title: Quinazolinone fungal efflux pump inhibitors. Part 3: (N-methyl)piperazine variants and pharmacokinetic optimization.
abstract: Further structure-activity relationships of a novel series of fungal efflux pump inhibitors with respect to potentiation of the activity of fluconazole against strains of C. albicans and C. glabrata over-expressing ABC-type efflux pumps are systematically explored. Rat protein binding and pharmacokinetics of selected analogues are reported.
authors.affiliation: Essential Therapeutics, Inc., 850 Maude Ave., Mountain View, CA 94043, USA. will.watkins@gilead.com
authors.forename: William J
authors.initials: WJ
authors.lastname: Watkins
authors.forename: Lee
authors.initials: L
authors.lastname: Chong
authors.forename: Aesop
authors.initials: A
authors.lastname: Cho
authors.forename: Ramona
authors.initials: R
authors.lastname: Hilgenkamp
authors.forename: Maria
authors.initials: M
authors.lastname: Ludwikow
authors.forename: Negar
authors.initials: N
authors.lastname: Garizi
authors.forename: Nadeem
authors.initials: N
authors.lastname: Iqbal
authors.forename: John
authors.initials: J
authors.lastname: Barnard
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: Padmapriya
authors.initials: P
authors.lastname: Kumaraswamy
authors.forename: Andrea
authors.initials: A
authors.lastname: Blecken
authors.forename: Shuang
authors.initials: S
authors.lastname: Bai
authors.forename: David J
authors.initials: DJ
authors.lastname: Loury
authors.forename: David C
authors.initials: DC
authors.lastname: Griffith
authors.forename: Michael N
authors.initials: MN
authors.lastname: Dudley
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D022781:Hepatocytes / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry*; D052999:Quinazolinones / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044967:Serum / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D026901:Membrane Transport Proteins; D010879:Piperazines; D052999:Quinazolinones; D000077489:Piperazine