Conjugate addition reaction of various nucleophiles across the vinyl group of 2-chloro-4-vinylpyrimidine, 2-chloro-4-(1-phenylvinyl)pyrimidine and 2-chloro-4-vinylquinazoline provides the corresponding 2-chloro-4-(2-substituted ethyl)pyrimidines and 2-chloro-4-(2-substituted ethyl)quinazolines. Treatment of these products, without isolation, with N-methylpiperazine results in nucleophilic displacement of chloride and yields the corresponding 2,4-disubstituted pyrimidines and quinazolines.
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http://dx.doi.org/10.3390/molecules15031973 | DOI Listing |
ACS Pharmacol Transl Sci
January 2025
Integrated Bioanalysis, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, 121 Oyster Point Blvd, South San Francisco, California 94080, United States.
Antibody-drug conjugates (ADCs) are a promising drug modality substantially expanding in both the discovery space and clinical development. Assessing the biotransformation of ADCs and is important in understanding their stability and pharmacokinetic properties. We previously reported biotransformation pathways for the anti-B7H4 topoisomerase I inhibitor ADC, AZD8205, puxitatug samrotecan, that underpin its structural stability using an intact protein liquid chromatography-high resolution mass spectrometry (LC-HRMS) approach.
View Article and Find Full Text PDF3 Biotech
February 2025
Shree. S. K. Patel College of Pharmaceutical Education and Research, Ganpat University, Kherva, Gujarat 384012 India.
This review assesses the antiviral capabilities of antimicrobial peptides (AMPs) against SARS-CoV-2 and other respiratory viruses, focussing on their therapeutic potential. AMPs, derived from natural sources, exhibit promising antiviral properties by disrupting viral membranes, inhibiting viral entry, and modulating host immune responses. Preclinical studies demonstrate that peptides such as defensins, cathelicidins, and lactoferrin can effectively reduce SARS-CoV-2 replication and inhibit viral spread.
View Article and Find Full Text PDFIn this Letter, we present a novel, to the best of our knowledge, approach for recovering objects directly from the Fraunhofer diffraction integral, where the diffraction field of an object is approximated by the Fourier transform of this object augmented by an additional phase factor. This phase factor at the observation plane is universal for the diffraction fields generated by objects located at the same plane and illuminated by the same monochromatic plane wave. It can be first extracted from dividing the Fraunhofer diffraction field by the Fourier transform of an object reference.
View Article and Find Full Text PDFClin Pharmacokinet
January 2025
Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, The Netherlands.
Background And Objective: Psilocybin is currently being extensively studied as a potential therapeutic agent for multiple psychiatric disorders. Here, a systematic literature review of all published pharmacokinetic data on the pharmacologically active metabolite of psilocybin, psilocin, is presented.
Methods: The review includes clinical studies that reported pharmacokinetic data and/or parameters after psilocybin administration in humans.
Chemistry
January 2025
University of Windsor Faculty of Science, Chemistry & Biochemsitry, 401 Sunset Avenue, N9B 3P4, Windsor, CANADA.
Attachment of three different heterocycles with electron donor or acceptor character to a central 1,3,5-triazine core generates readily soluble side-chain free dyes with two displaying soft crystalline mesomorphism and one displaying a nematic liquid crystal phase as confirmed by polarized optical microscopy, calorimetry, gravimetric analysis, and powder X-ray diffraction. Equally intriguing is the dyes' relatively strong electronic communication between donor and acceptor subchromophores that are meta-conjugated to one another, which is experimentally observed as a broad intramolecular charge-transfer absorption that can extend over 100 nm past the most intense absorption event and is computationally confirmed through density functional theory (DFT) evaluations of the molecular ground- and excited-state properties. This molecular design permits the preparation of dyes with panchromatic absorption not just based on the additive absorption of individual subchromophores.
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