Design, synthesis, and biological evaluation of scaffold-based tripeptidomimetic antagonists for CXC chemokine receptor 4 (CXCR4).

Structure-activity relationship studies of the cyclopentapeptide CXCR4 antagonists (cyclo(-l-/d-Arg(1)-Arg(2)-2-Nal(3)-Gly(4)-d-Tyr(5)-)) suggest that the l-/d-Arg(1)-Arg(2)-2-Nal(3) tripeptide sequence contained within these cyclopentapeptides serves as a recognition motif for peptidic CXCR4 antagonists. Starting by dissecting the cyclopentapeptide structure and reintroducing cyclic constraints in a stepwise manner, we here report a novel class of scaffold-based tripeptidomimetic CXCR4 antagonists based on the d-Arg-Arg-2-Nal motif. Biological testing of the prototype compounds showed that they represent new peptidomimetic hits; importantly, the modular nature of the scaffold provides an interesting starting point for future ligand optimization.

[Benzodiazepine-like hypnotics--attitudes and prescription practice among general practitioners].

Background: The large increase in sales of the benzodiazepine-like hypnotics (z-hypnotics) zopiclone and zolpidem over the last decade prompted an investigation into Norwegian general practitioners' prescription habits, knowledge of and attitudes to these drugs.

Material And Methods: A questionnaire was distributed to all 928 registered GPs in six Norwegian counties. The physicians were asked to assess statements, patient vignettes and drug preferences with regard to z-hypnotic and benzodiazepine prescription practice.