Fluorine-Substituted Pyrrolo[2,3-d]Pyrimidine Analogues with Tumor Targeting via Cellular Uptake by Folate Receptor α and the Proton-Coupled Folate Transporter and Inhibition of de Novo Purine Nucleotide Biosynthesis was written by Ravindra, Manasa;Wilson, Mike R.;Tong, Nian;OConnor, Carrie;Karim, Mohammad;Polin, Lisa;Wallace-Povirk, Adrianne;White, Kathryn;Kushner, Juiwanna;Hou, Zhanjun;Matherly, Larry H.;Gangjee, Aleem. And the article was included in Journal of Medicinal Chemistry in 2018.Electric Literature of C6H3BrFNO2 This article mentions the following:
Novel fluorinated 2-amino-4-oxo-6-substituted pyrrolo[2,3-d]pyrimidine analogs were synthesized and tested for selective cellular uptake by folate receptors (FRs) α and β or the proton-coupled folate transporter (PCFT) and for antitumor efficacy. Compounds I (n = 0, 1) and II (n = 0, 1) showed increased in vitro anti-proliferative activities (∼11-fold) over the nonfluorinated analogs toward engineered Chinese hamster ovary and HeLa cells expressing FRs or PCFT. Compounds I (n = 0, 1) and II (n = 0, 1) also inhibited proliferation of IGROV1 and A2780 epithelial ovarian cancer cells; in IGROV1 cells with knockdown of FRα, I (n = 0) and II (n = 0, 1) showed sustained inhibition associated with uptake by PCFT. All compounds inhibited glycinamide ribonucleotide formyltransferase, a key enzyme in the de novo purine biosynthesis pathway. Mol. modeling studies validated in vitro cell-based results. NMR evidence supports the presence of an intramol. fluorine-hydrogen bond. Potent in vivo efficacy of II (n = 1) was established with IGROV1 xenografts in severe compromised immunodeficient mice. In the experiment, the researchers used many compounds, for example, 5-Bromo-3-fluoropicolinic acid (cas: 669066-91-5Electric Literature of C6H3BrFNO2).
5-Bromo-3-fluoropicolinic acid (cas: 669066-91-5) belongs to pyridine derivatives. Pyridine has a conjugated system of six π electrons that are delocalized over the ring. The molecule is planar and, thus, follows the Hückel criteria for aromatic systems. One of the examples of pyridines is the well-known alkaloid lithoprimidine, which is an A3 adenosine receptor antagonist and N,N-dimethylaminopyridine (DMAP) analog, commonly used in organic synthesis.Electric Literature of C6H3BrFNO2