SMBA was selected as a bifunctional sulfa drug to design ternary cocrystals with pyridine amides and lactam coformers. Supramolecular assembly of five ternary cocrystals of p-sulfonamide benzoic acid with nicotinamide and 2-pyridone is demonstrated and reproducible heterosynthons are identified for crystal engineering.
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http://dx.doi.org/10.1039/c5cc06475a | DOI Listing |
Pharmaceutics
January 2025
Department of Chemical and Pharmaceutical Sciences, University of Trieste, Piazzale Europa 1, 34127 Trieste, Italy.
This study investigates the preparation of coamorphous systems composed entirely of active pharmaceutical ingredients (APIs), namely praziquantel, niclosamide, and mebendazole. The objective was to formulate and characterize binary and ternary coamorphous systems to evaluate their structural, thermal, and stability properties. Ten different mixtures (binary and ternary) were designed through a mixture design approach and prepared using a sustainable, one-step neat grinding process in a lab-scale vibrational mill.
View Article and Find Full Text PDFJACS Au
December 2024
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, No. 345 Lingling Road, Shanghai 200032, China.
Macrocyclization is a compelling strategy for conventional drug design for improving biological activity, target specificity, and metabolic stability, but it was rarely applied to the design of PROTACs possibly due to the mechanism and structural complexity. Herein, we report the rational design of the first series of "Head-to-Tail" macrocyclic PROTACs. The resulting molecule exhibited pronounced Brd4 protein degradation with low nM DC values while almost totally dismissing the "hook effect", which is a general character and common concern of a PROTAC, in multiple cancer cell lines.
View Article and Find Full Text PDFCryst Growth Des
November 2024
School of Biological and Chemical Sciences, University of Galway, Galway H91TK33, Ireland.
In the field of cocrystals, the synthon-based design of two-component crystals is well established and the interest is now shifting toward higher order cocrystals as the next challenge. Carboxylic acids form a robust synthon with pyridyl coformers and interact with 2-aminopyrimidines through a pair of strong, charge-assisted hydrogen bonds. In this work we describe the formation of higher order salts and salt cocrystals of trimesic acid using 2,4-diaminopyrimidine (pyrimethamine, trimethoprim) and pyridyl (4,4'-bipyridine, 1,2-di(4-pyridyl)ethylene, 1,3-di(4-pyridyl)propane, 4-phenylpyridine) coformers.
View Article and Find Full Text PDFJACS Au
October 2024
Department of Chemistry, Theoretical Chemistry Institute, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
Targeted protein degradation (TPD) is emerging as a promising therapeutic approach for cancer and other diseases, with an increasing number of programs demonstrating its efficacy in human clinical trials. One notable method for TPD is Proteolysis Targeting Chimeras (PROTACs) that selectively degrade a protein of interest (POI) through E3-ligase induced ubiquitination followed by proteasomal degradation. PROTACs utilize a warhead-linker-ligand architecture to bring the POI (bound to the warhead) and the E3 ligase (bound to the ligand) into proximity.
View Article and Find Full Text PDFJ Am Chem Soc
October 2024
Institut für Organische Chemie, Universität Würzburg, Am Hubland, 97074 Würzburg, Germany.
Construction of π-π stacking supramolecular complexes with more than two different components is challenging due to the weak and directionless nature of dispersion interactions. Here, we report ternary complexes of a ditopic nanographene tetraimide (), α-substituted phthalocyanine (), and polyaromatic hydrocarbons (PAHs) in solution and the crystalline state via allosteric regulation. Binding of one gives rise to significant distortion and conformational changes in that in turn lead to the inhibition of the second binding of .
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