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Details

Stereochemistry ACHIRAL
Molecular Formula C18H16N4O
Molecular Weight 304.3458
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FURAMIDINE

SMILES

NC(=N)C1=CC=C(C=C1)C2=CC=C(O2)C3=CC=C(C=C3)C(N)=N

InChI

InChIKey=ZJHZBDRZEZEDGB-UHFFFAOYSA-N
InChI=1S/C18H16N4O/c19-17(20)13-5-1-11(2-6-13)15-9-10-16(23-15)12-3-7-14(8-4-12)18(21)22/h1-10H,(H3,19,20)(H3,21,22)

HIDE SMILES / InChI

Molecular Formula C18H16N4O
Molecular Weight 304.3458
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

Curator's Comment: Pafuramidine is brain penetrant in mice. In monkeys, it has limited ability to cross the blood-brain barrier. No human data available.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: Q08477
Gene ID: 4051.0
Gene Symbol: CYP4F3
Target Organism: Homo sapiens (Human)
9.4 µM [IC50]
35.0 nM [IC50]
Conditions
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3.6 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FURAMIDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
15.9 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PAFURAMIDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
112 ng × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FURAMIDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
292 ng × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PAFURAMIDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
30.9 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FURAMIDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
17.2 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PAFURAMIDINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
PubMed

PubMed

TitleDatePubMed
A mouse diversity panel approach reveals the potential for clinical kidney injury due to DB289 not predicted by classical rodent models.
2012 Dec
Patents

Sample Use Guides

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
Created
by admin
on Thu Jul 06 01:29:41 UTC 2023
Edited
by admin
on Thu Jul 06 01:29:41 UTC 2023
Record UNII
08GH1YF0RA
Record Status Validated (UNII)
Record Version
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Name Type Language
FURAMIDINE
Systematic Name English
NSC-305831
Code English
2,5-BIS(4-AMIDINOPHENYL)FURAN
Common Name English
DB75
Code English
4,4'-(2,5-FURANDIYL)BIS [BENZENECARBOXIMIDAMIDE]
Systematic Name English
BENZENECARBOXIMIDAMIDE, 4,4'-(2,5-FURANDIYL)BIS-
Systematic Name English
DB-75
Code English
Code System Code Type Description
CAS
73819-26-8
Created by admin on Thu Jul 06 01:29:41 UTC 2023 , Edited by admin on Thu Jul 06 01:29:41 UTC 2023
PRIMARY
FDA UNII
08GH1YF0RA
Created by admin on Thu Jul 06 01:29:41 UTC 2023 , Edited by admin on Thu Jul 06 01:29:41 UTC 2023
PRIMARY
EPA CompTox
DTXSID00224264
Created by admin on Thu Jul 06 01:29:41 UTC 2023 , Edited by admin on Thu Jul 06 01:29:41 UTC 2023
PRIMARY
NSC
305831
Created by admin on Thu Jul 06 01:29:41 UTC 2023 , Edited by admin on Thu Jul 06 01:29:41 UTC 2023
PRIMARY
PUBCHEM
126437
Created by admin on Thu Jul 06 01:29:41 UTC 2023 , Edited by admin on Thu Jul 06 01:29:41 UTC 2023
PRIMARY
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ACTIVE MOIETY