Preparation of 3-(4-chlorophenyl)-2-(2-aminothiazol-4-yl)-5-methoxybenzo[b]furan derivatives and their leukotriene B(4) inhibitory activity

A series of 3-(4-chlorophenyl)-2-(2-aminothiazol-4-yl)benzo[b]furan derivatives 6-10 were prepared and their leukotriene B(4) inhibitory activity was evaluated. We found that several compounds showed strong inhibition of calcium mobilization in CHO cells overexpressing human BLT(1) and BLT(2) receptors. Among them, 3-(4-chlorophenyl)-2-[5-formyl-2-[(dimethylamino)methyleneamino]thiazol-4-yl]-5-methoxybenzo[b]furan 9b showed the most potent and selective inhibition for the human BLT(2) receptor, and its IC(50) value was smaller than that of the selected positive control compound, ZK-158252.     

Preparation of 2-, 3-, 4- and 7-(2-alkylcarbamoyl-1-alkylvinyl)benzo[b]furans and their BLT1 and/or BLT2 inhibitory activities

Several 2-alkylcarbamoyl-1-alkylvinylbenzo[b]furans were designed to find a selective leukotriene B4 (LTB4) receptor antagonist. 2-(2-Alkylcarbamoyl-1-alkylvinyl)benzo[b]furans having a substituent group at the 3-position, 4-(2-alkylcarbamoyl-1-methylvinyl)benzo[b]furans having a substituent group at the 3-position, and 7-(2-alkylcarbamoyl-1-methylvinyl)benzo[b]furans and 3-(2-alkylcarbamoyl-1-alkylvinyl)benzo[b]furans were prepared and evaluated for LTB4 receptor (BLT1 and BLT2) inhibitory activities. (E)-3-Amino-4-[2-[2-(3,4-dimethoxyphenyl)ethylcarbamoyl]-1-methylvinyl]benzo[b]furan ((E)-17c) showed potent and selective inhibitory activity for BLT2. On the other hand, (E)-7-(2-diethylcarbamoyl-1-methylvinyl)benzo[b]furan ((E)-27a) showed potent inhibitory activity for both BLT1 and BLT2.     

Synthesis of 2-, 4- and 5-(2-alkylcarbamoyl-1-methylvinyl)-7-alkyloxybenzo[b]furans and their leukotriene B4 receptor antagonistic activity

Variable benzo[b]furan derivatives having (E)- and (Z)-2-alkylcarbamoyl-1-methylvinyl groups at the 2-, 4- and 5-positions and a carboxylpropoxy or (1-phenyl)ethoxy group at the 7-position were prepared to find novel and selective leukotriene B4(LTB4) receptor antagonists. (E)-2-(2-diethylcarbamoyl-1-methylvinyl)-7-(1-phenylethoxy)benzo[b]furan (4v) showed selective inhibition to the human BLT2 receptor (hBLT2). On the other hand, (E)-2-acetyl-4-(2-diethylcarbamoyl-1-methylvinyl)-7-(1-phenylethoxy)benzo[b]furan (7v) inhibited both human BLT(1) receptor (hBLT1) and hBLT2. The (E)-2-(2-diethylcarbamoyl-1-methylvinyl) group lay on approximately the same plane as the benzo[b]furan ring, whereas the (E)-4-(2-diethylcarbamoyl-1-methylvinyl) group had the torsion angle (45.7 degree) from the benzo[b]furan ring plane. However, the (Z)-(2-alkylcarbamoyl-1-methylvinyl)benzo[b]furans were inactive. The inhibitory activity depended on the conformation of the 2-diethylcarbamoyl-1-methylvinyl group.     

Preparation of 2- and 4-(2-alkylcarbamoyl-1-methylvinyl)-7-alkyloxybenzo[b]furans having potent antagonistic activity against human leukotriene B4 BLT1 and/or BLT2 receptors

(E)-2-Acetyl-4-(2-diethylcarbamoyl-1-methylvinyl)-7-(1-phenylethoxy)benzo[b]furan (4b) with a characteristic conformation and (E)-2-(2-morpholinocarbo-1-methylvinyl)-7-ethoxycarbopropoxybenzo[b]furan ((E)-3b) were prepared and evaluated for their leukotriene B4(LTB4) antagonistic activity. Compound 4b showed potent antagonistic activity against human BLT1 and BLT2 receptors. Compound (E)-3b displayed selective BLT2 receptor antagonistic activity. Both compounds were inactive to cysteinyl LT receptors.     

Synthesis and characterization of novel 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) and dihydro-alkylthio-benzyloxopyrimidine (S-DABO) analogs containing a benzo[<Emphasis Type="Italic">d</Emphasis>]thiazol moiety

A series of novel dihydro-alkylthio-benzyloxopyrimidine (S-DABO) and 1-[(2-hydroxyethoxy) methyl]-6-(phenylthio)thymine (HEPT) analogs bearing a (benzo[d]thiazol-2-yl)methyl moiety at the C⁶ position of the pyrimidine core have been synthesized. 5-Allyl-6-{(benzo[d]thiazol-2-yl)methyl}-2-thiouracil and 5-allyl-6-{(benzo-[d]thiazol-2-yl)methyl}uracil were alkylated to give, respectively, S²- and N¹- ethoxymethyl and -methylthiomethyl uracil derivatives. 5-Allyl-6-[(benzo[d]thiazol-2-yl)methyl]-2-thiouracil was also alkylated by S² with methyl bromoacetate and hydrolyzed to the corresponding acid.     

2-[4-(2,6-二氟苯基)噻唑-2-基]-3-羟基丙烯腈衍生物的合成及生物活性

为了寻找生物活性良好的噻唑基丙烯腈类化合物, 利用2-[4-(2,6-二氟苯基)噻唑-2-基]乙腈(3)分别与取代氯甲酸酯4和取代苯基异氰酸酯6在碱存在下反应, 合成了8个2-[4-(2,6-二氟苯基)噻唑-2-基]-3-羟基-3-烃氧基丙烯腈化合物5和7个2-[4-(2,6-二氟苯基)噻唑-2-基]-3-羟基-3-取代苯胺基丙烯腈化合物7, 均为首次报道的丙烯腈类化合物. 化合物结构经1H NMR, IR, MS和元素分析表征. 初步生物活性测定结果表明, 在试验浓度下, 目标化合物均具有一定的杀虫和抑菌活性, 其中化合物5f和5h在100 mg/L浓度下对炭疽病菌的抑制率达95%; 化合物5g和7d在250 mg/L浓度下对棉红蜘蛛的致死率达85%.     

The synthesis and transition temperatures of 5-(4-alkyl- and 4-alkoxy-phenyl)-2-cyanobenzo[b]furans and a 5-(4'-alkylbiphenyl-4-yl)-2-cyanobenzo[b]furan: a comparison with their biphenyl and terphenyl analogues

The synthesis and transition temperatures of a series of 5-(4-alkyl- and 4-alkoxy-phenyl)2-cyanobenzo[b]furans and a 5-(4'-alkylbiphenyl-4-yl)-2-cyanobenzo[b]furan are presented. The 2-cyanobenzo[b]furans show similar mesophase types to the analogous biphenyl and terphenyl compounds, which are obtained by replacing the benzo[b]furan unit with a phenyl ring. The transition temperatures for the 2-cyanobenzo[b]furan compounds are always higher than for their biphenyl and terphenyl counterparts, but they are much lower than for the corresponding phenylnaphthalenes. Five mesogenic benzo[b]furans without a cyano group were prepared as intermediates and these compounds have lower clearing points than their biphenyl analogues.     

Synthesis and oral activity of pivaloyloxymethyl 7-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3(Z)- (4-methylthiazol-5-yl)vinyl-3-cephem-4-carboxylate (ME1207) and its related compound.

7-[2-(2-Aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido]-3(Z)- (4-methylthiazol-5-yl)vinyl-3-cephem-4-carboxylic acid (11, ME1206) and its 3-trans isomer (13) were prepared to test antibacterial activity. These compounds exhibited excellent antibacterial activity against both gram-positive and gram-negative bacteria, including beta-lactamase producing strains. The pivaloyloxymethyl esters (12 and 14) of the compounds (11 and 13) were prepared by esterification with pivaloyloxymethyl iodide. Among them, pivaloyloxymethyl 7-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]- 3(Z)-(4-methylthiazol-5-yl)vinyl-3-cephem-4-carboxylate (12, ME1207) showed good urinary recovery after oral administration in mice.     

Synthesis and cytotoxic activity of some novel N-pyridinyl-2-(6-phenylimidazo[2,1-b]thiazol-3-yl)acetamide derivatives

A series of novel compounds bearing imidazo[2,1-b]thiazole scaffolds were designed and synthesized based on the optimization of the virtual screening hit compound N-(6-morpholinopyridin-3-yl)-2-(6-phenylimidazo[2,1-b]thiazol-3-yl)acetamide (5a), and tested for their cytotoxicity against human cancer cell lines, including HepG2 and MDA-MB-231. The results indicated that the compound 2-(6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl)-N-(6-(4-(4-methoxybenzyl)piperazin-1-yl)pyridin-3-yl)acetamide (5l), with slightly higher inhibition on VEGFR2 than 5a (5.72% and 3.76% inhibitory rate at 20 μM, respectively), was a potential inhibitor against MDA-MB-231 (IC(50) = 1.4 μM) compared with sorafenib (IC(50) = 5.2 μM), and showed more selectivity against MDA-MB-231 than HepG2 cell line (IC(50) = 22.6 μM).     

Syntheses of 4-(benzo[b]furan-2 or 3-yl)- and 4-(benzo[b]-thiophen-3-yl)piperidines with 5-HT2 antagonist activity

The syntheses of 4-(benzo[b]furan-3-yl)piperidines, 4-(benzo[b]furan-2-yl)piperidines and 4-(benzo[b]thiophen-3-yl)piperidines with 5-HT₂ antagonist activity are described. Reaction of 1-acetyl-4-(2,4-difluorobenzo-yl)piperidine 2 with methyl glycolate gave methyl 6-fluoro-3-(1-acetylpiperidin-4-yl)benzo[b]furan-2-carboxylate 3 , which was converted to 2-[2-[4-(benzo[b]furan-3-yi)piperidin-1-yl]ethyl-5,6,7,8-tetrahydro-1,2,4-triazolo-[4,3-a]pyridin-3(2H)-one hydrochloride 9 . Analogous benzo[b]furans 17a-d and benzo[b]thiophenes 10a,b and 18a were prepared by a similar method. Cyclization of 4-fluoro-2-(4-pyridinylmethoxy)acetophenones 20a,b afforded 4-(benzo[b]furan-2-yl)pyridines 21a,b , which were converted to 2-[2-[4-(benzo[b]furan-2-yl)-piperidin-1-yl]ethyl-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyridin-3(2H)-one hydrochlorides 24a,b. Among them, benzo[b]furans 9 and 17a,d and benzo[b]thiophenes 10 and 18a showed potent 5-HT₂ antagonist activity in vitro.     

Synthetic cephalosporins. VII. Synthesis and antibacterial activity of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(3-(3-hydroxy-4-pyridon-1-yl)-3- carboxypropoxyimino)acetamido]-3-(1,2,3-thiadiazol-5-yl)-thiomethyl-3- cephem-4-carboxylic acid and its related compounds

Synthesis and antibacterial activity of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(3-(3-hydroxy-4-pyridon-1-y l)-3- carboxypropoxyimino)acetamido]-3-(1,2,3-thiadiazol-5-yl)thio methyl-3-cephem-4-carboxylic acid (12a) and its related compounds are described. Compound 12a exhibited excellent antibacterial activity against gram-negative bacteria, including Pseudomonas aeruginosa.     

Synthesis,cytotoxic, and carbonic anhydrase inhibitory effects of new 2-(3-(4-methoxyphenyl)-5-(aryl)-4,5-dihydro-1H-pyrazol-1-yl)benzo[d]thiazole derivatives

2-(3-[4-Methoxyphenyl]-5-aryl-4,5-dihydro-1H-pyrazol-1-yl)benzo[d]thiazoles ( 1b-7b ) were synthesized for the first time except 1b , and spectral methods such as ¹H NMR, ¹³C NMR and HRMS were utilized to illuminate the chemical structures of the synthesized compounds. Phenyl ( 1b ), 2-methoxyphenyl ( 2b ), 4-methoxyphenyl ( 3b ), 4-methoxy-3-hydroxyphenyl ( 4b ), 2,5-dimethoxyphenyl ( 5b ), 3,4,5-trimethoxyphenyl ( 6b ), or thiophene-2-yl ( 7b ) was used as a aryl part. The inhibitory effects of the compounds were evaluated toward human carbonic anhydrase I and II enzymes (hCA I and hCA II). In vitro cytotoxic effects of the compounds against human oral squamous carcinomas and human normal oral cells were carried out via MTT. The compounds ( 1b-7b ) had Ki values of 36.87 ± 11.62-66.24 ± 2.99 μM (hCA I) and 22.66 ± 1.41-89.95 ± 6.25 μM (hCA II). Compounds 1b (Ki = 36.87 ± 11.62 μM) toward hCA I, 6b (Ki = 22.66 ± 1.41 μM) toward hCA II had significant enzyme inhibitory potency. Compound 6b had the highest tumor selectivity (TS = 29.3) and potency selectivity expression (PSE = 272.3) values. Therefore, compounds 1b and 6b with CAs inhibition effect and compound 6b with the cytotoxicity may be forwarded to further studies as potent compounds.     

The synthesis and transition temperatures of 5-(4-alkyl- and 4-alkoxy-phenyl)-2-cyanobenzo[b]furans and a 5-(4'-alkylbiphenyl-4-yl)-2-cyanobenzo[b]furan: a comparison with their biphenyl and terphenyl analogues

The synthesis and transition temperatures of a series of 5-(4-alkyl- and 4-alkoxy-phenyl)2-cyanobenzo[b]furans and a 5-(4'-alkylbiphenyl-4-yl)-2-cyanobenzo[b]furan are presented. The 2-cyanobenzo[b]furans show similar mesophase types to the analogous biphenyl and terphenyl compounds, which are obtained by replacing the benzo[b]furan unit with a phenyl ring. The transition temperatures for the 2-cyanobenzo[b]furan compounds are always higher than for their biphenyl and terphenyl counterparts, but they are much lower than for the corresponding phenylnaphthalenes. Five mesogenic benzo[b]furans without a cyano group were prepared as intermediates and these compounds have lower clearing points than their biphenyl analogues.     

Synthesis, structure and antifungal activity of new 3-[(5-aryl-1,3,4-oxadiazol-2-yl)methyl]benzo[d]thiazol-2(3H)-ones

A series of new 3-[(5-aryl-1,3,4-oxadiazol-2-yl)methy])benzo[d]thiazol-2(3H)-ones were synthesized by reaction of (5-substituted-2-oxobenzothiazolin-3-yl)-acetohydrazide with various aromatic acids in POCl(3) under reflux conditions. The structures of the title compounds were confirmed by 1H-NMR, 13C-NMR, IR, MS and elemental analysis. Furthermore, the structure of compound 4i was determined by single-crystal X-ray diffraction. The preliminary bioassy results indicated that some of them showed moderate inhibition activity against Colletotrichum orbiculare, Botrytis cinerea and Rhizoctonia solani.     

2-Amino-4-(aminomethyl)thiazole-based derivatives as potential antitumor agents: design,synthesis, cytotoxicity and apoptosis inducing activities

Novel 2-amino-4-(aminomethyl)thiazole derivatives were designed and synthesized by a facile method including the Hantzsch construction of thiazole core followed by amidation and nucleophilic substitution steps. Bioassay results showed that 4-(tert-butyl)-N-[4-(piperazin-1-ylmethyl)thiazol-2-yl]-benzamide and 4-(tert-butyl)-N-{4-[(4-piperidinopiperidin-1-yl)methyl]thiazol-2-yl}benzamide possessed similar activities compared with 5-fluorouracil. The 4-piperidino-piperidin-1-yl-containing derivative also suppressed proliferation of cultured tumor cells by inducing apoptosis.     

Synthetic cephalosporins. VI. Synthesis and antibacterial activity of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(1-carboxy-1-methyl) ethoxyiminoacetamido]- 3-(3-hydroxy-4-pyridon-1-yl)methyl-3-cephem-4-carboxylic acid and related compounds

Synthesis and antibacterial activity of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(1-carboxy-1-methyl)ethoxyimin oacetamido]- 3-(3-hydroxy-4-pyridon-1-yl)-3-cephem-4-carboxylic acid (12) and its related compounds are described. Compound 12 exhibited excellent antibacterial activity against gram-negative bacteria, and its anti-pseudomonal activity was ten to fifteen times greater than that of ceftazidime.     

Synthesis,spectral and electrochemical properties of halogenated 6-alkyl-5-aryl-1-(benzo[d]thiazol-2-yl)-3-phenylverdazyls and 5-aryl-1-(benzo[d]thiazol-2-yl)-3-phenyl-6-vinylverdazyls

Chemistry of Heterocyclic Compounds - A sequence of alkylation, cyclization, and oxidation reactions was used to convert 5-aryl-1-(benzo[d]thiazol-2-yl)-3-phenylformazans into...     

Condensed Pyridine Bases. Synthesis and Reactions of Benzofuro[2,3-c]indeno[2,1-e]-, Benzothieno[2,3-c]Indeno[2,1-e]-, Benzofuro-[3,2-c]Indeno[2,1-e]- and Thieno[2,3:4′,5′]-thieno[3,2-c]indeno[2,1-e]pyridines

Condensation of hetarene carboxaldehydes with phthalide gave 2-(3-hydroxy-1-oxoinden-2-yl)benzo[b]furan and 2-(3-hydroxy-1-oxoinden-2-yl)-5-ethylthieno[2,3-b]thiophene. Starting from hetaryl acetic acids gave 3-(3-hydroxy-1-oxoinden-2-yl)benzo[b]furan and 3-(3-hydroxy-1-oxoinden-2-yl)benzo[b]thiophene. Acylation of 3-hydroxy-1-oxoinden-2-yl-substituted heterocycles using acetic anhydride in the presence of 70% HClO₄ leads to the formation of pentacyclic pyrilium salts. Pentacyclic indenopyridines are prepared by treating the pyrilium salts with ammonia. The reaction of the carbonyl group in the indenopyridines with hydroxylamine, hydrazine hydrate, and in reduction using NaBH₄ has been studied.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 435–443, March, 2005.     

Synthesis and microbial screening of 8-(benzyloxy)-5-(2-[1,3-diphenyl-1H-pyrazol-4-yl]thiazol-4-yl)quinolin-2(1H)-one derivatives

The present investigation describe the synthesis of 8-(benzyloxy)-5-(2-[1,3-diphenyl-1H-pyrazol-4-yl]thiazol-4-yl)quinolin-2(1H)-one derivatives. Quinolin-8-ol was transformed by five step synthetic procedures into 8-Benzyloxy-5-(2-bromo-acetyl)-1H-quinolin-2-one. Subsequently, 8-Benzyloxy-5-(2-bromo-acetyl)-1H-quinolin-2-one condensed with 1,3-Diphenyl-1H-pyrazole-4-carbothioic acid amide in the presence of acetonitrile to afford 8-(benzyloxy)-5-(2-[1,3-diphenyl-1H-pyrazol-4-yl]thiazol-4-yl)quinolin-2(1H)-one derivatives. Synthesized compounds were screened for their antimicrobial activity against gram-positive and gram-negative bacteria. Most of the synthesized compounds are found to be active against tested bacterial strains and fungal strain.     

Design,Synthesis, and Anticancer Evaluation of 2-{3-{4-[(5-Aryl-1,2,4-oxadiazol-3-yl)methoxy]phenyl}isoxazol-5-yl}-N-(3,4,5-trimethylphenyl)thiazol-4-amine Derivatives

Russian Journal of General Chemistry - A series of new 2-{3-{4-[(5-aryl-1,2,4-oxadiazol-3-yl)methoxy]phenyl}isoxazol-5-yl}-N-(3,4,5-tri-methylphenyl)thiazol-4-amine derivatives is synthesized, and...