14065-32-8Relevant articles and documents
Tumor-targeting with novel non-benzoyl 6-substituted straight chain pyrrolo[2,3-d ]pyrimidine antifolates via cellular uptake by folate receptor α and inhibition of de novo purine nucleotide biosynthesis
Wang, Yiqiang,Cherian, Christina,Orr, Steven,Mitchell-Ryan, Shermaine,Hou, Zhanjun,Raghavan, Sudhir,Matherly, Larry H.,Gangjee, Aleem
, p. 8684 - 8695 (2013)
A new series of 6-substituted straight side chain pyrrolo[2,3-d]pyrimidines 3a-d with varying chain lengths (n = 5-8) was designed and synthesized as part of our program to provide targeted antitumor agents with folate receptor (FR) cellular uptake specificity and glycinamide ribonucleotide formyltransferase (GARFTase) inhibition. Carboxylic acids 4a-d were converted to the acid chlorides and reacted with diazomethane, followed by 48% HBr to generate the α-bromomethylketones 5a-d. Condensation of 2,4-diamino-6-hydroxypyrimidine 6 with 5a-d afforded the 6-substituted pyrrolo[2,3-d]pyrimidines 7a-d. Hydrolysis and subsequent coupling with diethyl l-glutamate and saponification afforded target compounds 3a-d. Compounds 3b-d showed selective cellular uptake via FRα and -β, associated with high affinity binding and inhibition of de novo purine nucleotide biosynthesis via GARFTase, resulting in potent inhibition against FR-expressing Chinese hamster cells and human KB tumor cells in culture. Our studies establish, for the first time, that a side chain benzoyl group is not essential for tumor-selective drug uptake by FRα.
Novel (3,5-di-tert-butyl-2-hydroxy-phenylcarbamoyl)-alkanoic acids as potent antioxidants
Lodyato, Vladimir I.,Yurkova, Irina L.,Sorokin, Viktor L.,Shadyro, Oleg I.,Dolgopalets, Vladimir I.,Kisel, Mikhail A.
, p. 4253 - 4256 (2004)
A series of novel phenolic antioxidants of amphiphilic structure has been synthesized. Investigations into the influence of aliphatic spacer length and nature of a hydrophilic anchor on the antioxidant activity allowed elucidating certain structure requirements for the membrane-addressed antioxidant designing.
SYNTHETIC PROCESSES AND INTERMEDIATES
-
Page/Page column 31, (2021/06/26)
The invention provides synthetic processes and synthetic intermediate compounds that can be used to prepare therapeutic conjugates. The invention also provides methods for treating HBV and/or HDV infection in a human by administering a therapeutic conjugate prepared by the synthetic methods of the invention.
Defining a minimum pharmacophore for simocyclinone D8 disruption of DNA gyrase binding to DNA
Gaskell, Lauren M.,Nguyen, Thuy,Ellis, Keith C.
, p. 3632 - 3643 (2014/08/05)
The increasing occurrence of drug-resistant bacterial infections in the clinic has created a need for new antibacterial agents. Natural products have historically been a rich source of both antibiotics and lead compounds for new antibacterial agents. The natural product simocyclinone D8 (SD8) has been reported to inhibit DNA gyrase, a validated antibacterial drug target, by a unique catalytic inhibition mechanism of action. In this work, we have used a deconstruction-reconstruction approach to prepare analogs of the coumarin subunit of SD8 and evaluated their ability to disrupt binding of the DNA gyrase enzyme to DNA in a surface plasmon resonance assay. This has led to a minimum pharmacophore required for disruption of binding. Springer Science+Business Media 2014.
