Bioorganic and Medicinal Chemistry Letters This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Identification of 4-(6-((2-methoxyphenyl)amino)pyrazin-2-yl)benzoic acids as CSNK2A inhibitors with antiviral activity and improved selectivity over PIM3
We report the synthesis of 2,6-disubstituted pyrazines as potent cell active CSNK2A inhibitors. 4'-Carboxyphenyl was found to be the optimal 2-pyrazine substituent for CSNK2A activity, with little tolerance for additional modification. At the 6-position, modifications of the 6-isopropylaminoindazole substituent were explored to improve selectivity over PIM3 while maintaining potent CSNK2A inhibition. The 6-isopropoxyindole analogue 6c was identified as a nanomolar CSNK2A inhibitor with 30-fold selectivity over PIM3 in cells. Replacement of the 6-isopropoxyindole by isosteric ortho-methoxy anilines, such as 7c, generated an...
Source: Bioorganic and Medicinal Chemistry Letters - January 10, 2024 Category: Chemistry Authors: Kareem A Galal Andreas Kr ämer Benjamin G Strickland Jeffery L Smith Rebekah J Dickmander Nathaniel J Moorman Timothy M Willson Source Type: research

Single step synthesis of β- and γ- aryl-substituted ß- and γ-amino acid derivatives by electrochemistry
Bioorg Med Chem Lett. 2024 Jan 9;100:129614. doi: 10.1016/j.bmcl.2024.129614. Online ahead of print.ABSTRACTElectrochemical transformations are a subject of increasing interest in early drug discovery due to its ability to assemble complex scaffolds under rather mild reaction conditions. In this context, we became interested in electrochemical decarboxylative cross-coupling (DCC) protocols of redox-active esters (RAEs) and halo(hetero)arenes. Starting with the one-step electrochemical synthesis of novel methylamino-substituted heterocycles we recognized the potential of this methodology to deliver a novel approach to β- a...
Source: Bioorganic and Medicinal Chemistry Letters - January 10, 2024 Category: Chemistry Authors: Barbara Pavlovic Christoph Heubel Michael Kurz Elisabeth Oehl Siegfried R Waldvogel Maria M éndez Sven Ruf Source Type: research

Design, synthesis, and evaluation of dual EGFR/AURKB inhibitors as anticancer agents for non-small cell lung cancer
Bioorg Med Chem Lett. 2024 Jan 8;100:129612. doi: 10.1016/j.bmcl.2024.129612. Online ahead of print.ABSTRACTThe epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are first-line agents for mutant EGFR-positive (mEGFR+) NSCLC. However, secondary resistant mutations develop following therapy that prevent EGFR-TKI binding. The EGFR-TKIs are rendered ineffective in NSCLC expressing EGFR resistant mutations (rmEGFR+). Mutations in Kirsten rat sarcoma virus protein (mKRAS) support persistent signaling downstream of EGFR regardless of EGFR-TKI earlier in the signaling cascade. The EGFR-TKIs are ineffective in...
Source: Bioorganic and Medicinal Chemistry Letters - January 10, 2024 Category: Chemistry Authors: Sonali Kurup Dayna Gesinski Kaitlin Assaad Aidan Reynolds Source Type: research

Improved synthesis and evaluation of preclinical pharmacodynamic parameters of a new monocyclic β-lactam DPI-2016
Bioorg Med Chem Lett. 2024 Feb 1;99:129615. doi: 10.1016/j.bmcl.2024.129615. Epub 2024 Jan 8.ABSTRACTMonocyclic β-lactams are stable to a number of β-lactamases and are the focus of researchers for the development of antibacterial drugs, particularly against Enterobacterales. We recently synthesized and reported the bactericidal activity of diverse series of aztreonam appended with amidine moieties as siderophores. One of the derivatives exhibiting the highest MIC value in vitro was selected for further preclinical studies. The compound DPI-2016 was reassessed for its synthetic routes and methods that were improved to fi...
Source: Bioorganic and Medicinal Chemistry Letters - January 10, 2024 Category: Chemistry Authors: Lijuan Zhai Jian Sun Jingwen Ji Lili He Pengjuan Zhou Dong Tang Jinbo Ji Haikang Yang Zafar Iqbal Zhixiang Yang Source Type: research

Expanded library of novel 2,3-pyrrolidinedione analogues exhibit anti-biofilm activity
Bioorg Med Chem Lett. 2024 Feb 1;99:129609. doi: 10.1016/j.bmcl.2024.129609. Epub 2024 Jan 6.ABSTRACTHerein we report a new library of 2,3-pyrrolidinedione analogues that expands on our previous report on the antimicrobial studies of this heterocyclic scaffold. The novel 2,3-pyrrolidinediones reported herein have been evaluated against S. aureus and methicillin-resistant S. aureus (MRSA) biofilms, and this work constitutes our first report on the antibiofilm properties of this class of compounds. The antibiofilm activity of these 2,3-pyrrolidinediones has been assessed through minimum biofilm eradication concentration (MBE...
Source: Bioorganic and Medicinal Chemistry Letters - January 8, 2024 Category: Chemistry Authors: Minhua Nie M Alejandro Valdes-Pena Bram H Frohock Emma Smits Jennifer C Daiker Jessica M Gilbertie Lauren V Schnabel Joshua G Pierce Source Type: research

Expanded Library of Novel 2,3-Pyrrolidinedione Analogues Exhibit Anti-biofilm Activity
Bioorg Med Chem Lett. 2024 Jan 6:129609. doi: 10.1016/j.bmcl.2024.129609. Online ahead of print.ABSTRACTHerein we report a new library of 2,3-pyrrolidinedione analogues that expands on our previous report on the antimicrobial studies of this heterocyclic scaffold. The novel 2,3-pyrrolidinediones reported herein have been evaluated against S. aureus and methicillin-resistant S. aureus (MRSA) biofilms, and this work constitutes our first report on the antibiofilm properties of this class of compounds. The antibiofilm activity of these 2,3-pyrrolidinediones has been assessed through minimum biofilm eradication concentration (...
Source: Bioorganic and Medicinal Chemistry Letters - January 8, 2024 Category: Chemistry Authors: Minhua Nie M Alejandro Valdes-Pena Bram H Frohock Emma Smits Jennifer C Daiker Jessica M Gilbertie Lauren V Schnabel Joshua G Pierce Source Type: research

Design of cyclic peptides as novel inhibitors of ICOS/ICOSL interaction
Bioorg Med Chem Lett. 2024 Jan 5:129599. doi: 10.1016/j.bmcl.2024.129599. Online ahead of print.ABSTRACTCompared to small molecules and antibodies, cyclic peptides exhibit unique biochemical and therapeutic attributes in the realm of pharmaceutical applications. The interaction between the inducible costimulator (ICOS) and its ligand (ICOSL) plays a key role in T-cell differentiation and activation. ICOS/ICOSL inhibition results in a reduction in the promotion of immunosuppressive regulatory T cells (Tregs) in both hematologic malignancies and solid tumors. Herein, we implement the computational cPEPmatch approach to desig...
Source: Bioorganic and Medicinal Chemistry Letters - January 7, 2024 Category: Chemistry Authors: Somaya A Abdel-Rahman Brianda L Santini Laura Calvo-Barreiro Martin Zacharias Moustafa Gabr Source Type: research

Natural products fragment-based design and synthesis of a novel pentacyclic ring system as potential MAPK inhibitor
This study reports the development and synthesis of a novel pentacyclic ring system, the indole-pyrimidine-quinoline (IPQ) scaffold. The design of this scaffold was based on the structural characteristics of four natural products, namely tryptanthrin, luotonin A, rutaecarpine, and camptothecin. Several successive steps accomplished the effective synthesis of the IPQ scaffold. The constituent components of the pentacycle, containing the indole, quinazolinone, pyrimidone, and quinoline units, possess significant biological significance. Compound 1a demonstrated noteworthy anti-tumor activity efficacy against A549 cell lines ...
Source: Bioorganic and Medicinal Chemistry Letters - January 3, 2024 Category: Chemistry Authors: Bao-Long Hou Kenan Wu Rongrong Liu Jianli Liu Jinrui Wang Cuiling Wang Yanni Liang Zheng Wang Source Type: research

Natural products fragment-based design and synthesis of a novel pentacyclic ring system as potential MAPK Inhibitor
This study reports the development and synthesis of a novel pentacyclic ring system, the indole-pyrimidine-quinoline (IPQ) scaffold. The design of this scaffold was based on the structural characteristics of four natural products, namely tryptanthrin, luotonin A, rutaecarpine, and camptothecin. Several successive steps accomplished the effective synthesis of the IPQ scaffold. The constituent components of the pentacycle, containing the indole, quinazolinone, pyrimidone, and quinoline units, possess significant biological significance. Compound 1a demonstrated noteworthy anti-tumor activity efficacy against A549 cell lines ...
Source: Bioorganic and Medicinal Chemistry Letters - January 3, 2024 Category: Chemistry Authors: Bao-Long Hou Kenan Wu Rongrong Liu Jianli Liu Jinrui Wang Cuiling Wang Yanni Liang Zheng Wang Source Type: research

UltraFast PhotoInduced double duplex DNA invasion into a 400-mer dsDNA target
CONCLUSION: Based on the new design of pDDI probe with 5-cyano uridine led to a drastic increase in the efficiency of pDDI in (400-mer) double-stranded DNA with only 1 s of photo-irradiation.PMID:38154604 | DOI:10.1016/j.bmcl.2023.129597 (Source: Bioorganic and Medicinal Chemistry Letters)
Source: Bioorganic and Medicinal Chemistry Letters - December 28, 2023 Category: Chemistry Authors: Siddhant Sethi Hailili Zumila Yasuha Watanabe Junling Mo Kenzo Fujimoto Source Type: research