Synthesis of 1-(3-halotetrahydro-2-furyl) derivatives of uracil, 5-substituted uracils,and cytosine

The cis and trans isomers of 1-(3-halotetrahydro-2-furyl) derivatives of uracil, 5-substituted uracils, and cytosine were obtained by alkylation of 2,4-bis(trimethylsilyl) derivatives of uracil, 5-substituted uracils, and cytosine with 2,3-dihalotetrahydrofurans. 2,3-Anhydro compounds are also formed in the alkylation of 5-halouracil derivatives. The physicochemical properties of the compounds obtained and the antineoplastic activities of the 5-fluorouracil derivatives were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 94–99, January, 1987.     

Synthesis and anti-HIV-1 activity of S-dihydro(alkyloxy)benzyloxypyrimidine derivatives

Several 2-heteroaryl-, 2-heteroarylcarbonylmethyl-, 2-arylcarbonylmethyl, and 2-arylethyl derivatives of S-dihydro(alkyloxy)benzyloxypyrimidines have been synthesized and the anti-HIV activities of these compounds were tested in C8166 cell and against RT enzyme. It was found that some of these compounds showed good activity against HIV-1 (EC ₅₀ = 0.014–0.8 μM) with low toxicity (CC ₅₀ value of 222–564 μM) and high selectivity (SI value of 278–37743). The structure-activity relationships (SAR) of these compounds have also been discussed. First two authors contributed equally to this work Correspondence: Yan-Ping He, Key Laboratory of Medicinal Chemistry for Natural Resource Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, People’s Republic of China; Yong-Tang Zheng, Laboratory of Molecular Immunopharmacology, Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming, Yunnan 650223, People’s Republic of China.     

N1-(2-furoylmethyl) and N1-(5-nitro-2- furoylmethyl) derivatives of uracil and its 5-substituted derivatives

The corresponding N₁-(2-furoylmethyl) and N₁-(5-nitro-2-furoylmethyl) derivatives of uracil and its 5-substituted derivatives were obtained by the reaction of 2-bromo- and 5-nitro-2-bromoacetylfurans with uracil, 5-fluorouracil, and thymine. The structures of these compounds as N₁-substituted uracils were proved by a study of the UV spectra at various pH values. The computational method of expanding the UV spectra into individual bands was used.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1268–1270, September, 1971.     

Synthesis and nitrosation of 3- and 3,5-substituted hydantoins

The cyclization of N-alkylated (arylated) -ureidocarboxylic acids gives a series of 3-mono- and 3,5-disubstituted hydantoins, and nitrosation of the latter yields their nitroso derivatives. The rotational isomerism of 3-(-naphthyl)hydantoins has been studied by PMR spectroscopy.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1404–1406, October,Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1404–1406, October,     

Synthesis of 2-substituted (+/-)-(2r,3r,5r)-tetrahydrofuran-3,5-dicarboxylic acid derivatives

An efficient synthesis of 2-substituted (+/-)-(2R,3R,5R)-tetrahydrofuran-3,5-dicarboxylic acid derivatives has been developed. Starting from 5-norborne-2-ol, the key intermediate (+/-)-methyl 5,6-exo,exo-(isopropylidenedioxy)-2-oxabicyclo[2.2.1]heptane-3-exo-carboxylate (15) was synthesized in an efficient six-step sequence. The key transformation is the base-catalyzed methanolysis-rearrangement of (+/-)-6,7-exo,exo-(isopropylidenedioxy)-4-exo-iodo-2-oxabicyclo[3.2.1]octan-3-one (14). Further manipulation of the 3-substituent of (+/-)-methyl 5,6-exo,exo-(isopropylidenedioxy)-2-oxabicyclo[2.2.1]heptane-3-exo-carboxylate (15) followed by deprotection of the diol moiety and ring opening catalyzed by RuCl(3)/NaIO(4) gave the title compounds in good yield.     

Synthesis and antioxidant activity of 3-substituted guaiazulene derivatives

A series of 3-substituted guaiazulene derivatives has been synthesized and their antioxidant properties were evaluated by monitoring their capacity for scavenging the stable free-radical DPPH. 3-Vinylguaiazulene was the most potent, possessing antioxidant activity superior than alpha-tocopherol. These derivatives were also moderate inhibitors of the proliferation of human promyelocytic leukemia cells.     

New derivatives of 3-aminoindole. Synthesis of 2-aryl(hetaryl)-3-(3,5-dimethyl-1-pyrazolyl)indoles

The interaction of arylhydrazines with ù-(3,5-dimethyl-1-pyrazolyl)acetophenones and acetyl(2-thiophene) leads to arylhydrazones, which are converted by Fischer cyclization into 2-aryl(thienyl)-3-(3,3-dimethyl-1-pyrazolyl)indoles with substituents in positions 1, 5, and 7.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1662–1669, November, 2004.     

Synthesis and anti-HIV-1 activity of 1,5-dialkyl-6-(arylselenenyl)uracils and -2-thiouracils

The 1,5-dialkyl-6-(arylselenenyl)uracils 10a-h and -2-thiouracils 10i-p have been synthesized as potential anti-HIV-1 agents. Cyclization of N-alkyl-N'-[3,3-di(methylthio)-2-alkylacryloyl]ureas 6a-d and -thioureas 6e-h in acetic acid either containing a catalytic amount of methanesulfonic acid at 80°or containing 1 equivalent of methanesulfonic acid at room temperature afforded 1,5-dialkyl-6-(methylthio)uracils 7a-d in 84–96% yields and 1,5-dialkyl-5,6-dihydro-6,6-di(methylthio)-2-thiouracils 11a-d in 88–99% yields, respectively. Oxidation of 7a-d and 11a-d with either 3-chloroperoxybenzoic acid in benzene or aqueous sodium periodate solution in methanol gave 1,5-dialkyl-6-(methylsulfonyl)uracils 8a-d in 88–98% yields and 1,5-dialkyl-6-(methylsulfinyl)-2-thiouracils 12a-d in 57–73% yields, respectively, which were subsequently treated with arylselenol 9a-b in ethanolic sodium hydroxide solution to afford 10a-p in 6099% yields. Of these compounds, 6-[(3,5-dimethylphenyl)selenenyl]-5-isopropyl-1-(3-phenylpropyl)uracil ( 10h ) inhibited HIV-1 replication in MT-4 cells at a 50% effective concentration (EC₅₀) of 0.0006 μM with a selective index of 44833, which is 7.7-fold more potent than AZT.     

新型1-吡啶基-3,5-二甲基-1-氢吡唑类化合物的合成及晶体结构

以卤代吡啶为起始原料与水合肼反应合成肼基吡啶衍生物中间体,该中间体进一步与2,4-戊二酮关环合成了一类新型1-吡啶基-3,5-二甲基吡唑衍生物。对合成目标化合物进行了质谱、核磁表征。并且采用X射线单晶衍射分析方法进一步测定了目标化合物1-(3,5,6-三氯吡啶-2-基)-3,5-二甲基-1氢吡唑(3f)的晶体结构。     

Synthesis and antibacterial activity of 1-(2,4-dichlorobenzoyl)-4-substituted thiosemicarbazides, 1,2,4-triazoles and their methyl derivatives

A series of 1-(2,4-dichlorobenzoyl)thiosemicarbazides, s-triazoles and their methyl derivatives have been synthesised by condensation of 2,4-dichlorobenzoyl hydrazine with aryl isothiocyanates. Subsequent ring closure of the substituted thiosemicarbazides yielded the s-triazoles, and reaction with methyl iodide resulted methyl derivatives. All the compounds were subjected to in vitro testing against two gram-positive and two gram-negative bacteria. Antibacterial activity was found to be moderate to good in most of the compounds.     

Synthesis and biological activity of (3,5-disubstituted-1H-1,2,4-triazol-1-yl)benzophenone derivatives

The synthesis of (5-acylaminomethyl-3-carbamoyl-1H-1,2,4-triazol-1-yl)benzophenone derivatives 4a-i, 14a-d, 15a-d, 16a-c , is described. Acylation of the key intermediate, 1-benzoylphenylazo-1-aminoacetamide 7, followed by cyclization in the presence of acid afforded 1H-1,2,4-triazole derivatives. These compounds were evaluated for their central nervous system (CNS) activity. Some of these compounds exhibited high activities in anti-pentylene tetrazole and rotarod test in mice when orally administered.     

3-丁烯酮-吲哚衍生物的合成

吲哚类化合物广泛存在于植物界中, 且具有多种生理活性。其中, 月橘烯碱具有抗生育活性。本文以合成月橘烯碱的中间体3-(1-丁烯酮-3)吲哚为起始物, 并设计了10个与其结构类似的单吲哚化合物, 并做了小鼠的药理实验。     

Synthesis and anti-HBV activity of novel 5-substituted pyridin-2(1H)-one derivatives

<正>Four novel 5-substituted pyridine-2(1H)-one derivatives were designed and synthesized by using addition-elimination reactions.The structures of these novelly synthesized compounds were verified by ~1H NMR,ESI-MS and single crystal X-ray diffraction.Furthermore,all four compounds(most notably compound 7a) were found to be highly efficient against hepatitis B virus (HBV) in cultured HepG2 2.2.15 cell,making them promising drug candidates for potential bioactive molecule against hepatitis B.     

Synthesis and anti-HIV-1 activity of a series of 1-(alkoxymethyl)-5-alkyl-6-(arylselenenyl)uracils and -2-thiouracils

A series of 1-(alkoxymethyl)-5-alkyl-6-(phenylselenenyl)uracils and -2-thiouracils modified at the 3- and/or 5-position of the C-6 phenylselenenyl ring with methyl or fluoro substituent has been synthesized and tested for their ability to inhibit HIV-1 replication. Lithiation of the acyclic uracil and 2-thiouracil derivatives 11-14 and 27-32 with lithium diisopropylamide or lithium bis(trimethylsilyl)amide followed by reaction with an appropriate diaryl diselenide afforded 6-arylselenenyl compounds 18-26 after removal of the tert-butyldimethylsilyl protecting group and 35-47 . Compounds 48-54 were prepared from compounds 38-44 by oxidative hydrolysis of the thione function. Of these compounds, 50 inhibited HIV -1 replication in human T₄ lymphoblastoid cells at a 50% effective concentration (EC₅₀) of 0.0047 μM with a selectivity index of >42600.     

Synthesis of 2-substituted 1-tosyl-3-(1-tosyliminoalkyl)imidazolidines and-hexahydropyrimidines

Reactions of N-tosylimidoyl chlorides with the Schiff bases of the general formula TsNH(CH₂)_nN=CHR (n = 2 or 3; R = Prⁱ, 4-MeOC₆H₄, 4-Me₂NC₆H₄, and 3-O₂NC₆H₄) afforded 2-substituted 1-tosyl-3-(1-tosyliminoalkyl)imidazolidines (n = 2) or-hexahydropyrimidines (n = 3). Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 872–875, May, 2006.     

Synthesis and antibacterial activity of C-2(S)-substituted pleuromutilin derivatives

<正>In order to probe the effect of C-2(S)-substituted groups in the antibacterial activity,a series of novel C-2(S)-substituted pleuromutilin analogues of SB-225586 were synthesized and evaluated for their in vitro antibacterial activity.The results of antibacterial activities indicated that C-2(S)-substituted pleuromutilin derivatives retained appreciable antibacterial activity,and the 2-fluorination compounds 6a and 6b are more potent than the corresponding 2-hydroxylation analogues 7a and 7b.     

Synthesis of isoselenazole and its 3- and 5-substituted derivatives

A new method of synthesis for isoselenazole and its 3- and 5-substituted derivatives by one-pot procedure which uses α-acetylenic aldehydes or ketones besides hydroxylamine-O-sulphonic acid and potassium selenide in buffered aqueous solution, is described. When α-acetylenic aldehydes are used, selenobisalkenylnitriles are obtained as side products.