RESUMO
As part of an anti-psychotic drug discovery program, we report the crystal structure of the title compound, C(24)H(23)ClN(4)O. The mol-ecule has a tricyclic framework with a characteristic buckled V-shaped pyridobenzoxazepine unit, with the central seven-membered heterocycle in a boat configuration. The piperazine ring displays a chair conformation with the 2-phenyl-ethyl substituent assuming an equatorial orientation. There are two crystallographically independent, but virtually identical, mol-ecules in the asymmetric unit.
RESUMO
Since ancient times the operation of the brain has elicited more than usual interest. Data mining of the human genome is revealing that many CNS abnormalities have a genetic component. As yet this information can not be used directly to cure or ameliorate specific CNS disorders although this is regarded as having great potential for future therapies. Current CNS drug design and 3D QSAR is based on knowing either the structures of key proteins and how smaller molecules interact with them to obtain a pharmacological response, or on hypothesising about key structural features and interactions by a variety of molecular modelling and computational techniques. Methods used include conformational analyses, pharmacophore development and QSAR which are now being actively applied to increase our understanding of how molecules interact with specific sites within the CNS as a basis for the design of new pharmacologically active compounds. In this review we give an overview of the latest strategies used in 3D-QSAR based drug design and survey the most recent applications of these strategies to the CNS. By way of example, accounts are given of computer-based research aimed at drugs targeting GABA, glutamate, dopamine and opioid receptors.
