1,5-Benzodiazepines quantitative structure-activity study

Singh, R, Qjha, T.N., Sharma, R.C. and Tiwari, K.S. (1993). Quantitative Structure-Activity Relationship Study of Benzodiazepine Receptor Ligands. 3. Indian J.Chem., 32B, 555-561. 

Micheli, A., Sperduti, A., Starita, A., and Bianucci, A. M. (2001) Analysis of the internal representations developed by neural networks for structures applied to quantitative structure-activity relationship studies of benzodiazepines. J. Chem. Inf. Comput. Sci. 41,202-218. 

Gupta S, Paleti A (1998) Quantitative structure-activity relationship studies on some nonbenzodiazepine series of compounds acting at the benzodiazepine receptor. Bioorg Med Chem 6 2213-2218... 

Comparative Quantitative Structure-Activity Relationship Studies (QSAR) on Nonbenzodiazepine Compounds Binding to Benzodiazepine Receptor (BzR). 

From the examination of structure-activity relationships, it has been concluded that a phenyl moiety at C-6 as well as a 4-hydroxypiperidine side-chain attached to C-3 of the pyridazine system is essential for anticonvulsant activity in this class of compounds [184], Compounds (54) and (55) have been found to have similar anticonvulsant profiles in animals (mice, rats and baboons) [165, and literature cited therein] and to represent potent broad-spectrum antiepileptic drugs. Their potency with regard to antagonizing seizures (induced by electro-shock or various chemicals) has been compared with standard anticonvulsants like carbamazepine and phenobarbitone [185, 186], A quantitative electroencephalographic analysis of (55) has been published [187]. From in vitro studies it has been concluded that the anticonvulsant activities of these compounds are not mediated by an enhancement of GABAergic transmission or by an interaction with benzodiazepine receptor sites [ 165,186,187], On the other hand, in vivo experiments showed that (54), at anticonvulsant doses, increases the affinity of flunitrazepam for its central receptor site [ 186], Investigations of (54) and (55) in a behavioural test predictive of antianxiety activity revealed a marked difference in the pharmacological profiles of these structurally closely related compounds the dichloro compound SR 41378 (55) has also been found to possess anxiolytic (anticonflict) properties [165],... 

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