737-76-8Relevant academic research and scientific papers
Synthesis of triazole-linked SAM-adenosine conjugates: Functionalization of adenosine at N-1 or N-6 position without protecting groups
Atdjian, Colette,Braud, Emmanuelle,Coelho, Dylan,Ethève-Quelquejeu, Mélanie,Iannazzo, Laura
, (2020)
More than 150 RNA chemical modifications have been identified to date. Among them, methylation of adenosine at the N-6 position (m6A) is crucial for RNA metabolism, stability and other important biological events. In particular, this is the most abundant
Potent SARS-CoV-2 mRNA Cap Methyltransferase Inhibitors by Bioisosteric Replacement of Methionine in SAM Cosubstrate
Bobi?eva, Olga,Bobrovs, Raitis,Ka?epe, Iveta,Patetko, Liene,Kalni??, Gints,?i?ovs, Mihails,Bula, Anna L.,Grī Nberga, Solveiga,Borodu??is, Mā Rti??,Ramata-Stunda, Anna,Rostoks, Nils,Jirgensons, Aigars,Tā Rs, Kaspars,Jaudzems, Kristaps
supporting information, p. 1102 - 1107 (2021/06/30)
Viral mRNA cap methyltransferases (MTases) are emerging targets for the development of broad-spectrum antiviral agents. In this work, we designed potential SARS-CoV-2 MTase Nsp14 and Nsp16 inhibitors by using bioisosteric substitution of the sulfonium and amino acid substructures of the cosubstrate S-adenosylmethionine (SAM), which serves as the methyl donor in the enzymatic reaction. The synthetically accessible target structures were prioritized using molecular docking. Testing of the inhibitory activity of the synthesized compounds showed nanomolar to submicromolar IC50 values for five compounds. To evaluate selectivity, enzymatic inhibition of the human glycine N-methyltransferase involved in cellular SAM/SAH ratio regulation was also determined, which indicated that the discovered compounds are nonselective inhibitors of the studied MTases with slight selectivity for Nsp16. No cytotoxic effects were observed; however, this is most likely a result of the poor cell permeability of all evaluated compounds.
Redox-Neutral P(O)-N Coupling between P(O)-H Compounds and Azides via Dual Copper and Photoredox Catalysis
Wu, Yanan,Chen, Ken,Ge, Xia,Ma, Panpan,Xu, Zhiyuan,Lu, Hongjian,Li, Guigen
, p. 6143 - 6149 (2020/07/30)
We report a redox-neutral P(O)-N coupling reaction of P(O)-H compounds with azides via photoredox and copper catalysis, providing new access to useful phosphinamides, phosphonamides, and phosphoramides. This transformation tolerates a wide range of nucleophilic functionalities including alcohol and amine nucleophiles, which makes up for the deficiency of classical nitrogen nucleophilic substitution reactions. As a demonstration of the broad potential applications of this new methodology, late-stage functionalization of a diverse array of azido-bearing natural products and drug molecules, a preliminary asymmetric reaction, and a continuous visible-light photoflow process have been developed.
A broad spectrum anticancer nucleoside with selective toxicity against human colon cells in vitro
Shelton, Jadd R.,Burt, Scott R.,Peterson, Matt A.
scheme or table, p. 1484 - 1487 (2011/04/23)
2′,3′-Bis-O-tert-butyldimethylsilyl-5′-deoxy-5′-[N- (methylcarbamoyl)amino]-N6-(N-phenylcarbamoyl)adenosine, a new member of the N6,5′-bis-ureidoadenosine class of anticancer nucleosides, is found to exhibit broad spectrum antiproliferative activity. A majority of the cell lines in the NCI-60 are inhibited with an average GI 50 = 3.13 μM. Selective toxicity against human colon cancer cell lines (COLO 205, HCC-2998, HCT-116, HT29, KM12) was also exhibited (LC 50's = 6-10 μM).
Preliminary SAR analysis of novel antiproliferative N6,5′-bis-ureidoadenosine derivatives
Peterson, Matt A.,Oliveira, Marcelio,Christiansen, Michael A.,Cutler, Christopher E.
supporting information; experimental part, p. 6775 - 6779 (2010/06/17)
A preliminary library of novel N6,5′-bis-ureidoadenosine analogs and related derivatives was prepared and tested for activity against the NCI 60 panel of human cancers. A 2′-O-TBS group was found to be necessary, but not sufficient, for optimal
Design, synthesis, and molecular modeling studies of 5′-deoxy-5′-ureidoadenosine: 5′-ureido group as multiple hydrogen bonding donor in the active site of S-adenosylhomocysteine hydrolase
Wang, Ting,Lee, Hyun Joo,Tosh, Dilip K.,Kim, Hea Ok,Pal, Shantanu,Choi, Sun,Lee, Yoonji,Moon, Hyung Ryong,Zhao, Long Xuan,Lee, Kang Man,Jeong, Lak Shin
, p. 4456 - 4459 (2008/02/10)
5′-Deoxy-5′-ureidoadenosine was designed and synthesized as a potent inhibitor of S-adenosylhomocysteine hydrolase (SAH), in which 5′-ureido group acted as multiple hydrogen bonding donor in binding with active site residues of SAH in the molecular modeli
Adenylate Deaminase (5′-Adenylic Acid Deaminase, AMPDA)-Catalyzed Deamination of 5′-Deoxy-5′-Substituted and 5′-Protected Adenosines: A Comparison with the Catalytic Activity of Adenosine Deaminase (ADA)
Ciuffreda, Pierangela,Loseto, Angela,Alessandrini, Laura,Terraneo, Giancarlo,Santaniello, Enzo
, p. 4748 - 4751 (2007/10/03)
The enzyme adenylate deaminase (AMPDA) is able to catalyze the hydrolytic deamination of 5′-substituted and 5′-protected 5′ -deoxyadenosines, whereas limited or no activity is shown by adenosine deaminase (ADA) towards the same substrates. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
Expeditious synthesis of aziridine-based cofactor mimics
Comstock, Lindsay R,Rajski, Scott R
, p. 6019 - 6026 (2007/10/03)
S-Adenosyl-L-methionine mimics were synthesized in a linear fashion highlighting methodology that bypasses the need for adenine base protection. These aziridine-based cofactor mimics are envisioned as useful biochemical tools and potential therapeutic agents whose mechanism of action hinges upon aberrant methyltransferase enzymes. Aziridination of the 5′ position of adenosine was effected by convergence of suitably protected 5′-aminoadenosine with various dibromopropionates. The economy and high yields for this route to said aziridine-based cofactors is highly amenable to large-scale chemistry which no doubt will be vital to their development as therapeutics and biochemical tools.
