Glucuronidation of HMR1098 in human microsomes: evidence for the involvement of UGT1A1 in the formation of S-glucuronides.

HMR1098, a novel KATP-blocking agent, is metabolized to form an S-glucuronide in rat and dog bile. Synthesis of the S-glucuronide metabolite was studied in human liver and kidney microsomes. Recombinant UPD-glucuronosyltransferases (UGTs) were screened for activity, and kinetic analysis was performed to identify the isoform or isoforms responsible for the formation of this novel S-glucuronide in humans.

14C-labeled and large-scale synthesis of the angiotensin-(1-7)-receptor agonist AVE 0991 by cross-coupling reactions.

The synthesis of (14)C-labeled AVE 0991 ((14)()C-1a) and large-scale synthesis of AVE 0991 (1a) are described. In the key step of the synthesis, the C-C coupling reaction of the imidazole (2) and thiophene (3) building blocks was studied under Suzuki and Stille reaction conditions, respectively. Suzuki reaction gave only moderate yields, whereas the best results were obtained under Stille reaction conditions with up to 64% yield.