84647-20-1Relevant articles and documents
POLYCYCLIC AMIDES AS MUSCARINIC M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
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Page/Page column 19, (2019/05/15)
The present invention relates to compounds of formula (I), or their isotopic forms, stereoisomers, tautomers or pharmaceutically acceptable salt (s) thereof as muscarinic M1 receptor positive allosteric modulators (M1 PAMs). The present invention describes the preparation, pharmaceutical composition and the use of compound formula (I).
2-Aminonicotinic acid 1-oxides are chemically stable inhibitors of quinolinic acid synthesis in the mammalian brain: A step toward new antiexcitotoxic agents
Vallerini, Gian Paolo,Amori, Laura,Beato, Claudia,Tararina, Margarita,Wang, Xiao-Dan,Schwarcz, Robert,Costantino, Gabriele
, p. 9482 - 9495 (2014/01/06)
3-Hydroxyanthranilic acid 3,4-dioxygenase (3-HAO) is the enzyme responsible for the production of the neurotoxic tryptophan metabolite quinolinic acid (QUIN). Elevated brain levels of QUIN are observed in several neurodegenerative diseases, but pharmacological investigation on its role in the pathogenesis of these conditions is difficult because only one class of substrate-analogue 3-HAO inhibitors, with poor chemical stability, has been reported so far. Here we describe the design, synthesis, and biological evaluation of a novel class of chemically stable inhibitors based on the 2-aminonicotinic acid 1-oxide nucleus. After the preliminary in vitro evaluation of newly synthesized compounds using brain tissue homogenate, we selected the most active inhibitor and showed its ability to acutely reduce the production of QUIN in the rat brain in vivo. These findings provide a novel pharmacological tool for the study of the mechanisms underlying the onset and propagation of neurodegenerative diseases.
Novel Hepatitis C virus replicon inhibitors: Synthesis and structure-activity relationships of fused pyrimidine derivatives
Chris Krueger,Madigan, Darold L.,Beno, David W.,Betebenner, David A.,Carrick, Robert,Green, Brian E.,He, Wenping,Liu, Dachun,Maring, Clarence J.,McDaniel, Keith F.,Mo, Hongmei,Molla, Akhteruzzaman,Motter, Christopher E.,Pilot-Matias, Tami J.,Tufano, Michael D.,Kempf, Dale J.
, p. 2212 - 2215 (2012/04/18)
The synthesis of several pyrido[2,3-d]pyrimidine and pyrimido[4,5-d] pyrimidine analogs is described with one such analog possessing subnanomolar potency in both genotype 1a and 1b cell culture HCV replicon assays.