 18 Health Status: unhealthy Condition: HIV infection Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 18 Sources: Page: p.29 |
Nausea | 5.6% Disc. AE |
120 mg 1 times / day multiple, oral MTD Dose: 120 mg, 1 times / day Route: oral Route: multiple Dose: 120 mg, 1 times / day Sources: Page: p.29 |
unhealthy, ADULT n = 18 Health Status: unhealthy Condition: HIV infection Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 18 Sources: Page: p.29 |
Vomiting | 5.6% Disc. AE |
120 mg 1 times / day multiple, oral MTD Dose: 120 mg, 1 times / day Route: oral Route: multiple Dose: 120 mg, 1 times / day Sources: Page: p.29 |
unhealthy, ADULT n = 18 Health Status: unhealthy Condition: HIV infection Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 18 Sources: Page: p.29 |
Elevated triglycerides | 12.5% DLT |
150 mg 1 times / day multiple, oral Studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: Page: p.29 |
unhealthy, ADULT n = 8 Health Status: unhealthy Condition: HIV infection Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 8 Sources: Page: p.29 |
Methemoglobinemia | 12.5% DLT, Disc. AE |
150 mg 1 times / day multiple, oral Studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: Page: p.29 |
unhealthy, ADULT n = 8 Health Status: unhealthy Condition: HIV infection Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 8 Sources: Page: p.29 |
Fever | 12.5% Disc. AE |
150 mg 1 times / day multiple, oral Studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: Page: p.29 |
unhealthy, ADULT n = 8 Health Status: unhealthy Condition: HIV infection Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 8 Sources: Page: p.29 |
Flushing | 12.5% Disc. AE |
150 mg 1 times / day multiple, oral Studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: Page: p.29 |
unhealthy, ADULT n = 8 Health Status: unhealthy Condition: HIV infection Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 8 Sources: Page: p.29 |
Histoplasmosis | 12.5% Disc. AE |
150 mg 1 times / day multiple, oral Studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: Page: p.29 |
unhealthy, ADULT n = 8 Health Status: unhealthy Condition: HIV infection Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 8 Sources: Page: p.29 |
Skin rash | 12.5% Disc. AE |
150 mg 1 times / day multiple, oral Studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: Page: p.29 |
unhealthy, ADULT n = 8 Health Status: unhealthy Condition: HIV infection Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 8 Sources: Page: p.29 |
Methemoglobinemia | 37.5% DLT |
150 mg 1 times / day multiple, oral Studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: Page: p.29 |
unhealthy, ADULT n = 8 Health Status: unhealthy Condition: HIV infection Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 8 Sources: Page: p.29 |
Acute renal failure | 3.6% Disc. AE |
2.5 mg/kg 1 times / day multiple, oral Studied dose Dose: 2.5 mg/kg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg/kg, 1 times / day Sources: Page: p.1008 |
unhealthy, CHILD,ADULT n = 28 Health Status: unhealthy Condition: visceral leishmaniasis Age Group: CHILD,ADULT Sex: M+F Food Status: UNKNOWN Population Size: 28 Sources: Page: p.1008 |
Bone marrow depression | 3.6% Disc. AE |
2.5 mg/kg 1 times / day multiple, oral Studied dose Dose: 2.5 mg/kg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg/kg, 1 times / day Sources: Page: p.1008 |
unhealthy, CHILD,ADULT n = 28 Health Status: unhealthy Condition: visceral leishmaniasis Age Group: CHILD,ADULT Sex: M+F Food Status: UNKNOWN Population Size: 28 Sources: Page: p.1008 |
Bone marrow depression | 3.6% Disc. AE |
2.5 mg/kg 1 times / day multiple, oral Studied dose Dose: 2.5 mg/kg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg/kg, 1 times / day Sources: Page: p.1008 |
unhealthy, CHILD,ADULT n = 28 Health Status: unhealthy Condition: visceral leishmaniasis Age Group: CHILD,ADULT Sex: M+F Food Status: UNKNOWN Population Size: 28 Sources: Page: p.1008 |
Glomerulonephritis | 7.2% Disc. AE |
2.5 mg/kg 1 times / day multiple, oral Studied dose Dose: 2.5 mg/kg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg/kg, 1 times / day Sources: Page: p.1008 |
unhealthy, CHILD,ADULT n = 28 Health Status: unhealthy Condition: visceral leishmaniasis Age Group: CHILD,ADULT Sex: M+F Food Status: UNKNOWN Population Size: 28 Sources: Page: p.1008 |
Nephrotic syndrome | 7.2% Disc. AE |
2.5 mg/kg 1 times / day multiple, oral Studied dose Dose: 2.5 mg/kg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg/kg, 1 times / day Sources: Page: p.1008 |
unhealthy, CHILD,ADULT n = 28 Health Status: unhealthy Condition: visceral leishmaniasis Age Group: CHILD,ADULT Sex: M+F Food Status: UNKNOWN Population Size: 28 Sources: Page: p.1008 |
Cardio-respiratory failure | grade 5, 3.6% Disc. AE |
2.5 mg/kg 1 times / day multiple, oral Studied dose Dose: 2.5 mg/kg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg/kg, 1 times / day Sources: Page: p.1008 |
unhealthy, CHILD,ADULT n = 28 Health Status: unhealthy Condition: visceral leishmaniasis Age Group: CHILD,ADULT Sex: M+F Food Status: UNKNOWN Population Size: 28 Sources: Page: p.1008 |
PubMed
Title | Date | PubMed |
---|---|---|
8-Aminoquinolines from Walter Reed Army Institute for Research for treatment and prophylaxis of Pneumocystis pneumonia in rat models. | 1991 Feb |
|
New drug developments for opportunistic infections in immunosuppressed patients: Pneumocystis carinii. | 1995 Nov 24 |
|
Sitamaquine (GlaxoSmithKline/Walter Reed Army Institute). | 2002 Oct |
|
Orally effective drugs for kala-azar (visceral leishmaniasis): focus on miltefosine and sitamaquine. | 2003 Jul |
|
Transition metal complexes of quinolino[3,2-b]benzodiazepine and quinolino[3,2-b]benzoxazepine: synthesis, characterization, and antimicrobial studies. | 2007 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21633025
oral sitamaquine, 2 mg/kg/day, once a day for 21 days
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12431016
Sitamaquine (1 ug/ml) almost completely inhibited P carinii
growth in human lung fibroblasts over 10 days. Some inhibition was seen at 0.1 ug/ml, which was a similar level of activity to that of primaquine.
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5330-29-0
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ASU02O7NS8
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DTXSID80967884
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226-224-0
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m9961
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2452
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PARENT (SALT/SOLVATE)
SUBSTANCE RECORD