Recent advances in bioisosteric modifications for targeting Alzheimer's disease pathways

The drug development process is highly challenging due to high cost, ethical consideration and takes a long time to reach in to the market for the ultimate benefit of the patients. Considering the global health issues, brain disorders such as Parkinsons disease (PD) and Alzheimer's disease (AD) are major concerns and are difficult to treat because of the complex nature of the disease. The complexity of these diseases, poor efficacy of the current drugs, and their low ability to cross blood brain barrier (BBB) limits the overall biological effectiveness of the treatment. These challenges must be addressed urgently to reduce the burden of these diseases and to improve the quality and expectancy of life. In a drug molecule its molecular properties are the key attributes in determining selectivity, stability, pharmacokinetics and BBB permeability. Any unfavorable changes in these molecular properties may compromise, whereas favorable modification can enhance the overall biological effectiveness of the drug molecule. Bioisosterism is a powerful chemical tool that offers replacement of undesired functional group on the drug molecule with more suitable group resulting in improved pharmacokinetics, minimizing side effects and toxicity, and could tailored it to complex environments such as brain. In this review we present recent bioisosteric replacement approaches which have been employed to optimize the existing molecular properties of the compound to improve their biological effectiveness particularly focusing on AD.