This communication reports a new synthetic route of pyridopyrimidines to facilitate their structural optimization in a library fashion and describes the development of pyridopyrimidines that have excellent enzymatic and cell potency against Akt1 and Akt2. This series also shows a high level of selectivity over other closely related kinases and significantly improved caspase-3 activity with the more optimized compounds.
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http://dx.doi.org/10.1016/j.bmcl.2008.01.054 | DOI Listing |
Chem Biodivers
August 2024
Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail, 81442, Saudi Arabia.
Breast cancer remains a major global health issue, particularly affecting women and contributing significantly to mortality rates. Current treatments for estrogen receptor-positive breast cancers, such as aromatase inhibitors, are effective but often come with side effects and resistance issues. This study addresses these gaps by targeting aromatase, an enzyme crucial for estrogen synthesis, which plays a pivotal role in breast cancer progression.
View Article and Find Full Text PDFEur Rev Med Pharmacol Sci
March 2024
Third Department of Medicine, Oncology Unit, National and Kapodistrian University of Athens, Athens, Greece.
Background: The recent advent of the cyclin-dependent kinase (CDK) 4/6 inhibitors has considerably evolved hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer treatment. Palbociclib, an orally administered pyridopyrimidine derivative, was the first CDK4/6 inhibitor to be introduced into daily clinical practice in combination with classic endocrine backbone, based on progression-free survival (PFS) benefit assessed in the pivotal PALOMA series of randomized clinical trials. Regarding its safety profile, neutropenia and leukopenia are the most common and well-defined adverse effects, while cardiac complications are rather scarce.
View Article and Find Full Text PDFOrg Lett
October 2023
Chemical Sciences & Technology Division, Council of Scientific and Industrial Research (CSIR)-National Institute for Interdisciplinary Science & Technology (NIIST), Thiruvananthapuram, Kerala 695019, India.
The tandem cyclization of easily accessible allenoates and cyclic amidines for the synthesis of functionalized tricyclic pyridopyrimidines is reported herein. The annulation featured a broad substrate scope with good functional group tolerance under very mild conditions (35 examples, 32-85% yields). The pyridopyrimidines were obtained in a very short reaction time (1 min), at room temperature, under neat conditions, which offers an alternative way to the sustainable synthesis of functionalized pyridopyrimidines.
View Article and Find Full Text PDFMolecules
August 2023
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
This article sheds light on the various scaffolds that can be used in the designing and development of novel synthetic compounds to create DPP-4 inhibitors for the treatment of type 2 diabetes mellitus (T2DM). This review highlights a variety of scaffolds with high DPP-4 inhibition activity, such as pyrazolopyrimidine, tetrahydro pyridopyrimidine, uracil-based benzoic acid and esters, triazole-based, fluorophenyl-based, glycinamide, glycolamide, β-carbonyl 1,2,4-triazole, and quinazoline motifs. The article further explains that the potential of the compounds can be increased by substituting atoms such as fluorine, chlorine, and bromine.
View Article and Find Full Text PDFSteroids
November 2023
Department of Chemistry, College of Science and Humanities in Al-Kharj, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia; Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koam, Egypt. Electronic address:
Reports on structural modification of heterosteroids through various reactions, and developed synthetic routes have considerably increased over the last decade. The present review encompasses the applicable approaches dealing with the utility of reactive moieties in various steroids for the synthesis of fused bicyclic pyridines, and binary bicyclic pyridines all over the years. The different sections include the synthesis of steroids-fused, and binary quinolines, pyridopyrimidines, imidazopyridines, spirocyclic imidazopyridines, pyrazolopyridines, thienopyridines, pyridinyl-thiazoles, and tetrazolopyridine hybrids, as well as, the diverse biological applications of these heterocyclic steroids.
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