100397-96-4Relevant articles and documents
NOVEL INHIBITOR COMPOUNDS OF PHOSPHODIESTERASE TYPE 10A
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Paragraph 0334-0335, (2014/06/11)
The present invention relates to compounds of the formula I and their salts etc. which are inhibitors of phosphodiesterase type 10A and to their use for the manufacture of a medicament and which thus are suitable for treating or controlling of medical disorders selected from neurological disorders and psychiatric disorders, for ameliorating the symptoms associated with such disorders and for reducing the risk of such disorders. wherein Y1 and Y2 are adjacent atoms in Het1, which are independently selected from the group consisting of carbon and nitrogen; k is 0, 1, 2 or 3; Het1 is a bivalent monocyclic 5- or 6-membered heteroaromatic radical, having 1, 2 or 3 heteroatoms or heteroatom moieties selected from O, S, N and N—Ra as ring members, or a bivalent fused bicyclic 8-, 9- or 10-membered heteroaromatic radical, having 1, 2, 3 or 4 heteroatoms or heteroatom moieties selected from O, S, N and N—Ra as ring members; Het2 is inter alia monocyclic 5- or 6-membered hetaryl, having 1, 2 or 3 heteroatoms or heteroatom moieties selected from O, S, N and N—R1a as ring members, Cyc is inter alia optionally substituted monocyclic 5- or 6-membered hetaryl or optionally substituted fused 8-, 9- or 10-membered bicyclic hetaryl; Ar is optionally substituted phenylene or optionally substituted bivalent 6-membered hetaryl; R is attached to a carbon atom of Het1 and inter alia-halogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-alkoxy, C1-C6-fluoroalkyl, C1-C6-fluoroalkoxy, C3-C6-cycloalkyl etc.
Synthesis and in vitro biological evaluation of pyrazole group-containing analogues for PDE10A
Li, Junfeng,Jin, Hongjun,Zhou, Haiying,Rothfuss, Justin,Tu, Zhude
, p. 443 - 449 (2013/06/04)
Twenty eight new analogues were synthesized by optimizing the structure of MP-10 and their in vitro binding affinities towards PDE10A, PDE3A/B, and PDE4A/B were determined. Among these new analogues, 10a, 10b, 10d, 11a, 11b and 11d are very potent towards PDE10A and have IC50 values of 0.40 ± 0.02, 0.28 ± 0.06, 1.82 ± 0.25, 0.24 ± 0.05, 0.36 ± 0.03 and 1.78 ± 0.03 nM respectively; these six compounds displayed high selectivity for PDE10A versus PDE3A/3B/4A/4B. The promising compounds will be further validated in vivo to identify PDE10A imaging tracers. The Royal Society of Chemistry.