269717-68-2Relevant academic research and scientific papers
Synthesis of 6,8-diazabicyclo[3.2.2]nonanes: Conformationally restricted piperazine derivatives
Weigl, Manuela,Wuensch, Bernhard
, p. 1177 - 1179 (2000)
(equation presented) Starting with the proteinogenic amino acid (S)-glutamate, a general method for the synthesis of 3-(piperazin-2-yl)propionic acid esters 7 with various substituents at N-4 of the piperazine ring system is presented. An intramolecular ester condensation of 7 is the key step in the formation of the 6,8-diazabicyclo[3.2.2]nonane derivatives 8-10, which are of interest as conformationally restricted piperazines.
Synthesis of bridged piperazines with σ receptor affinity
Weigl, Manuela,Wuensch, Bernhard
, p. 1247 - 1262 (2008/09/16)
Bridged piperazines 4 were designed as conformationally restricted piperazine σ receptor ligands. The chiral pool synthesis started from (S)-glutamate, which was transformed in five reaction steps into the piperazinediones 5 bearing a propionic acid ester side chain. A two-step Dieckmann analogous cyclization provided the bicyclic ketones 7 as key intermediates. The alcohols 8 were prepared by LiAlH4 reduction of the ketones 7. NaBH4 reduction, Williamson ether synthesis and LiAlH4 reduction led to the methyl and benzyl ethers 12 and 13. High σ1 affinity is attained when one large substituent is introduced either at N-8 or O-2. The most potent σ1 ligand in this series of compounds is the methyl ether 12b with the N-butyl substituent (Ki = 13.2 nM, selectivity σ2:σ1 = 16). Moreover, the N-methyl derivatives 13a (σ2: Ki = 30.4 nM) and 12a (σ2 preference) represent promising starting points for the development of potent and selective σ2 ligands.
Conformationally constrained ethylenediamines: Synthesis and receptor binding of 6,8-diazabicyclo[3.2.2]nonanes
Weigl, Manuela,Beduerftig, Stephan,Maier, Christoph A.,Wuensch, Bernhard
, p. 2245 - 2257 (2007/10/03)
The synthesis and receptor affinity of 6,8-diazabicyclo[3.2.2]nonanes representing conformationally constrained ethylenediamines are described. The Dieckmann analogous cyclization of the (piperazin-2-yl)propionate 9 provided the bicyclononane 10 only, when the first cyclization product was trapped with chlorotrimethylsilane. 10 was stereoselectively transformed into the bicyclic amines 19a,b and amides 22a,b, which were investigated in competition experiments with radioligands for their σ1-, σ2-, κ-, and μ-receptor affinities. The (2R)-configured dimethylamine 19a showed promising σ1-receptor affinity (Ki=23.8 nM) and selectivity, whereas the (2S)-configured (dichlorophenyl)acetamide 22b displayed a σ-receptor binding profile (σ1: Ki=184 nM; σ2: Ki=263 nM) very similar to the binding profile of the atypical antipsychotic BMY-14802 (26).
