F2g Limited

F2g Ltd British Body Corporate

F2g Limited British Body Corporate

Graham Edward Morris Sibley

Philip N Edwards

Jason David Oliver

Derek Law

Michael Birch

Gareth Morse Davies

Robert Downham

Lloyd James Payne

Philip Edwards

Mike Birch

John Leslie Thain

Michael John Bromley

The invention provides a pyrrole compound, which compound is (a) 2-(1,5-dimethyl-3-phenyl-1H-pyrrol-2-yl)-N-(4-(4-(5-fluoropyrimidin-2-yl)piperazin-1-yl)phenyl)-2-oxoacetamide or a deuterated derivative thereof, or (b) 2-(1,5-dimethyl-3-phenyl-1H-pyrrol-2-yl)-N-(4-(4-(5-fluoropyrimidin-2-yl)piperazin-1-yl)-3-hydroxyphenyl)-2-oxoacetamide or a deuterated derivative thereof, or (c) a prodrug of compound (a) or a prodrug of compound (b), or a pharmaceutically acceptable salt or agriculturally acceptable salt of (a), (b) or (c). Also provided are combinations and compositions comprising the compound and known antifungal agents. The invention also relates to the therapeutic use of a compound of the invention in prevention or treatment of fungal diseases. It also relates to the use of: 2-(1,5-dimethyl-3-phenyl-1H-pyrrol-2-yl)-N-(4-(4-(5-fluoropyrimidin-2-yl)piperazin-1-yl)phenyl)-2-oxoacetamide or an agriculturally acceptable salt thereof, or 2-(1,5-dimethyl-3-phenyl-1H-pyrrol-2-yl)-N-(4-(4-(5-fluoropyrimidin-2-yl)piperazin-1-yl)-3-hydroxyphenyl)-2-oxoacetamide or an agriculturally acceptable salt thereof, as an agricultural fungicide.

Antifungal agents

A pharmaceutical composition suitable for oral administration comprising particles of 2-(1,5-dimethyl-3-phenyl-1H-pyrrol-2-yl)-N-(4-(4-(5-fluoropyrimidin-2-yl)piperazin-1-yl)phenyl)-2- oxoacetamideis provided. Also provided is a pharmaceutical composition suitable for parenteral administration wherein the composition comprises 2-(1,5-dimethyl-3-phenyl-1H-pyrrol-2-yl)-N-(4-(4-(5-fluoropyrimidin-2-yl)piperazin-1-yl)phenyl)-2-oxoacetamide. The compositions are useful in the treatment of fungal infection in a subject in need thereof.

Pharmaceutical formulation

The invention provides compounds of formula (I), and pharmaceutically and agriculturally acceptable salts thereof; wherein: R1, R2, R3, R4, R5, R6, A1, L1 and n are as defined herein. These compounds and their pharmaceutically acceptable salts are useful in prevention or treatment of a fungal disease. Compounds of formula (I), and agriculturally acceptable salts thereof, may also be used as agricultural fungicides. 

Pyrrole antifungal agents

A method of identifying an antifungal agent which targets a DHODH protein (alias PyrE, dihydroorotate dehydrogenase, EC: 1.3.99.11) of a fungus comprising contacting a candidate substance with a fungal DHODH protein and determining whether the candidate substance binds or modulates the DHODH protein, wherein binding or modulation indicates that the candidate substance is an antifungal agent. Specific examples concernandDHODH proteins. DHODH inhibitors with a Quinazolinone core are also disclosed.

Dihydroorotate dehydrogenase as antifungal drug target and quinazolinone-based inhibitors thereof

The invention provides compounds of formula (I), and pharmaceutically acceptable salts thereof wherein: R1, R2, R3, R4, R5, R6, R7, X and Xare as defined herein. These compounds are useful in the manufacture of medicaments for use in the prevention or treatment of a fungal disease. Compounds of formula (I), and agriculturally acceptable salts thereof, may also be used as agricultural fungicides. 

2-[(2-substituted)-indolizin-3-yl]-2-oxo-acetamide derivatives as antifungal agents

The invention provides compounds of formula (I), and pharmaceutically and agriculturally acceptable salts thereof: wherein: R1, R2, R3, R4, R5, R6, R7, R8, A1, L1 and n are as defined herein. These compounds and their pharmaceutically acceptable salts are useful in the manufacture of medicaments for use in the prevention or treatment of a fungal disease. Compounds of formula (I), and agriculturally acceptable salts thereof, may also be used as agricultural fungicides. 

Growing community of inventors

Manchester, United Kingdom

Graham Edward Morris Sibley