Franz Esser

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.

Cyclic guanidines. Part 2. Rearrangement of N-substituted 2-arylamino-4,5,6,7-tetrahydro-1H-1,3-diazepines. X-Ray molecular structure of 1-(2,6-dichlorophenyl)-2-(2-methylallylimino)hexahydro-1,3-diazepine

1,3-Aryl migrations of title compounds (2) are shown to be triggered by base catalysis under mild conditions. Alternative rearrangement conditions, limiting factors, as well as the occurrence of byproducts, and competing products are investigated. A crossover experiment reveals the purely intramolecular nature of the Chapman-type rearrangement. The structure of the rearrangement product 1-(2,6-dichlorophenyl)-2-(2-methylallylimino)hexahydro-1,3-diazepine (3a) is confirmed by X-ray analysis. An explanation for the directionality of the reaction is furnished by an MNDO calculation on the reaction enthalpy.

Cyclic guanidines. Part 6.1 Synthesis of benzimidazoles by intramolecular vicarious nucleophilic substitution of hydrogen

m-Nitrophenylguanidines, which carry a vicarious leaving group, cyclize under basic conditions yielding nitrobenzimidazoles. Preliminary observations of the regioselectivity of the ring closure reaction are reported.