Aryl azoles can be found in numerous active pharmaceutical ingredients (APIs). Milvexian is a Factor Xia inhibitor currently in phase III for the treatment of thrombotic events containing an ortho-substituted 1-aryl-1H-1,2,3-triazole moiety. During the process development of Milvexian, we assessed multiple approaches for the preparation of 4-chloro-1,2,3-triazole, intermediate 1. In this review article, we will detail how we initiated several academic collaborations to speed up the selection of the best synthesis for commercial manufacturing. Ultimately, those results not only helped us to achieve our goal but yielded general methodologies for the functionalization of azoles that extended even beyond our initial scope.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2533/chimia.2024.104 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Physical properties of chlorophyll-quinone conjugates prepared via Friedel-Crafts reaction.
Photosynth Res
January 2025
Graduate School of Life Sciences, Ritsumeikan University, Kusatsu, Shiga, 525-8577, Japan.
Pheophytin-a derivatives possessing plastoquinone and phylloquinone analogs in the peripheral 3-substituent were prepared by Friedel-Crafts reactions of a 3-hydroxymethyl-chlorin as one of the chlorophyll-a derivatives with benzo- and naphthohydroquinones, respectively, and successive oxidation of the 1,4-dihydroxy-aryl groups in the resulting dehydration products. The 3-quinonylmethyl-chlorins exhibited ultraviolet-visible absorption and circular dichroism spectra in acetonitrile, which were composed of those of the starting 3-hydroxymethyl-chlorin and the corresponding methylated benzo- and naphthoquinones. No intramolecular interaction between the chlorin and quinone π-systems was observed in the solution owing to the methylene spacer.
View Article and Find Full Text PDF-Monoarylated dihydrophenazines in reduced and oxidized states as efficient organo-photocatalysts.
Chem Commun (Camb)
January 2025
Department of Chemical and Pharmaceutical Sciences, CENMAT, Centre of Excellence for Nanostructured Materials, INSTM UdR Trieste, University of Trieste, via Licio Giorgieri 1, 34127 Trieste, Italy.
In this work, the synthesis of an -monoarylated dihydrophenazine is reported together with its interconversion to its oxidized mono-cationic form. While the reduced state was employed for the dechlorination of aromatic substrates, the oxidized mono-cationic one was exploited for the formation of C-N bonds between aryl rings and azoles, which was achieved with high yields and very low catalyst loadings (down to 0.5 mol%).
View Article and Find Full Text PDFPrediction of Potential Risk for Ten Azole and Benzimidazole Fungicides with the Aryl Hydrocarbon Receptor Agonistic Activity to Aquatic Ecosystems.
J Agric Food Chem
January 2025
Fujian Engineering Research Center for Green Pest Management/Fujian Key Laboratory for Monitoring and Integrated Management of Crop Pests/East China Branch of the National Center for Agricultural Biosafety Sciences, Institute of Plant Protection, Fujian Academy of Agricultural Sciences, Fuzhou 350013, China.
Azole and benzimidazole fungicides are widely used agrochemicals to prevent and treat fungal growth and are frequently detected in aquatic environments. Here, we aimed to assess the aquatic ecological risks of ten currently used azole and benzimidazole fungicides, which with the aryl hydrocarbon receptor (AhR) agonistic activity, and their transformation products (TPs). We obtained over 400 types of aerobic TPs for ten fungicides.
View Article and Find Full Text PDFUse of Biotin-Labeled Geranyl Pyrophosphate for Analysis of Ykt6 Geranylgeranylation.
Methods Mol Biol
January 2025
Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Functionally derivatized analogs of prenyl lipids are valuable tools for the detection and analysis of prenylated proteins. Using a biotinylated analog of geranylgeranyl, we previously identified Ykt6 as a substrate for a novel protein prenyltransferase, termed geranylgeranyltransferase type III (GGTase-III). Ykt6 is an evolutionarily highly conserved SNARE protein that regulates multiple intracellular trafficking pathways, including intra-Golgi trafficking and autophagosome-lysosome fusion.
View Article and Find Full Text PDFDesign, synthesis, and structure-activity relationships of five-membered heterocyclic incorporated aryl(alkyl)azoles: From antiproliferative thiazoles to safer anticonvulsant oxadiazoles.
Bioorg Chem
December 2024
Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address:
In the current study, a novel series of 1,2,4-oxadiazoles were designed, synthesized, and evaluated for their biological activities. A cell-based antiproliferative screening was accomplished on the newly synthesized 1,2,4-oxadiazoles along with our previously reported aryl(alkyl)azoles (AAAs) containing middle heterocyclic cores thiazole and oxazole. Among the tested compounds, naphthyl- thiazoles demonstrated higher antiproliferative activity and B3 was identified as the most potent compound with IC values in the range of 2.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!