- SMALL MOLECULE INDUCERS OF GDNF AS POTENTIAL NEW THERAPEUTICS FOR NEUROPSYCHIATRIC DISORDERS
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The invention provides a compound having the structure (I), wherein A is a substituted or unsubstituted ring; Z is present or absent and when present is (II), wherein n is 0, 1, 2, 3, or 4; Y is -(CR11R12)-, -NH(CR11R12)- or -O(CR11R12)- wherein R11 and R12 are each hydrogen or combine to form a carbonyl; and wherein R1 to R10 are herein as described.
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Page/Page column 101; 102
(2013/03/26)
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- Design, synthesis, and structure - Activity relationship studies of novel 3-alkylindole derivatives as selective and highly potent myeloperoxidase inhibitors
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Due to its production of potent antimicrobial oxidants including hypochlorous acid, human myeloperoxidase (MPO) plays a critical role in innate immunity and inflammatory diseases. Thus MPO is an attractive target in drug design. (Aminoalkyl)fluoroindole derivatives were detected to be very potent MPO inhibitors; however, they also promote inhibition of the serotonin reuptake transporter (SERT) at the same concentration range. Via structure-based drug design, a new series of MPO inhibitors derived from 3-alkylindole were synthesized and their effects were assessed on MPO-mediated taurine chlorination and low-density lipoprotein oxidation as well as on inhibition of SERT. The fluoroindole compound with three carbons in the side chain and one amide group exhibited a selectivity index of 35 (Ki/IC50) with high inhibition of MPO activity (IC50 = 18 nM), whereas its effect on SERT was in the micromolar range. Structure-function relationships, mechanism of action, and safety of the molecule are discussed.
- Soubhye, Jalal,Aldib, Iyas,Elfving, Betina,Gelbcke, Michel,Furtmüller, Paul G.,Podrecca, Manuel,Conotte, Rapha?l,Colet, Jean-Marie,Rousseau, Alexandre,Reye, Florence,Sarakbi, Ahmad,Vanhaeverbeek, Michel,Kauffmann, Jean-Michel,Obinger, Christian,Nève, Jean,Prévost, Martine,Zouaoui Boudjeltia, Karim,Dufrasne, Francois,Van Antwerpen, Pierre
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p. 3943 - 3958
(2013/06/27)
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- SUBSTITUTED INDOLE DERIVATIVES
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Provided herein are indole derivatives, pharmaceutical compositions containing them, methods for their use, and methods for preparing these compounds.
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Page/Page column 78
(2008/06/13)
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