Synthesis of 6H-naphtho[2,3-c]chromene-7,12-diones via palladium-catalyzed intramolecular cyclization of 2-bromo-3-aryloxymethyl-1,4-naphthoquinones

6H-Naphtho[2,3-c]chromene-7,12-diones, to be considered as tetracyclic derivatives of the natural product pentalongin, were conveniently synthesized for the first time via palladium-catalyzed intramolecular cyclization of 2-bromo-3-aryloxymethyl-1,4-naphthoquinones.     

Synthesis and X-ray diffraction studies of 3-cyano-2-trifluoromethyl-4H-pyrido[1,2-a]pyrimidine derivatives

Reactions of 2-chloro-1-cyano-2-trifluoromethylethylenes with 2-aminopyridines were studied. According to the data of NMR spectroscopy and X-ray diffraction analysis, the first stage of the reaction involves alkenylation of the exocyclic nitrogen atom of 2-aminopyridines followed by formation of pyrido[1,2-a]pyrimidines. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1261–1264, July, 2000.     

Synthesis of Structurally Related Purines: Benzimidazo[1,2-a]pyridines, Benzimidazo-[1,2-c]pyrimidines, and Pyrazolo-[1,5-a]pyrimidines

Summary.  Reactions of sodium salts of 3-hydroxymethylene-2-alkanones with 2-cyanomethylbenzimidazole afforded benzimidazo[1,2-a]pyridines. Analogues reactions with 2-aminobenzimidazole and 5-aminopyrazoles afforded benzimidazo[1,2-c]pyrimidines and pyrazolo[1,5-a]pyrimidines. Received December 12, 1999. Accepted (revised) February 12, 2000     

Synthesis and Neurotropic Activity of New Heterocyclic Systems: Pyridofuro[3,2-d]pyrrolo[1,2-a]pyrimidines,Pyridofuro[3,2-d]pyrido[1,2-a]pyrimidines and Pyridofuro[3′,2′:4,5]pyrimido[1,2-a]azepines

Background: Neurotic disturbances, anxiety, neurosis-like disorders, and stress situations are widespread. Benzodiazepine tranquillizers have been found to be among the most effective antianxiety drugs. The pharmacological action of benzodiazepines is due to their interaction with the supra-molecular membrane GABA-a-benzodiazepine receptor complex, linked to the Cl-ionophore. Benzodiazepines enhance GABA-ergic transmission and this has led to a study of the role of GABA in anxiety. The search for anxiolytics and anticonvulsive agents has involved glutamate-ergic, 5HT-ergic substances and neuropeptides. However, each of these well-known anxiolytics, anticonvulsants and cognition enhancers (nootropics) has repeatedly been reported to have many adverse side effects, therefore there is an urgent need to search for new drugs able to restore damaged cognitive functions without causing significant adverse reactions. Objective: Considering the relevance of epilepsy diffusion in the world, we have addressed our attention to the discovery of new drugs in this field Thus our aim is the synthesis and study of new compounds with antiepileptic (anticonvulsant) and not only, activity. Methods: For the synthesis of compounds classical organic methods were used and developed. For the evaluation of biological activity some anticonvulsant and psychotropic methods were used. Results: As a result of multistep reactions 26 new, five-membered heterocyclic systems were obtained. PASS prediction of anticonvulsant activity was performed for the whole set of the designed molecules and probability to be active Pa values were ranging from 0.275 to 0.43. The studied compounds exhibit protection against pentylenetetrazole (PTZ) seizures, anti-thiosemicarbazides effect as well as some psychotropic effect. The biological assays evidenced that some of the studied compounds showed a high anticonvulsant activity by antagonism with pentylenetetrazole. The toxicity of compounds is low and they do not induce muscle relaxation in the studied doses. According to the study of psychotropic activity it was found that the selected compounds have an activating behavior and anxiolytic effects on the models of “open field” and “elevated plus maze” (EPM). The data obtained indicate the anxiolytic (anti-anxiety) activity of the derivatives of pyrimidines, especially pronounced in compounds 6n, 6b, and 7c. The studied compounds increase the latent time of first immobilization on the model of “forced swimming” (FST) and exhibit some antidepressant effect similarly to diazepam. Docking studies revealed that compound 6k bound tightly in the active site of GABA_A receptor with a value of the scoring function that estimates free energy of binding (ΔG) at −7.95 kcal/mol, while compound 6n showed the best docking score and seems to be dual inhibitor of SERT transporter as well as 5-HT_1A receptor. Conclusions: Тhe selected compounds have an anticonvulsant, activating behavior and anxiolytic effects, at the same time exhibit some antidepressant effect.     

Reactions with Naphthoylhydroxlmoyl Chlorides: Synthesis of Derivatives of Isoxazole,Pyrrolidino[3,4-d]isoxazoiin-4,6-dione,lmidazo[1,2-a]pyridine,lmidazo[1,2-a]pyrimidine,Benzotriazine and Benzothiadiazine

Hydroximoyl chlorides 3 react with acrylonitrile, N-arylmaleimide and maleic anhydride to give isoxazolines 5 , pyrrolidino[3,4-d]isoxazolines 8 , and furolidino[3,4-d]isoxazolines 9 , respectively. 3 reacted with 2-aminopyridine, 2-aminopyrimidine, o-phenylenediamine and o-aminothiophenol to yield 3-ni-trosoimidazo[1,2-α]pyridines 20 , 3-nitrosopyrimidines 22 , 3-naphthoyl-1,4-dihydrobenzo-1,2,4-triazines 24 , and 3-naphthoyl-4H-1,3,4-benzothiadiazine 27 , respectively. Compound 3 reacted with benzoylacetonitrile, acetoacetanilide, thiophenol, benzencsulfinic acid in ethanolic sodium ethoxide solution to give the corresponding isoxazoles 12–13 and oximes 16–17 , respectively. The structures of these products were confirmed by elemental analyses, spectral data and, wherever possible, alternative synthesis.     

4-Hydroxy-2-quinolones. 93. Synthesis and biological properties of 2-hydroxy-4-imino-1,4-dihydroquinoline-3-carboxylic acid N-R-amides

Various methods of synthesizing amides of 2-hydroxy-4-imino-1,4-dihydroquinoline-3-carboxylic acids have been studied. Results of investigations on the antitubercular and antiinflammatory activity of the obtained compounds are discussed. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 542–555, April, 2006.     

Heterocyclic analogs of 5,12-naphthacenequinone. 4. Synthesis of 4,11-dimethoxy-anthra[2,3-d]isoxazole-5,10-dione

A preparative synthetic method has been developed for 3-chloro-2-formyl-1,4-dimethoxyanthraquinone starting from available 2-methylquinizarine. The condensation of the α-chloroaldehyde obtained with acetone oxime gives 4,11-dimethoxyanthra[2,3-d]isoxazole-5,10-dione. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1421–1427, September, 2006.     

Synthesis and study of some properties of 1-aryl-2-oxo-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole 4-oxides

A number of 1-aryl-2-oxo-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole 4-oxides were synthesized based on 3-[N-aryl-N-(chloroacetyl)amino]-2-formylindoles. The nature of the substituent in the 1-aryl fragment has a pronounced influence on the course of reactions throughout the whole sequence of transformations during the synthesis of diazepinoindoles. The reduction of 4-oxides by formamidinosulfinic acid, hydrogen in the presence of Pd/C, and sodium bisulfite was studied. The structures of the reaction products were confirmed using IR and ¹H NMR spectroscopy and mass spectrometry.     

Synthesis of 5H-thiazolo[3,2-a]pyrimidine derivatives from 6-methyl-2-thiouracil and 1-acyl-2-bromoacetylenes. X-ray structural study of 3-benzoyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one

3-Acyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-ones were synthesized by the reaction of 1-acyl-2-bromoacetylenes with 6-methyl-2-thiouracil, carried out with heating in DMF, dioxane, or acetonitrile in the presence of triethylamine. The structure of 3-benzoyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one was established by X-ray structural analysis.Deceased in 1995.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 2306–2308, September, 1996.     

Synthesis and insecticidal evaluation of tetrahydroimidazo[1,2-a]pyridin-5(1H)-one derivatives

A series of novel tetrahydroimidazo[1,2-a]pyridine-5(1H)-one derivatives containing a electronegative pharmacophore(=CNO₂) were synthesized via practical aza-ene reaction and characterized by ¹H NMR, ¹³C NMR, ¹⁹F NMR and HRMS. Preliminary bioassays showed that some of the target compounds exhibited good insecticidal activity against brown planthopper(Nilaparvata lugens) and cowpea aphids(Aphis craccivora) at 500 mg L^-1. Among them, compound 11h was active against brown planthopper at 100 mg L^-1. The insecticidal activities varied significantly depending on the types and patterns of the substituents, which provided guidance for further investigation on structure modifications.     

不对称加氢催化剂[Ru(BINAP)(OAc)2]的合成及其固载化研究

对文献报道的实验反应条件进行优化改进后,合成了不对称加氢催化剂[Ru((S)-BINAP)(OAc)2]和[Ru((R)-BINAP)(OAc)2]。将合成的催化剂应用于惕各酸的不对称催化氢化,(S)-2-甲基丁酸得率为88%,立体选择性可达85%e.e.。为了提高催化剂的利用率,将催化剂[Ru(BINAP)(OAc)2]负载在新型介孔分子筛SBA-15上,用于惕各酸的不对称催化氢化,循环应用3次后,(S)-2-甲基丁酸得率仍可达到59%,立体选择性达57%e.e.。     

A novel and convenient method for the synthesis of new derivatives of pyrido[3,2-e]pyrrolo[1,2-a][1,4]diazepine-6,11-dione

A novel methodology has been developed for the efficient synthesis of 1,4-pyridopyrrolodiazepine derivatives. The key reaction is the bromination under mild conditions by NBS of compounds resulting via peptide coupling of l-proline methyl ester with 3-aminopyridine-2-carboxylic acid 1, then intramolecular cyclization in the construction of 2-bromo-6a,7,8,9-tetrahydro-5H-pyrido[3,2-e]pyrrolo[1,2-a][1,4]diazepine-6,11-dione 4. This latter is then engaged in cross-coupling reactions to generate 1,4-pyridopyrrolodiazepines derivatives 5a-m, 6a-i, 7, and 8a-c. This strategy provides an efficient method to access a library of compounds based on privileged substructures that are of great interest in drug discovery.     

Angular Regioselectivity in the Reactions of 2-Thioxopyrimidin-4-ones and Hydrazonoyl Chlorides: Synthesis of Novel Stereoisomeric Octahydro[1,2,4]triazolo[4,3-a]quinazolin-5-ones

The regioselective synthesis of cis and trans stereoisomers of variously functionalized octahydro[1,2,4]triazolo[4,3-a]quinazolin-5-ones was performed. The 2-thioxopyrimidin-4-ones used in the synthesis reacted with hydrazonoyl chlorides in a regioselective manner to produce the angular regioisomers [1,2,4]triazolo[4,3-a]quinazolin-5-ones rather than the linear isomers [1,2,4]triazolo[4,3-a]quinazolin-5-ones. The synthesis process took place with electronic control. The angular regiochemistry of the products was confirmed by X-ray experiments and two-dimensional NMR studies.     

2H-1, 2, 4-噻二唑并[2, 3-a]嘧啶衍生物的合成及除草活性测 定

合成了12种新的2-苯甲酰亚胺基-2H-1,2,4-噻二唑并[2,3-a]嘧啶类化合物,结构经IR,^1HNMR,MS和元素分析所确证,除草活性测定表明部分目标化合物具有较好的除草活性且选择性较好,对单子植物安全。     

Synthesis and cytotoxicity of new 2-oxo-7-phenyl-2,3-dihydrothiazolo[4,5-b]pyridine-5-carboxylic acid amides

Abstract

The synthesis and anticancer activity evaluation of new thiazolo[4,5-b]pyridine-5-carboxylic acid amides is described. The structures of the synthesized compounds were confirmed by spectroscopic data and a single crystal X-ray diffraction analysis for 2.4. The synthesized compounds were screened for their in vitro anticancer activity according to US NCI protocols. The most active 7-(4-fluorophenyl)-2-oxo-2,3-dihydrothiazolo[4,5-b]pyridine-5-carboxylic acid (4-chlorophenyl)amide 2.2 and 7-(4-chlorophenyl)-2-oxo-2,3-dihydrothiazolo[4,5-b]pyridine-5-carboxylic acid (4-chlorophenyl)amide 2.5 were screened for their cytotoxicity effects on C6 Rat glioma cells and U373 Human glioblastoma astrocytoma cells which revealed promising results comparable to temozolamide as reference control according MTT assay data.     

4-Hydroxy-2-quinolones 120. Synthesis and structure of ethyl 2-hydroxy-4-oxo-4H-pyrido-[1,2-a]pyrimidine-3-carboxylate

An improved method for the preparation and purification of ethyl 2-hydroxy-4-oxo-4H-pyrido[1,2-a]-pyrimidine-3-carboxylates is proposed. According to ¹H and ¹³C NMR spectroscopic data the synthesized compounds exist in DMSO solution in the 2-hydroxy-4-oxo form while in the crystal (at least for the case of the unsubstituted derivative) X-ray analysis shows that it occurs in the bipolar 2,4-dioxo form. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 864–876, June, 2007.     

噻唑并[3,2-a]嘧啶衍生物的合成及其在水介质中识别Fe3 的性能

噻唑[3,2-a]并嘧啶衍生物具有多种生物活性,但其较差的溶解性限制了其应用。本文在7-(3-氨基苯并呋喃-2-基)-噻唑并[3,2-a]嘧啶-5-酮的芳香环上引入三乙二醇单甲醚,成功合成了化合物L,并利用核磁、质谱对其结构进行了表征。在pH 3.4~6.4范围内,化合物L可在HEPES水溶液中荧光"开-关"识别Fe~(3+),其他金属离子对识别作用没有干扰,该荧光探针具有较高的选择性和较低的检测限。     

One-Pot,Multicomponent Condensation Reaction in Neutral Conditions: Synthesis,Characterization, and Biological Studies of Fused Thiazolo[2,3-b]quinazolinone Derivatives

A new series of 12-(2-chloro-6-quinoline-3-yl)-3,3,8-substituted-2,3,4,12-tetrahydro-benzo[4,5]thiazolo[2,3-b]quinazolin-1-ones 4 was synthesized in one pot by condensing various 2-chloro-3-formylquinolines 1, 2-amino-6-substituted-benzothiazoles 2, and 1,3-cyclohexanedione 3 in ethanol. All the compounds were characterized by IR, ¹H NMR, ¹³C NMR spectra and elemental analysis. All the synthesized compounds were screened for their antibacterial activity against Grampositive bacterial species Bacillus cereus and Bacillus substilus, Gram-negative bacterial species Escherichia coli, and their fungicidal activity against Aspergillus niger, Fuserium oxisporum, and Rhizopus species.