Synthesis and biological evaluation of novel derivatives of desloratadine

Synthesis and Biological Evaluation of Substituted Desloratadines as Potent Arginine Vasopressin V2 Receptor Antagonists

“…The in vitro evaluation was done by a slightly modified method we reported previously [31]. An in vitro radioligand binding assay was performed to determine the binding affinity of the candidates to human V2 and V1a receptors.…”

“…The structures of most extant AVP receptor antagonists include a benzene-fused seven membered ring system (ring A) and two aromatic rings (ring B and ring C) linked through amide bonds. Recently, we reported some amide and sulfamide derivatives of desloratadine, which are potent AVP V2 receptor antagonists [31]. Desloratadine is a selective, H 1 -receptor antagonist, and also has anti-inflammatory activity [32].…”

Synthesis and biological evaluation of novel phenothiazine derivatives as non-peptide arginine vasopressin V2 receptor antagonists

“…44 A number of compounds with non-benzazepine scaffolds were 45 screened and the phenothiazine scaffold compounds were found to 46 have excellent affinity to V2 receptors. Furthermore, our previous 47 study indicated that the introduction of sulfonyl bond linkage may 48 enhance the biological activity [20,21]. Herein, the synthesis and 49 biological activity of the potent AVP V2 receptor selective agonists 50 based on the phenothiazine scaffold was presented here and the 51 structure-activity relationship (SAR) was discussed.…”

“…Thus, there is 17 potential to develop a AVP V2 receptor antagonist for the 18 treatment of disorders such as hyponatremia [3,4], congestive 19 heart failure [5,6], renal disease [7], edema and syndrome of 20 inappropriate antidiuretic hormone secretion (SIADH) [8]. 21 A few AVP receptor antagonists have undergone sufficient 22 clinical development to be on the market, such as conivaptan and 23 tolvaptan for the treatment of hyponatremia in the USA. Lixivaptan, 24…”

“…The Sprague-130 Dawley rats were obtained from Shanchuanhong Experimental 131 Animals Co., Ltd (Tianjin, China). The in vitro evaluation was done 132 by the same method we reported previously[20,21]. The in vitro 133 radioligand binding assay was performed to determine the 134 binding affinity of the candidates to human V2 and V1a receptors.142The structures of the target compounds 1a-1y and evaluation of 143 the biological features were summarized inTable 1.…”