Horst Dollinger

BIIE0246: A selective and high affinity neuropeptide Y Y2 receptor antagonist

The in vitro biological characterisation of the first potent and selective non-peptide neuropeptide Y Y(2) receptor antagonist, (S)-N(2)-[[1-[2-[4-[(R,S)-5,11-dihydro-6(6h)-oxodibenz[b, e]azepin-11-yl]-1-piperazinyl]-2-oxoethyl] cylopentyl] acetyl]-N-[2-[1,2-dihydro-3,5(4H)-dioxo-1,2-diphenyl-3H-1,2, 4-triazol-4-yl]ethyl]-argininamid (BIIE0246) is reported. BIIE0246 displaced [125I]neuropeptide Y with high affinity (IC(50)=3.3 nM) from the human neuropeptide Y Y(2) receptor and proved to be highly selective. BIIE0246 displayed antagonistic properties and thus represents the first selective non-peptide neuropeptide Y Y(2) receptor antagonist.

Synthesis of 5-Thioxo-hexahydrobenzo[b]thiopheno[2,3-d]-1,2,4-triazolo[1,5-c]pyrimidines and Related Compounds Based on Cyclocondensations of 2-Isothiocyanato-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene

5-Thioxo-4,6,8,9,10,11-hexahydro-benzo[b]thiopheno[2,3-d]-1,2,4-triazolo[1,5-c]pyrimidines and related compounds were prepared based on cyclizations of 2-isothiocyanato-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene with aminoketones and carboxylic hydrazides.

Rodent selectivity of piperidine-4-yl-1H-indoles, a series of CC chemokine receptor-3 (CCR3) antagonists: insights from a receptor model.

Rodent selectivity data of piperidine-4-yl-1H-indoles, a series of CC chemokine receptor-3 (CCR3) antagonists, are presented and discussed as part of an overall optimization effort within this lead compound class. Although attachment of an acidic moiety to the 1-position of the indole led to an overall balanced in vitro profile, in particular reducing inhibition of the hERG channel, potency on the rat and mouse receptor worsened. These findings could be rationalized in the context of a CCR3 homology model.