有机锡2-[(1,2,4-三唑-1-基)甲基硫代]苯甲酸酯的合成与生物活性

通过硫代水杨酸与(1-氯甲基)-1,2,4-三唑盐酸盐在碱性条件下的反应, 合成了2-[(1,2,4-三唑-1-基)甲基硫代]苯甲酸. 利用该酸与(R₃Sn)₂O(R=Et, n-Bu, Ph), Cy₃SnOH(Cy为环己基)或Et₂SnO反应, 得到了5个有机锡羧酸酯. 用X射线单晶衍射测定了三正丁基锡2-[(1,2,4-三唑-1-基)甲基硫代]苯甲酸酯的晶体结构. 在该化合物中, 锡为五配位的三角双锥结构. 该化合物通过三唑四位氮原子与锡配位, 形成一维链状配位高分子. 初步的生物活性测试结果表明, 所有的有机锡化合物都表现出了明显的抗真菌活性.     

2-[(吡啶-3-基)甲氨基]-1H-咪唑-4(5H)-酮衍生物的合成及其抑菌活性

本文以2-硫代乙内酰脲、取代苯甲醛、碘甲烷、吡啶甲胺等为原料,经Knoevenagel缩合、甲基化和取代反应,合成了一系列5-取代苯亚甲基-2-[(吡啶-3-基)甲氨基]-1H-咪唑-4(5H)-酮(3a~3i),其结构经IR、~1H NMR、~13C NMR和HRMS确证。初步抑菌活性试验表明,在药剂浓度为100μg/m L时,目标化合物对灰霉菌均有中等抑制活性,抑制率为69.5%~83.2%;在相同浓度下大部分化合物对菌核菌有较高的抑制活性,抑制率为87.9%~100%,其活性高于对照药三唑酮和百菌清。     

3-（5-H/CH3-苯并咪唑-2-亚甲硫基）-5-取代-[1,2,4]三唑-4-胺衍生物的合成、结构和生物活性

利用3-巯基-4-氨基-5-取代-1,2,4-三唑和2-氯甲基-5-取代-苯并咪唑在氢氧化钠溶液中反应,得到17个3-(5-H/CH3-苯并咪唑-2-亚甲硫基)-5-取代-[1,2,4]三唑-4-胺衍生物.所有目标化合物经元素分析、红外光谱、核磁共振氢谱确定结构;采用溶液法得到化合物3f与Co2+形成的配合物,通过X射线单晶衍射确定结构.初步的生物活性测试结果表明,所合成的化合物对小麦芽鞘和绿豆发芽有着较好的生长调节作用;化合物3d,3i对金黄色葡萄球菌具有一定的抑制作用.     

Synthesis,Crystal Structure and Biological Activities of O-[（Z）-2-Methylbenzyl] 1-Phenyl-2-（1H-1,2,4-triazol-1-yl）ethanone Oxime

The crystal structure of the title compound （C18H18N4O, Mr = 306.36） has been determined by single-crystal X-ray diffraction. The crystal is of triclinic, space group P1 with α = 4.783（0）, b = 13.577（1）, c = 13.830（1） A, α = 63.581（2）, β = 88.326（2）, γ = 86.161（2）°, V= 802.5（1） A3, Z= 2, Dc = 1.268 g/cm^3, F（000） = 324, μ（MoKa） = 0.082 mm^-1, the final R = 0.0497 and wR = 0.1199 for 3094 observed reflections （I 〉 2σ（I））. The dihedral angles between the phenyl （C（1）-C（4）-（6）） and triazole, the phenyl （C（13）-C（15）-C（18）） and triazole, and the two phenyl rings are 7.9（1）, 69.9（1） and 67.8（1）°, respectively. Strong C-H…π interaction joins molecules into a chain along the c axis and contributes to the stability of the structure. Preliminary bioassay results show that the title compound possesses excellent and selective fungicidal activity against Colletotrichum gossypii but displays moderate to weak insecticidal activity against aphides.     

Synthesis of Novel 2-(Pyridin-2-yl) Pyrimidine Derivatives and Study of Their Anti-Fibrosis Activity

A pyrimidine moiety exhibiting a wide range of pharmacological activities has been employed in the design of privileged structures in medicinal chemistry. To prepare libraries of novel heterocyclic compounds with potential biological activities, a series of novel 2-(pyridin-2-yl) pyrimidine derivatives were designed, synthesized and their biological activities were evaluated against immortalized rat hepatic stellate cells (HSC-T6). Fourteen compounds were found to present better anti-fibrotic activities than Pirfenidone and Bipy55′DC. Among them, compounds ethyl 6-(5-(p-tolylcarbamoyl)pyrimidin-2-yl)nicotinate (12m) and ethyl 6-(5-((3,4-difluorophenyl)carbamoyl)pyrimidin-2-yl)nicotinate (12q) show the best activities with IC₅₀ values of 45.69 μM and 45.81 μM, respectively. Furthermore, the study of anti-fibrosis activity was evaluated by Picro-Sirius red staining, hydroxyproline assay and ELISA detection of Collagen type I alpha 1 (COL1A1) protein expression. Our study showed that compounds 12m and 12q effectively inhibited the expression of collagen, and the content of hydroxyproline in cell culture medium in vitro, indicating that compounds 12m and 12q might be developed the novel anti-fibrotic drugs.     

Synthesis,Crystal Structure and Biological Evaluation of 14-O-[(2-chloroacetamide-6-aminopyrimidine-2-yl)thioacetyl] Mutilin

The title compound 14-O-[(2-chloroacetamide-6-aminopyrimidine-2-yl) thioacetyl] mutilin(4), C_(28)H_(39)ClN_4O_5S, was prepared and characterized by IR, NMR, HRMS and singlecrystal X-ray diffraction. The title compound crystallizes in orthorhombic system, space group P2_12_12_1 with a = 11.5388(8), b = 14.5282(10), c = 19.8301(14) ?, V = 3324.3(4) ?~3, Z = 4, D_c = 1.396 g/cm~3, μ(Mo Kα) = 0.462 mm~(-1), F(000) = 1464, S = 1.003, R = 0.0386 and wR = 0.1014 for 5170 independent reflections(Rint = 0.0224) with I 2σ(I)). The preliminary in vitro antibacterial bioassay against methicillin-resistant Staphylococcus aureus(MRSA-ATCC25923), Staphylococcus aureus(S. aureus), Escherichia coli(E. coli), and Staphylococcus warneri(S.warneri) were screened and the MIC values of the title compound were 0.125, 0.0625, 8 and 0.5 μg/m L, respectively.     

Synthesis,Crystal Structure and Biological Activity of 1-(4-(4-Ethoxybenzyl)piperazin-1-yl)-2-(2-methylphenoxy)ethanone

One novel phenoxyacetamide derivative(C_(22)H_(28)N_2O_3, Mr = 368.47) has been synthesized and determined by means of NMR spectroscopy, high resolution mass spectra and single-crystal X-ray diffraction. The single crystal belongs to the monoclinic system, space group Cc with a = 14.910(3), b = 14.592(3), c = 38.683(8) ?, β = 100.37(3)°, V = 8279(3) ?3, Z = 16, Dc = 1.183 g/cm3, F(000) = 3168, μ = 0.079 mm-1, Mo Kα radiation(λ = 0.71073 ?), the final R = 0.0508 and wR = 0.0666 for 4120 observed reflections with I 2σ(I). There are four independent molecules in an asymmetric unit cell. The four symmetry-independent molecules have a variety of different conformations indicating considerable conformational freedom. The bioassay results indicated that the title compound displayed effective activities against glutamine-induced neurotoxicity in PC12 cells and significantly prolonged the survival time of mice subjected to acute cerebral ischemia.     

Facile and Simple Synthesis of Novel 1-Methyl-2-(2-substituted-oxazol-4-yl)-1H-benzimidazole Derivatives

Novel 1-methyl-2-(2-substituted-oxazol-4-yl)-1H-benzimidazole derivatives were obtained in good yields and purity by treating corresponding 2-benzimidazolyl esters with acetamide in the presence of BF₃-etherate, a Lewis acid.     

N-(5-三氟甲基-1,3,4-噻二唑-2-基)-N''-芳酰基脲的合成、晶体结构及生物活性

通过2-氨基-5-三氟甲基-1,3,4-噻二唑与芳酰基异氰酸酯反应,合成了10种新的芳酰基脲.它们的结构经元素分析、红外光谱、核磁共振氢谱进行了表征.并用X射线单晶衍射法测定了化合物2j的晶体结构,结果表明,该化合物晶体属三斜晶系,空间群为P-1,a=0.54191(15)nm,b=0.7766(2)nm,c=1.7161(5)nm,α=98.668(5)°,β=95.103(5)°,γ=101.070(5)°,V=0.6955(3)nm3,Z=2,Dc=1.653g/cm3,F(000)=352,μ=0.289mm-1.初步的生测试验结果表明一些目标化合物具有良好的植物生长调节活性.     

Synthesis and Biological Activity of New 2-{[6-Methyl-2-(pyrrolidin-1-yl)pyrimidin-4-yl]oxy}acetohydrazide Derivatives

Russian Journal of General Chemistry - The reaction of 6-methyl-2-(pyrrolidin-1-yl)pyrimidin-4(3H)-one with methyl chloroacetate, followed by hydrazinolysis, gave...     

1-(1-甲氧基-1-二茂铁基-3-芳基-丙烷-2-基)-1H-1,2,4-三唑类衍生物的合成及生物活性研究

通过在三唑类活性结构中引入较大空间位阻的二茂铁基设计合成了11个新颖的含二茂铁取代的1H-1,2,4-三唑类化合物, 其结构经元素分析, ¹H NMR谱和单晶X-ray衍射分析得到确证. 初步的生物活性测试表明, 部分化合物具有明显的植物生长调节活性.     

3-取代苄氧基-6-(取代-1H-吡唑-1-基)哒嗪的合成与生物活性

3-氯-6-肼基哒嗪分别与乙酰丙酮和3-二甲胺基丙烯醛反应, 合成了中间体3-氯-6-(3,5-二甲基-1H-吡唑-1-基)哒嗪(2)和3-氯-6-(1H-吡唑-1-基)哒嗪(4), 它们与多种取代苄醇反应, 得到了一系列未见报道的3-取代苄氧基-6-(取代-1H-吡唑-1-基)哒嗪, 其结构均经1H NMR, IR和元素分析确证. 初步的生物活性测试结果表明, 所合成的化合物对油菜和稗草均具有一定的抑制作用.     

(Z)-3,3-二甲基-1-(1H-1,2,4-三唑-1-基)-2-丁酮肟(5-芳基-1,3,4-噁二唑-2-基)甲基醚的合成和抑菌活性

以3,3-二甲基-1-（1H-1,2,4-三唑基）-2-丁酮肟为原料,经醚化、肼解及腙化3步反应得到（E）-N'-（取代苯亚甲基）-2-[（Z）-3,3-二甲基-1-（1H-1,2,4-三唑-1-基）丁基-2-亚甲氨氧基]乙酰肼（3a~3u）,化合物3与二乙酸碘苯（IBD）反应,合成了21个（Z）-3,3-二甲基-1-（1H-1,2,4-三唑-1-基）-2-丁酮肟-（5-芳基-1,3,4-噁二唑-2-基）甲基醚（4a~4u）,化合物4的化学结构经核磁共振谱、高分辨质谱和元素分析确证.采用单晶X射线衍射仪测定了化合物4c的晶体结构.抑菌活性测试结果表明,在500 mg/L浓度下,化合物4k,4f,4j和4n对纹枯病菌的防效率分别为70.9%,60.2%,60.0%和60.6%;在25 mg/L浓度下,化合物4b,4c,4d和4e对菌核病菌的抑制率为71.8%~76.9%.     

Synthesis and Crystal Structure of 2-[（2-Chloropyridin-4-yl）oxy]-3,3-diphenyl-3-methoxypropionic Acid

The title compound was synthesized and its crystal structure was determined by single-crystal X-ray diffraction.The crystal is of orthorhombic system(C21H18ClNO4,Mr = 383.81),space group Pca21 with a = 13.913(3),b = 10.273(2),c = 26.488(5),V = 3786.1(13) 3,Z = 8,Dc = 1.347 g/cm3,F(000) = 1600,μ = 0.228 mm-1,the final R = 0.0550 and wR = 0.1278 for 5065 observed reflections(I > 2σ(I)).The title compound in a racemic form was found to exist as a mixture of two enantiomers in an equal ratio in the unit cell.The intermolecular hydrogen bonds link the molecules in a head-to-end manner to generate an infinite chain.     

Synthesis of New 2-[(Substituted-pyrazolin-1-yl)carbonyl]-thieno[2,3-b]pyridine Derivatives

The reaction of 3-amino-4,6-dimethyl-2-thieno[2,3-b]pyridine carbohydrazide ( 1 ) with appropriate chalcones 2a-2d in the presence of acid catalyst produced the corresponding 3-amino-2-[(3,5-disubstituted-pyrazolin-1-yl)carbonyl]-4,6-dimethylthieno[2,3-b]pyridines 3a-3d . 3-Amino-2-[(3-substituted-pyrazolin-1-yl)carbonyl]-4,6-dimethylthieno[2,3-b]pyridines 7a, 7b were also obtained by the cyclization reaction of carbohydrazide 1 with Mannich base derivatives 6a, 6b under basic condition.     

5-取代氨基-12-取代苯并[c]菲啶衍生物的合成、晶体结构及生物活性

为了寻找新的高活性农药, 利用2-甲基苯甲腈与不同的醛反应, 再通过2,3-二氯-5,6-二氰基-1,4-苯醌(DDQ)脱氢或NaH和CH3I氮甲基化, 合成了3个系列共18个5-取代氨基-12-取代苯并[c]菲啶衍生物, 其中15个是未见文献报道的化合物. 它们的结构均经1H NMR, 13C NMR, IR和高分辨质谱表征; 用X射线衍射测定了化合物5-氨基-12-(4-二乙氨基苯基)-11,12-2H-苯并[c]菲啶盐酸盐(3c)的晶体结构. 初步的生物活性测试结果表明, 部分化合物具有一定的杀菌活性和促进黄瓜子叶生根活性.     

Synthesis,Crystal Structure and Biological Activity of 2-((2,2-Dimethyl-2,3-dihydrobenzofuran-7-yl)oxy)-N-(3-(furan-2-yl)-1-phenyl-1H-pyrazol-5-yl)acetamide

The title compound 2-((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)oxy)-N-(3-(furan-2-yl)-1-phenyl-1H-pyrazol-5-yl) acetamide(C25H23N3O4, Mr = 429.46) has been synthesized, and its structure was characterized by 1H-NMR, 13C-NMR, H RMS, and single-crystal X-ray diffraction. The crystal belongs to the monoclinic system, space group P21/c with a = 20.6205(18), b = 5.2930(5), c = 18.9282(17) ?, β = 94.089(2)°, V = 2060.6(3) ?3, Z = 4, Dc = 1.384 g/cm~3, μ(Mo Ka) = 0.71073 mm~(-1), F(000) = 904, R = 0.0345 and w R = 0.0930. The intramolecular hydrogen bond at N(1)–H(1)···O(2), intermolecular weak interactions at O(3)···H(4) and weak π-π interactions connected the molecules to lead to one-dimensional tapes. Bioassay results indicated that the title compound had moderate herbicidal and fungicidal activities.     

Synthesis,Structure, and Biological Activity of (2Z)-2-[(2,4-Dinitrophenyl)hydrazinylidene]butanedioic Acid Esters

Dialkyl (2Z)-2-[(2,4-dinitrophenyl)hydrazinylidene]butanedioates have been synthesized by reaction of dialkyl (2Z)-2-hydroxybut-2-enedioates with 2,4-dinitrophenylhydrazine, and their structure has been studied by IR and ¹H NMR spectroscopy, mass spectrometry, and X-ray analysis.

     

Synthesis,Crystal Structure and Biological Activity of 5-(2-Methylphenyl)-1,3,4-oxadiazol-2(3H)-one Derivatives

3-Methyl-5-(2-methylphenyl)-1,3,4-oxadiazol-2(3H)-one(6) and N,N-diethyl-2-(2-methylbenzoyl)-hydrazinecarboxamide(7) were designed and synthesized from 5-(2-methylphenyl)-1,3,4-oxadiazol-2(3H)-one(5) by substituting and ring-opening, respectively. The target compounds were confirmed by IR, 1H NMR spectroscopy, MS, elemental analysis and single-crystal X-ray diffraction. Compound 6(C10H10N2O2, Mr = 190.20) crystallizes in the triclinic system, space group P 1 with a = 7.4645(16), b = 10.868(2), c = 12.970(3) A, α= 110.542(2), β= 98.142(2), γ=99.766(2)°, V = 947.7(3) A3, Z = 4, F(000) = 400, Dc = 1.333 g/cm3, μ= 0.095 mm-1, the final R =0.0550 and wR = 0.1483 for 2956 observed reflections with I 2γ(I). Compound 7(C13H19N3O2, Mr= 249.31) crystallizes in the monoclinic system, space group C2/c with a = 18.926(3), b =12.1853(17), c = 14.740(2) o,(I) = 125.6380(10)°, V = 2762.7(7) A3, Z = 8, F(000) = 1072, Dc=1.199 g/cm3, μ= 0.083 mm-1, the final R = 0.0554 and w R = 0.1468 for 2395 observed reflections with I 2σ(I). The preliminary bioassay results indicate that compound 6 exhibits notable fungicidal activities against Fusarium graminearum, Botrytis cinerea, Rhizoctonia cerealis and Colletotrichum capsici at the concentration of 100 μg/mL.