1029805-88-6Relevant articles and documents
From a novel HTS hit to potent, selective, and orally bioavailable KDM5 inhibitors
, p. 2974 - 2981 (2017)
A high-throughput screening (HTS) of the Genentech/Roche library identified a novel, uncharged scaffold as a KDM5A inhibitor. Lacking insight into the binding mode, initial attempts to improve inhibitor potency failed to improve potency, and synthesis of
2-(Aryloxy)ethylamine derivatives: Ring opened congeners of long chain 1-arylpiperazines with high 5-HT(1A) receptor affinity and selectivity versus D2 and α1 receptors
Perrone, Roberto,Berardi, Francesco,Colabufo, Nicola A.,Leopoldo, Marcello,Tortorella, Vincenzo
, p. 340 - 353 (2007/10/03)
1-Aryl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1- yl)propyl]piperazine derivatives, previously reported as 5-HT(1A)/D2 ligands, were modified by opening the piperazine ring. Twenty-two ring opened congeners were prepared and their affinity for serotonin 5-HT(1A), dopamine D2, and α1-adrenergic receptors was measured in vitro. Among the herein reported compounds, the 2(aryloxy)ethylamine derivatives 38-40, 43 and 44 displayed 5-HT(1A) receptor affinity in the nanomolar range. In particular, compound 44 was found to be a potent and selective 5-HT(1A) ligand (K(i)= 0.71 nM), completely devoid of D2 and α1 receptor binding affinity. Our data indicate that removal of the ethylene chain of the piperazine ring, together with an isosteric substitution, can lead to ligand with high 5- HT(1A) receptor affinity and selectivity. Furthermore, compounds 40 and 44 were submitted to the [35S]GTPγS binding assay for a preliminary evaluation of their intrinsic activity on the 5-HT(1A) receptor.
