RESUMEN
Phenotypic screening of an annotated small molecule library and initial SAR studies identified compound 2 as a robust enhancer of progranulin secretion. Detailed SAR development on conformationally restricted carbamate isosteres led to the identification of compound 60 with a 3-fold improvement in BV-2 potency and a 9-fold decrease in hERG inhibition over compound 2, substantially improving this important margin of safety relative to compound 2.
Asunto(s)
Demencia Frontotemporal , Péptidos y Proteínas de Señalización Intercelular , Humanos , ProgranulinasRESUMEN
Using data from a case study presented in Chiat (1989), Marshall and Chiat (2003) compare two different approaches to account for the realization of intervocalic consonants in child phonology: "coda capture theory" and the "foot domain account". They argue in favour of the latter account. In this note, we present a reappraisal of this argument using the same data. We conclude that acceptance of the foot domain account, in the specific way developed by the authors, is unmotivated for both theoretical and empirical reasons. We maintain that syllable-based coda capture is (still) the better approach to account for the relevant facts.