- Synthesis and Evaluation of Radiolabeled Phosphoramide Mustard with Selectivity for Hypoxic Cancer Cells
-
Tumor hypoxia has been widely explored over the years as a diagnostic and therapeutic marker. Herein, we synthesized an alkyne functionalized version of evofosfamide, a hypoxia-selective prodrug. The purpose of this effort was to investigate if this novel 2-nitroimidazole phosphoramide nitrogen mustard (2-NIPAM) retained hypoxia selectivity and could be utilized in radiopharmaceutical development to significantly increase retention of conjugated agents in hypoxic cells. 2-NIPAM demonstrated good hypoxia selectivity with a 62- and 225-fold increase in cytotoxicity toward PC-3 and DU145 human prostate cancer cell lines, respectively, under hypoxic conditions. Radiolabeling of 2-NIPAM with 125I was accomplished through a Cu(I)-mediated azide-alkyne cycloaddition reaction. The 125I-conjugate demonstrated 13.6 and 17.8% lower efflux rates for DU145 and PC-3 cells, correspondingly, under hypoxic conditions, suggesting that the increased retention is likely due to the known intracellular trapping mechanism. In conclusion, these studies demonstrate the potential of 2-NIPAM in serving as a trapping agent for radiopharmaceutical development.
- Zhang, Wenting,Fan, Wei,Zhou, Zhengyuan,Garrison, Jered
-
-
Read Online
- Monitoring and Modulating mtDNA G-Quadruplex Dynamics Reveal Its Close Relationship to Cell Glycolysis
-
The mitochondrial DNA G-quadruplex (mtDNA G4) is a potential regulatory element for the regulation of mitochondrial functions; however, its relevance and specific roles in diseases remain largely unknown. Here, we engineered a set of chemical probes, incl
- Chen, Shuo-Bin,Chen, Xiu-Cai,Dai, Jing,Huang, Zhi-Shu,Luo, Wen-Hua,Shao, Wen,Tan, Jia-Heng,Tang, Gui-Xue,Zeng, Shu-Tang
-
supporting information
p. 20779 - 20791
(2021/12/14)
-
- Enantio- and Regioselective Palladium(II)-Catalyzed Dioxygenation of (Aza-)Alkenols
-
An oxidative Pd-catalyzed intra-intermolecular dioxygenation of (aza-)alkenols has been reported, with total regioselectivity. To study the stereoselectivity, different chiral ligands as well as different hypervalent-iodine compounds have been compared. I
- Giofrè, Sabrina,Molteni, Letizia,Nava, Donatella,Lo Presti, Leonardo,Beccalli, Egle Maria
-
supporting information
p. 21723 - 21727
(2021/09/08)
-
- HETEROCYCLIC COMPOUNDS AND THEIR USE IN PREVENTING OR TREATING BACTERIAL INFECTIONS
-
The invention relates to a compound of formula (I) and a racemate, an enantiomer, a diastereoisomer, a geometric isomer or a pharmaceutically acceptable salt thereof, and its use as antibacterial agent.
- -
-
Page/Page column 161
(2018/04/17)
-
- Vinyl dihydropyrans and dihydrooxazines: Cyclizations of catalytic ruthenium carbenes derived from alkynals and alkynones
-
A novel synthesis of 2-vinyldihydropyrans and dihydro-1,4-oxazines (morpholine derivatives) from alkynals and alkynones has been developed. The cyclizations require a mild generation of catalytic ruthenium carbenes from terminal alkynes and (trimethylsilyl)diazomethane followed by trapping with carbonyl nucleophiles. Mechanistic aspects of the new cyclizations are discussed. Setting a trap: A novel synthesis of 2-vinyldihydropyrans and dihydro-1,4-oxazines (morpholine derivatives) from alkynals and alkynones has been developed. The cyclizations require a mild generation of catalytic ruthenium carbenes from terminal alkynes and (trimethylsilyl)diazomethane followed by trapping with carbonyl nucleophiles.
- Cambeiro, Fermin,Lopez, Susana,Varela, Jesus A.,Saa, Carlos
-
supporting information
p. 5959 - 5963
(2014/06/10)
-
- Thermally induced substrate release via intramolecular cyclizations of Amino esters and Amino carbonates
-
The relative cleavage of an alcohol from a panel of amino esters and amino carbonates via intramolecular cyclization was examined as a mechanism for substrate release. Thermal stability at 37 °C was observed only for the seven-membered ring progenitors. Applicability of the approach was illustrated by δ-lactam formation within a poly(dimethylsiloxane) microchannel for release of a captured fluorescent probe.
- Knipp, Ralph J.,Estrada, Rosendo,Sethu, Palaniappan,Nantz, Michael H.
-
p. 3422 - 3429
(2014/05/06)
-
- Ring-annulated dihydropyrrolo[2,1-alpha]isoquinolines
-
The invention relates to ring-annulated dihydropyrrolo[2,1-a]isoquinoline compounds according to general Formula I or a pharmaceutically acceptable salt thereof. The compounds can be used for the treatment of infertility.
- -
-
Page/Page column 28-29
(2011/02/25)
-
- RING-ANNULATED DIHYDROPYRROLO[2,1-A]ISOQUINOLINES
-
The invention relates to ring-annulated dihydropyrrolo[2,1-a]isoquinoline compounds according to general Formula (I) or a pharmaceutically acceptable salt thereof. The compounds can be used for the treatment of infertility
- -
-
Page/Page column 60-61
(2011/02/24)
-
- Synthesis of pyridines and pyrazines using an intramolecular hydroamination-based reaction sequence
-
A management issue! Various pyridines and pyrazines can be efficiently accessed from simple acyclic precursors using an intramolecular hydroamination/isomerization/aromatization sequence (see scheme). ρ-Toluenesulfonic acid (2 mol%) is used to catalyze this novel alkyne annulation, in which the oxime group allows for a subsequent redoxneutral aromatization step to occur.
- Rizk, Toni,Bilodeau, Eric J.-F.,Beauchemin, Andre M.
-
supporting information; experimental part
p. 8325 - 8327
(2010/01/16)
-
- Ketyl-allene cyclizations promoted by samarium(II) iodide
-
(Chemical Equation Presented) Samarium(II) iodide has proven to be an effective reagent for intramolecular reductive coupling Sreactions. Previous investigations of intramolecular ketyl-olefin coupling reactions provided carbocycles in excellent yield and good diastereoselectivity. This method has been extended to ketyl cyclizations with allenes. Substrates leading to both carbocycles and heterocycles in a selective manner are explored.
- Molander, Gary A.,Cormier, Elizabeth Pollina
-
p. 2622 - 2626
(2007/10/03)
-
- Steric acceleration of activated ene reactions
-
Steric buttressing has been used to effect ene reactions involving conjugated enoic esters under relatively mild conditions and with improved control of observed stereoselectivities.
- Sammes, Peter G.,Smith, Graham,Ward, Robert W.
-
p. 785 - 788
(2007/10/03)
-