Design, syntheses, and structure-activity relationships of indan derivatives as endothelin antagonists; new lead generation of non-peptidic antagonist from peptidic leads.

A new lead generation of non-peptidic ET(A) antagonists from two peptidic ET(A)-selective ones, BQ-123 and FR139317, was performed. Using computer assisted molecular modeling, a putative pharmacophore was constructed from the superposition of the reported three-dimensional structure of the cyclic peptide BQ-123 and a presumable beta-turn active conformation of the linear peptide FR139317 formed by an intramolecular hydrogen bond. According to this model, a new series of indan derivatives were designed and synthesized. Among these, 5-isobutyrylamino-6-(1-naphthylmethyloxy)-3-(2-thienyl)-1-indancarboxylic acid (1b) showed a moderate ET(A) antagonistic activity (IC50 = 28 microM).

Lesion of a higher-order song nucleus disrupts phrase level complexity in Bengalese finches.

Studies in zebra finches failed to demonstrate the involvement of the NIf, a higher-order song nucleus afferent to the HVc, in the production of learned song. The song of the Bengalese finch, a related species, has a higher level of temporal organization; multiple song phrases are organized into a song. We hypothesized that the NIf might control this complexity. To test this, we bilaterally lesioned the NIf in adult male Bengalese finches. The songs of birds with multi-phrase organization changed into simpler, mono-phrase songs. This is the first demonstration of the NIfs involvement in the production of birdsong. Zebra finch songs are syntactically simple and deterministic, and this might have caused the difficulty in demonstrating the function of the NIf in zebra finches.