Intra-molecular hydrogen bonding with organic fluorine in the solution state: Deriving evidence by a two dimensional NMR experiment

Kumari, Divya; Hebbar, Sankeerth; Suryaprakash, N.

doi:10.1016/j.cplett.2011.12.051

Cited by 19 publications

(1 citation statement)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Evidence has been published supporting the concept that a fluorine substituted on an sp 2 carbon can serve as a hydrogen bond acceptor . The presence of a fluorine–hydrogen bond in analogues 8 , 9 , 11 , and 12 is further supported by literature reports confirming the occurrence of hydrogen bonds in 2-fluorobenzamide derivatives. − This NMR study (Figure ) strongly indicates that the fluorine and amide NH are in a relative syn orientation akin to the docked (bound) conformations in the target proteins (FRα/β and GARFTase, Figures A,B and ).…”

Section: Biological Evaluation and Discussionsupporting

confidence: 79%

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

et al. 2018

View full text Add to dashboard Cite

Novel fluorinated 2-amino-4-oxo-6-substituted pyrrolo[2,3-d]pyrimidine analogues 7–12 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 8, 9, 11, and 12 showed increased in vitro antiproliferative activities (~11-fold) over the nonfluorinated analogues 2, 3, 5, and 6 toward engineered Chinese hamster ovary and HeLa cells expressing FRs or PCFT. Compounds 8, 9, 11, and 12 also inhibited proliferation of IGROV1 and A2780 epithelial ovarian cancer cells; in IGROV1 cells with knockdown of FRα, 9, 11, and 12 showed sustained inhibition associated with uptake by PCFT. All compounds inhibited glycinamide ribonucleotide formyltransferase, a key enzyme in the de novo purine biosynthesis pathway. Molecular modeling studies validated in vitro cell-based results. NMR evidence supports the presence of an intramolecular fluorine−hydrogen bond. Potent in vivo efficacy of 11 was established with IGROV1 xenografts in severe compromised immunodeficient mice.

show abstract

Section: Biological Evaluation and Discussionsupporting

confidence: 79%

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

et al. 2018

View full text Add to dashboard Cite

show abstract

Intramolecular OH⋅⋅⋅FC Hydrogen Bonding in Fluorinated Carbohydrates: CHF is a Better Hydrogen Bond Acceptor than CF₂

2013

View full text Add to dashboard Cite

Eine intramolekulare, gegabelte Wasserstoffbrücke zwischen der axialen HO2‐Gruppe, dem axialen F4‐Atom und dem O5‐Atom von α‐D‐Hexopyranosiden wurde in apolaren Lösungsmitteln mittels 1H‐NMR‐Spektren nachgewiesen. Die Wasserstoffakzeptorfähigkeit des F‐Atoms wird durch die Orientierung des O‐Substituenten am C3‐Atom und durch ein zusätzliches F‐Atom am C4‐Atom moduliert (siehe Bild).

show abstract

Intramolecular OH⋅⋅⋅FC Hydrogen Bonding in Fluorinated Carbohydrates: CHF is a Better Hydrogen Bond Acceptor than CF₂

2013

View full text Add to dashboard Cite

show abstract

Intra-molecular hydrogen bonding with organic fluorine in the solution state: Deriving evidence by a two dimensional NMR experiment

Cited by 19 publications

References 27 publications

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

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

Intramolecular OH⋅⋅⋅FC Hydrogen Bonding in Fluorinated Carbohydrates: CHF is a Better Hydrogen Bond Acceptor than CF₂

Intramolecular OH⋅⋅⋅FC Hydrogen Bonding in Fluorinated Carbohydrates: CHF is a Better Hydrogen Bond Acceptor than CF₂

Contact Info

Product

Resources

About

Intra-molecular hydrogen bonding with organic fluorine in the solution state: Deriving evidence by a two dimensional NMR experiment

Cited by 19 publications

References 27 publications

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

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

Intramolecular OH⋅⋅⋅FC Hydrogen Bonding in Fluorinated Carbohydrates: CHF is a Better Hydrogen Bond Acceptor than CF2

Intramolecular OH⋅⋅⋅FC Hydrogen Bonding in Fluorinated Carbohydrates: CHF is a Better Hydrogen Bond Acceptor than CF2

Contact Info

Product

Resources

About

Intramolecular OH⋅⋅⋅FC Hydrogen Bonding in Fluorinated Carbohydrates: CHF is a Better Hydrogen Bond Acceptor than CF₂

Intramolecular OH⋅⋅⋅FC Hydrogen Bonding in Fluorinated Carbohydrates: CHF is a Better Hydrogen Bond Acceptor than CF₂