Science exchange logo white
  • Solutions
      Buyers

      We are making R&D services readily available to every organization that seeks to make scientific impact. Learn More

      Providers

      We are changing the way providers access and engage customers to streamline the sale and delivery of R&D services. Learn More

      Industries Agriscience Animal Health Basic Research Biopharmaceutical Chemicals Consumer Health Food Science Medical Devices
      Reproducibility

      We believe that good experiments can and should be independently replicated and validated. Learn More

  • Resources
    Innovation Blog
    Customer Stories
    Events
    Industry Trends
    News
    Product Updates
    Help Center
  • About
    About
    Our Story
    Leadership
    Partners
    Join the Team
  • Contact
  • Log In Sign Up
  • Get a Demo
  • High affinity central benzodiazepine receptor ligands. Part 3: insights into the pharmacophore and pattern recognition study of intrinsic activities of pyrazolo[4,3-c]quinolin-3-ones.

    Bioorg Med Chem. 11(23):5259-72. November 17, 2003. View on PubMed.
  • Authors

    Manuel Mameli (Institut du Fer a Moulin), Carotti A, Altomare C, Savini L, Chiasserini L, Pellerano C, Mascia MP, Maciocco E, Busonero F, Biggio G, and Sanna E
  • Abstract

    Novel 2-phenyl-2,5-dihydropyrazolo[4,3-c]quinolin-3-(3H)-ones (PQs) endowed with high affinity for central benzodiazepine receptor (BzR) were synthesized. In particular, 9-fluoro-2-(2-fluorophenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (2(2)) showed binding affinity in the subnanomolar concentration range and proved to be in vitro a potent antagonist. This finding allowed the nature of the hydrogen bonding receptor site H(2) to be established, as located between the N-1 nitrogen of the PQ nucleus and the ortho position of the N-2-aryl group. [35S]tert-Butylbicyclophosphorothionate ([35S]TBPS) binding assays and electrophysiological measurements of the effects on GABA-evoked Cl(-) currents at recombinant human alpha(1)beta(2)gamma(2)(L) GABA(A) receptors, expressed in Xenopus laevis oocytes, were used to assess the intrinsic activities of a large series of PQs. With the aim of extracting discriminant information and distinguishing BzR ligands with different profiles of efficacy, 51 PQ derivatives, including full and partial agonists, antagonists, and inverse agonists, were analyzed in a multidimensional chemical descriptor space, defined by the lipophilicity parameter CLOG P and 3-D molecular WHIM descriptors, by means of principal component analysis, k-nearest neighbors (k-NN) method, and linear discriminant analysis (LDA). The classification methods were applied to subsets of pairs of efficacy classes, and lipophilicity and 3-D size descriptors were detected as the discriminant variables by a stepwise linear discriminant analysis. LDA proved to be superior to k-NN, especially in classifying PQ ligands (60-84% of success in prediction ability) into categories of efficacies which were contiguous and quite overlapped in the hyperspace of variables.

Science exchange logo white

  • Facebook
  • Twitter
  • LinkedIn

Solutions

  • Buyers
  • Providers
  • Reproducibility

Industries

  • Agriscience
  • Animal Health
  • Basic Research
  • Biopharmaceutical
  • Chemicals
  • Consumer Health
  • Food Science
  • Medical Devices

Resources

  • Innovation Blog
  • Customer Stories
  • Events
  • Industry Trends
  • News
  • Product Updates

About

  • Our Story
  • Leadership
  • Partners
  • Join the Team

Support

  • Contact Us
  • Help Center
  • Trust
  • Terms of Use
  • Privacy Policy

Copyright © 2021 Science Exchange, Inc. All rights reserved.