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Development of a Backbone Cyclic Peptide Library as Potential Antiparasitic Therapeutics Using Microwave Irradiation
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Macrocyclic Compounds: Emerging Opportunities for Current Drug Discovery.

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Area of Science:

  • Medicinal Chemistry
  • Drug Discovery
  • Chemical Biology

Background:

  • Macrocycles represent a unique chemical class between small molecules and large biomolecules.
  • They have gained significant attention in drug discovery due to their favorable properties.
  • Recent advancements in synthesis and diversification have accelerated their development.

Purpose of the Study:

  • To highlight the growing importance of macrocycles in drug discovery.
  • To discuss the advantages of macrocycles in targeting challenging biological targets.
  • To review the current status and future prospects of macrocycles in therapeutic development.

Main Methods:

  • Review of recent advancements in macrocyclization synthesis and structure diversification.
  • Analysis of the properties of macrocycles enabling engagement of difficult targets.
  • Examination of clinical trial data for approved and investigational macrocyclic drugs.

Main Results:

  • Macrocycles offer high potency, selectivity, favorable pharmacokinetics, and unique intellectual property (IP) space.
  • Approximately 70 macrocyclic drugs are approved, with over 76 in clinical trials (Phase I-III).
  • Macrocycles can effectively engage previously undruggable targets through distributed binding interactions.

Conclusions:

  • Macrocycles are increasingly vital in drug discovery, offering distinctive opportunities.
  • Continued development in synthetic methodology, screening, and computational studies will further enhance their role.
  • Macrocycles are poised to play a more significant role in future therapeutics.