Sch-37370

A series of novel derivatives of desloratadine designed as arginine vasopressin receptor antagonists was synthesized.Their in vivo diuretic activities were evaluated on rats, and several target compounds showed promising diuretic results, especially compounds I [X = CO, R = (CH₂)₃Cl; X = CO, R = 2,5-F₂C₆H₃; X = SO₂, R = 3-O₂NC₆H₄; X = SO₂, R = 2-Me-5-NO₂-C₆H₃].Further an in vitro bonding assay and a cAMP assay showed that these compounds had a higher affinity to vasopressin V2 receptor than V1a receptor.The studies indicated that desloratadine may be an active substructure for novel arginine vasopressin receptor antagonist development.

We reported the development of an ion-pair chromatographic method to separate desloratadine and all known related compounds in Clarinex Tablets, which use desloratadine as active pharmaceutical ingredient (API). For the first time, baseline separation for desloratadine and all known related compounds was achieved by utilizing a YMC-Pack Pro C(18) column (150 mm x 4.6 mm I.D., 3 microm particle size, 120A pore size) and a gradient elution method. The mobile phase A contains 3 mM sodium dodecylsulfate (SDS), 15 mM sodium citrate buffer at pH 6.2, and 40 mM sodium sulfate, while the mobile phase B is acetonitrile. Chromsword, an artificial intelligence method development tool, was used to optimize several key chromatographic parameters simultaneously including buffer pH/solvent strength, and temperature/gradient profile. The resolution of desloratadine and desloratadine 3,4-dehydropiperidine derivative, one of the critical pairs was improved by adding 40 mM sodium sulfate. Ultraviolet detection at 267 nm was used to achieve the detection for desloratadine and all compounds. This method has been successfully validated according to ICH guidelines in terms of linearity, accuracy, quantitation limit/detection limit, precision, specificity and robustness. It could be used as a stability indicating method for desloratadine drug substances or drug products that use desloratadine as active pharmaceutical ingredient.