- DITERPENOID COMPOUNDS THAT ACT ON PROTEIN KINASE C (PKC)
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This present disclosure relates to protein kinase C (PKC) modulating compounds, methods of treating a subject with cancer using the compounds, and combination treatments with a second therapeutic agent.
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Paragraph 0463; 0464
(2021/04/02)
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- Synthesis and biological evaluation of some undecanone derivatives
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The total synthesis of Ardisinone E [15, 1-(2,4,6-trihydroxy phenyl)-11-(2-hydroxyphenyl)-undecan-1-one], a natural diarylundecanone, isolated from Ardisia arborescens, was accomplished along with 16 new diarylundecanone analogs (18a–p), by modified Wittig reaction. The structures of the compounds were confirmed by 1H, 13C and mass spectral data. Compound 15 showed potent cytotoxic activity with an ED50 of 4.19 μg/mL in brine shrimp lethality assay model. Compounds 18c, 18e, 18j, 18k, 18l, and 18m exhibited strong anti-oxidant activity with IC50 values of 18.75, 12.28, 18.35, 11.04, 12.05, and 11.32 μg/mL, respectively, in NBT free radical assay. Compounds 18e, 18k, and 18m also showed significant 5-lipoxyganase enzyme inhibitory potential with IC50 values of 12.8, 15.23, and 15.23 μg/mL, respectively.
- Meka, Bharani,Ravada, Suryachandra Rao,Kancharla, Harikrishna,Golakoti, Trimurtulu
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p. 3106 - 3124
(2017/10/06)
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- Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
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The present invention provides compounds and pharmaceutical compositions for inhibiting N-acylethanolamine acid amidase (NAAA). Inhibition of NAAA is contemplated as a method to sustain the levels of palmitoylethanolamide (PEA) and oleylethanolamide (OEA), two substrates of NAAA, in conditions characterized by reduced concentrations of PEA and OEA. The invention also provides methods for treating inflammatory diseases and pain, and other disorders in which decreased levels of PEA and OEA are associated with the disorder.
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Page/Page column 93
(2016/06/28)
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- Synthesis, biological evaluation, and 3D QSAR study of 2-methyl-4-oxo-3-oxetanylcarbamic acid esters as N -acylethanolamine acid amidase (NAAA) inhibitors
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N-(2-Oxo-3-oxetanyl)carbamic acid esters have recently been reported to be noncompetitive inhibitors of the N-acylethanolamine acid amidase (NAAA) potentially useful for the treatment of pain and inflammation. In the present study, we further explored the
- Ponzano, Stefano,Berteotti, Anna,Petracca, Rita,Vitale, Romina,Mengatto, Luisa,Bandiera, Tiziano,Cavalli, Andrea,Piomelli, Daniele,Bertozzi, Fabio,Bottegoni, Giovanni
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supporting information
p. 10101 - 10111
(2015/02/02)
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- Design, Synthesis, and Antibacterial Activity of Demethylvancomycin Analogues against Drug-Resistant Bacteria
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Five novel N-substituted demethylvancomycin derivatives were rationally designed and synthesized by using a structure-based approach. The invitro antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA), gentamicin-resistant Enterococcus faecalis (GRE), methicillin-resistant Streptococcus pneumoniae (MRS), and vancomycin-resistant Enterococcus faecalis (VRE) were evaluated. One of the compounds, N-(6-phenylheptyl)demethylvancomycin (12a), was found to exhibit more potent antibacterial activity than vancomycin and demethylvancomycin. Compound 12a was also found to be ～18-fold more efficacious than vancomycin against MRSA; however, the two compounds were found to have similar efficacy against MRS. Furthermore, compound 12a exhibited a favorable pharmacokinetic profile with a half-life of 5.11±0.52h, which is longer than that of vancomycin (4.3±1.9h). These results suggest that 12a is a promising antibacterial drug candidate for further preclinical evaluation.
- Chang, Jun,Zhang, Si-Ji,Jiang, Yong-Wei,Xu, Liang,Yu, Jian-Ming,Zhou, Wen-Jiang,Sun, Xun
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p. 976 - 984
(2013/07/27)
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- DISUBSTITUTED BETA-LACTONES AS INHIBITORS OF N-ACYLETHANOLAMINE ACID AMIDASE (NAAA)
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The present invention provides compounds and pharmaceutical compositions for inhibiting N-acylethanolamine acid amidase (NAAA). Inhibition of NAAA is contemplated as a method to sustain the levels of palmitoylethanolamide (PEA) and oleylethanolamide (OEA), two substrates of NAAA, in conditions characterized by reduced concentrations of PEA and OEA. The invention also provides methods for treating inflammatory diseases and pain, and other disorders in which decreased levels of PEA and OEA are associated with the disorder.
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Paragraph 0261
(2013/06/06)
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- Structure-activity relationships of natural and non-natural amino acid-based amide and 2-oxoamide inhibitors of human phospholipase A2 enzymes
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A variety of 2-oxoamides and related amides based on natural and non-natural amino acids were synthesized. Their activity on two human intracellular phospholipases (GIVA cPLA2 and GVIA iPLA2) and one human secretory phospholipase (GV
- Antonopoulou, Georgia,Barbayianni, Efrosini,Magrioti, Victoria,Cotton, Naomi,Stephens, Daren,Constantinou-Kokotou, Violetta,Dennis, Edward A.,Kokotos, George
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scheme or table
p. 10257 - 10269
(2009/04/12)
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- Zwitterionic sulfobetaine inhibitors of squalene synthase
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A substantial number of sulfobetaines (e.g., 10) have been synthesized and evaluated as inhibitors of squalene synthase (SS) on the basis of the idea that their zwitterionic structure would have properties conducive both to binding in the active site and to passage through cell membranes. When the simple sulfobetaine moiety is incorporated into compounds containing hydrophobic portions like those in farnesyl diphosphate (1) or presqualene diphosphate (2), inhibition of SS in a rat liver microsomal assay was indeed observed. For example, farnesylated sulfobetaine 10 has IC50 = 10 μM and aromatic derivative 35 has IC50 = 2 μM for SS inhibition. A wide variety of structural modifications, exemplified by compounds 43, 52, 76, 85, 91, 99, 111, and 115, was investigated. Unfortunately, no inhibitors in the submicromolar range were discovered, and exploration of a different type of zwitterion seems necessary if this appealing approach to inhibition of SS is going to provide a potential antihypercholesterolemic agent.
- Spencer, Thomas A.,Onofrey, Thomas J.,Cann, Reginald O.,Russel, Jonathon S.,Lee, Laura E.,Blanchard, Daniel E.,Castro, Alfredo,Gu, Peide,Jiang, Guojian,Shechter, Ishaiahu
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p. 807 - 818
(2007/10/03)
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- Synthesis of long chain ω-aralkylbromides
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1-Iodo-4-acetoxybutane is a useful 4 carbon synthon which reacts selectively with Grignards under copper catalysis. The immediate products are converted to bromides.
- Forth,Smith
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p. 951 - 959
(2007/10/02)
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- Synthesis of Malabaricone-A - Confirmation of its Structure
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Wittig reaction of 7-phenylheptyl bromide (I) with 2,6-dimethoxyphenylglyoxal (II) affords 1-(2,6-dimethoxybenzoyl)-8-phenyl-oct-1-ene (III).III on hydrogenation over Pd/C catalyst followed by demethylation with pyridine hydrobromide yields malabaricone-A
- Parthasarathy, M. R.,Gupta, Sushma
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