753021-49-7Relevant academic research and scientific papers
Medicinal chemistry driven approaches toward novel and selective serotonin 5-HT6 receptor ligands
Holenz, J?rg,Mercè, Ramon,Díaz, José Luis,Guitart, Xavier,Codony, Xavier,Dordal, Alberto,Romero, Gonzalo,Torrens, Antoni,Mas, Josep,Andaluz, Blas,Hernández, Susana,Monroy, Xavier,Sánchez, Elisabeth,Hernández, Enrique,Pérez, Raquel,Cubí, Roger,Sanfeliu, Olga,Buschmann, Helmut
, p. 1781 - 1795 (2005)
Based on a medicinal chemistry guided hypothetical pharmacophore model, novel series of indolyl sulfonamides have been designed and prepared as selective and high-affinity serotonin 5-HT6 receptor ligands. Furthermore, based on a screening appr
Synthesis of new benzoxazinone derivatives as neuropeptide Y5 antagonists for the treatment of obesity
Torrens, Antoni,Mas, Josep,Port, Adriana,Castrillo, José Aurelio,Sanfeliu, Olga,Guitart, Xavier,Dordal, Alberto,Romero, Gonzalo,Fisas, Ma. Angeles,Sánchez, Elisabeth,Hernández, Enrique,Pérez, Pilar,Pérez, Raquel,Buschmann, Helmut
, p. 2080 - 2092 (2007/10/03)
Screening of our internal chemical collection against the neuropeptide Y5 (NPY Y5) receptor allowed the identification of a benzoxazine derivative 5f as a hit that showed moderate affinity (IC50 = 300 nM). With the aim of improving the in vitro potency, a series of 2-benzoxazinone derivatives have been synthesized and tested for NPY Y5 activity. Most of the compounds were found to be potent and selective NPY Y5 antagonists having nanomolar binding affinities for the NPY Y5 receptor and showing functional antagonism in the forskolin-induced cyclic AMP test. Prelimminary studies in order to understand the structure-activity relationship were undertaken. Selected compounds were further evaluated for in vivo efficacy, affording the lead compound 2-[4-(8-methyl-2-oxo-4H-benzo[d][1,3]oxazin-1-yl)piperidin-1-yl] -N-(9-oxo-9H-fluoren-3-yl)acetamide 5p, which displayed in vivo activity reducing food intake in rodents.
