Constrained NBMPR analogue synthesis, pharmacophore mapping and 3D-QSAR modeling of equilibrative nucleoside transporter 1 (ENT1) inhibitory activity was written by Zhu, Zhengxiang;Buolamwini, John K.. And the article was included in Bioorganic & Medicinal Chemistry in 2008.Electric Literature of C11H13IN4O4 The following contents are mentioned in the article:
Conformationally constrained analog synthesis was undertaken to aid in pharmacophore mapping and 3D-QSAR anal. of nitrobenzylmercaptopurine riboside (NBMPR) congeners as equilibrative nucleoside transporter 1 (ENT1) inhibitors. In our previous study, novel regioisomeric nitro-1,2,3,4-tetrahydroisoquinoline conformationally constrained analogs of NBMPR were synthesized and evaluated as ENT1 ligands. 7-NO2-1,2,3,4-Tetrahydroisoquino-2-yl purine riboside was identified as the analog with the nitro group in the best orientation at the NBMPR binding site of ENT1. In the present study, further conformational constraining was introduced by synthesizing 5′-O,8-cyclo derivatives The flow cytometrically determined binding affinities indicated that the addnl. 5′-O,8-cyclo constraining was unfavorable for binding to the ENT1 transporter. The structure-activity relation (SAR) acquired was applied to pharmacophore mapping using the PHASE program. The best pharmacophore hypothesis obtained embodied an anti-conformation with three hydrogen-bond acceptors, one hydrophobic center, and two aromatic rings involving the 3′-OH, 4′-oxygen, the NO2 group, the benzyl Ph and the imidazole and pyrimidine portions of the purine ring, resp. A PHASE 3D-QSAR model derived with this pharmacophore yielded an r2 of 0.916 for four (4) PLS components, and an excellent external test set predictive r2 of 0.78 for 39 compounds This pharmacophore was used for mol. alignment in a comparative mol. field anal. (CoMFA) 3D-QSAR study that also afforded a predictive model with external test set validation predictive r2 of 0.73. Thus, although limited, this study suggests that the bioactive conformation for NBMPR at the ENT1 transporter could be anti. The study has also suggested an ENT1 inhibitory pharmacophore, and established a predictive CoMFA 3D-QSAR model that might be useful for novel ENT1 inhibitor discovery and optimization. This study involved multiple reactions and reactants, such as (2R,3R,4S,5R)-2-(4-Amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (cas: 24386-93-4Electric Literature of C11H13IN4O4).
(2R,3R,4S,5R)-2-(4-Amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (cas: 24386-93-4) belongs to tetrahydrofuran derivatives. Tetrahydrofurans and furans are important oxygen-containing heterocycles that often exhibit interesting properties for biological applications or applications in the cosmetic industry. THF (Tetrahydrofuran) is also used as a starting material for the synthesis of poly(tetramethylene ether) glycol (PTMG), etc.Electric Literature of C11H13IN4O4
Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem