Literature DB >> 18790643

A study of the structure-activity relationship of GABA(A)-benzodiazepine receptor bivalent ligands by conformational analysis with low temperature NMR and X-ray analysis.

Dongmei Han1, F Holger Försterling, Xiaoyan Li, Jeffrey R Deschamps, Damon Parrish, Hui Cao, Sundari Rallapalli, Terry Clayton, Yun Teng, Samarpan Majumder, Subramaniam Sankar, Bryan L Roth, Werner Sieghart, Roman Furtmuller, James K Rowlett, Michael R Weed, James M Cook.   

Abstract

The stable conformations of GABA(A)-benzodiazepine receptor bivalent ligands were determined by low temperature n class="Chemical">NMR spectroscopy and confirmed by single crystal X-ray analysis. The stable conformations in solution correlated well with those in the solid state. The linear conformation was important for these dimers to access the binding site and exhibit potent in vitro affinity and was illustrated for alpha5 subtype selective ligands. Bivalent ligands with an oxygen-containing linker folded back upon themselves both in solution and the solid state. Dimers which are folded do not bind to Bz receptors.

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Year:  2008        PMID: 18790643      PMCID: PMC3703926          DOI: 10.1016/j.bmc.2008.08.072

Source DB:  PubMed          Journal:  Bioorg Med Chem        ISSN: 0968-0896            Impact factor:   3.641


  28 in total

1.  Pharmacophore/receptor models for GABA(A)/BzR subtypes (alpha1beta3gamma2, alpha5beta3gamma2, and alpha6beta3gamma2) via a comprehensive ligand-mapping approach.

Authors:  Q Huang; X He; C Ma; R Liu; S Yu; C A Dayer; G R Wenger; R McKernan; J M Cook
Journal:  J Med Chem       Date:  2000-01-13       Impact factor: 7.446

Review 2.  A new benzodiazepine pharmacology.

Authors:  H Möhler; J M Fritschy; U Rudolph
Journal:  J Pharmacol Exp Ther       Date:  2002-01       Impact factor: 4.030

3.  QUINAZOLINES AND 1,4-BENZODIAZEPINES. XVII. SYNTHESIS OF 1,3-DIHYDRO-5-PYRIDYL-2H-1,4-BENZODIAZEPINE DERIVATIVES.

Authors:  R I FRYER; R A SCHMIDT; L H STERNBACH
Journal:  J Pharm Sci       Date:  1964-03       Impact factor: 3.534

4.  Pharmacology of recombinant gamma-aminobutyric acidA receptors rendered diazepam-insensitive by point-mutated alpha-subunits.

Authors:  J A Benson; K Löw; R Keist; H Mohler; U Rudolph
Journal:  FEBS Lett       Date:  1998-07-24       Impact factor: 4.124

5.  Selective antagonism of the ataxic effects of zolpidem and triazolam by the GABAA/alpha1-preferring antagonist beta-CCt in squirrel monkeys.

Authors:  Donna M Platt; James K Rowlett; Roger D Spealman; James Cook; Chunrong Ma
Journal:  Psychopharmacology (Berl)       Date:  2002-09-04       Impact factor: 4.530

6.  Benzodiazepine actions mediated by specific gamma-aminobutyric acid(A) receptor subtypes.

Authors:  U Rudolph; F Crestani; D Benke; I Brünig; J A Benson; J M Fritschy; J R Martin; H Bluethmann; H Möhler
Journal:  Nature       Date:  1999-10-21       Impact factor: 49.962

Review 7.  Aromatic-aromatic interaction: a mechanism of protein structure stabilization.

Authors:  S K Burley; G A Petsko
Journal:  Science       Date:  1985-07-05       Impact factor: 47.728

8.  Benzodiazepine receptor-mediated experimental "anxiety" in primates.

Authors:  P T Ninan; T M Insel; R M Cohen; J M Cook; P Skolnick; S M Paul
Journal:  Science       Date:  1982-12-24       Impact factor: 47.728

9.  Synthesis and pharmacological properties of novel 8-substituted imidazobenzodiazepines: high-affinity, selective probes for alpha 5-containing GABAA receptors.

Authors:  R Liu; R J Hu; P Zhang; P Skolnick; J M Cook
Journal:  J Med Chem       Date:  1996-04-26       Impact factor: 7.446

10.  High affinity ligands for 'diazepam-insensitive' benzodiazepine receptors.

Authors:  G Wong; P Skolnick
Journal:  Eur J Pharmacol       Date:  1992-01-14       Impact factor: 4.432

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  1 in total

Review 1.  A Review of the Updated Pharmacophore for the Alpha 5 GABA(A) Benzodiazepine Receptor Model.

Authors:  Terry Clayton; Michael M Poe; Sundari Rallapalli; Poonam Biawat; Miroslav M Savić; James K Rowlett; George Gallos; Charles W Emala; Catherine C Kaczorowski; Douglas C Stafford; Leggy A Arnold; James M Cook
Journal:  Int J Med Chem       Date:  2015-11-10
  1 in total

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