Advances in the chemistry of tetrahydroquinolines.

The carbamate group is a key structural motif in many approved drugs and prodrugs. There is an increasing use of carbamates in medicinal chemistry and many derivatives are specifically designed to make drug–target interactions through their carbamate moiety. In this Perspective, we present properties and stabilities of carbamates, reagents and chemical methodologies for the synthesis of carbamates, and recent applications of carbamates in drug design and medicinal chemistry.

Organic carbamates in drug design and medicinal chemistry.

Alzheimer’s disease (AD) is the most common origin of dementia in the elderly. Although the cause of AD remains unknown, several factors have been identified that appear to play a critical role in the development of this debilitating disorder. In particular, amyloid precursor protein (APP), tau hyperphosphorylation, and the secretase enzymes, have become the focal point of recent research. Over the last two decades, several transgenic and non-transgenic animal models have been developed to elucidate the mechanistic aspects of AD and to validate potential therapeutic targets. Transgenic rodent models over-expressing human β-amyloid precursor protein (β-APP) and mutant forms of tau have become precious tools to study and understand the pathogenesis of AD at the molecular, cellular and behavioural levels, and to test new therapeutic agents. Nevertheless, none of the transgenic models of AD recapitulate fully all of the pathological features of the disease. Octodon degu, a South American rodent has been recently found to spontaneously develop neuropathological signs of AD in old age. This review aims to address the limitations and clinical relevance of transgenic rodent models in AD, and to highlight the potential for O. degu as a natural model for the study of AD neuropathology.

Recent rodent models for Alzheimer’s disease: clinical implications and basic research

Recent Advances in the Identification of γ-Secretase Inhibitors To Clinically Test the Aβ Oligomer Hypothesis of Alzheimer’s Disease

A review of the recent literature is given focusing on synthetic approaches to 1,2,3,4-tetrahydroquinolines, 2,3-dihydro-4(1H)-quinolinones and 4(1H)-quinolinones using domino reactions. These syntheses involve: (1) reduction or oxidation followed by cyclization; (2) SNAr-terminated sequences; (3) acid-catalyzed ring closures or rearrangements; (4) high temperature cyclizations and (5) metal-promoted processes as well as several less thoroughly studied reactions. Each domino method is presented with a brief discussion of mechanism, scope, yields, simplicity and potential utility.

https://www.mdpi.com/1420-3049/19/1/204/pdf

Wei Li

Papers

2,6-Disubstituted N-arylsulfonyl piperidines as γ-secretase inhibitors

Tetrahydroquinoline sulfonamides as γ-secretase inhibitors

Discovery of γ-secretase inhibitors efficacious in a transgenic animal model of Alzheimer’s disease