| 19559623 |
Zhang J, Zhang H, Cai W, Yu L, Zhen X, Zhang A: 'Click' D (1) receptor agonists with a 5-HT (1A) receptor pharmacophore producing D (2) receptor activity. Bioorg Med Chem. 2009 Jul 15;17(14):4873-80. Epub 2009 Jun 16.
A series of new 1-aryl-3-benzazepine derivatives containing an arylpiperazinyl function as the N3 substituent were synthesized by combining a D (1) receptor agonistic pharmacophore and a 5-HT (1A) receptor pharmacophore through Click reaction. Interestingly, these compounds generally do not have good binding affinity at the D (1) receptor, but most compounds are potent at both D (2) and 5-HT (1A) receptors. Compound 8h, containing 1-m-tolyl-benzazepine scaffold and 2-methoxyphenylpiperazine core, displayed good affinity at all tested receptors, with K (i) values of 144, 80, and 133nM, for the D (1), D (2), and 5-HT (1A) receptors, respectively. Compound 13 with the triazole moiety formed differently from that in 8h showed the highest affinity at the D (2) receptor with K (i) value of 19nM. This compound also showed moderate affinity at the 5-HT (1A) (K (i), 105nM), and D (1) (K (i), 551nM) receptors. Functional assays indicated that both compounds 13 and 8h are antagonists at D (1) and D (2) receptors, whereas full agonistic activity at the 5-HT (1A) receptor was observed. In agreement with the binding affinity, compound 13 is a high efficacy D (2) antagonist and 5-HT (1A) agonist. |
6(0,0,0,6) |