Structure-activity relationships of 6-nitroquinazolines: dual-acting compounds with inhibitory activities toward both TNF-alpha production and T cell proliferation

We synthesized various 6-nitroquinazolines by modifying the structure of compound 1 and evaluated their inhibitory activities toward both TNF-alpha production and T cell proliferation responses. The presence of the unsubstituted piperazine ring at the C(7)-position was required for both inhibitory activities. In this series of compounds, 5d and 5f, containing the 4-fluorophenyl and 3,4-difluorophenyl moiety, respectively, at the C(4)-position, showed the suppressing effects toward both responses with low cell growth inhibition. Furthermore, the oral administration of these compounds mentioned above at doses of 30 and 100 mg/kg also resulted in significant inhibition of TNF-alpha production induced by LPS in vivo.     

Synthesis of (4-nitro-1H-indol-6-yl)- and (4-amino-1H-indol-6-yl)phosphonic acid derivatives

Chemistry of Heterocyclic Compounds - A convenient methodology for the synthesis of previously unreported (1H-indol-6-yl)phosphonic acid derivatives has been described. Reaction of...     

Synthesis and structure of 6- and 7-(acylmethyl)pteridines

6-(Acylmethyl)-7-hydroxypteridines 7-14 as well as the isomeric 7-(acylmethyl)-6-hydroxypteridines 15-22 were prepared by condensation of 5,6-diaminouracils 1 and 2 with ethyl aroylpyruvates 3-6 in pyridine and hydrochloric acid, respectively. The structures of the newly synthesized compounds were confirmed by their hydrolysis into the 7-hydroxy-6-methyl- 23 , 24 and 6-hydroxy-7-methylpteridines 25 and 26 . The synthesis of the 2-(methylthio) derivative 28 is also described.     

Synthesis and spectral properties of n-alkyl-4-methyl-7(8)-nitro-2,3,4,5-tetrahydro-(1h)-1,5-benzodiazepin-2-ones

Alkylation of 4-methyl-7(8)-nitro-2,3,4,5-tetrahydrobenzodiazepin-2-ones under phase transfer catalytic conditions or in dry acetone occurs only at position 1. The 5-alkyl isomers are obtained by reductive alkylation of 4-methyl-7(8)-nitro-2,3-dihydro-1,5-benzodiazepin-2-ones. The UV, IR, PMR, and mass spectra of the isomeric compounds are reported.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 959–963, July, 1992.     

4-氯-6-甲氧基-7-(N-甲基-4-哌啶甲氧基)喹唑啉的合成

凡德他尼(vandetanib)是由阿斯利康公司研发的口服小分子多靶点酪酸激酶抑制剂,可同时作用于肿瘤细胞EGFR、VEGFR和RET酪氨酸激酶[1,2],2006年1月获欧洲罕见病药品委员会(COMP)批准推荐,用于治疗髓甲状腺癌、乳腺癌、骨髓瘤等[3].     

6α-取代的(1S, 7aS)-(+)-1-叔丁氧基-7a-甲基-2, 3, 5, 6, 7, 7a-六氢茚-5- 酮的合成

用化学动力学控制的方法在化合物3的5-C上C=O与6-C发生烯醇化生成锂盐,然后可在6-C位分别引入甲基、烯丙基、苄基、溴以及羟基取代基。产物6、7、8、9a和11经鉴定,除9α外其他都是α和β构型的混合物,其中以α-构型取代物为主。     

1-[(6-烷(苄)氧基-3,4-亚甲二氧基)苯基]-2-(1H-1,2,4-三唑)-乙酮(醇)类化合物的合成及抑菌活性

为了寻找新的低毒高效杀菌剂,以芝麻酚和1-H-1,2,4-三唑为主要原料,合成了12个1-[6-烷(苄)氧基-3,4-二氧亚甲基）苯基] -2 -(1H-1,2,4-三唑)-乙酮(醇)类化合物。所有化合物的结构经IR, 1HNMR, 13C NMR确证。初步生物测试结果表明：在质量浓度为100μgmL下,化合物Ⅴc对小麦赤霉病菌的抑制率达到了81.3%;化合物Ⅳe对马铃薯干腐病菌的抑制率达到了83.4%;化合物Ⅴe,Ⅴf对玉米弯孢病菌的抑制率也分别达到了79.7%和72.4%;化合物Ⅳd对小麦赤霉病菌和马铃薯干腐病菌的抑制率分别达到了68.9%和65.7%。     

2-(7-methyl-1H-benzoimidazol-2-yl)-6-(1-aryliminoethyl)pyridinylnickel complexes: Synthesis, characterization and their ethylene oligomerization

A series of 2-(methyl-substituted-1H-benzoimidazol-2-yl)-6-(1-aryliminoethyl)pyridines (L1–L6) were synthesized and used as N^N^N tridentate ligands for their nickel complexes (C1–C12). All ligands were fully characterized by elemental, NMR and IR spectroscopic analyses, while their nickel complexes were characterized by elemental and IR spectroscopic analyses. The single-crystal X-ray diffraction reveals that the complexes C1, C3 and C9 have distorted octahedral geometry around the Ni center. All nickel complexes, activated with Et₂AlCl, exhibit good catalytic activities toward ethylene oligomerization with major dimerization.     

Synthesis and properties of 1-methyl(aryl)-7-ethoxycarbonylindolizines

The previously unknown 2-substituted indolizine-7-carboxylic acids and their derivatives were synthesized, and some of their properties were studied.     

Synthesis of 6- and 7-propargyloxy derivatives of 4-(3-fluoroanilino)-quinazoline

The preparation of the novel isomeric 6- and 7-propargyloxy derivatives of 4-(3-fluoroanilino)-quinazoline was achieved using a six-step process. An alternate method to the 7-propargyloxy derivative and analogous 7-propargyloxy containing compounds is also described.     

Synthesis of quaternary 8-(1-acylethene-1-yl)-13-methylcoptisine chlorides and their selective growth inhibitory activity between human cancer cell lines and normal intestinal epithelial cell-6

Quaternary 8-(1-acylethene-1-yl)-13-methylcoptisine chlorides targeting TrxRs were designed and synthesized. An in vitro evaluation for the growth inhibitory activities against cancer cell lines and for the viability of the normal intestinal epithelial cell-6 cell line is reported.     

Synthesis and in vitro antibacterial activities of 7-(4-alkoxyimino-3-hydroxypiperidin-1-yl)quinolone derivatives

<正>A series of novel 7-(4-alkoxyimino-3-hydroxypiperidin-1-yl)quinolone derivatives were designed,synthesized and evaluated for in vitro antibacterial activities.Compounds 8f,8g,8i and 8j with the potencies similar to or better than those of levofloxacin and IMB against Staphylococcus aureus and Staphylococcus epidermidis,worth further investigation.     

1-（N-（2-（2-Methoxyphenylthio）benzyl）-N-methylamino-3-aryloxypropan-2-ols： Synthesis and evaluation for dual 5-HT1A/SSRI activities

A series of 1-（N-（2-（2-methoxyphenylthio）benzyl）-N-methylamino-3-aryloxypropan-2-ols derivatives were designed and synthesized based on 5-HT1A/SSRI drugs design strategies. The synthesized compounds were evaluated for their dual 5-HT1A/ 5-HTT activities. 2007 Ai Jun Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.