113713-24-9Relevant articles and documents
Regioselective hydroxylation pathway of tenatoprazole to produce human metabolites by Bacillus megaterium CYP102A1
Le, Thien-Kim,Cha, Gun-Su,Jang, Hyun-Hee,Nguyen, Thi Huong Ha,Doan, Tiep Thi My,Lee, Young Ju,Park, Ki Deok,Shin, Yumi,Kim, Dong-Hyun,Yun, Chul-Ho
, p. 95 - 104 (2019)
Tenatoprazole, a proton pump inhibitor drug candidate, is developed as an acid inhibitor to treat gastric acid hypersecretion disorders, such as gastric ulcer and reflux esophagitis. Tenatoprazole is known to be metabolized to three major metabolites—tenatoprazole sulfone, 5’-hydroxylated metabolite, and tenatoprazole sulfide—in human livers mainly by CYP2C19 and CYP3A4. In this study, an enzymatic strategy for the production of human metabolites of tenatoprazole was developed using bacterial P450 enzymes. A set of CYP102A1 mutants catalyzed the regioselective hydroxylation reactions of tenatoprazole. The major product of tenatoprazole by CYP102A1 is 5’-OH tenatoprazole, a major human metabolite produced by human CYP2C19 and CYP3A4. As another major metabolite of tenatoprazole, tenatoprazole sulfide is formed via a non-enzymatic conversion without a P450 system. In addition, 5’-OH tenatoprazole sulfide was found as a minor metabolite, which can be formed via a 5’-hydroxylation reaction of tenatoprazole sulfide by CYP102A1 and/or a non-enzymatic reduction of 5’-OH tenatoprazole to a sulfide form. Chemical synthesis of the 5’-OH tenatoprazole is not currently possible. In conclusion, an enzymatic synthesis of 5’-OH tenatoprazole, a major human metabolite of tenatoprazole, was developed by using mutants of CYP102A1 from Bacillus megaterium as a biocatalyst and tenatoprazole as a substrate.
An improved synthesis of antiulcerative drug: Tenatoprazole
Sripathi, Somaiah,Bojja, Ramachandra Reddy,Karnati, Venugopal Reddy,Prasada Raju,Khunt, Mayur D.
experimental part, p. 804 - 806 (2010/04/22)
An efficient, cost-effective and multikilogram-scale process for the synthesis of tenatoprazole 1, an antiulcerative drug, is described. The key steps in this synthesis involve the coupling of 2-mercapto-5-methoxyimidazo[4,5- b]pyridine 2 with 2-chloromethyl-4-methoxy-3,5-dimethyl pyridine hydrochloride 3 to yield 4 and its subsequent oxidation with m-CPBA to produce sulfoxide 1. The process has been scaled up for the multikilogram-scale of compound 1 with an overall yield of 72%. The new process requires no purification process and affords the target compound 1 with 99.8% purity by HPLC.
Synthesis and characterization of metabolites and potential impurities of the antiulcerative drug tenatoprazole
Reddy, Ganta Madhusudhan,Prasada Raju,Babu, J. Moses,Praveen,Khunt, Mayur,Mukkanti,Pratap Reddy, Padi
, p. 1725 - 1736 (2008/09/20)
Tenatoprazole (Ulsacare) is a recently developed antiulcerative drug used for the treatment of both erosive and nonerosive gastroesophageal reflux disease. During the bulk synthesis of tenatoprazole, we have observed four impurities (tenatoprazole N-oxide, tenatoprazole sulfone N-oxide, N-methyl tenatoprazole, and desmethoxy tenatoprazole) and two metabolites (tenatoprazole sulfide and tenatoprazole sulfone). The present work describes the synthesis and characterization of these impurities. Copyright Taylor & Francis Group, LLC.