A Novel Systematic Approach for Selection of Prodrugs Designed to Improve Oral Absorption was written by Shimizu, Mai;Fukami, Tatsuki;Taniguchi, Toshio;Nomura, Yukihiro;Nakajima, Miki. And the article was included in Journal of Pharmaceutical Sciences (Philadelphia, PA, United States) in 2020.COA of Formula: C33H34N6O6 This article mentions the following:
To increase the success rate in development of prodrugs, we sought to establish a systematic in vitro method to appropriately select candidate prodrugs. Physicochem./biopharmaceutical properties of 21 com. available prodrugs (16 with improved membrane permeability of pharmacol. active metabolites and 5 with improved solubility) and their active metabolites were characterized in terms of solubility in artificial intestinal fluids and membrane permeability using Caco-2 cells. Their in vitro metabolic profiles were also evaluated, using human and animal enterocytes, hepatocytes, and sera. Log D values of prodrugs with improved membrane permeability were higher than those of their active metabolites, whereas those of prodrugs with improved aqueous solubility were lower than those of active metabolites. The prodrugs with improved aqueous solubility were highly soluble in artificial intestinal fluids. All prodrugs were efficiently converted to active metabolites with human matrixes, whereas some were not with dog or monkey matrixes. This study demonstrated that physicochem./biopharmaceutical properties could be useful information to facilitate design of prodrugs and for selection of candidate prodrugs. Moreover, the in vitro evaluation of conversion efficiency to active metabolites would be helpful for selecting ideal prodrugs as well as appropriate animals for in vivo PK studies. In the experiment, the researchers used many compounds, for example, 1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5COA of Formula: C33H34N6O6).
1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5) belongs to imidazole derivatives. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Imidazole has become an important synthon in the development of new drugs. Imidazole has been usedin the lysis, wash and elution buffer for the purification of histidine tagged Sonic Hedgehog(shh-N) protein, in elution buffer in stepwise gradient for the purification of histidine tagged aldo keto reductases using nickel affinity chromatography, as a component of homogenization buffer for the purification of phagosomal compartments from dendritic cells.COA of Formula: C33H34N6O6
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem