Anabasine and cytisine derivatives as reversible cholinesterase inhibitors

A number of analogs of acetyl--methylcholine, containing residues of the alkaloids anabasine and cytisine as cyclic ammonium groupings, have been synthesized. The structures of the substances obtained have been confirmed by their IR and PMR spectra and the result of elementary analysis. The kientic parameters of the interaction of the compounds synthesized with acetylcholinesterase (ACE) of human blood erythrocytes and with butylcholinesterase (BuCE) of horse blood serum have been investigated. All the substances synthesized proved to be reversible inhibitors of ACE and BuCE.Institute of Bioorganic Chemistry, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 97–100, January–February, 1988.     

Synthesis of novel flavonoid derivatives as potential HIV‐ Integrase inhibitors

Eighteen novel flavonoid derivatives ‐ substituted chalcones and flavones were synthesized and characterized by using NMR, IR, UV/Vis spectroscopy and elemental analysis. The target compounds were achieved by using a sequence of simple and effective reactions starting from phloroglucinol. The initial hydroxyl groups were protected by methylation and in the final flavones the 5‐OH group was selectively demethylated by means of AlBr₃. 5‐methoxy flavones exhibit a strong fluorescence, which was quenched after the removal of the methyl group.     

Synthesis of pterostilbene and resveratrol carbamate derivatives as potential dual cholinesterase inhibitors and neuroprotective agents

Pterostilbene and resveratrol carbamate derivatives were designed and synthesized by use of a multi-target directed drug-design strategy. Their acetylcholinesterase and butylcholinesterase inhibitory activity and neuroprotective effects against hydrogen peroxide-induced PC12 cell injury were evaluated in vitro. The results indicated that some of the compounds had dual inhibitory potency against acetylcholinesterase and butylcholinesterase, and potential neuroprotective effects, and could be considered as potential multi-target-directed agents.     

Novel 3‐benzoyl‐2‐piperazinylquinoxaline derivatives as potential antitumor agents

A series of new benzoylquinoxaline derivatives ( 7‐26 ) was synthesized and evaluated for antitumor activity against a panel of 60 human cell lines at the NCI of Bethesda. Among the compounds which have passed the preliminary screening, compound 23 exhibited the best profile and growth inhibition activity at 100 ‐ 10 μM. The compounds were then tested towards a folate‐dependent enzymes bio‐library including Thymidylate synthases enzymes and human Dihydrofolate reductase at 10 μM. The most of compounds exhibited a moderate inhibitory activity towards all or some of the enzymes tested with detectable inhibition constants (K_i) values in the range of 0.6‐70 μM. Compounds 21, 23, 24 showed K_i in the range of 10‐38 μM against both hDHFR and hTS.     

Synthesis of new uracil non‐nucleoside derivatives as potential inhibitors of HIV‐1

6‐(2‐Phenylethyl) and 6‐cyclohexyl 5‐cyanouracils ( 1a,b ) were synthesized and reacted with chloromethyl ethyl ether, benzyl chloromethyl ether, chloromethyl methyl sulfide and (2‐acetoxyethoxy)methyl bromide. New uracil analogues of (S)‐DHPA were synthesized by reaction of compounds ( 1a,b ) with ((S)‐2,2‐dimethyl‐1,3‐dioxolane‐4‐yl) alkyl p‐toluenesulfonate.     

Preparation of derivatives of 1‐(2‐pyrimidinyl)piperazine as potential antianxiety,antidepressant, and antipsychotic agents

This paper describes the preparation of twenty‐eight derivatives of 1‐(2‐pyrimidinyl)piperazine as potential antianxiety, antidepressant, and antipsychotic agents. In twenty‐six of the preparations a chloro nitrogen heterocycle was caused to react with an excess of 1‐(2‐pyrimidinyl)piperazine in the absence of solvent. A specific example is given above.     

Synthesis of 2-quinolinecarboxamide derivatives as potential HDAC inhibitors

Inhibition of histone deacetylase activity appears as an original and effective approach for the treatment of cancer. A series of novel quinoline-containing derivatives has been synthesized and found that some of these compounds possess nanomolar histone deacetylase inhibitory activity.     

Novel multiblock‐co‐ionomers as potential polymer electrolyte membrane materials

In this contribution a series of novel multiblock‐co‐ionomers consisting of hydrophobic (partially fluorinated) and hydrophilic (sulfonated) domains has been prepared and characterised in terms of their applicability as fuel cell membranes. The synthesis of these multiblock‐co‐ionomers is a four‐step procedure including (1) the sulfonation of the monomer 4,4′‐difluorodiphenylsulfone, (2) the preparation of hydrophilic telechelic macromonomers by molecular‐weight controlled step‐growth polycondensation of the sulfonated monomer with various bis(thio)phenols, (3) the preparation of a hydrophobic telechelic macromonomer and (4) the coupling of both telechelic macromonomers to yield microphase‐separated block‐co‐ionomers. This study focuses on the investigation of the influence of various linkage groups and atoms within the hydrophilic domains of the multiblock‐co‐ionomers. Both the telechelic macromonomers and the multiblock‐co‐ionomers were structurally investigated by ¹H‐ and ¹⁹F‐NMR spectroscopy and gel permeation chromatography (GPC). All multiblock‐co‐ionomers of this series could be cast into membranes and their membrane properties (ion‐exchange capacity, specific resistance, swelling ratio, water uptake, thermal and oxidative stability) were measured and discussed in dependence of the various linkage groups within the hydrophilic domains. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5237–5255, 2007     

Novel 1,2,3-triazolo phosphonate derivatives as potential antibacterial agents

We describe the synthesis, characterization, and in vitro antibacterial evaluation of a library of novel compounds based on 1,2,3-triazolo phosphonate framework along with the evaluation of DNA gyrase inhibitory potential of a promising molecule in silico. Preparation of these compounds was carried out via a multistep sequence comprising of the Abramov reaction followed by the Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) as the key steps. Various α-hydroxyphosphonate derivatives containing either a secondary or tertiary alcohol at the α position were prepared. When screened for their antibacterial activities in vitro using a Gram-positive (Staphylococcus aureus) and three Gram-negative (Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa) strains, majority of these derivatives exhibited reasonable to good effects with the analogue 5k being active against all the strains. The SAR analysis indicated that the activity was influenced by the position of the α-hydroxyphosphonate moiety as well as the substituent present on the benzene ring attached to the 1,2,3-triazole ring. Moreover, the compound 5k showed strong interactions with the DNA active site when docked into the DNA gyrase in silico. Thus, the 1,2,3-triazolo phosphonate derivative 5k appeared to be a novel and promising hit molecule that deserves further study as a potential antibacterial agent.     

Synthesis of indazol‐4,7‐dione derivatives as potential trypanocidal agents

The synthesis of new indazol‐4,7‐dione derivatives via 1,3‐dipolar cycloaddition of diazomethane with 2,3‐dimethyl‐1,4‐benzoquinone ( 2 ) and 1,4‐naphthoquinone ( 7 ) followed by N‐alkylation of the pyrazol nitrogen atom of the corresponding quinones ( 3 ) and ( 8 ) with methyl chloroacetate is described. A series of amides from esters ( 5 ) and ( 10 ) were also obtained. These compounds were tested in vitro as potential anti‐trypanosomal agents. Compounds ( 4 ) and ( 8 ) were found to have significant activity.     

Syntheses and studies of hydantoin derivatives as potential anti-tuberculosis inhibitors

A short and efficient synthesis of(Z)-2-substituted-5-(4-((2-substitued-5-oxoimidazolidin-4-ylidene)methyl)benzamido)ben-zoic acid derivatives(8a-g) as potential type of FabH inhibitors is described.Their structures were confirmed by MS,NOE and ~1H NMR.     

Lipase-catalysed one-pot synthesis of thiazole-based Betti bases and their evaluation as potential cholinesterase inhibitors

Research on Chemical Intermediates - A series of 1-[aryl-(thiazol-2-ylamino)-methyl]-naphthalen-2-ol derivatives were synthesized using porcine pancreatic lipase as a catalyst. The major assets of...     

Synthesis of pyrazole derivatives as potential bioisosteres of thromboxane-synthetase inhibitors

A series of ω-carboalkenyl pyrazole derivatives have been synthesized as potential thromboxane-synthetase inhibitors considering the close bioisosteric relationship between the pyrazole ring and other heteroaromatic carboalkenyl compounds exhibiting inhibitory activity. (E)-7-(1-Phenylpyrazol-4-yl)hept-2-enoic acid (4b) were prepared in 28% overall yield from its minor bis-homologue, (E)-5-(1-phenylpyrazol-4-yl)pent-2-enoic acid (4a) , obtained from 4-formyl-1-phenylpyrazole (6) in 17% overall yield. Compounds 4a, 4b, 7, 8 and 13 were screened for their ability to inhibit the in vitro rabbit blood platelet aggregation induced by collagen using the Born test. Among the active compounds 4a exhibited an important inhibition at 1 μM concentration.     

Novel Thiazolo[5,4‐d]thiazole‐Based Organic Dyes for Quasi‐Solid‐State Dye‐Sensitized Solar Cells

A series of novel metal‐free organic dyes containing the thiazolo[5,4‐d]thiazole moiety were designed and synthesized for quasi‐solid‐state dye‐sensitized solar cells (DSSCs). Different alkoxy chains were introduced into the electron donor part of the dye molecules for comparison. The optical, electrochemical, and photovoltaic properties for all sensitizers were systematically investigated. It was found that the sensitizers with the different alkoxy groups have similar photophysical and electrochemical properties, such as absorbance and energy levels, owing to their close chemical structures. However, the quasi‐solid‐state DSSCs based on the resulting sensitizers exhibit different performance parameters. The quasi‐solid‐state DSSC based on sensitizer FNE74 with two octyloxy chains possessed the highest solar energy conversion efficiency of 5.10 % under standard AM 1.5G sunlight illumination without the use of coadsorbant agents.     

Synthesis of several derivatives of methylthiophosphonic acids,cholinesterase inhibitors

Conclusions A series of O,S-dialkylmethyl thiophosphonates were synthesized.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 3, pp. 583–587, March, 1968.