- Design of enamides as new selective monoamine oxidase-B inhibitors
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Objectives: To develop of new class of selective and reversible MAO-B inhibitors from enamides. Methods: Syntheses of the titled derivatives (AD1–AD11) were achieved by reacting cinnamoyl chloride and various primary and secondary amines in basic medium. All eleven compounds were investigated for in vitro inhibitory activities against recombinant human MAO-A and MAO-B. The reversibilities of lead compound inhibitions were analysed by dialysis. MTT assays of lead compounds were performed using normal VERO cell lines. Key findings: Compounds AD3 and AD9 exhibited the greatest inhibitory activity against MAO-B with IC50 values of 0.11 and 0.10?μm, respectively, and were followed by AD2 and AD1 (0.51 and 0.71?μm, respectively). Most of the compounds weakly inhibited MAO-A, with the exceptions AD9 and AD7, which had IC50 values of 4.21 and 5.95?μm, respectively. AD3 had the highest selectivity index (SI) value for MAO-B (>363.6) and was followed by AD9 (SI 42.1). AD3 and AD9 were found to be competitive inhibitors of MAO-B with Ki values of 0.044?±?0.0036 and 0.039?±?0.0047?μm, respectively. Reversibility experiments showed AD3 and AD9 were reversible inhibitors of MAO-B; dialysis restored the activity of MAO-B to the reference level. MTT assays revealed AD3 and AD9 were non-toxic to normal VERO cell lines with IC50 values of 153.96 and 194.04?μg/ml, respectively. Computational studies provided hypothetical binding modes for AD3 and AD9 in the binding cavities of MAO-A and MAO-B. Conclusions: These results encourage further studies on the enamide scaffold as potential drug candidates for the treatment of Alzheimer's and Parkinson's diseases.
- Kavully, Fathima Sahla,Oh, Jong Min,Dev, Sanal,Kaipakasseri, Swafvan,Palakkathondi, Ashique,Vengamthodi, Ajeesh,Abdul Azeez, Rinshana Fathima,Tondo, Anna Rita,Nicolotti, Orazio,Kim, Hoon,Bijo
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p. 916 - 926
(2020/04/15)
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- Aminoquinoline-rhodium(II) conjugates as src-family SH3 ligands
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High-affinity, selective ligands are sought for a variety of biomolecules but are particularly difficult to generate in the protein-protein interaction space. Rhodium(II) conjugates provide a structure-based approach to improved affinity and specificity f
- Martin, Samuel C.,Ball, Zachary T.
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supporting information
p. 1380 - 1385
(2019/10/11)
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- Synthesis of Cinnamanilide Derivatives and Their Antioxidant and Antimicrobial Activity
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The amide derivatives of cinnamic acid were synthesized and their antimicrobial and antioxidant activities were investigated. The investigation of antimicrobial potentials of the compounds demonstrated a strong activity against 21 bacterial strains comprising Gram-positive and Gram-negative bacteria. Compounds 2a, 2b, and 3b showed strong antimicrobial activity against all microorganisms with the pMIC value ranging from 2.45 to 3.68. Compounds 2a, 3a, and 3b demonstrated strong antioxidant activity with % inhibition of the DPPH radical of 51% (±1.14), 41% (±1.01), and 50% (±1.23), respectively. These findings indicate that the amide derivatives of the cinnamic acid possess strong antibacterial and antioxidant activities.
- Nimse, Satish Balasaheb,Pal, Dilipkumar,Mazumder, Avijit,Mazumder, Rupa
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- ROR MODULATORS AND THEIR USES
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The invention relates to ROR modulators; compositions comprising an effective amount of a ROR modulator; and methods for treating or preventing diseases associated with ROR.
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Paragraph 0106; 0107; 0108
(2013/11/19)
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- DDQ-promoted direct transformation of benzyl hydrocarbons to amides via tandem reaction of the CDC reaction and Beckmann rearrangement
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An atom-efficient and transition metal-free approach to amides from the corresponding benzyl hydrocarbons through C-H and C-C bond cleavage has been developed. Mechanistic studies have shown that a DDQ-promoted cross-dehydrogenative coupling (CDC) reaction with subsequent oxidation and rearrangement are involved in this transformation. The Royal Society of Chemistry.
- Qiu, Jun,Zhang, Ronghua
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supporting information
p. 6008 - 6012
(2013/09/12)
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- A novel one-step synthesis of benzo[b]furo[3,2-b]pyridines having an amino group at the 4-position from benzo[b]furo[3,2-d][1,3]oxazine
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A novel one-step synthesis of benzo[b]furo[3,2-b]pyridines having an amino group at the 4-position from benzo[b]furo[3,2-d][1,3]oxazine by treatment of various amines is described.
- Tabuchi, Yukako,Kakumoto, Yusa,Uchimoto, Hitomi,Kawasaki, Ikuo,Ohishi, Yoshitaka,Nishide, Kiyoharu
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p. 177 - 191
(2013/03/13)
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- Synthesis, SAR and in vivo activity of novel thienopyridine sulfonamide pyrrolidinones as factor Xa inhibitors
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Thienopyridine sulfonamide pyrrolidinones were found to be potent and selective inhibitors of the coagulation cascade enzyme factor Xa. SAR studies led to several compounds that were selected for further in vivo investigation. These novel aryl binding pocket moieties represent a structural modification to a series of fXa inhibitors. Several compounds proved to be efficacious iv antithrombotic agents.
- Becker, Michael R.,Ewing, William R.,Davis, Roderick S.,Pauls, Henry W.,Ly, Cuong,Li, Aiwen,Mason, Helen J.,Choi-Sledeski, Yong Mi,Spada, Alfred P.,Chu, Valeria,Brown, Karen D.,Colussi, Dennis J.,Leadley, Robert J.,Bentley, Ross,Bostwick, Jeff,Kasiewski, Charles,Morgan, Suzanne
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p. 2753 - 2758
(2007/10/03)
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