- Aminobenzimidazoles and Structural Isomers as Templates for Dual-Acting Butyrylcholinesterase Inhibitors and hCB2R Ligands To Combat Neurodegenerative Disorders
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A pharmacophore model for butyrylcholinesterase (BChE) inhibitors was applied to a human cannabinoid subtype 2 receptor (hCB2R) agonist and verified it as a first-generation lead for respective dual-acting compounds. The design, synthesis, and pharmacological evaluation of various derivatives led to the identification of aminobenzimidazoles as second-generation leads with micro- or sub-micromolar activities at both targets and excellent selectivity over hCB1and AChE, respectively. Computational studies of the first- and second-generation lead structures by applying molecular dynamics (MD) on the active hCB2R model, along with docking and MD on hBChE, has enabled an explanation of their binding profiles at the protein levels and opened the way for further optimization. Dual-acting compounds with “balanced” affinities and excellent selectivities could be obtained that represent leads for treatment of both cognitive and pathophysiological impairment occurring in neurodegenerative disorders.
- Dolles, Dominik,Nimczick, Martin,Scheiner, Matthias,Ramler, Jacqueline,Stadtmüller, Patricia,Sawatzky, Edgar,Drakopoulos, Antonios,Sotriffer, Christoph,Wittmann, Hans-Joachim,Strasser, Andrea,Decker, Michael
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supporting information
p. 1270 - 1283
(2016/07/27)
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- ISOTHIOCYNATES AND GLUCOSINOLATE COMPOUNDS AND ANTI-TUMOR COMPOSITIONS CONTAINING SAME
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The present invention provides glucosinolate and isothiocyanate compounds and related methods for synthesizing these compounds and analogs. In certain embodiments, these glucosinolate and isothiocyanate compounds are useful and chemopreventive and or chemotherapeutic agents.
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Paragraph 0094; 0096; 0098
(2013/05/21)
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- Synthesis and antifungal activity of 1,2,4-triazole derivatives containing cyclopropane moiety
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A new series of 1,2,4-triazoles containing cyclopropane moiety were synthesized and characterized by 1H NMR and elemental analyses. The biological activities results showed that most of them exhibited significant fungicidal activity towards six test fungi. Among them, several showed superiority over the commercial fungicide during the present study.
- Tan, Cheng-Xia,Shi, Yan-Xia,Weng, Jian-Quan,Liu, Xing-Hai,Li, Bao-Ju,Zhao, Wei-Guang
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experimental part
p. 431 - 435
(2012/07/03)
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- ISOTHIOCYANATES AND GLUCOSINOLATE COMPOUNDS AND ANTI-TUMOR COMPOSITIOS CONTAINING SAME
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The present invention provides glucosinolate and isothiocyante compounds and related methods for synthesizing these compounds and analogs. In certain embodiments, these glucosinolate and isothiocyanate compounds are useful and chemopreventive and or chemotherapeutic agents.
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Page/Page column 26
(2008/06/13)
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- SUBSTITUTED N-ALKYLPYRIMIDINONES
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This invention is directed generally to substituted pyrimidinone compounds that generally inhibit p38 kinase, TNF, and/or cyclooxygenase activity. Such substituted pyrimidinone include compounds generally corresponding in structure to the following formula (I): wherein R1, R2, R3, R4A, R4B, R4C, R4D and R4E are as defined in this specification. This invention also is directed to compositions of such substituted pyrimidinones (particularly pharmaceutical compositions), intermediates for the syntheses of such substituted pyrimidinones, methods for making such substituted pyrimidinones, and methods for treating (including preventing) conditions (typically pathological conditions) associated with p38 kinase activity, TNF activity, and/or cyclooxygenase-2 activity.
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Page/Page column 200
(2010/11/08)
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