Mode of insertion of miconazole, ketoconazole and deacylated ketoconazole in lipid layers. A conformational analysis was written by Brasseur, R.;Vandenbosch, C.;Van den Bossche, H.;Ruysschaert, J. M.. And the article was included in Biochemical Pharmacology in 1983.SDS of cas: 67914-61-8 This article mentions the following:
The conformation of three imidazole derivatives, miconazole, ketoconazole and deacylated ketoconazole (R 39519) inserted in a lipid layer was calculated using a procedure of conformational anal. For each imidazole derivative all probable conformers were inserted into a dipalmitoyl phosphatidylcholine (DPPC) monolayer. Miconazole maintains its two dichlorophenyl groups in the hydrophobic phase whereas the imidazole moiety is orientated in the hydrophilic phase. Ketoconazole orientates in dichlorophenyl group in the hydrophobic phase whereas its acylated piperazine moiety is oriented towards the hydrophobic region. Deacylation inverses completely the orientation of the compound The most probable conformer of R 39519 is inserted in the lipid layer with its piperazine moiety orientated towards the aqueous phase. The inversion increases the area occupied per drug mol. from 30 Å2 for ketoconazole to 90 Å2 for R39519 equal to the mean area occupied per miconazole mol. and higher than that occupied per DPPC mol. (60 Å2). Such a conformation should result in a destabilizing effect of microconazole and R 39519; this was proved using differential scanning calorimetry. In the experiment, the researchers used many compounds, for example, rel-1-(4-(((2R,4S)-2-((1H-Imidazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazine (cas: 67914-61-8SDS of cas: 67914-61-8).
rel-1-(4-(((2R,4S)-2-((1H-Imidazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazine (cas: 67914-61-8) belongs to piperazine derivatives. The piperazine scaffold is often found in biologically active compounds in different therapeutic areas. These therapeutic areas include antifungals, antidepressants, antivirals, and serotonin receptor (5-HT) antagonists/agonists. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.SDS of cas: 67914-61-8
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics