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Phenoxyalkyl cyclic and acyclic amine derivatives: what do they teach us about scaffold-based drug design?

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Abstract

Fragment-based drug design of new bioactive scaffolds is a recent aspect of medicinal chemistry that provides a faster and more efficient road in drug discovery. Phenoxyethyl piperidine and morpholine derivatives have various pharmacological activities, from antitussive to anticancer properties. They are also widely used in selective estrogen receptor modulator (SERM) drugs and can be used to prevent osteoporosis in postmenopausal women. Also, other recent findings suggest that these compounds exhibit high anticholinergic and H3 inverse agonistic activities. We outlined the process of developing novel medications for Alzheimer’s disease, malaria, cancer, and various other illnesses, which could entail modifying or incorporating these structures into a different biologically active framework. Pharmacokinetic assessment and organic pathways for synthesizing these scaffolds are also indicated. This review will discuss the recent pharmaceutical advances of phenoxyethyl cyclic amine derivatives in experimental, investigational, and FDA-approved drugs to draw an apparent viewpoint for future drug research and discovery.

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Abbreviations

FBDD:

Fragment-Based Drug Design

SBDD:

Scaffold-Based Drug Design

SERM:

Selective Estrogen Receptor Modulatory

AF1:

Activation Function Domain I

AF2:

Activating Function Domain II

ER:

Estrogen Receptor

HSP90:

Heat Shock Protein 90

EREs:

Estrogen-Responsive Elements

QSAR:

Quantitative Structure-Activity Relationship

ESR1:

Estrogen Receptor 1

U.S.:

United States

FDA:

Food and Drug Administration

AChE:

Acetylcholinesterase

BChE:

Butyrylcholinesterase

eeAChE:

Electric Eel Acetylcholinesterase

eqBuChE:

Equine Butyrylcholinesterase

MAO:

Monoamine oxidase

CAS:

Catalytic Anionic Site

Erα:

estrogen receptor alpha

GERD:

gastroesophageal reflux disease

UGTs:

UDP-glucuronosyltransferases

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Authors and Affiliations

  1. Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

    Mohammad Mahdi Rezaeifar

  2. Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA

    Ardavan Abiri

  3. Integrated Graduate Program in Physical and Engineering Biology, Yale University, New Haven, CT, 06520, USA

    Ardavan Abiri

  4. Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, P.O. Box 71345-1583, Shiraz, Iran

    Hojjat Rezaiezadeh

  5. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutics Research Center, Kerman University of Medical Sciences, Kerman, Iran

    Marziye Ranjbar Tavakoli & Mohammad Amin Langarizadeh

  6. Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran

    Yaghoub Pourshojaei

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Rezaeifar, M.M., Abiri, A., Rezaiezadeh, H. et al. Phenoxyalkyl cyclic and acyclic amine derivatives: what do they teach us about scaffold-based drug design?. Med Chem Res (2024). https://doi.org/10.1007/s00044-024-03215-1

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