- Loratadine and analogues: Discovery and preliminary structure-activity relationship of inhibitors of the amino acid transporter B0AT2
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B0AT2, encoded by the SLC6A15 gene, is a transporter for neutral amino acids that has recently been implicated in mood and metabolic disorders. It is predominantly expressed in the brain, but little is otherwise known about its function. To identify inhibitors for this transporter, we screened a library of 3133 different bioactive compounds. Loratadine, a clinically used histamine H1 receptor antagonist, was identified as a selective inhibitor of B0AT2 with an IC50 of 4 μM while being less active or inactive against several other members of the SLC6 family. Reversible inhibition of B0AT2 was confirmed by electrophysiology. A series of loratadine analogues were synthesized to gain insight into the structure-activity relationships. Our studies provide the first chemical tool for B0AT2.
- Cuboni, Serena,Devigny, Christian,Hoogeland, Bastiaan,Strasser, Andrea,Pomplun, Sebastian,Hauger, Barbara,H?fner, Georg,Wanner, Klaus T.,Eder, Matthias,Buschauer, Armin,Holsboer, Florian,Hausch, Felix
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supporting information
p. 9473 - 9479
(2015/01/09)
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- Synthesis and biological evaluation of novel derivatives of desloratadine
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Series of novel derivatives of desloratadine designed as arginine vasopressin receptor antagonists were synthesized and structurally characterized by melting points, 1H NMR and HRMS. Their in vivo diuretic activities were evaluated on rats, and
- Mu, Shuai,Xie, Xiao-Shuai,Niu, Duan,Zhang, Da-Shuai,Liu, Deng-Ke,Liu, Chang-Xiao
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p. 531 - 534
(2013/07/27)
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- A new addition compound of desloratadine with carbon dioxide
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The addition compound of 8-chloro-6,11-dihydro-11-(4-pip-eridylidene)-5H- benzo[5,6]cyclohepta[1,2-b]pyridine (descarboet-hoxyloratadine, desloratadine) with CO2, in molar ratio 2:1, is described. This unique form of desloratadine drug substance can be prepared in exceedingly high purity by a simple process from crude desloratadine. The addition compound is a useful intermediate in the manufacturing process of desloratadine Form I polymorph. An improved, environmental friendly manufacturing process for the synthesis of desloratadine starting from loratadine is also disclosed here.
- Mezei, Tibor,Volk, Balazs,Kiraly, Imre,Simig, Gyula
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p. 855 - 859
(2013/01/03)
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- 6,11-Dihydro-11-(N-substituted-4-piperidylidene)-5H-benzo(5,6)cyclohepta(1,2-B)pyridines and compositions and methods of use
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Derivatives of 6,11-dihydro-11-(4-piperidylidene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine, and pharmaceutically acceptable salts and solvates thereof are disclosed, which possess anti-allergic and anti-inflammatory activity. Methods for preparing and using the compounds are also described.
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