Anomalous H NMR chemical shift behavior of substituted benzoic acid esters.

Benzoic acid esters represent key building blocks for many drug discovery and development programs and have been advanced as potent PDE4 inhibitors for inhaled administration for treatment of respiratory diseases. This class of compounds has also been employed in myriad industrial processes and as common food preservatives. Recent work directed toward the synthesis of intermediates for a proprietary medicinal chemistry program led us to observe that the H NMR chemical shifts of substituents ortho to the benzoic acid ester moiety defied conventional iterative chemical shift prediction protocols.

Mechanistic Investigation of Site-specific DNA Methylating Agents Targeting Breast Cancer Cells.

We previously described the development of a DNA-alkylating compound that showed selective toxicity in breast cancer cells. This compound contained an estrogen receptor α (ERα)-binding ligand and a DNA-binding/methylating component that could selectively methylate the N3-position of adenines at adenine-thymine rich regions of DNA. Herein, we describe mechanistic investigations that demonstrate that this class of compounds facilitate the translocation of the ERα-compound complex to the nucleus and induce the expression of ERα target genes.

Synthesis, biological evaluation and docking studies of 1,2,4-oxadiazole linked 5-fluorouracil derivatives as anticancer agents.

Background: 1,2,4-oxadiazole derivatives exhibited significant anti-cancer activity when they were evaluated, against human cancer cell lines. They also showed anti-inflammatory, analgesic, diabetic, immunosuppressive, α,β-receptor antagonist, antimicrobial, anti-helminthic, histamine-H3 and antiparasitic properties. A pyrimidine analog, 5 fluoro-uracil is a chemotherapeutic drug used for treating multiple solid malignant tumors.