Starting from an appropriate 6-chloro-2-TMS-purine derivative, a regioselective functionalization of the purine scaffold was achieved successively at positions 8, 6, and 2 via zinc and magnesium intermediates which were generated either by a direct zincation with TMPZnCl·LiCl or by an I/Mg exchange with iPrMgCl.
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Expert Opin Ther Pat
December 2024
Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, China.
Introduction: Xanthine oxidase (XO) catalyzes the oxidation of both hypoxanthine and xanthine in the last two steps of the purine metabolic pathway, serving as a rate-limiting enzyme for uric acid production as well as a key target for the treatment of gout and other hyperuricemia-related conditions.
Areas Covered: This paper reviews XO inhibitors in patents from 2021 to the present. We summarize in detail the structural classes and characteristics, in vitro and in vivo biological results, and structure‒activity relationships of synthetic inhibitors, as well as the sources, specific structures, research methods, and biological activities of XO inhibitors from natural products.
Eur J Med Chem
December 2024
Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga-142 001 (Punjab), India. Electronic address:
The inhibition of enzyme DPP-4 is pivotal for targeting type 2 diabetes mellitus (DM). The study introduces two series of novel 1,3-dimethyl-3,7-dihydro-1H-purine-2,6-diones derivatives (PB01-PB10) and 3,7-dihydro-1H-purine-2,6-diones compounds (PB11-PB16) were developed using linagliptin scaffold. Sixteen derivatives were synthesized and screened in vitro against DPP-4, revealing IC ranging from 15.
View Article and Find Full Text PDFBioorg Chem
November 2024
Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt. Electronic address:
Thieno[2,3-d]pyrimidine fragment is not only bioistostere to quinazoline ring but also to purines which exist in nucleic acids responsible for several key biological processes of the living cells, thus it is of a great interest for many researchers. Thieno[2,3-d]pyrimidine ring has become an important scaffold for different compounds with versatile pharmacological activities including anticancer. These compounds exert their anticancer activity through variant mechanisms of action; one of these is the induction of different programmed cell death types as apoptosis and necroptosis which is an effective approach for cancer treatment.
View Article and Find Full Text PDFCell Death Dis
November 2024
Department of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical University, 510000, Guangzhou, Guangdong, P. R. China.
Despite the advancements in treatment strategies, the long-term survival of hepatocellular carcinoma (HCC) is still pessimistic. Therefore, understanding the mechanisms of hepatocellular carcinoma may offer substantial benefits for patients. Our previous research has revealed that Hornerin promoted HCC progression by regulating the AKT signaling pathway.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
Materials Science Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550.
Dynamin 1 (Dyn1) GTPase, a principal driver of membrane fission during synaptic endocytosis, self-assembles into short mechanoactive helices cleaving the necks of endocytic vesicles. While structural information about Dyn1 helix is abundant, little is known about the nanoscale dynamics of the helical scaffolding at the moment of fission, complicating mechanistic understanding of Dyn1 action. To address the role of the helix dynamics in fission, we used High-Speed Atomic Force Microscopy (HS-AFM) and fluorescence microscopy to track and compare the spatiotemporal characteristics of the helices formed by wild-type Dyn1 and its K44A mutant impaired in GTP hydrolysis on minimal lipid membrane templates.
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