Conformational investigation of alpha,beta-dehydropeptides. X. Molecular and crystal structure of Ac-DeltaAla-NMe2 compared with those of Ac-L-Ala-NMe2, Ac-DL-Ala-NMe2 and other dimethylamides.

A series of three homologous dimethyldiamides Ac-DeltaAla-NMe2, Ac-L-Ala-NMe2 and Ac-DL-Ala-NMe2 has been synthesized and the structures of these amides determined from single-crystal X-ray diffraction data. To learn more about the conformational preferences of compounds studied, the fully relaxed (phi-psi) conformational energy maps in vacuo (AM1) of Ac-DeltaAla-NMe2 and Ac-L-Ala-NMe2 were obtained, and the calculated minima reoptimized with the DFT/B3LYP/6-31G** method. The crystal-state results have been compared with the literature data. Ac-DeltaAla-NMe2 and other alpha,beta-dehydroamino acid dimethyldiamides, Ac-DeltaXaa-NMe2 adopt the conservative conformation of the torsion angles phi, psi = approximately -45 degrees, approximately 130 degrees, which are located in the high-energy region (region H) of Ramachandran diagram. Ac-L-Ala-NMe2 and Ac-DL-Ala-NMe2, as well as other saturated amino acid dimethylamides Ac-L/DL-Xaa-NMe2, present common peptide structures, and no conformational preferences are observed. Molecular packing of the amides analysed reveals two general hydrogen-bonded motifs. Dehydro and DL-species are paired into centrosymmetric dimers, and L-compounds form catemers. However, Ac-DeltaAla-NMe2 and Ac-DL-Ala-NMe2 constitute exceptions: their molecules also link into catemers.

Synthesis and pharmacological activity of new carbonyl derivatives of 1-aryl-2-iminoimidazolidine. Part 1. Synthesis and pharmacological activity of chain derivatives of 1-aryl-2-iminoimidazolidine containing urea moiety.

The synthesis and physicochemical properties of new carbonyl derivatives of 1-aryl-2-iminoimidazolidine are presented. Isomeric 1-(1-arylimidazolidine-2-ylidene)-3-arylureas (series A) and 1-aryl-2-imine-3-arylaminocarbonylimidazolidines (series B) were obtained after the condensation reaction of 1-aryl-2-iminoimidazolidines and arylisocyanates. 1-Aryl-2-iminoimidazolidines were synthesised in a two-step reaction from the respective anilines. The molecular structure of 1-(1-phenylimidazolidine-2-ylidene)-3-(4-chlorophenyl)urea (A2) has been determined by X-ray crystallography. The representatives of both investigated series were evaluated in behavioural animal tests. They exhibited significant, especially analgesic, activity on the animal central nervous system (CNS). They displayed substantial effect on the serotonine and catecholamine neurotransmission as well, at very low toxicity (LD(50) over 2000 mg kg(-1) i.p.). In the binding affinity tests they exhibited moderate affinity (on the micromolar level) toward opioid (mu) and serotonine (5HT(2)) receptors. The derivatives of series A had moderate affinity toward benzodiazepine (BZD) receptor as well. Distinctive differences observed in their activity spectra can be connected with the presence of particular structural features such as relative orientation of the two aromatic rings and the carbonyl moiety.

Conformational properties of N',N'-dimethylamides of N-acetyldehydroalanine and N-acetyl-(Z)-dehydrophenylalanine.

Conformational preferences of Ac-deltaAla-NMe2 and Ac-(Z)-deltaPhe-NMe2 were studied and compared with those of their monomethyl counterparts as well as with those of their saturated analogues. X-Ray data and energy calculations revealed a highly conservative conformation of the dehydro dimethylamides, which is located in a high-energy region of the Ramachandran map.