title: Novel pyrazole derivatives as potent inhibitors of type II topoisomerases. Part 1: synthesis and preliminary SAR analysis.
abstract: In an attempt to search for a new class of antibacterial agents, we have discovered a series of pyrazole analogs that possess good antibacterial activity for Gram-positive and Gram-negative organisms via inhibition of type II bacterial topoisomerases. We have investigated the structure-activity relationships of this series, with an emphasis on the length and conformation of the linker. This work led to the identification of tetrahydroindazole analogs, such as compound 1, as the most potent class of compounds.
authors: Johnson & Johnson Pharmaceutical Research & Development L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA.
authors: Laurent
authors: L
authors: Gomez
authors: Michael D
authors: MD
authors: Hack
authors: Jiejun
authors: J
authors: Wu
authors: John J M
authors: JJ
authors: Wiener
authors: Hari
authors: H
authors: Venkatesan
authors: Alejandro
authors: A
authors: Santillán
authors: Daniel J
authors: DJ
authors: Pippel
authors: Neelakandha
authors: N
authors: Mani
authors: Brian J
authors: BJ
authors: Morrow
authors: S Timothy
authors: ST
authors: Motley
authors: Karen Joy
authors: KJ
authors: Shaw
authors: Ronald
authors: R
authors: Wolin
authors: Cheryl A
authors: CA
authors: Grice
authors: Todd K
authors: TK
authors: Jones
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D018432:Drug Resistance, Multiple / Q000502:physiology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D059005:Topoisomerase II Inhibitors