Acylthioxanthenes: agents which selectively reduce decerebrate rigidity in the cat

Area of Science:

• Medicinal Chemistry
• Neuropharmacology

Background:

• Decerebrate rigidity in cats is a model for studying muscle tone.
• Thioxanthene derivatives have shown potential in modulating neurological pathways.

Purpose of the Study:

• To synthesize and evaluate novel 2-acylthioxanthene-delta 9 (gamma)-propylamine derivatives.
• To identify compounds with potent muscle rigidity-reducing effects and minimal sedative side effects.

Main Methods:

• Synthesis of a series of 2-acylthioxanthene-delta 9 (gamma)-propylamine compounds.
• In vivo evaluation of anti-rigidity effects in decerebrate cats.
• Assessment of sedative properties at effective anti-rigidity doses.
• Isomer separation and characterization using 1H NMR spectroscopy with an europium shift reagent.

Main Results:

• Several compounds demonstrated the ability to reduce intercollicular decerebrate rigidity.
• (Z)-2-propionyl-9-[3-(dimethylamino)propylidene]thioxanthene exhibited the most favorable therapeutic index, showing significant rigidity reduction with minimal sedation.
• 1H NMR spectroscopy effectively differentiated between Z and E isomers.

Conclusions:

• The synthesized thioxanthene derivatives show promise as potential therapeutic agents for conditions involving muscle rigidity.
• (Z)-2-propionyl-9-[3-(dimethylamino)propylidene]thioxanthene is a lead compound warranting further investigation.
• NMR spectroscopy is a valuable tool for isomer characterization in this chemical series.