title: Quinazolinone-based fungal efflux pump inhibitors. Part 1: Discovery of an (N-methylpiperazine)-containing derivative with activity in clinically relevant Candida spp.
abstract: The discovery of a series of quinazolinone-based fungal efflux pump inhibitors by high-throughput screening for potentiation of fluconazole in C. albicans is described. Attempts to improve the aqueous solubility of screening hits led to the discovery of an analog with greatly improved physical properties and activity against clinically-relevant Candida spp.
authors.affiliation: Essential Therapeutics, Inc., 850 Maude Ave., Mountain View, CA 94043, USA. remy.lemione@roche.com
authors.forename: Rémy C
authors.initials: RC
authors.lastname: Lemoine
authors.forename: Tomasz W
authors.initials: TW
authors.lastname: Glinka
authors.forename: William J
authors.initials: WJ
authors.lastname: Watkins
authors.forename: Aesop
authors.initials: A
authors.lastname: Cho
authors.forename: Jessie
authors.initials: J
authors.lastname: Yang
authors.forename: Nadeem
authors.initials: N
authors.lastname: Iqbal
authors.forename: Rajeshwar
authors.initials: R
authors.lastname: Singh
authors.forename: Deidre
authors.initials: D
authors.lastname: Madsen
authors.forename: Karen
authors.initials: K
authors.lastname: Lolans
authors.forename: Olga
authors.initials: O
authors.lastname: Lomovskaya
authors.forename: Uma
authors.initials: U
authors.lastname: Oza
authors.forename: Michael N
authors.initials: MN
authors.lastname: Dudley
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors*; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002175:Candida / Q000187:drug effects* / Q000201:enzymology; D025141:Drug Resistance, Fungal; D004357:Drug Synergism; D015725:Fluconazole / Q000737:chemistry / Q000494:pharmacology; D005656:Fungal Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D066298:In Vitro Techniques; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents; C094693:CDR1 protein, Candida albicans; D005656:Fungal Proteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D010879:Piperazines; D011799:Quinazolines; D015725:Fluconazole