A new therapeutic approach in Alzheimer disease: Some novel pyrazole derivatives as dual MAO-B inhibitors and antiinflammatory analgesics

Goekhan-Kelekci N., Yabanoglu S., Kuepeli E., Salgin Goksen U., Oezgen O., Ucar G., ...More

BIOORGANIC & MEDICINAL CHEMISTRY, vol.15, no.17, pp.5775-5786, 2007 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 15 Issue: 17
  • Publication Date: 2007
  • Doi Number: 10.1016/j.bmc.2007.06.004
  • Page Numbers: pp.5775-5786
  • Keywords: Alzheimer, pyrazole derivatives, monoamine oxidase-A/B, inhibition, analgesic-antiinflamrnatory activity, MONOAMINE-OXIDASE, 1-N-SUBSTITUTED THIOCARBAMOYL-3-PHENYL-5-THIENYL-2-PYRAZOLINES, DRUGS, STEREOCHEMISTRY, PRINCIPLE, DEPRENYL, AGENTS, BRAIN, ACID


The increasing life expectancy in our population makes Alzheimer's disease (AD) a growing public health problem. There is a great need to find a way to prevent and delay the disease. It was shown that monoamine oxidase-B (MAO-B) inhibitors and antiinflammatory agents might be effective in treating AD. Therefore, a novel series of 1-thiocarbamoyl-3-substituted phenyl-5(2-pyrrolyl)-4,5-dihydro-(1 H)-pyrazole derivatives as promising MAO-B inhibitors was synthesized and investigated for the ability to inhibit selectively the activity of the A and B isoforms of monoamine oxidase (MAO). Most of the synthesized compounds showed high activity against both the MAO-A (compounds 3e-3h) and the MAO-B (compounds 3i-3l) isoforms. All the synthesized Compounds were also tested for their in vivo antiinflarnmatory activity by two different bioassays namely, carrageenan-induced oedema and acetic acid-induced increase in capillary permeability in mice. In addition, analgesic and ulcerogenic activities were determined. The combined antiinflammatory data from in vivo animal models showed that compound 3k exhibited anti-inflammatory activity comparable to that of indomethacin with no ulcerogenic effects. Since compound 3k exhibits both antiinflammatory-analgesic activity and MAO-B inhibition, it needs further detailed studies. (c) 2007 Elsevier Ltd. All rights reserved.