Synthesis of 3-hydroxy desloratadine, the hydroxyl metabolite of loratadine
نویسندگان
چکیده
The structure of a major active metabolite of the nonsedating antihistamine loratadine was confirmed by synthesis. The metabolite 3 was prepared from 3-methyl pyridine in twelve steps.
منابع مشابه
The Importance of Full and Correct Prediction of Human Metabolites in Discovery and Preclinical Development
The clinical development history of the non-sedating antihistamine desloratadine (Clarinex®) exemplifes the regulatory challenges that can arise when the lack of metabolically adequate in vitro tools causes an important human metabolite (in this case, 3-hydroxy-desloratadine) to be missed early in pre-clinical development. Recent in vitro studies of the metabolism of desloratadine, performed on...
متن کاملLoratadine is an antihistaminergic drug with a tricyclic structure and a selective peripheral H-1-receptor activity [1]. Desloratadine is its primary active metabolite and is a non-sedating, long-acting histamine antagonist. After oral administration, desloratadine selectively blocks peripheral histamine H1-receptors
Loratadine is an antihistaminergic drug with a tricyclic structure and a selective peripheral H-1-receptor activity [1]. Desloratadine is its primary active metabolite and is a non-sedating, long-acting histamine antagonist. After oral administration, desloratadine selectively blocks peripheral histamine H1-receptors because the substance is excluded from entry to the central nervous system [2]...
متن کاملIn vitro characterization of the inhibition profile of loratadine, desloratadine, and 3-OH-desloratadine for five human cytochrome P-450 enzymes.
The purpose of this study was to evaluate loratadine, desloratadine, and 3-OH-desloratadine as inhibitors of certain human liver cytochrome P-450 enzymes. Pooled human liver microsomes were used to determine whether loratadine, desloratadine, and 3-OH-desloratadine were inhibitors of cytochrome P-450 (CYP) 1A2, 2C9, 2C19, 2D6, and 3A4. Loratadine did not inhibit CYP1A2 or CYP3A4 at concentratio...
متن کاملDmd065011 1294..1302
Desloratadine (Clarinex), the major active metabolite of loratadine (Claritin), is a nonsedating antihistamine used for the treatment of seasonal allergies and hives. Previously we reported that the formation of 3-hydroxydesloratadine, the major human metabolite of desloratadine, involves three sequential reactions, namely N-glucuronidation by UGT2B10 followed by 3-hydroxylation by CYP2C8 follo...
متن کاملRapid micellar HPLC analysis of loratadine and its major metabolite desloratadine in nano-concentration range using monolithic column and fluorometric detection: application to pharmaceuticals and biological fluids
Background: Loratadine is a commonly used selective non‐sedating antihistaminic drug. Desloratadine is the active metabolite of loratadine and, in addition, a potential impurity in loratadine bulk powder stated by the United States Pharmacopeia as a related substance of loratadine. Published methods for the determination of both analytes suffer from limited throughput due to the time‐consuming ...
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