137695-84-2Relevant academic research and scientific papers
Synthesis of novel 2-phenyl-2H-pyrazolo[4,3-c]isoquinolin-3-ols: Topological comparisons with analogues of 2-phenyl-2,5-dihydropyrazolo[4,3- c]quinolin-3(3H)-ones at benzodiazepine receptors
Allen,Skolnick,Cook
, p. 368 - 374 (2007/10/02)
Based on the topology of pyrazoloquinolinones 10-12, a series of 2-phenyl- 2H-pyrazolo[4,3-c]isoquinolines 6a-d, 7a-d, 8, and 9 have been synthesized and evaluated for their ability to inhibit radioligand binding to benzodiazepine receptors (BzR). Modification of the hydrogen bonding donor and acceptor characteristics of the NH and C=O functionalities of the pyrazoloquinolinones 10-12 resulted in ligands with dramatically reduced affinities (IC50 >> 2 μM) for BzR. The low affinities of 6a-d, 7a-d, 8, and 9 are consistent with the involvement of the NH function present on diverse classes of inverse agonists (β-carbolines, diindoles, and pyrazoloquinolinones) with a hydrogen bond acceptor site (A2) on the binding protein. Moreover, it supports the involvement of the carbonyl function of the pyrazoloquinolinones and the pyridine nitrogen atom of β-carbolines and diindoles with a hydrogen bond donor site (H1). Finally, the results from this work indicate that a simultaneous interaction at both hydrogen bond donor (H1) and acceptor sites (A2) at BzR is required for high affinity binding of inverse agonists.
