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Updated: Jul 25, 2026
11:51
Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Tetrahydroisoquinolines as MCH-R1 antagonists
T K Sasikumar1, L Qiang, W-L Wu
1Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. thavalakulamgar.sasikumar@spcorp.com
Bioorganic & Medicinal Chemistry Letters
|July 11, 2006
Summary
Researchers developed potent inhibitors for the human melanin-concentrating hormone receptor 1 (h-MCH-R1). Tetrahydroisoquinoline compounds demonstrated improved pharmacokinetics and excellent rat pharmacokinetic profiles for compounds 12d and 12g.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Drug Discovery
Background:
- The human melanin-concentrating hormone receptor 1 (h-MCH-R1) is a target for treating metabolic and psychiatric disorders.
- Previous inhibitors based on piperidine glycineamide scaffolds showed promise but required optimization.
Purpose of the Study:
- To develop novel, potent, and selective inhibitors of h-MCH-R1.
- To explore structure-activity relationships and improve pharmacokinetic properties.
Main Methods:
- Synthesis of novel tetrahydroisoquinoline derivatives.
- In vitro evaluation of receptor binding and functional activity.
- In vivo pharmacokinetic studies in rats.
Main Results:
- A series of potent and selective h-MCH-R1 inhibitors were successfully synthesized.
- Structurally rigidified tetrahydroisoquinolines (III and IV) exhibited enhanced pharmacokinetic profiles compared to earlier compounds.
- Compounds 12d and 12g demonstrated excellent pharmacokinetic parameters in rat models.
Conclusions:
- Tetrahydroisoquinoline-based compounds represent a promising scaffold for developing h-MCH-R1 inhibitors.
- Optimized structures show potential for further development as therapeutic agents targeting h-MCH-R1 related conditions.
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