Identification of CYP3A4 as the primary cytochrome P450 responsible for the metabolism of tandospirone by human liver microsomes was written by Natsui, Kiyohi;Mizuno, Yoshiko;Tani, Naoko;Yabuki, Masashi;Komuro, Setsuko. And the article was included in European Journal of Drug Metabolism and Pharmacokinetics in 2007.Synthetic Route of C27H37N5O9 This article mentions the following:
The present study was carried out to characterize the human P 450 isoforms involved in the metabolism of tandospirone, an anxiolytic agent known for its superior efficacy and safety. Among 11 yeast-expressed recombinant P 450 isoforms tested, CYP2D6 and CYP3A4 exhibited the highest tandospirone metabolic activity. Although there was no qual. difference between the two isoforms, a quant. difference in metabolite profiling was found i.e., M4 (hydroxylation of the pyrimidine ring) was the major metabolite formed with CYP2D6 while M2 (hydroxylation of the norbornan ring) and 1-PP (oxidative cleavage of the Bu chain) predominated with CYP3A4. The metabolite profile on incubation with CYP3A4 was qual. and quant. similar to that obtained with human liver microsomes. In vitro intrinsic clearance (CLint) values derived from kinetic anal. using both P 450 isoforms were similar (2.2 and 1.6 mL/min/nmol P 450), but the hepatic content of CYP3A4 was found to be more abundant than that of CYP2D6. The in vitro metabolism of tandospirone by human liver microsomes was markedly inhibited by ketoconazole (a CYP3A4 inhibitor) but not by quinidine (a CYP2D6 inhibitor). These results indicate that the metabolism of tandospirone by human liver microsomes primarily involves CYP3A4, and to a lesser extent CYP2D6. In the experiment, the researchers used many compounds, for example, rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate (cas: 112457-95-1Synthetic Route of C27H37N5O9).
rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate (cas: 112457-95-1) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. Synthetic Route of C27H37N5O9
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics