Design and synthesis of novel isoquinoline monoamineoxidase inhibitors
Citation:Mary T. Breen, 'Design and synthesis of novel isoquinoline monoamineoxidase inhibitors', [thesis], Trinity College (Dublin, Ireland). School of Pharmacy & Pharmaceutical Sciences, 2003, pp 371
Breen TCD THESIS 7325 Design and.pdf (PDF) 203.2Mb
The work described in this thesis consists of the synthesis and biological evaluation of a series of reduced isoquinoline derivatives. MAO is an enzyme involved in the metabolic degradation of catecholamine neurotransmitters. Human MAO exists as two isozymes - MAO-A and MAO-B. Selective MAO-A and MAO-B inhibitors are used in the treatment of depression and Parkinson’s disease respectively. Naturally occurring salsolinol and related isoquinoline alkaloids have been shown to be inhibitors of MAO. Isoquinolines are discussed with regard to their natural occurrence and pharmacological activities, particularly in the context of MAO inhibition. Certain isoquinoline derivatives have shown potential as combined MAO-B/COMT inhibitors. COMT inhibitors may be used in combination with selective MAO-B inhibitors in the treatment of Parkinson’s disease. Acetylcholinesterase inhibitors are used in the treatment of Alzheimer’s disease. There are suggestions that MAO-B inhibitors may also be useful in the treatment of this disease. Isoquinoline derivatives which inhibit MAO-B have not yet been examined for AChE inhibitory activity but are worthy of further exploration. Chapter 2 discusses the synthesis of simple 3,4-dihydro- and 1,2,3,4-tetrahydroisoquinoiines by a number of established methods. l-Methyl-3,4-dihydroisoquinoline and 6,7-dimethoxy-l-alkyl- dihydroisoquinolines were prepared by a number of these routes, along with substituted nitro and amino derivatives. Several of these compounds were reduced to their corresponding 1,2,3,4- tetrahydroisoquinolines.
Author: Breen, Mary T.
Advisor:Meegan, Mary Jane
Publisher:Trinity College (Dublin, Ireland). School of Pharmacy & Pharmaceutical Sciences
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Type of material:thesis
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