H2 antagonists - SAR+QSAR

• What are 61-4112 antagonists associated with?

  SHR and QSAR
• What are lead compounds in drug development?

  • Prototype chemical structure
  • Series of molecules with desired biological activity
• Where can lead compounds be found?

  They can be found in natural receptor ligands, enzyme substrates, existing drugs, and unusual pathways.
• What is the significance of structure-activity relationship (SAR) in lead compound development?

  • Allows observation of how structural variations affect activity
  • Involves synthesis of a range of compounds related to the lead compound
• What is the next step after establishing a lead compound?

  Design a molecule that binds to the receptor but does not activate it.
• What are the strategies for converting agonists to antagonists?

  1. Non-covalent binding to change receptor shape
  2. Membrane analogue binding with subtle structural units
  3. Adding extra hydrophobic groups to block receptor activation
• What happens when extra hydrophobic groups are added to histamine?

  They do not produce any activity.
• What is the effect of adding extra hydrophilic groups to a compound?

  They match to an extra polar binding site.
• What is a breakthrough compound mentioned in the study material?

  Guanidinothiorine
• How does guanidine promote hydrogen bonding compared to histamine?

  It promotes hydrogen bonding but less strongly than the histamine lead.
• What is the result of a weak affinity in the hydrophobic side of a compound?

  It may result in no bond to the binding site and complete antagonism.
• What does binding theory involve?

  • Preparation of binding oxygen
  • Substitutable oxygen becomes polar
  • Agonists are attenuated by antagonists
• How does the charge of N-guanidinium affect its properties?

  It is more pure and potent than other groups.
• What is the goal for the further development of JRK 16, an antagonist?

  • Synthesize more molecules
  • Modulate receptor interactions
  • Obtain pure compounds
• What is one method to enhance the binding of an antagonist?

  Chain extension to push polar groups further out.
• What is the purpose of altering polar groups in drug design?

  To differentiate between agonist and antagonist regions.
• What is the concept of Quantitative Structure Activity Relationship (QSAR)?

  • Identifies and quantifies physicochemical properties of drugs
  • Investigates their effect on biological activity
  • Aims to derive mathematical formulas relating activity to properties
• What are some physicochemical properties investigated in QSAR?

  Hydrophobicity and steric properties.
• How does ranitidine compare to cimetidine?

  Ranitidine has fewer side effects, longer action, and appears more active than cimetidine.
• What is a notable characteristic of ranitidine regarding the CNS?

  It does not inhibit the CNS.