4788-79-8Relevant academic research and scientific papers
Tumor Targeting with Novel 6-Substituted Pyrrolo [2,3-d] Pyrimidine Antifolates with Heteroatom Bridge Substitutions via Cellular Uptake by Folate Receptor α and the Proton-Coupled Folate Transporter and Inhibition of de Novo Purine Nucleotide Biosynthesis
Golani, Lalit K.,Wallace-Povirk, Adrianne,Deis, Siobhan M.,Wong, Jennifer,Ke, Jiyuan,Gu, Xin,Raghavan, Sudhir,Wilson, Mike R.,Li, Xinxin,Polin, Lisa,De Waal, Parker W.,White, Kathryn,Kushner, Juiwanna,O'Connor, Carrie,Hou, Zhanjun,Xu, H. Eric,Melcher, Karsten,Dann, Charles E.,Matherly, Larry H.,Gangjee, Aleem
, p. 7856 - 7876 (2016/10/12)
Targeted antifolates with heteroatom replacements of the carbon vicinal to the phenyl ring in 1 by N (4), O (8), or S (9), or with N-substituted formyl (5), acetyl (6), or trifluoroacetyl (7) moieties, were synthesized and tested for selective cellular uptake by folate receptor (FR) α and β or the proton-coupled folate transporter. Results show increased in vitro antiproliferative activity toward engineered Chinese hamster ovary cells expressing FRs by 4-9 over the CH2 analogue 1. Compounds 4-9 inhibited de novo purine biosynthesis and glycinamide ribonucleotide formyltransferase (GARFTase). X-ray crystal structures for 4 with FRα and GARFTase showed that the bound conformations of 4 required flexibility for attachment to both FRα and GARFTase. In mice bearing IGROV1 ovarian tumor xenografts, 4 was highly efficacious. Our results establish that heteroatom substitutions in the 3-atom bridge region of 6-substituted pyrrolo[2,3-d]pyrimidines related to 1 provide targeted antifolates that warrant further evaluation as anticancer agents.
Open chain nitrogen compounds. Part XI. 3,7-Bis(arylazo)-1,3,5,7-tetraazabicyclononanes: the reaction of diazonium ions with ammonia-formaldehyde mixtures
Singer, Robert D.,Vaughan, Keith,Hooper, Donald L.
, p. 1567 - 1572 (2007/10/02)
Reaction of a series of diazonium salts with either hexamine or an aqueous mixture of ammonia-formaldehyde affords 3,7-bis(arylazo)-1,3,5,7-tetraazabicyclononanes; several new examples of this novel class of bicycloheterocycle have been prepared and characterized.Analysis of the low-temperature nmr spectra of one compound in this series shows that the bicyclic system prefers the chair-chair conformation.The bis(arylazo)tetraazabicyclononanes, which are surprisingly stable in aqueous buffer compared to analogous triazenes of open-chain structure, do undergo slow decomposition at slight acidic pH in an acetone-buffer mixture.The apparent product of this decomposition is the arylamine, which is observed as the Mannich condensation product, ArNH.CH2CH2COCH3.
