Quinazolinone fungal efflux pump inhibitors. Part 3: (N-methyl)piperazine variants and pharmacokinetic optimization.
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.
Watkins
William J
WJ
Essential Therapeutics, Inc., 850 Maude Ave., Mountain View, CA 94043, USA. will.watkins@gilead.com
Chong
Lee
L
Cho
Aesop
A
Hilgenkamp
Ramona
R
Ludwikow
Maria
M
Garizi
Negar
N
Iqbal
Nadeem
N
Barnard
John
J
Singh
Rajeshwar
R
Madsen
Deidre
D
Lolans
Karen
K
Lomovskaya
Olga
O
Oza
Uma
U
Kumaraswamy
Padmapriya
P
Blecken
Andrea
A
Bai
Shuang
S
Loury
David J
DJ
Griffith
David C
DC
Dudley
Michael N
MN
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
D000935:Antifungal Agents; D026901:Membrane Transport Proteins; D010879:Piperazines; D052999:Quinazolinones; D000077489:Piperazine