- Novel Substituted Purine Isosteres: Synthesis, Structure-Activity Relationships and Cytotoxic Activity Evaluation
-
A number of pyrrolo[2,3-c]pyridines, pyrrolo[3,2-d]pyrimidines and pyrazolo[4,3-d]pyrimidines were designed and synthesized as antiproliferative agents. The target compounds possessed selected substituents in analogous positions on the central scaffold th
- Dimitrakis, Spyridon,Gavriil, Efthymios-Spyridon,Gioti, Katerina,Lougiakis, Nikolaos,Marakos, Panagiotis,Pouli, Nicole,Pousias, Athanasios,Tenta, Roxane
-
-
- Design and synthesis of new substituted pyrazolopyridines with potent antiproliferative activity
-
Background: Purine isosteres are often endowed with interesting pharmacological properties, due to their involvement in cellular processes replacing the natural purines. Among these compounds, pyrazolopyridines are under active investigation for potential anticancer proper-ties. Objectives: Based on previously discovered substituted pyrazolopyridines with promising antipro-liferative activity, we designed and synthesized new, suitably substituted analogues aiming to investigate their potential activity and contribute to SAR studies of this class of bioactive com-pounds. Methods: The new compounds were synthesized using suitably substituted 2-amino-4-picolines, which upon ring-closure provided substituted pyrazolo[3,4-c] pyridine-5-carbonitriles that served as key intermediates for the preparation of the target 3,5,7 trisubstituted derivatives. The antipro-liferative activity of 31 new target derivatives was evaluated against three cancer cell lines (MIA PaCa-2, PC-3 and SCOV3), whereas cell-cycle perturbations of exponentially growing PC-3 cells, using three selected derivatives were also performed. Results: Eight compounds displayed IC50 values in the low μM range, allowing the extraction of interesting SAR’s. Two of the most potent compounds against all cell lines share a common pat-tern, by accumulating cells at the G0/G1 phase. From this project, a new carboxamidine-substituted hit has emerged. Conclusion: Among the new compounds, those possessing the 3-phenylpyrazolo[3,4-c]pyridine scaffold, proved to be worth investigating and the majority of them showed strong cytotoxic activity against all cell lines, with IC50 values ranging from 0.87-4.3 μM. A carboxamidine analogue that resulted from the synthetic procedure, proved to be highly active against the cancer cells and could be considered as a useful lead for further optimization.
- Giannouli, Vassiliki,Gioti, Katerina,Horne, David A.,Kostakis, Ioannis K.,Lougiakis, Nikolaos,Mara-Kos, Panagiotis,Nam, Sangkil,Pouli, Nicole,Skaltsounis, Alexios-Leandros,Tenta, Roxane
-
p. 176 - 191
(2020/03/10)
-
- Simple preparation method of nevirapine
-
The invention relates to a simple preparation method of nevirapine. In the invention, 2-nitro-3-methyl-4-halo-5-oxo-n-valerate is obtained by 1,4-addition reaction of 2-nitroacetate and 2-halogenatedcrotonaldehyde, then 3-nitro-4-methylpyridine-2-one is obtained by cyclization with ammonia, and 2-chloro-3-nitro-4-methylpyridine is prepared by chlorination reagent. 2-cyclopropyl aminonicotinic acid is prepared from 2-chloronicotinic acid and cyclopropylamine through a first substitution reaction, 2-[N-cyclopropyl-N-(3-nitro-4-methylpyridine-2-yl)] aminonicotinic acid is prepared from 2-chloro-3-nitro-4-methylpyridine through a second substitution reaction, and nevirapine is prepared through catalytic hydrogenation and amidation reaction. The method has the advantages of cheap and easily available raw materials, mild process, simple and convenient operation, high reaction activity, high product yield and purity, and small amount of three wastes.
- -
-
Paragraph 0054; 0073-0076
(2019/10/01)
-
- Synthesis, docking study and kinase inhibitory activity of a number of new substituted pyrazolo[3,4-c]pyridines
-
A series of new pyrazolo[3,4-c]pyridines bearing various 1, 3, 5 or 1, 3, 7 pattern substitutions, were designed and synthesized. Some of them showed interesting inhibitory activity mainly against glycogen synthase kinase 3 (GSK3)α/β as well as against cdc2-like kinases 1 (CLK1) and dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), with good selectivity and remarkable structure-activity relationships (SARs), without being cytotoxic. Molecular simulations in correlation with biological data revealed the importance of the existence of N1-H as well as the absence of a bulky 7-substituent.
- Sklepari, Meropi,Lougiakis, Nikolaos,Papastathopoulos, Athanasios,Pouli, Nicole,Marakos, Panagiotis,Myrianthopoulos, Vassilios,Robert, Thomas,Bach, Stéphane,Mikros, Emmanuel,Ruchaud, Sandrine
-
-
- Synthesis and Antiproliferative Activity of New pyrazolo[3,4-c]pyridines
-
Background: Several pyrazolopyridines possess promising pharmacological activities, mainly attributed to their antagonistic nature towards the natural purines in many biological processes. Cytotoxicity and anticancer potential of this class of compounds a
- Gavriil, Efthymios-Spyridon,Lougiakis, Nikolaos,Pouli, Nicole,Marakos, Panagiotis,Skaltsounis, Alexios-Leandros,Nam, Sangkil,Jove, Richard,Horne, David,Gioti, Katerina,Pratsinis, Harris,Kletsas, Dimitris,Tenta, Roxane
-
p. 365 - 374
(2017/06/21)
-
- THE NITROPYRIDINYL ETHYLENEIMINE COMPOUND, THE PHARMACEUTICAL COMPOSITION CONTAINING IT, THE PREPARATION METHOD AND USE THEREOF
-
The present invention discloses a nitropyridinyl ethyleneimine compound as shown in the formula I and a preparation method of the same, as well as use of the compound in manufacture of a prodrug and in manufacture of a drug for treating a tumor.
- -
-
-
- Synthesis of some fluorine-containing pyridinealdoximes of potential use for the treatment of organophosphorus nerve-agent poisoning
-
Fluoroheterocyclic aldoximes were screened as therapeutic agents for the treatment of anticholinesterase poisoning. 2-Fluoropyridine-3- and -6-aldoxime, and 3-fluoropyridine-2- and -4-aldoxime, were synthesised. Attempts to obtain 3,5,6-trifluoropyridine-2,4-bis(aldoxime) and -2-aldoxime, however, proved unsuccessful. Pentafluorobenzaldoxime was prepared by oximation of pentafluorobenzaldehyde. Acid dissociation constants (pKa) and second-order rate constants (kox-) of the fluorinated pyridinealdoximes towards sarin were measured. 2,3,5,6-Tetrafluoropyridine-4- aldoxime had the best profile: its kox- approached that of the therapeutic oxime P2S (310 vs. 120 l mol-1 min-1), but its higher pKa (9.1 vs. 7.8) fell short of the target figure of 8 required for reactivation of inhibited acetylcholinesterase in vivo. N-alkylation of the fluorinated pyridine-aldoximes may reduce their pK a nearer to 8 and enhance their therapeutic potential. Crown Copyright
- Timperley, Christopher M.,Banks, R. Eric,Young, Ian M.,Haszeldine, Robert N.
-
scheme or table
p. 541 - 547
(2011/09/15)
-
- Design, synthesis and dopamine D4 receptor binding activities of new N-heteroaromatic 5/6-ring Mannich bases
-
A series of phenylpiperazine-methyl-substituted 1H-pyrrolo[2,3-c]pyridine, imidazo[1,2-c]-, pyrrolo[2,3-d]- and pyrrolo[3,2-d]pyrimidines were prepared as selective dopamine D4-ligands. The pyrrolo[2,3-d]pyrimidine derivatives 12d (Ki = 1,9 nM)
- Linz, Sabine,Mueller, Joerg,Huebner, Harald,Gmeiner, Peter,Troschuetz, Reinhard
-
experimental part
p. 4448 - 4458
(2009/12/04)
-
- Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity
-
Ten dipyridodiazepinone derivatives were synthesized and evaluated for their anti HIV-1 reverse transcriptase activity against wildtype and mutant type enzymes, K103N and Y181C. Two of them were found to be promising inhibitors for HIV-1 RT.
- Khunnawutmanotham, Nisachon,Chimnoi, Nitirat,Techasakul, Supanna,Thitithanyanont, Arunee,Saparpakorn, Patchreenart,Hannongbua, Supa,Choowongkomon, Kiattawee,Pungpo, Pornpan
-
supporting information; experimental part
(2010/04/22)
-
- Synthesis and antiviral activity evaluation of some novel acyclic C-nucleosides
-
The preparation of novel 5-amino or 7-hydroxy substituted pyrazolo[4,3-b]pyridine and pyrazolo[3,4-c]pyridine acyclic C-nucleosides is described. Their synthesis was carried out by condensation of suitably substituted lithiated picolines with 2-benzyloxyethoxymethylchloride followed by pyrazole ring annulation. The compounds were evaluated for their antiviral activity against a wide panel of viruses, but were found inactive at subtoxic concentrations.
- Lougiakis, Nikolaos,Marakos, Panagiotis,Poul, Nicole,Balzarini, Jan
-
scheme or table
p. 775 - 780
(2009/06/25)
-
- 5,11-dihydro-6H-dipyrido(3,2-B:2',3'-E)(1,4)diazepines and their use in the prevention or treatment of HIV infection
-
Disclosed are novel 5,11-dihydro-6H-dipyrido[3,2-b; 2',3'-e][1,4]diazepines. These are useful in the prevention or treatment of HIV infection.
- -
-
-
- Nitro, amino and aroylamino-N-phenylpyridinamines in a process for preparing pyrido[1,4]benzodiazepines
-
Nitro, amino and aroylamino-N-phenylpyridinamines as chemical intermediates and/or having antidepressant activity having the formula STR1 wherein R3 is nitro, amino or aroylamino, and Q is hydrogen, --NR1 R2 or halogen are disclosed in a process for preparing pyrido[1,4]benzodiazepines.
- -
-
-
