208259-47-6Relevant academic research and scientific papers
Discovery of Novel Azetidine Amides as Potent Small-Molecule STAT3 Inhibitors
Brotherton-Pleiss, Christine,Yue, Peibin,Zhu, Yinsong,Nakamura, Kayo,Chen, Weiliang,Fu, Wenzhen,Kubota, Casie,Chen, Jasmine,Alonso-Valenteen, Felix,Mikhael, Simoun,Medina-Kauwe, Lali,Tius, Marcus A.,Lopez-Tapia, Francisco,Turkson, James
, p. 695 - 710 (2021/01/14)
We optimized our previously reported proline-based STAT3 inhibitors into an exciting new series of (R)-azetidine-2-carboxamide analogues that have sub-micromolar potencies. 5a, 5o, and 8i have STAT3-inhibitory potencies (IC50) of 0.55, 0.38, and 0.34 μM, respectively, compared to potencies greater than 18 μM against STAT1 or STAT5 activity. Further modifications derived analogues, including 7e, 7f, 7g, and 9k, that addressed cell membrane permeability and other physicochemical issues. Isothermal titration calorimetry analysis confirmed high-affinity binding to STAT3, with KD of 880 nM (7g) and 960 nM (9k). 7g and 9k inhibited constitutive STAT3 phosphorylation and DNA-binding activity in human breast cancer, MDA-MB-231 or MDA-MB-468 cells. Furthermore, treatment of breast cancer cells with 7e, 7f, 7g, or 9k inhibited viable cells, with an EC50 of 0.9-1.9 μM, cell growth, and colony survival, and induced apoptosis while having relatively weaker effects on normal breast epithelial, MCF-10A or breast cancer, MCF-7 cells that do not harbor constitutively active STAT3.
COMPOUNDS AND METHOD OF USE
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, (2019/09/06)
This present disclosure relates to compounds with ferroptosis inducing activity, a method of treating a subject with cancer with the compounds, and combination treatments with a second therapeutic agent.
Potent α-amino-β-lactam carbamic acid ester as NAAA inhibitors. Synthesis and structure-activity relationship (SAR) studies
Nuzzi, Andrea,Fiasella, Annalisa,Ortega, Jose Antonio,Pagliuca, Chiara,Ponzano, Stefano,Pizzirani, Daniela,Bertozzi, Sine Mandrup,Ottonello, Giuliana,Tarozzo, Glauco,Reggiani, Angelo,Bandiera, Tiziano,Bertozzi, Fabio,Piomelli, Daniele
supporting information, p. 138 - 159 (2016/02/18)
4-Cyclohexylbutyl-N-[(S)-2-oxoazetidin-3-yl]carbamate (3b) is a potent, selective and systemically active inhibitor of intracellular NAAA activity, which produces profound anti-inflammatory effects in animal models. In the present work, we describe structure-activity relationship (SAR) studies on 3-aminoazetidin-2-one derivatives, which have led to the identification of 3b, and expand these studies to elucidate the principal structural and stereochemical features needed to achieve effective NAAA inhibition. Investigations on the influence of the substitution at the β-position of the 2-oxo-3-azetidinyl ring as well as on the effect of size and shape of the carbamic acid ester side chain led to the discovery of 3ak, a novel inhibitor of human NAAA that shows an improved physicochemical and drug-like profile relative to 3b. This favourable profile, along with the structural diversity of the carbamic acid chain of 3b, identify this compound as a promising new tool to investigate the potential of NAAA inhibitors as therapeutic agents for the treatment of pain and inflammation.
Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
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Page/Page column 120, (2016/06/28)
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.
CARBAMATE DERIVATIVES OF LACTAM BASED N-ACYLETHANOLAMINE ACID AMIDASE (NAAA) INHIBITORS
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Paragraph 0485; 0486, (2014/09/29)
Described herein are compounds and pharmaceutical compositions which inhibit N-acylethanolamine acid amidase (NAAA). Described herein are methods for synthesizing the compounds set forth herein and methods for formulating these compounds as pharmaceutical compositions which include these compounds. Also described herein are methods of inhibiting NAAA in order to sustain the levels of palmitoylethanolamide (PEA) and other N-acylethanolamines (NAE) that are substrates for NAAA, in conditions characterized by reduced concentrations of NAE. Also, described here are methods of treating and ameliorating pain, inflammation, inflammatory diseases, and other disorders in which modulation of fatty acid ethanolamides is clinically or therapeutically relevant or in which decreased levels of NAE are associated with the disorder.
Synthesis, biological evaluation, and 3D QSAR study of 2-methyl-4-oxo-3-oxetanylcarbamic acid esters as N -acylethanolamine acid amidase (NAAA) inhibitors
Ponzano, Stefano,Berteotti, Anna,Petracca, Rita,Vitale, Romina,Mengatto, Luisa,Bandiera, Tiziano,Cavalli, Andrea,Piomelli, Daniele,Bertozzi, Fabio,Bottegoni, Giovanni
supporting information, p. 10101 - 10111 (2015/02/02)
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
STAT3 DIMERIZATION INHIBITORS
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, (2014/05/24)
The subject matter disclosed herein relates to compositions and methods of making and using the compositions. In a further aspect, the subject matter disclosed herein relates to inhibitors of STAT3 dimerization. Methods of making these compositions as wel
DISUBSTITUTED BETA-LACTONES AS INHIBITORS OF N-ACYLETHANOLAMINE ACID AMIDASE (NAAA)
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Paragraph 0346, (2013/06/06)
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.
Development of new N-arylbenzamides as STAT3 dimerization inhibitors
Urlam, Murali K.,Pireddu, Roberta,Ge, Yiyu,Zhang, Xiaolei,Sun, Ying,Lawrence, Harshani R.,Guida, Wayne C.,Sebti, Said M.,Lawrence, Nicholas J.
, p. 932 - 941 (2013/07/27)
The O-tosylsalicylamide S3I-201 (10) was used as a starting point for design and synthesis of novel STAT-3 dimerization inhibitors with improved drug-like qualities. The phosphonic acid 12d and salicylic acids 13f, 13g with a shorter amide linker lacking
Synthesis and immunomodulating activity of new analogues of fingolimod
Feng, Xiang-Jun,Yang, Xiao-Ying,Luo, Yu,Li, Xin,Tang, Wei,Zuo, Jian-Ping,Lu, Wei
, p. 93 - 100 (2012/04/04)
Five new immunomodulators 1a-1e by using a trans-4-alkyl-substituted cyclohexane to replace the flexible C8 alkyl chain of Fingolimod were synthesized. For in-vitro test, the compounds were dissolved in DMSO as a stock solution and diluted to a desired co
