CAS 186953-56-0|Pafuramidine

Introduction：Basic information about CAS 186953-56-0|Pafuramidine, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Pafuramidine BiologicalActivity
3. Chemical & Physical Properties
4. Synonyms

Common Name	Pafuramidine
CAS Number	186953-56-0	Molecular Weight	364.39800
Density	1.25	Boiling Point	/
Molecular Formula	C₂₀H₂₀N₄O₃	Melting Point	192.5-193ºC
MSDS	/	Flash Point	/

Names

Name	N'-methoxy-4-[5-[4-[(Z)-N'-methoxycarbamimidoyl]phenyl]furan-2-yl]benzenecarboximidamide
Synonym	More Synonyms

Pafuramidine BiologicalActivity

Description	Pafuramidine (DB289) is an orally bioavailable prodrug of furamidine, which has clinical activity against Pneumocystis pneumonia.IC50 Value: 4.5 nM (In vitro inhibitory activity against Trypanosoma brucei rhodesiense) [4]Target: AntiparasiticDB289 (pafuramidine maleate; 2,5-bis[4-(N-methoxyamidino)phenyl]furan monomaleate) is a prodrug of DB75 (furamidine dihydrochloride; 2,5-bis(4-guanylphenyl)furan dihydrochloride), an aromatic dication related to pentamidine that has demonstrated good efficacy against African trypanosomiasis, Pneumocystis carinii pneumonia, and malaria, but lacks adequate oral availability. in vitro: The results of this investigation suggest that DB75 inhibits mitochondrial function. Yeast cells relying upon mitochondrial metabolism for energy production are especially sensitive to DB75 [1].in vivo: Clearance of DB289 approximated the liver plasma flow and its large volume of distribution was consistent with extensive tissue binding. Plasma protein binding of DB289 was 97 to 99% in four animal species and humans, but that of DB75 was noticeably less and more species- and concentration-dependent [2]. Despite excellent oral activity against early-stage sleeping sickness, oral administration of DB289 exhibited limited efficacy in mouse models of late-stage disease [3].Clinical trial: DB289, a novel orally active prodrug of DB75, is undergoing phase IIb clinical trials for early-stage human African trypanosomiasis, Pneumocystis jiroveci carinii pneumonia, and malaria [1].
Related Catalog	Signaling Pathways >>Anti-infection >>ParasiteResearch Areas >>Infection
References	[1]. Lanteri CA, Trumpower BL, Tidwell RR, DB75, a novel trypanocidal agent, disrupts mitochondrial function in Saccharomyces cerevisiae. Antimicrob Agents Chemother. 2004 Oct;48(10):3968-74. [2]. Midgley I, Fitzpatrick K, Taylor LM, Pharmacokinetics and metabolism of the prodrug DB289 (2,5-bis[4-(N-methoxyamidino)phenyl]furan monomaleate) in rat and monkey and its conversion to the antiprotozoal/antifungal drug DB75 (2,5-bis(4-guanylphenyl)furan d [3]. Sturk LM, Brock JL, Bagnell CR, Distribution and quantitation of the anti-trypanosomal diamidine 2,5-bis(4-amidinophenyl)furan (DB75) and its N-methoxy prodrug DB289 in murine brain tissue. Acta Trop. 2004 Jul;91(2):131-43. [4]. In vitro inhibitory activity against Trypanosoma brucei rhodesiense - BioAssay Summary.

Description

Pafuramidine (DB289) is an orally bioavailable prodrug of furamidine, which has clinical activity against Pneumocystis pneumonia.IC50 Value: 4.5 nM (In vitro inhibitory activity against Trypanosoma brucei rhodesiense) [4]Target: AntiparasiticDB289 (pafuramidine maleate; 2,5-bis[4-(N-methoxyamidino)phenyl]furan monomaleate) is a prodrug of DB75 (furamidine dihydrochloride; 2,5-bis(4-guanylphenyl)furan dihydrochloride), an aromatic dication related to pentamidine that has demonstrated good efficacy against African trypanosomiasis, Pneumocystis carinii pneumonia, and malaria, but lacks adequate oral availability. in vitro: The results of this investigation suggest that DB75 inhibits mitochondrial function. Yeast cells relying upon mitochondrial metabolism for energy production are especially sensitive to DB75 [1].in vivo: Clearance of DB289 approximated the liver plasma flow and its large volume of distribution was consistent with extensive tissue binding. Plasma protein binding of DB289 was 97 to 99% in four animal species and humans, but that of DB75 was noticeably less and more species- and concentration-dependent [2]. Despite excellent oral activity against early-stage sleeping sickness, oral administration of DB289 exhibited limited efficacy in mouse models of late-stage disease [3].Clinical trial: DB289, a novel orally active prodrug of DB75, is undergoing phase IIb clinical trials for early-stage human African trypanosomiasis, Pneumocystis jiroveci carinii pneumonia, and malaria [1].

Related Catalog

Signaling Pathways >>Anti-infection >>ParasiteResearch Areas >>Infection

References

[1]. Lanteri CA, Trumpower BL, Tidwell RR, DB75, a novel trypanocidal agent, disrupts mitochondrial function in Saccharomyces cerevisiae. Antimicrob Agents Chemother. 2004 Oct;48(10):3968-74.

[2]. Midgley I, Fitzpatrick K, Taylor LM, Pharmacokinetics and metabolism of the prodrug DB289 (2,5-bis[4-(N-methoxyamidino)phenyl]furan monomaleate) in rat and monkey and its conversion to the antiprotozoal/antifungal drug DB75 (2,5-bis(4-guanylphenyl)furan d

[3]. Sturk LM, Brock JL, Bagnell CR, Distribution and quantitation of the anti-trypanosomal diamidine 2,5-bis(4-amidinophenyl)furan (DB75) and its N-methoxy prodrug DB289 in murine brain tissue. Acta Trop. 2004 Jul;91(2):131-43.

[4]. In vitro inhibitory activity against Trypanosoma brucei rhodesiense - BioAssay Summary.

Chemical & Physical Properties

Density	1.25
Melting Point	192.5-193ºC
Molecular Formula	C₂₀H₂₀N₄O₃
Molecular Weight	364.39800
Exact Mass	364.15400
PSA	108.36000
LogP	4.54760
InChIKey	UKOQVLAXCBRRGH-UHFFFAOYSA-N
SMILES	CON=C(N)c1ccc(-c2ccc(-c3ccc(C(N)=NOC)cc3)o2)cc1
Storage condition	2-8℃

Synonyms

UNII-H1VG379J2X

Pafuramidine

Recommended......