5451-40-1Relevant academic research and scientific papers
Purine-benzimidazole hybrids: Synthesis, single crystal determination and in vitro evaluation of antitumor activities
Sharma, Alka,Luxami, Vijay,Paul, Kamaldeep
, p. 414 - 422 (2015)
In an effort to identify novel compounds for the treatment of cancer, a diverse array of potential bioactive hybrid, purine-benzimidazole was synthesized in good yields through nucleophilic substitution at C6 position of purine ring with versatile cyclic amines at C2 position. The structures of newly prepared compounds were confirmed by IR, 1H, 13C NMR, mass spectroscopy and, in case of 19, by single crystal Xray diffraction analysis. The newly synthesized compounds were evaluated against 60 human tumour cell lines at one dose concentration level. Compound 6 exhibited significant growth inhibition and was evaluated as 60 cell panel at five dose concentration levels. Compound 6 proved to be 1.25 fold more active than the positive control 5-FU, with GI50 value of 18.12 μM (MG-MID). Interaction of the compounds with Aurora-A enzyme involved in the process of propagation of cancer, has also been investigated. Compound 6 showed selectivity towards Aurora-A kinase inhibition with IC50 value of 0.0l mM. Molecular docking studies in the active binding site provided theoretical support for the experimental biological data acquired.
Facile and practical synthesis of 2,6-dichloropurine
Zeng, Qi,Huang, Bangzhou,Danielsen, Knut,Shukla, Rajesh,Nagy, Thomas
, p. 962 - 963 (2004)
A facile and industrially viable process for preparation of 2,6-dichloropurine is reported. The process involves direct chlorination of xanthine with phosphorus oxychloride and a weak nucleophilic organic base, such as amidine, guanidine base, or Proton-Sponge.
SUBSTITUTED BICYCLIC PYRIMIDINE-BASED COMPOUNDS AND COMPOSITIONS AND USES THEREOF
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Paragraph 00230; 00231, (2018/08/20)
Novel C-2-substituted bicyclic compounds of Formula I have been prepared and found to be useful as potent inhibitors of hGGPPS by inhibiting geranylgeranylation of proteins and inhibiting the biosynthesis of GGPP. The application is directed to these compounds, to compositions comprising these compounds, and to their use, in particular as medicaments for use in the treatment of cancer and other conditions which are treatable by inhibiting human geranylgeranylation pyrophosphate hGGPPS activity.
Design, Synthesis, and Immunological Evaluation of a Multicomponent Construct Based on a Glycotripeptoid Core Comprising B and T Cell Epitopes and a Toll-like Receptor 7 Agonist That Elicits Potent Immune Responses
Szekely, Thomas,Roy, Olivier,Dériaud, Edith,Job, Aurélie,Lo-Man, Richard,Leclerc, Claude,Taillefumier, Claude
supporting information, p. 9568 - 9582 (2018/11/23)
We present here for the first time the synthesis and immunological evaluation of a fully synthetic three-component anticancer vaccine candidate that consists of a β-glycotripeptoid core mimicking a cluster of Tn at the surface of tumor cells (B epitope), conjugated to the OVA 323-339 peptide (T-cell epitope) and a Toll-like receptor 7 (TLR7) agonist for potent adjuvanticity. The immunological evaluation of this construct and of precursor components demonstrated the synergistic activity of the components within the conjugate to stimulate innate and adaptive immune cells (DCs, T-helper, and B-cells). Surprisingly, immunization of mice with the tricomponent GalNAc-based construct elicited a low level of anti-Tn IgG but elicited a very high level of antibodies that recognize the TLR7 agonist. This finding could represent a potential vaccine therapeutic approach for the treatment of some autoimmune diseases such as lupus.
Prolinamides of Aminouracils, Organocatalyst Modifiable by Complementary Modules
Ruíz-Pérez, Karen M.,Quiroz-García, Beatriz,Hernández-Rodríguez, Marcos
supporting information, p. 5763 - 5772 (2018/11/10)
We report the synthesis and evaluation of prolinamide organocatalysts that incorporate aminouracils. The features of these catalysts are enhanced NH acidity of the amide because of the electron-withdrawing nature of the heterocycle, an additional hydrogen-bond donor at the α or β positions of this functional group (using 6-aminouracil or 5,6-diaminouracil respectively), and it can be recovered due to its low solubility and used again without decreasing the enantioselectivity. A unique feature of these systems is the self-assembly capability with complementary modules by Watson–Crick interactions. These supramolecular adducts behave differently from the catalyst alone, some of them have lower performance but others improve the selectivity of the product. Therefore, this approach avoids the synthesis of many catalysts.
Design, synthesis and evaluation of 4-aminoquinoline-purine hybrids as potential antiplasmodial agents
Reddy, P. Linga,Khan, Shabana I.,Ponnan, Prija,Tripathi, Mohit,Rawat, Diwan S.
, p. 675 - 686 (2016/12/14)
A novel series of 4-aminoquinoline-purine hybrids were synthesized and assessed for their antiplasmodial activity against CQ-sensitive and CQ-resistant strains of P. falciparum. It was envisaged that linking of the 4-aminoquinoline pharmacophore (targeting heme-detoxification pathway of malarial parasite) with the purine functionality (targeting plasmodial HG(X)PRT enzyme) will produce a hybrid antiplasmodial agent with increased potency. The synthesized hybrids displayed good antiplasmodial activities against both the sensitive and resistant strains of P. falciparum with up to six-fold better activity (compound 10i, IC50: 0.08?μM) compared to the reference drug CQ (IC50: 0.5?μM) against the resistant strain. The synthesized compounds were also checked for their cytotoxicity towards mammalian cells and with the exception of two compounds out of the twenty synthesized hybrids, all others were non-cytotoxic up to 11.86?μM concentration. Mechanistic heme-binding studies were performed to identify the mechanism of action of the synthesized molecules and good binding interactions were observed. Computational docking studies showed that the most active hybrids dock well within the binding site of HGPRT protein. In silico ADME predictions of the most active hybrids showed that these compounds possess good pharmacokinetic behavior.
Identification of 2,4-diamino-6,7-dimethoxyquinoline derivatives as G9a inhibitors
Srimongkolpithak, Nitipol,Sundriyal, Sandeep,Li, Fengling,Vedadi, Masoud,Fuchter, Matthew J.
, p. 1821 - 1828 (2015/01/08)
G9a is a histone lysine methyltransferase (HKMT) involved in epigenetic regulation via the installation of histone methylation marks. 6,7-Dimethoxyquinazoline analogues, such as BIX-01294, are established as potent, substrate competitive inhibitors of G9a. With an objective to identify novel chemotypes for substrate competitive inhibitors of G9a, we have designed and synthesised a range of heterocyclic scaffolds, and investigated their ability to inhibit G9a. These studies have led to improved understanding of the key pharmacophoric features of BIX-01294 and the identification of a new core quinoline inhibitory scaffold, which retains excellent potency and high selectivity. Molecular docking was carried out to explain the observed in vitro data. This journal is
Facile synthesis of 8-azido-6-benzylaminopurine
Steklov, Mikhail Yu.,Tararov, Vitali I.,Romanov, Georgy A.,Mikhailov, Sergey N.
, p. 503 - 511 (2011/12/21)
Bromination of 6-benzylaminopurine (1) with Br2 in AcOH in the presence of AcONa afforded 6-benzylamino-8-bromopurine (2) in 59% yield. The position of bromination was confirmed by direct transformation of bromide 2 by reaction with NaN3 in dimethyl sulfoxide to 8-azido-6-benzylaminopurine (3) in a yield of 70% and comparison of its properties with the known compound 2-azido-6- benzylaminopurine (11). Compounds 3 and 11 were checked for their biological activity in specific biotests based on the primary cytokinin effects in living plants. Both synthesized compounds displayed effects similar to the typical cytokinin 6-benzylaminopurine (1). Copyright Taylor and Francis Group, LLC.
Microwave assisted synthesis of 2,6-substituted aromatic-aminopurine derivatives
Lu, Hong-Fei,Zhang, Liang-Ze,Wu, Ding-Ming,Zhou, Jun-Tao
scheme or table, p. 1140 - 1144 (2011/11/04)
A series of novel 2, 6-diaromatic-aminopurines (6a-6t) have been synthesized from guanine and characterized fully. The effects of different catalysts on the N-alkylation of 2-position of purine ring were discussed.
Solvent-free or low-solvent large-scale preparation of chloropyrimidine and analogues
Sun, Zhihua,Wang, Han,Wen, Kun,Li, Ya,Fan, Erkang
experimental part, p. 4149 - 4153 (2011/07/07)
Chloropyrimidine or other N-containing aromatic heterocyclic analogues can be efficiently prepared from the corresponding hydroxylated precursors under solvent-free or low-solvent conditions with equimolar or less chlorinating reagents. This high-yielding protocol allows successful preparations of multigram and kilogram batches of these important synthetic intermediates.
