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Details

Stereochemistry ACHIRAL
Molecular Formula C20H20N4O3.C4H4O4
Molecular Weight 480.47
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of PAFURAMIDINE MALEATE

SMILES

OC(=O)\C=C/C(O)=O.CONC(=N)C1=CC=C(C=C1)C2=CC=C(O2)C3=CC=C(C=C3)C(=N)NOC

InChI

InChIKey=SWMNGXODFOCPKQ-BTJKTKAUSA-N
InChI=1S/C20H20N4O3.C4H4O4/c1-25-23-19(21)15-7-3-13(4-8-15)17-11-12-18(27-17)14-5-9-16(10-6-14)20(22)24-26-2;5-3(6)1-2-4(7)8/h3-12H,1-2H3,(H2,21,23)(H2,22,24);1-2H,(H,5,6)(H,7,8)/b;2-1-

HIDE SMILES / InChI

Molecular Formula C4H4O4
Molecular Weight 116.0722
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Molecular Formula C20H20N4O3
Molecular Weight 364.3978
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Pafuramidine or DB289, [2,5-bis-(4-amidinophenyl)furan bis-O-methylamidoxime] is a pro-drug of DB75, [2,5-bis(4-amidinophenyl)furan] also known as furamidine. The biotransformation process of DB289 to DB75 in the human liver consists of three O-demethylation reactions catalyzed by the Cyp4F enzyme subfamily and three N-dehydroxylation reactions catalyzed by cytrochrome b5 and NADH-cytochrome b5 reductase. DB289 was studied for therapeutic treatment against human African trypanosomiasis, Pneumocystis pneumonia and malaria. In November 2006, Immtech Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) had granted orphan drug designation for pafuramidine (DB289) to treat Pneumocystis jiroveci pneumonia (PCP), a common life-threatening opportunistic infection in HIV/AIDS and other immunosuppressed patients. Despite the high efficacy of DB289 in patients, the mechanism of action of DB75 is unknown. The mechanism of antimicrobial activity of diamidine compounds is incompletely understood. They undergo active uptake by purine transporter systems in trypanosomes and their mechanism of action may involve interference with DNA-associated enzymes inhibition of heme crystallization11 or/and collapse of the transmitochondrial membrane potential.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
9.4 µM [IC50]
35.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
Unknown
Curative
Unknown
Curative
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
3.6 ng/mL
100 mg single, oral
FURAMIDINE plasma
Homo sapiens
15.9 ng/mL
100 mg single, oral
PAFURAMIDINE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
112 ng × h/mL
100 mg single, oral
FURAMIDINE plasma
Homo sapiens
292 ng × h/mL
100 mg single, oral
PAFURAMIDINE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
30.9 h
100 mg single, oral
FURAMIDINE plasma
Homo sapiens
17.2 h
100 mg single, oral
PAFURAMIDINE plasma
Homo sapiens

PubMed

Sample Use Guides

In Vivo Use Guide
Sleeping sickness (human African trypanosomiasis [HAT]) patients were treated 100 mg of pafuramidine orally twice a day for 10 days (Phase 3 Clinical Trial)
Route of Administration: Oral
In Vitro Use Guide
Unknown
Substance Class Chemical
Record UNII
K27F04K3A9
Record Status Validated (UNII)
Record Version