Hit-to-lead optimization of pyrrolo[1,2-a]quinoxalines as novel cannabinoid type 1 receptor antagonists

György Szabó; Róbert Kiss; Dóra Páyer-Lengyel; Krisztina Vukics; Judit Szikra; Andrea Baki; László Molnár; János Fischer; György M Keseru

doi:10.1016/j.bmcl.2009.05.010

Hit-to-lead optimization of pyrrolo[1,2-a]quinoxalines as novel cannabinoid type 1 receptor antagonists

Bioorg Med Chem Lett. 2009 Jul 1;19(13):3471-5. doi: 10.1016/j.bmcl.2009.05.010. Epub 2009 May 7.

Authors

György Szabó¹, Róbert Kiss, Dóra Páyer-Lengyel, Krisztina Vukics, Judit Szikra, Andrea Baki, László Molnár, János Fischer, György M Keseru

Affiliation

¹ Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary. [email protected]

PMID: 19457667
DOI: 10.1016/j.bmcl.2009.05.010

Abstract

Hit-to-lead optimization of a novel series of N-alkyl-N-[2-oxo-2-(4-aryl-4H-pyrrolo[1,2-a]quinoxaline-5-yl)-ethyl]-carboxylic acid amides, derived from a high throughput screening (HTS) hit, are described. Subsequent optimization led to identification of in vitro potent cannabinoid 1 receptor (CB1R) antagonists representing a new class of compounds in this area.

MeSH terms

Animals
Binding Sites
Computer Simulation
Piperidines / chemistry
Pyrazoles / chemistry
Quinoxalines / chemical synthesis
Quinoxalines / chemistry*
Quinoxalines / pharmacology
Rats
Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
Receptor, Cannabinoid, CB1 / metabolism
Rimonabant
Structure-Activity Relationship

Substances

Piperidines
Pyrazoles
Quinoxalines
Receptor, Cannabinoid, CB1
Rimonabant