title: Synthesis and biological evaluation of 3-(1H-indol-3-yl)pyrazole-5-carboxylic acid derivatives.
abstract: A series of novel compounds bearing a 3-(1H-indol-3-yl)pyrazole-5-carboxylic acid nucleus were synthesized. Analytical and spectral data confirmed the structures of the new compounds. The structures of the regioisomers in this series were determined by (1)H-NMR spectra. The title compounds were evaluated for their endothelin-1 antagonist activities. In the in vitro functional assay, compounds 23, 24, 28 and 29 exhibited significant efficacy at the concentration of 1 μg/mL, and compounds 5b, 5c, 26 and 28 were as potent as the positive control bosentan at high concentration. In the experiment to assess prevention of endothelin-1-induced sudden death in mice, compound 5b showed comparable activity to bosentan, and 30 was more potent than bosentan. The final compounds were also screened for antibacterial activity against four Gram-positive and -negative bacteria. Some of the tested compounds showed weak antibacterial activity.
authors.affiliation: School of Chemical Engineering, Shandong Polytechnic University, Jinan, China. dt_zhang@yahoo.com.cn
authors.forename: Datong
authors.initials: D
authors.lastname: Zhang
authors.forename: Guangtian
authors.initials: G
authors.lastname: Wang
authors.forename: Chubing
authors.initials: C
authors.lastname: Tan
authors.forename: Weiren
authors.initials: W
authors.lastname: Xu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Pei
authors.forename: Lingyan
authors.initials: L
authors.lastname: Huo
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D003645:Death, Sudden / Q000517:prevention & control; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D019332:Endothelin-1; D011720:Pyrazoles; D014665:Vasodilator Agents