Kishor Amratral Desai

Synthesis, sar and pharmacology of CP-293,019 : A potent, selective dopamine D4 receptor antagonist

A series of novel, potent and selective pyrido[1,2-a]pyrazine dopamine D4 receptor antagonists are reported including CP-293,019 (D4 Ki = 3.4 nM, D2 Ki > 3,310 nM), which also inhibits apomorphine-induced hyperlocomotion in rats after oral dosing.

5-cyano-1-[3-(N-methylpyrrolidin-2R-ylmethyl)indol-5-yl] benzimidazole (CP-161,242): A potent, centrally active 5-HT1D receptor agonist and benzodiazepine partial agonist

Abstract The discovery of CP-161,242 (5-cyano-1-[3-(N-methylpyrrolidin-2R-ylmethyl)indol-5-yl]benzimidazole), a potent, selective, orally active central serotonin (5-HT1D) agonist [IC50 (binding) = 1.3 nM, EC50 (inhibition of adenylate cyclase) = 42 pM] and benzodiazepine ligand [IC50 (binding) = 3.3 nM], is presented.

THE DISCOVERY OF A NOVEL AND POTENT BENZODIAZEPINE RECEPTOR PHARMACOPHORE

Abstract 1-(Indol-5-yl)pyrido[2,3-b]imidazoles and 1-(indol-5-yl)benzimidazoles (1) have been found to be unique, novel templates for potent benzodiazepine receptor affinity. The “molecular switch” for this activity lies in the imidazole N3 atom: replacement of this nitrogen for carbon [i.e., as in 5-(indol-1-yl)indoles (2)] affords compounds devoid of affinity for the benzodiazepine receptor (Figure 1).