3691-50-7Relevant academic research and scientific papers
Lead optimization and biological evaluation of fragment-based cN-II inhibitors
Guillon, Rémi,Rahimova, Rahila,Preeti,Egron, David,Rouanet, Sonia,Dumontet, Charles,Aghajari, Nushin,Jordheim, Lars Petter,Chaloin, Laurent,Peyrottes, Suzanne
, p. 28 - 44 (2019/02/25)
The development of cytosolic 5′-nucleotidase II (cN-II) inhibitors is essential to validate cN-II as a potential target for the reversion of resistance to cytotoxic nucleoside analogues. We previously reported a fragment-based approach combined with molecular modelling, herein, the selected hit-fragments were used again in another computational approach based on the Ilib-diverse (a software enabling to build virtual molecule libraries through fragment based de novo design) program to generate a focused library of potential inhibitors. A molecular scaffold related to a previously identified compound was selected and led to a novel series of compounds. Ten out of nineteen derivatives showed 50–75% inhibition on the purified recombinant protein at 200 μM and among them three derivatives (12, 13 and 18) exhibited Ki in the sub-millimolar range (0.84, 2.4 and 0.58 mM, respectively). Despite their only modest potency, the cN-II inhibitors showed synergistic effects when used in combination with cytotoxic purine nucleoside analogues on cancer cells. Therefore, these derivatives represent a family of non-nucleos(t)idic cN-II inhibitors with potential usefulness to overcome cancer drug resistance especially in hematological malignancies in which cN-II activity has been described as an important parameter.
Regioselective and efficient synthesis of N 7-substituted adenines, guanines, and 6-mercaptopurines
Maryska, Michal,Chudikova, Nadezda,Kotek, Vladislav,Dvorak, Dalimil,Tobrman, Tomas
, p. 501 - 507 (2013/07/26)
A simple and efficient protocol for the preparation of N 7-substituted adenines, guanines, and 6-mercaptopurines is described. The key step is the regioselective preparation of 7-substituted 6-chloropurines which are building blocks for the div
DIKETO ACIDS WITH NUCLEOBASE SCAFFOLDS: ANTI-HIV REPLICATION INHIBITORS TARGETED AT HIV INTEGRASE IN COMBINATION THERAPY
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Page/Page column 60; 64; 69, (2008/06/13)
A new class of diketo acids constructed on nucleobase scaffolds, designed as inhibitors of HIV replication through inhibition of HIV integrase, is described. These compounds are useful in the prevention or treatment of infection by HFV and in the treatmen
Heterocyclic Ambident Nucleophiles. III* The Alkylation of Sodium Adenide
Rasmussen, Malcolm,Hope, Janet M.
, p. 525 - 534 (2007/10/02)
The alkylation of sodium adenide in HCONMe2 (30 deg) with various alkylating agents was analysed by 1H n.m.r. spectroscopy.Widely varying N3:N7:N9 alkylation patterns were observed, depending on the alkylating agent.These patterns are interpreted in terms of the electrostatic, thermodynamic and steric factors involved in the different SN2 transition states appropriate to each alkylating agent.Hydrogen bonding association between the 6-amino group and certain carbonyl containing alkylating agents is proposed to explain the enhancedN7-alkylation in some cases.Support for this latter proposal was obtain from a comparison of the adenine alkylation results with the corresponding alkylation patterns of 6-pivaloylamino- and 6-chloro-purine.
Heterocyclic Ambident Nucleophiles. IV* The alkylation of Metal Salts of Adenine
Rasmussen, Malcolm,Hope, Janet M.
, p. 535 - 542 (2007/10/02)
The N3:N7:N9 alkylation patterns for reactions of the lithium, sodium, and potassium salts of adenine with various alkylating agents in dimethyl sulfoxide were determined by 1H n.m.r. spectroscopy.Only for the Li+ salt was any significant effect of ionic association noticed.Of the alkylating agents used, only chloromethyl pivalate gave a concentration dependent alkylation pattern.The latter effect was most pronounced with the heterogenous alkylation conditions of anhydrous Na2CO3/HCONMe2, adenine, and chloromethyl pivalate; here, increasingconcentrations changed the main reaction from N7- to N9-alkylation.Solvent effects on the alkylation patterns were also studied.Within the common dipolar aprotic solvent group, (Me2N)3PO, HCONMe2 and Me2SO, effects were small; in protic solvents, particularly formamide, enhanced N3-alkylation was observed.
