New 3-[4-(3-substituted phenyl)piperazin-1-yl]-1-(benzo[b]thiophen-3-yl)propanol derivatives with dual action at 5-HT1A serotonin receptors and serotonin transporter as a new class of antidepressants

In this paper a series of new 3-[4-(3-substituted phenyl)piperazin-1-yl]-1-(benzo[b]thiophen-3-yl)propanol derivatives is presented as a new class of antidepressant drugs with dual activity at 5-HT1A serotonin receptors and serotonin transporter. The 5-HT1A receptor and 5-HT transporter binding affinities of hydroxylic compounds 4 a-e have been determined. The new compounds present nanomolar affinity for both activities, and 1-(benzo[b]thiophen-3-yl)-3-[4-(3-methoxyphenyl)piperazin-1-yl]propan-1-ol (4d) shows values (nM) of Ki = 86 for 5-HT1A receptors and Ki = 76 for the serotonin transporter, respectively.     

New 3-[4-(2,3-dihydro-14-benzodioxin-5-yl)piperazin-1-yl]-1-(5-substituted benzo[b]thiophen-3-yl)propanol derivatives with dual action at 5-HT(1A) serotonin receptors and serotonin transporter as a new class of antidepressants

Compounds derived from 2,3-dihydro-(1,4-benzodioxin-5-yl)piperazine and benzo[b]thiophene with different substituents in 5 position (H, F, NO2, NH2, CH3 and OH) have been synthesized in order to obtain new dual antidepressant drugs. The final compounds were evaluated for in vitro 5-HT(1A) receptor affinity and serotonin reuptake inhibition by radioligand assays. Compounds 1-(5-nitrobenzo[b]thiophen-3-yl)-3-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazin-1-yl]propan-1-ol (4c) (Ki = 6.8 for 5-HT(1A) receptor and Ki = 14 for 5-HT transporter) and 1-(5-hydroxybenzo[b]thiophen-3-yl)-3-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazin-1-yl] propan-1-ol (4f) (Ki = 6.2 for 5-HT(1A) receptor and Ki = 18.2 for 5-HT transporter) showed the best results for both activities.     

Synthesis and anti-inflammatory activity of certain piperazinylthienylpyridazine derivatives

In this study, a novel series of 2-(4-substituted piperazin-l-ylmethyl)-6-(thien-2-yl)-2H-pyridazin-3-ones (3a-f), 2-(4-substituted piperazin-l-yl carbonylmethyl)-6-(thien-2-yl)-2H-pyridazin-3-ones (4a-c) and 2-[2-(4-substituted piperazin-l-ylcarbonylethyl)]-6-(thien-2-yl)-2H-pyridazin-3-ones (5a,b) were prepared from 6-(thien-2-yl)-2H- pyridazin-3-one (1). In addition, 3-(4-substituted piperazin-l-ylcarbonyl methyl thio)-6-(thien-2-yl) pyridazines (6a-c) and 3-[2-(4-substitutedpiperazin-1-ylcarbonyl ethylthio]-6-(thien-2-yl) pyridazines (7a,b) were synthesized. Furthermore, 5-(4-substituted piperazin-l-ylmethyl)-6-(thien-2-yl)-2H-pyridazin-3-ones (12a,b) were prepared. The structures of the new compounds were confirmed by elemental analysis as well as by 1H-NMR, IR and MS data. Some of the newly prepared compounds were subjected to evaluation for their anti-inflammatory activity against carrageenan-induced paw edema at a dose of 10 mg/kg using indomethacin as the reference standard.     

New dammaranes, esterified with malonic acid, from leaves of Betula pendula

Three known and five new dammarane triterpenes, esterified with malonic acid at C-3 with hemolytic activity were identified from the ethanol-water extract of leaves of Betula pendula Roth: 12-O-acetyl-3alpha,12beta,20(S),24(R)-tetrahydroxydammar-25-en-3-yl hydrogen propanedioate, 12-O-acetyl-3alpha,12beta20(S),24(S)-tetrahydroxydammar-25-en-3-yl hydrogen propanedionate, 12-O-acetyl-3alpha,12beta,17alpha,20(S),24(R)-pentahydroxydammar-25-en-3-yl hydrogen propanedioate, [12beta-acetoxy-4,4,8,10,14-pentamethyl-17-(2-methyl-5-oxotetrahydrofuran2(S)-yl)-hexadecahydrocyclopenta[A]phenanthren-3alpha-yl] hydrogen propanedioate, 12- O-acetyl-3alpha,12beta,20(S),25-pentahydroxydammar-23(E)-en-3-yl hydrogen propanedioate, and one which was new for Betula pendula but found in other Betula species: 12-O-acetyl-20,24-epoxy-3alpha,12beta,20(S),24(R),25-pentahydroxydammar-3-yl hydrogen propanedioate. The structures were elucidated by MS, (1)H-NMR, (13)C-NMR, (1)H-(1)H-COSY, DEPT, (1)H-(13)C-NMR (HMQC, HMBC) experiments.     

Synthesis and Evaluation of 3-(Indol-3-yl)-4-(Pyrazolo[3,4-c]Pyridazin-3-yl)-Maleimides as Potent Mutant Isocitrate Dehydrogenase-1 Inhibitors

Pharmaceutical Chemistry Journal - A series of new 3-(indol-3-yl)-4-(pyrazolo[3,4-c]pyridazin-3-yl)-maleimides were synthesized and evaluated for their inhibitory activity against IDH1-R132H. Most...     

Synthesis and cytotoxicity of bis-1,3,4-oxadiazoles and bis-pyrazoles derived from 1,4-bis[5-thio-4-substituted-1,2,4-triazol-3-yl]-butane and their DNA binding studies

A new series of 1,4-bis[5-(5-mercapto-1,3,4-oxadiazol-2-yl-methyl)-thio-4-substituted-1,2,4-triazol-3-yl]-butane 7-12 and 1,4-bis[5-(1-oxo-1-(3,5 dimethyl pyrazol-1-yl)-methyl)-thio-4-substitued-1,2,4-triazol-3-yl]-butane 13-18 were prepared from 1,4-bis(5[hydrazinocarbonylmethylthio]-4-substituted-1,2,4-triazol-3-yl) butane based derivativess were synthesized 1-6. All the synthesized compounds were characterized by IR, NMR and Mass spectral studies. The synthesized compounds 7-18 were screened for in-vitro cytotoxicity potential using the standard MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay against a panel of three human cancer cell lines: Lung carcinoma A-549, colon carcinoma HT-29 and breast cancer MDA MB-231. DNA binding studies were conducted for three potent molecules by absorption titration method.     

Synthesis of some 2-benzoxazolinone derivatives and their analgesic properties

In this study, eight new 1-(2-benzoxazolinone-6-yl)-2-(4-arylpiperazine-1-yl)ethanol and -propanol derivatives have been prepared. Their structures have been elucidated by IR- and 1H-NMR-spectra and by elementary analysis. The analgesic activities of these compounds, using modified Koster's test have been investigated. 1-(5-Chloro-3-methyl-2-benzoxazolone-6-yl)-2-[4-(2-methoxyphenyl)p iperazine-1- yl]ethanol has been found more active than O-acetyl-salicylic acid, respectively.     

Synthesis and antimicrobial activity of some (3-phenyl-5-(1-phenyl-3-aryl-1H-pyrazol-4-yl)-4,5-dihydro-1H-pyrazol-1-yl)(pyridin-4-yl)methanones: new derivatives of 1,3,5-trisubstituted pyrazolines

A series of (3-phenyl-5-(1-phenyl-3-aryl-1H-pyrazol-4-yl)-4,5-dihydro-1H-pyrazol-1-yl)(pyridin-4-yl)methanones was synthesized by condensing suitably substituted chalcones, i.e., 3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-1-phenylprop-2-en-1-ones, and isoniazid in acetic acid. The structure of newly synthesized compounds has been established on the basis of analytical and spectral data. The new compounds were screened for antimicrobial activity and most of them showed good activity comparable with that of standard drugs ciprofloxacin and fluconazole. Compounds containing methoxy group showed high antimicrobial activity.     

甲磺酸伊马替尼有关物质的合成

为了控制甲磺酸伊马替尼产品质量,分别合成了质量标准所载的5种有关物质:4-[(哌嗪-1-基)甲基]-N-[4-甲基-3-[ [4- (3-吡啶基)嘧啶-2-基]氨基]苯基]苯甲酰胺(A),4-[(4-甲基-1,4-二氧化哌嗪-1-基)甲基]-N-[4-甲基-3-[ [4- (3-吡啶基)嘧啶-2-基]氨基]苯基]苯甲酰胺(B),4-[(4-甲基-1-氧化哌嗪-1-基)甲基]-N-[4-甲基-3-[ [4- (3-吡啶基)嘧啶-2-基]氨基]苯基]苯甲酰胺(C),4-[ (4-甲基-4-氧化哌嗪-1-基)甲基]-N-[4-甲基-3-[ [4- (3-吡啶基)嘧啶-2-基]氨基]苯基]苯甲酰胺(D)和1,4-双[4-[4-甲基-3-[ [4- (3-吡啶基)嘧啶-2-基]氨基]苯基]氨甲酰基]苄基哌嗪(E),并经1H NMR、MS等确证结构.     

Synthesis and biological evaluation of some novel 2-phenyl benzimidazole-1-acetamide derivatives as potential anthelmintic agents

The present study describes synthesis of a series of 2-phenyl benzimidazole-1-acetamide derivatives and their evaluation for anthelmintic activity using Indian adult earthworms, Pheretima posthuma. The structure of the title compounds was elucidated by elemental analysis and spectral data. The compounds 4-({[2-(4-nitrophenyl)-1H-benzimidazol-1-yl]acetyl}amino) benzoic acid (3a), N-ethyl-2-[2-(4-nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3c), N-benzyl-2-[2-(4-nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3d), N-(4-hydroxyphenyl)-2-[2-(4-nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3f), 2-[2-(4-nitrophenyl)-1H-benzimidazol-1-yl]-N-phenyl acetamide (3h), 2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N'-phenylacetohydrazide (3k), 2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N-(4-nitrophenyl) acetamide (3n) and 2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N-phenyl acetamide (3q) were found better to paralyze worms whereas N-ethyl-2-[2-(4-nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3c), N-(4-nitrophenyl)-2-[2-(4-nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3e), 4-({[2-(4-chlorophenyl)-1H-benzimidazol-1-yl] acetyl}amino) benzoic acid (3j), 2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N-ethyl acetamide (31) and 2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N-phenyl acetamide (3q) were better to cause death of worms compared to the anthelmintic drug albendazole.     

Synthesis and antimicrobial activities of some new nitroimidazole derivatives

In this study, some new nitroimidazole derivatives were obtained from 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethylamine dihydrochloride (4) and 1-(2-bromoethyl)-2-methyl-5-nitroimidazole (5), which were prepared using metronidazole. Compound 4 was reacted with arylisothiocyanates (6) to obtain 1-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]-3-arylthioureas (7) and the latter with alpha-bromoacetophenones (8) to give 3-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]-2-arylimino-4-aryl-4-thiazolines (9). Also 1-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]-2-phenyl-4-arylideneimidazolin-5-ones (11) were prepared by reaction of 4 with 2-phenyl-4-arylidene-5-oxazolones (10). The reaction of the other starting material 5 with 5-arylidenethiazolidin-2,4-dione (12) gave 3-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]-5-arylidenethiazolidin-2,4-dione (13) derivatives. Structural elucidation of the compounds was performed by IR, 1H-NMR and MASS spectroscopic data and elemental analysis results. Antimicrobial activities of the compounds were examined and moderate activity was obtained.     

Convenient synthesis and antimicrobial activity of new 3-substituted 5-(benzofuran-2-yl)-pyrazole derivatives

The reaction of ethyl 4-(benzofuran-2-yl)-2,4-dioxobutanoate 2 with two moles of hydrazine hydrate afforded 5-(benzofuran-2-yl)-1H-pyrazole-3-carbohydrazide 4a, while its reaction with equimolar amount of phenylhydrazine gave ester 3b which then converted to 5-(benzofuran-2-yl)-1-phenyl-1H-pyrazole-3-carbohydrazide 4b. Various new compounds such as imides 5 and 6, acyl hydrazones 7 and 8, bi-pyrazoles 9-12, and 1,3-thiazole derivatives 14 and 15 were prepared from carbohydrazide derivatives 4a, b. The new compounds are tested for their antimicrobial activity. Compounds 2, 5, 7, and 8 showed antifungal activities against C. albicans. Also, compounds 2, 6, 8, and 15 showed antibacterial activities.     

Three new secolignan glycosides from Urtica fissa E. Pritz

Three new secolignan glycosides {3,4-trans-4-[bis(3,4-dimethoxyphenyl)methyl]-2-oxotetrahydrafuran-3-yl}methyl-O-β-glucopyranoside (1), {3,4-trans-4-[(3-methoxy-4-hydroxyphenyl)(3,4-dimethoxyphenyl)methyl]-2-oxotetrahydrafuran-3-yl}methyl-O-β-glucopyranoside (2) and {3,4-cis-4-[(3-methoxy-4-hydroxyphenyl)(3,4-dimethoxyphenyl)methyl]-2-oxotetrahydrafuran-3-yl}methyl-O-β-glucopyranoside (3) were isolated from the roots of Urtica fissa E. Pritz. Their structures were identified by spectral methods including 1D NMR, 2D NMR and HR-EI-MS.     

Three new compounds from Dictamnus dasycarpus

Phytochemical investigation of the ethyl acetate extracts from root barks of Dictamnus dasycarpus led to the isolation of three new compounds, named as dasycarpusenester A (1), dasycarpusester B (2), dasycarpusacid (3). Their structures were elucidated as (2S)-4-(2,2-dimethyl-5-oxotetrahydrofuran-3-yl)-2-hydroxypent-3-enoic acid methyl ester (1), (2R)-4-(2,2-dimethyl-5-oxotetrahydrofuran-3-yl)-2-hydroxypent-3-anoic acid methyl ester (2), and (2S)-4-(2,2-dimethyl-5-oxotetrahydrofuran-3-yl)-2-hydroxypent-3-anoic acid (3), respectively, on the basis of modern spectroscopic methods and chemical analysis.     

Pyrrole alkaloids from Bolbostemma paniculatum

Three pyrrole alkaloids were isolated from Bolbostemma paniculatum. Their structures were elucidated as 4-(2-formyl-5-methoxymethylpyrrol-1-yl)butyric acid methyl ester (1), 2-(2-formyl-5-methoxymethylpyrrol-1-yl)-3-phenylpropionic acid methyl ester (2) and alpha-methyl pyrrole ketone (3) by spectroscopic techniques. Among them, 1 and 2 are new compounds.     

Macrocyclic peptides II. Synthesis and structure of a novel dipeptide, (2S,3′S)-2-(2′-oxo-3′-methylpiperazin-1′-yl)-propanoic acid,and its use as the unit of cyclic peptides

A new cyclic compound [(2S,3′S)-2-(2′-oxo-3′-methylpiperazin-1′-yl)-propanoic acid] obtained using (2S,7S)-2,7-dimethyl-3,6-diazaoctanedioic acid as a starting material was derived from N-t-butyloxycarbonyl-(2S,3′S)-2-(2′-oxo-3′-methylpiperazin-1′-yl)-propanoic acid in order to determine the molecular structure by X-ray crystal analysis. Two new macrocyclic peptides were prepared using the above cyclic compound and sarcosine as peptide units.     

Synthesis and structure-activity relationships of 7 beta-[2-(2-aminothiazol-4-yl)acetamido]cephalosporin derivatives. V. Synthesis and antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-cephalosporin derivates and related compounds

In order to improve the antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)acetamido]-cephalosporins new derivatives having a methoxyimino moiety in the 7-acyl side chain and related compounds were synthesized. Of these, 7 beta-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-cephalosporins were found to possess excellent activity against a variety of Gram-positive and Gram-negative bacteria including beta-lactamase-producing strains. An extensive study of structure-activity relationships led to the selection of 7 beta-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-ceph-3-em-4-carboxylic acid, SCE-1365, for further biological and clinical evaluation.     

Norsesquiterpenoid glucosides and a rhamnoside of pyrrolizidine alkaloid from Tephroseris kirilowii

Four new glycosylated compounds have been isolated from the whole plant of Tephroseris kirilowii, including (-)-(1R,5R,6S,7R,8S)-8-O-beta-D-glucopyranosyloxy-7-hydroxy-6-(2-hydroxypropan-2-yl)-9-methylenebicyclo[4.3.0]non-3-one (tephroside A, 1), (-)-(1R,5R,6R,8R)-6-(2-O-beta-D-glucopyranosyloxypropan-2-yl)-8-hydroxy-9-methylenebicyclo[4.3.0]non-3-one (tephroside B, 2), thesinine-4'-O-alpha-L-rhamnoside (3), and p-coumaric acid 4-O-alpha-L-rhamnoside (4), together with the known roseoside. The structures of the new compounds were established by means of spectroscopic analysis.     

Synthesis and antinociceptive activity of some 3-substituted benzothiazolone derivatives

Thirteen 3-substituted benzothiazolone derivatives have been synthesized. Their chemical structures have been elucidated by IR and NMR spectral data and by elemental analyses. Among these compounds, 1-?3-[2(3H)-benzothiazolon-3-yl[propanoyl]morpholine (5b); 1-?3-[2(3H)-benzothiazolon-3-yl[propanoyl]-4-benzylpiperidine++ + (5c); 1-?3-[2(3H)-benzothiazolon-3-yl[-propanoyl]-4-phenylpiperazine (5d); 3-[3-(4-benzylpiperidine-1-yl)propyl]-2(3H)-benzothiazolone (5k); 3-[3-(4-benzylpiperazine-1-yl)propyl]-2(3H)-benzothiazolone (5I); 3-[3-(4-phenylpiperazine-1-yl)propyl]-2(3H)-benzothiazolone (5m) have been found to be significantly more active than the others.     

Non-steroidal antiinflammatory agents. Synthesis of novel 2-pyrazolyl-4(3H)-quinazolinones

Four novel series of pyrazolyl-4(3H)-quinazolinones have been prepared through the reaction of 3-aryl-2-hydrazino-4(3H)-quinazolinones with antipyrylazo-derivatives of ethyl acetoacetate, acetylacetone or diethyl malonate. These series of compounds are 3-aryl-2-[1-ethoxycarbonyl-1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H - pyrazol-4-yl)hydrazono-2-propylidene]hydrazino-4(3H)-quinazo linones; 3-aryl-2-[4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl) hydrazono-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]-4(3H)-quinaz olinones; 3-aryl-2-[4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)azo -3,5- dimethyl-1H-pyrazol-1-yl]-4(3H)-quinazolinones and 3-aryl-2-[4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl) hydrazono-3,5-dioxo-pyrazolidin-2-yl]-4(3H)-quinazolinones. The antiinflammatory activity of some representatives of the prepared compounds was studied.