Tetrahydroindazole inhibitors of bacterial type II topoisomerases. Part 2: SAR development and potency against multidrug-resistant strains.
We have previously reported a novel class of tetrahydroindazoles that display potency against a variety of Gram-positive and Gram-negative bacteria, potentially via interaction with type II bacterial topoisomerases. Herein are reported SAR investigations of this new series. Several compounds possessing broad-spectrum potency were prepared. Further, these compounds exhibit activity against multidrug-resistant Gram-positive microorganisms equivalent to that against susceptible strains.
Wiener
John J M
JJ
Johnson & Johnson Pharmaceutical Research & Development L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA. Jwiener@prdus.jnj.com
Gomez
Laurent
L
Venkatesan
Hariharan
H
Santillán
Alejandro
A
Allison
Brett D
BD
Schwarz
Kimberly L
KL
Shinde
Shirin
S
Tang
Liu
L
Hack
Michael D
MD
Morrow
Brian J
BJ
Motley
S Timothy
ST
Goldschmidt
Raul M
RM
Shaw
Karen Joy
KJ
Jones
Todd K
TK
Grice
Cheryl A
CA
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D018432:Drug Resistance, Multiple / Q000502:physiology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D007191:Indazoles; D059005:Topoisomerase II Inhibitors