Novel pyrazolo[5,1-f][1,6]naphthyridines, pyrazolo[5,1-a][2,6]naphthyridines, pyrazolo[5,1-a][2,7]naph- thyridines and pyrazolo[5,1-a]isoquinolines phenylimidazole/benzimidazole ethylene-linked were designed and synthesized for PDE10A interaction. An AgOTf and proline-cocatalyzed multicomponent methodology based on use of o-alkynylaldehydes, tosylhydrazide and ketones was developed and proved to be a convenient route for assembly of most of the novel tricyclic pyrazoles synthesized. Pyrazolo[5,1-f] [1,6]naphthyridine 43 and 59, pyrazolo[5,1-a][2,6]naphthyridine 66, and pyrazolo[5,1-a][2,7]naphthyr- idine 42 showed the highest affinity for PDE10A enzyme (IC50 1⁄4 40, 42, 40, 55 nM, respectively).
Synthesis and SAR study of novel tricyclic pyrazoles as potent phosphodiesterase 10A inhibitors / Dore, A; Asproni, Battistina; Scampuddu, A; Pinna, Gerard Aime; Christoffersen, C. T.; Laggard, M; Keller, J.. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 84:(2014), pp. 181-193. [10.1016/j.ejmech.2014.07.020]
Synthesis and SAR study of novel tricyclic pyrazoles as potent phosphodiesterase 10A inhibitors
ASPRONI, Battistina;PINNA, Gerard Aime;
2014-01-01
Abstract
Novel pyrazolo[5,1-f][1,6]naphthyridines, pyrazolo[5,1-a][2,6]naphthyridines, pyrazolo[5,1-a][2,7]naph- thyridines and pyrazolo[5,1-a]isoquinolines phenylimidazole/benzimidazole ethylene-linked were designed and synthesized for PDE10A interaction. An AgOTf and proline-cocatalyzed multicomponent methodology based on use of o-alkynylaldehydes, tosylhydrazide and ketones was developed and proved to be a convenient route for assembly of most of the novel tricyclic pyrazoles synthesized. Pyrazolo[5,1-f] [1,6]naphthyridine 43 and 59, pyrazolo[5,1-a][2,6]naphthyridine 66, and pyrazolo[5,1-a][2,7]naphthyr- idine 42 showed the highest affinity for PDE10A enzyme (IC50 1⁄4 40, 42, 40, 55 nM, respectively).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
