Central nervous system agents

Cyclocondensation of the amine 151 with the ketoester 152 gave 153 that can be selectively alkylated to give 154 which upon benzylation and alkylation gave 155 as central nervous system agent (83EP90516) (Scheme 30). 

Bandarage, U.K., Kuehne, M.E., GUck, S.D. (2001) Chemical Synthesis and Biological Evaluation of 18-Methoxycoronaridine (18-MC) as a Potential Anti-Addictive Agent. Current Medicinal Chemistry Central Nervous System Agents, 1, 113-123. 

Hansch and Leo [13] described the impact of Hpophihdty on pharmacodynamic events in detailed chapters on QSAR studies of proteins and enzymes, of antitumor drugs, of central nervous system agents as well as microbial and pesticide QSAR studies. Furthermore, many reviews document the prime importance of log P as descriptors of absorption, distribution, metabolism, excretion and toxicity (ADMET) properties [5-18]. Increased lipophilicity was shown to correlate with poorer aqueous solubility, increased plasma protein binding, increased storage in tissues, and more rapid metabolism and elimination. Lipophilicity is also a highly important descriptor of blood-brain barrier (BBB) permeability [19, 20]. Last, but not least, lipophilicity plays a dominant role in toxicity prediction [21]. 

Atkinson, F., Cole, S., Green, C., Van de Waterbeemd, H. Lipophilidty and other parameters affecting brain penetration. Curr. Med. Chem. Central Nervous System Agents 2002, 2, 229-240. 

Fowler, C.J. (2004) Curr. Med. Chem. Central Nervous System Agents 4, 161-174. 

Lopez-Rodriguez, M.L., Viso, A., Ortega-Gutierrez, S., Fernandez-Ruiz, J. and Ramos, J.A. (2002) Curr. Med. Chem Central Nervous System Agents 2, 129-141. 

Central nervous system agents (analgesics, anticonvulsants, sedative-hypnotics)... 

Prokai L, Zharikova A, Janaky T, Li X, Braddy AC, et al. 2001. Integration of mass spectrometry into early-phase discovery and development of central nervous system agents. J Mass Spectrom 36 1211. 

CENTRAL NERVOUS SYSTEM AGENTS Antianxiety Agents... 

E. Rucker (1987). Structure, function and assembly of membrane proteins. Science 235 959-961. G. Schneider, W. Neidhart, G. Adam (2001). Integrating virtual screening methods to the quest for novel membrane protein ligands. Current Medicinal Chemistry Central Nervous System Agents 1 99-112. 

A large number of compounds in which thiophene was fused to other heterocyclic rings have been investigated, notably in the central nervous system agents. For example, the benzodiazepine derivative (365) is reported to be more active than Clozapine in conditioned avoidance response tests in the rat (80JMC878). The activity of such fused-ring thiophenes has been reviewed (81JHC1277). 

Mertsch, K., and J. Maas. 2002. Blood-brain barrier penetration and drug development from an industrial point of view. Curr Med Chem—Central Nervous System Agents 2 187. 

Central nervous system agents Dizziness, drowsiness, headache, hallucination, neuroleptic malignant syndrome, serotonin syndrome... 

Special warnings, precautions or use limitations cited in the product monograph should be included in the body copy. Examples include abuse potential for narcotics or central nervous system agents, or specific directions for use in special patient groups such as elderly people, children, pregnant women, nursing mothers, women of childbearing age. 

Hansch, C., Bjorkroth, J. P, and Leo, A. Hydrophobicity and central nervous system agents On the principle of minimal hydrophobicity in drug design. J. Pharm. Sci. 76 683-686,1987. 

Steiner, G., Franke, A., Hadicke, E., Lenke, D., Teschendorf, H.-J., Hofmann, H.P., Kreiskott, H., and Worstmann, W., Tricyclic epines. Novel ( )- and (Z)-ll//-dibenz[h,e]azepines as potential central nervous system agents. Variation of the basic side chain, 7. Med. Chem., 29, 1877, 1986. 

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