Benzazepines, tetrahydro-benzazepines and aryl-substituted-tetrahydro-benzazepines are important heterocyclic rings present in many pharmaceutical drugs and natural products.1 Structurally, tetrahydro-benzazepines (THB) 1,2,3 possess a 7-membered aza-hetero cyclic ring fused with the aromatic ring. Due to the independent properties of substituted THB, this class of compounds have been extensively investigated towards many biological activities. Tetrahydro-1-benzazepines, represented by (benazepril 4) is a commercially used antihypertensive drug.2a,b The natural product galantamine 5, with tetrahydro-2-benzazepine as a core structure is found to be an excellent drug in treatment for mild to moderate Alzheimer’s disease.3 Tetrahydro-3-benzazepines, represented by compound 6 is a novel anti-obesity drug approved by USFDA in 2012, with commercial name as lorcaserin 6. 4a,b The structural modification on the THB ring through substituents have enabled emergence of another class of compounds, 1-aryl-tetrahydro-3-benzazepines represented by 7 and 8. The former displays selective dopamine D1 receptor antagonist activity,5 whereas the later, known as Fenoldopam has emerged as an oral anti- hypertensive drug.6a,b Screening of aryl-substituted THB for the dopaminergic activities (central nervous system receptors D1 and D2 type receptors) have showing the promising activity and revealed importance of structural variation.7a,b The modifications on the THB and aryl-substituted THB’s and their biological importance will be discussed.







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