Showing papers in "Indian Journal of Chemistry Section B-organic Chemistry Including Medicinal Chemistry in 2005"

Synthesis and antidiabetic activity of 2-amino [5'(4-sulphonylbenzylidine)-2,4-thiazolidinedione]-7-chloro-6-fluorobenzothiazole

Abstract: A new series of 2-amino[5'(4-sulphonylbenzylidine)-2,4-thiazolidinedione]-7-chloro-6-fluorobenzothiazole were synthesized The structures of the compounds were confirmed by UV-Vis, IR and NMR spectroscopy The title compounds were screened for their antidiabetic activity on albino rats.

Vilsmeier-haack reagent : A facile synthesis of 2 -chloro -3 -formylquinolines from n-arylacetamides and transformation into different functionalities

Abstract: A simple and regioseleetive synthesis of 2-chloro-3-formylquinolines through Vilsmeier-Haack cyclisation of N-arylacetamides has been reported. The cyclisation is facilitated by N-arylacctamides bearing electron donating groups at m-position. However, yields of quinolines having electron donating groups are good in all cases. Further, the nucleophilie substitution reaction of the quinolines is also investigated. Similarly, the formyl group in the quinolines is subjected to further transformation into cyano (CAN-NH 3 ) and alkoxycarbonyl (NIS-K 2 CO 3 /alcohols) groups to afford corresponding 3-cyano and 3-alkoxycarbonylquinolincs, respectively.

Synthesis and anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation activities of 3,5-dimethyl pyrazoles, 3-methyl pyrazol-5-ones and 3,5-disubstituted pyrazolines

Abstract: 3,5-Dimethyl pyrazole 3a-d and 3-methyl pyrazol-5-one 4a-d derivatives of diclofenac, ibuprofen, flurbiprofen and 2,4-dichlorophenoxy acetic acid have been synthesized. In addition, substituted pyrazoline derivatives of ibuprofen 6a-e have also been prepared by treating different chalcones 5a-e with ibuprofen hydrazide. Some of the newly synthesized compounds are screened for anti-inflammatory activity and few compounds showing 80% activity are selected for analgesic, ulcerogenic and lipid peroxidation activities.

Kinetic study on lipase-catalyzed esterification in organic solvents

Abstract: A twin inhibition is observed for the esterification reaction between ethanol and isovaleric acid using immobilized lipase from Rluzomucor miehei in hexane and in mixed solvent system. The observed bi-substrate inhibitionpattern follows a Ping-Pong Bi-Bi mechanism with dead-end inhibition of enzyme by both the substrates. An increase in K m value for alcohol in mixed solvent (0.645 M) than in hexane (0.256 M), indicates that the enhanced salvation of ethanol in mixed solvent results in lower degree of inhibition.

Synthesis, antimicrobial and antiinflammatory activities of 4-oxothiazolidines and their 5-arylidenes

Abstract: As a part of systematic investigation of synthesis and biologically active compounds of 2-mercaptobenzothiazoles, several new 2-[(aryl)-3-(acetylamino)-1,3-thiazolidin-4-ones]-2-mercaptobenzothiazole 4 and 2-[5-arylidene-2-phenyl-3-(acetylamino)-1,3-thiazolidine 4-ones)-2-mercaptobenzothiazole 5 from 2-mercaptobenzothiazole have been synthesised and tested for their antimicrobial and antiinflammatory activities. The structures of all the synthesized compounds have been determined by spectral and chemical methods.

Composition of a new chemotype of Tanacetum nubigenum

Abstract: (3R,6R)-Tctrahydro-6-ethenyl-2,2,6-trimethyl-4H-pyran-3-acetate [3R,6R)-linalool oxide acetate] 1 (69.37%) along with 2-hydroxy-4,6-dimethoxyacetophenone 2, (E)- and (Z)-2-(2,4-hexadiynylidene)-l,6-dioxaspiro[4,4]non-3-ene 3 and 4, β-eudesmol 5 and selin-11-en-4α-ol 6 have been isolated from Tanacetum nubigenum Wall of Kumaon region of North Western Himalaya at an altitude of 3600-4300 m. (3R,6R)-linalool oxide acetate 1 has not been reported in Tanacetum species or from any other natural source. Presence of compounds 1-6 and absence of previously reported chrysanthenol and related esters makes it a new chemotype within the genus Tanacetum.

Novel fluoro substituted benzo[b]pyran with anti-lung cancer activity

Abstract: 6-Fluorobenzo[b]pyran-4-one 1 on condensation with aromatic aldehydes yields 3-arylmethylene-6-fluoro-2,3-dihydrobenzo[b]pyran-4-ones 2 which on treatment with phenylhydrazine and thiourea gives the pyrazole and pyrimidine thione derivatives 3 and 4, respectively. Compound 4 reacts with chloroacetic acid in acetic acid-acetic anhydride mixture to afford the thiazolopyrimidines 5 which on condensation with aromatic aldehyde furnish the corresponding arylmethylene-thiazolopyrimidine derivatives 6. The product 6 could be prepared directly by the action of chloroacetic acid and the proper aldehyde on 4 in the presence of acetic acid-acetic anhydride mixture. Product 2 reacts with malononitrile in the presence of ammonium acetate or piperidine to afford the pyridine- and pyran- 7 and 8 derivatives, respectively. Also, compound 1 on treatment with arylmethylenecyanoacetamide yields the pyridone derivatives 9. Condensation of 1 with malononitrile affords the yliedinemalononitrile 10, which on reaction with p-chlorobenzaldehyde-ammonium acetate or arylmethylenecyanoacetamide yields the pyridine derivative 11 (isomer of 8) and the dicarbonitrile derivative 12, respectively. The synthesized compounds have been tested against three cell lines of human cancer (lung, breast and CNS cancer), and these compounds show anticancer activity at low concentration as compared to reference drug 5-fluorodeoxyuridine.

Combinatorial chemistry: A novel method in drug discovery and its application

Abstract: Combinatorial chemistry is a new technique developed in pharmaceutical industry, which involves synthesis of compounds in mass instead of a single compound, which are screened as a whole mixture for particular biological activity. Because of the rapid synthesis of compounds, this method saves the time and cost associated with the drug discovery. This brief review article includes combinatorial strategies, screening methods and encoding technologies and some of the applications in drug discovery.

Synthesis and anticancer activity studies on some 2-chloro-1,4-bis-(5-substituted- 1,3,4-oxadiazol-2-ylmethyleneoxy) phenylene derivatives

Abstract: 2-Chloro-1,4-phenylenedioxy-bis-acetyl hydrazine 1 on reacting with aromatic carboxylic acids in the presence of phosphorus oxychloride affords 2-chloro-bis-1,3,4-oxadiazoles 3a-f and 4a-d. Aroyl hydrazine 1 on reacting with carbon disulphide under basic condition gives oxadiazole-2-thione 2. Three out of four tested compounds show anticancer activity in the primary anticancer assay. These compounds have been extensively screened against a panel of sixty cancer cell lines derived from leukemia, lung, colon, CNS, melanoma, ovarian, renal, prostate and breast cancer, respectively. It is interesting to note that compounds 3d and 3f show significant anticancer activity against most of the cell lines with GI50 values <100 μM concentrations.

Synthesis and preliminary anticancer activity of new 1 H -4,5-dihydro-3-(3-hydroxy-2-naphthyl)-4-substituted-1,2,4-triazoline-5-thiones. Part II

Abstract: The compounds 1H-4,5-dihydro-3-(3-hydroxy-2-naphthyl)-4-substituted-1,2,4-triazoline-5-thiones have been synthesised from 3-hydroxy-2-naphthoic acid hydrazide in two steps. The structural elucidation of the synthesised compounds has been performed by 1 H NMR and mass spectroscopic data besides elemental analyses. Some of the compounds are tested in vitro for their ability to inhibit growth of 60 different human cancer cell lines by the National Cancer Institute and notable cytotoxic effect on some cancer cell lines is observed from some of them as expected in comparison with the control agent 5-fluorouracil.

Synthesis and antimicrobial activity of some 3-alkyl-4-(arylmethyleneamino)-4,5-dihydro- 1H-1,2,4-triazol-5-ones

Abstract: Eight new ethyl N'-(3-methyl-4-arylmethyleneamino-4,5-dihydro-1H-1,2,4-triazolyl-5-one)acetates 2 and N'-(3-methyl-4-arylmethyleneamino-4,5-dihydro-1H-1,2,4-triazolyl-5-one)acetyl-hydrazines 3 have been synthesized. The structures of the compounds have been confirmed by IR and 1 H NMR spectra and microanalysis. The compounds show some antimicrobial activities. Compound 2a shows antibacterial activity against B. subtilis. Compounds 3a, 3b and 3d have antifungal activity against Candida species.

Synthesis, characterization and biological activity of 1,3,4-substituted 2-azetidinones

Abstract: Amido/imido alcohol/2-phenyl-3-hydroxyethylquinazolin-4 (3H) -one 1 on treatment with benzoic acid in the presence of conc. H2SO4 yields m-(aralkylamido/imidoalkyl/2-phenyl-3-ethyl-3H-4-oxoquinazolinyl) benzoic acids 2. The acid chloride of 2 on reaction with hydrazine hydrate affords m-(aralkylamido/imidoalkyl/2-phenyl-3-ethyl-3H-4-oxoquinazolinyl) benzoic acid hydrazides 4 which on condensation with an aromatic aldehyde in acetic acid gives m(aralkylamido/imidoalkyl/2-phenyl-3-ethyl-3H-4-oxo-quinazolinyl) benzoic acid hydrazones 5. Compounds 5 undergo cyclization with phenoxy acetic acid in the presence of thionyl chloride in dry benzene to furnish 1-[m(aralkylamido/imidoalkyl/2-phenyl-3-ethyl-3H-4-oxo-quinazolinyl-benzamido)]-3-phenoxy-4-phenyl-2-azetidinones 6. The antiviral and antifungal activities of 6 have been reported. IPC: Int.Cl. 7 C 07 C 59/54 // A 61 P 31/12

One pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones/-thiones catalysed by zinc chloride: An improved procedure for the Biginelli reaction using microwaves under solvent free condition

Abstract: Zinc chloride efficiently catalyzes the three-component coupling of I²-keto ester, substituted aldehyde and urea or thiourea to afford the corresponding 3,4-dihydropyrimidin-2(1H)-ones/thiones respectively, the new protocol for the Biginelli reaction under microwave irradiation works in the absence of solvent, the yields are high and the reaction goes to completion within 20-35 sec.

1,8-dihydroxyanthraquinone derivatives from rhizomes of Rheum emodi Wall

Abstract: Two 1,8-dihydroxyanthraquinones isolated from rhizomes of Rheum emodi Wall. have been characterized as 6-methyl-rhein 1 and 6-methyl-aloe-emodin 2 by spectral data and chemical studies.

Isolation, antihypertensive activity and structure activity relationship of flavonoids from three medicinal plants

Abstract: Eight flavonoids, namely naringenin 1, 3-β-hydroxynaringenin designated as isoaromadendrin 2, taxifolin 3, isoaromadendrin-7-O-β-D-glucopyranoside designated as isosinensin 4 have been isolated from Euphorbia cuneata Vahl; 5hydroxy-3, 4′, 7-trimethoxyflavone 5, 5-hydroxy-3, 3′, 4′, 7-tetramethoxyflavone (retusin) 6, 4′, 5-dihydroxyflavone-5-O-βD-glucopyranoside named as verbenacoside 7 are obtained from Salvia verbenaca L; and epicatchin 8 is isolated from Osyris abyssinica. Their structures have been established by spectral and chemical methods, whereupon the compounds 2, 4 and 7 are found to be new flavonoids. Compounds 1-5, 7, 8 and alcoholic extract of Salvia verbenaca have also been screened biologically for antihypertensive activity in normotensive albino rats, which showed a varied degree in the decrease of blood pressure and heart rate. The flavonoids 2, 3 and 5 are found most potent exhibiting the decrease in blood pressure 36.5, 20.0 and 30.0 (mmHg) respectively in comparison to normal values. Other compounds also exhibit a good activity. The structure activity relationship (SAR) has also been discussed. IPC: Int.Cl. 7 C 07 D 311/30 The flavonoids are considered potential for human health as well as constitute an important part of human diet. They are also considered as active principles in various medicinal plants 1 , and have been reported to possess anticancer, antioxidant, antimicrobial, antihypertensive, antiulcer, antipyretic and antidiabetic properties etc. In the present article we report the isolation of some flavonoids, three of them new, from Euphorbia cuneata, Salvia verbenaca and Osyris abyssinica, and evaluation of their antihypertensive activity by measuring the arterial blood pressure and heart rate in normotensive albino rats. Euphorbia cuneata (Euphorbiaceae), locally known as Abu-Laban is reported to be used for the treatment of ringworm, scorpion sting and snake bite by the traditional medicine practitioners of Saudi Arabia 2 . We have isolated naringenin 1, 3-βhydroxynaringenin designated as isoaromadendrin 2, taxifolin 3 and isoaromadendrin-7-O-β-D-glucopyranoside designated as isosinensin 4 from the alcoholic extract of aerial parts of the plant. Salvia verbenaca L. (Labiatae) is distributed in tropical region including Saudi Arabia. The alcoholic extract of the aerial parts has been reported to potentiate smooth muscle contractions induced by acetylcholine, histamine, BaCl2, and serotonin 3 . We have isolated 5-hydroxy-3, 4′, 7-trimethoxyflavone 5, 5-hydroxy-3,3′,4′,7-tetramethoxyflavone (retusin) 6 and 4′,5-dihydroxy flavone-5-O-β-D-glucopyranoside designated as verbenacoside 7 from the alcoholic extract of aerial parts of the plant. The plant Osyris abyssinica var. speciosa (Santalaceae) is distributed in South Africa including Saudi Arabia 4 . We have isolated epicatechin 8 from the aerial parts of the plant. The literature survey revealed that the antihypertensive activity of the above flavonoids has not yet been reported so far. We have, therefore, tested the above flavonoids and ethanolic extract of Salvia verbenaca for their antihypertensive activity, which showed a significant decrease in blood pressure and heart rate in normotensive albino rats, wherein the compounds 2, 3 and 5 were found most potent exhibiting 36.5, 20.0 and 30.0 (mmHg) decrease in blood pressure respectively. Other compounds also displayed a good decrease in blood pressure and heart rate.

Revised synthesis of the pentasaccharide related to the repeating unit of the O-antigen from Shigella dysenteriae type-4 in the form of its methyl ester 2-(trimethylsilyl)ethyl glycoside

Abstract: A revised and simplified method has been developed for the synthesis of the pentasaccharide, related to the repeating unit of the O-antigen from Shigella dysenteriae type-4. The disaccharide donor 10 and the trisaccharideacceptor 8 with two hydroxyl groups are first synthesized which are then allowed to react in the presence on NIS and TfOH to give a pentasaccharide derivative from which, removal of protecting groups affords the desired repeating unit, namely methyl α-L-fucopyranosyl-(1→3)-2-acetamido-2-deoxy-a-D-glucopyranosyl-(1→3)-2-acetamido-2-deoxy-4-O-(a-L-fucopyranosyl)-α-D-glucopyranosyl-(1→4)-[2-(trimethylsilyl)ethyl β-D-glucopyranosid] uronate 15.

Synthesis of some 3,5-diphenyl-4 H -1,2,4-triazole derivatives as antitumor agents

Abstract: A series of 4-arylidenamino-4H-1,2,4-triazoles 2-14 and 4-(1-aryl)ethylidenamino-4H-1,2,4-triazoles 28-30 have been synthesized by the treatment of 4-amino-4H-1,2,4-triazole 1 with certain aldehydes and ketones. Compounds2-14 and 28-30 have been reduced with NaBH 4 to afford the corresponding 4-arylmethylamino-4H-1,2,4-triazoles 15-27 and 4-(1-aryl)ethylamino-4H-1,2,4-triazoles 31-33. The compounds 2-33 have been characterized by 'H NMR, 1 3 C NMR, IR, Mass and UV-Vis spectral data. Compounds 12, 17, 18, 19, 20, 21, 22, 24, 29 and 32 have been screened on three human tumor cell lines, breast cancer (MCF7), non small cell lung cancer (NCI-H460), and CNS cancer (SF-268) at the National Cancer Institute (NIH), USA. The compounds are found to exhibit low antiproliferative activity in the anticancer tests.

New 1,3-dipolar cycloadducts of 3-azidoacetylcoumarins with DMAD and their antimicrobial activity

Abstract: 3-Bromoacetylcoumarins 1 have been treated with sodium azide in aqueous acetone to give 3-azidoacetylcoumarins 2 which on further reaction with dimethylacetylenedicarboxylate 3 in dry xylene produce 1,3-dipolar cycloadducts 4. All the newly synthesized azidoacetylcoumarins and their DMAD cycloadducts have been characterized by 1R, NMR and mass spectroscopic techniques and also screened for their antimicrobial activity.

Two dimeric flavonoids from Baiihinia purpured

Abstract: Baubhinia purpurea leaves yield two new dimeric flavonoids namely bis [3',4'-dihydroxy-6-methoxy-7,8-furano-5',6'-monomethylallyloxy ]-5-C-5-biflavonyl 1 and (4'-hydroxy-7-methyl 3-C-α-L-rhamnopyranosyl) -5-C-5- (4'-hydroxy-7-methyl-3-C-α-D-glucopyranosyl) biflavonoid 2 with protein precipitating capacity 214.4 and 199.24 μg BSA /g, respectively. Their identity has been established on basis of spectroscopic data and chemical reactions.

Synthesis of some 1,2,4-triazoles as potential antifungal agents

Abstract: Some new 3-(p-substituted anilinoethyl)-4-(p-substituted phenyl)-5-thioxo-1,2,4-triazoles 3a-p are synthesized and evaluated for antifungal activity against Candida albicans and Aspergillus niger.

Synthesis and antimicrobial activity of some succinimides

Abstract: A series of substituted succinimides 3 are prepared from hydrazides and maleimides. The compounds are characterized and screened for their antimicrobial activities.

Studies on the chemical constituents of Nardostachys jatamansi DC (Valerianaceae)

Abstract: A new sesquiterpene acid, nardin and a new pyranocoumarin have been isolated from the rhizomes of Nardostachys jatamansi and characterized as E-2-methyl, 3-(5,9-dimethylbicyclo[4.3.0]-nonen-9-yl)-2-propenoic acid and 2',2'-dimethyl-3'-methoxy-3',4'-dihydropyranocoumarin, respectively using spectral studies and chemical correlation. The stereochemistry of nardin has been determined using X-ray crystallographic studies.

Synthesis of some isatin based novel spiroheterocycles and their biological activity studies

Abstract: Some new 1-{3'-(substituted phenyl)-spiro[3H-indole-3,2'-thiazolidine]-2,4'(1H)-dione-l'-ylacetamido}-2-phenyl-4-arylid-ine-5-oxoimidazolines have been prepared by reacting 3'- (substituted phenyl)-spiro[3H-indole-3,2'-thiazolidine]-2,4'(1H)-dione-1-ylacetylhydrazine with various azalactones which have been evaluated for their antibacterial activity.

Reactions of amidines with some carboxylic acid hydrazides

Abstract: Ten amidrazone derivatives (seven new compounds) and twelve 1,2,4-triazole derivatives (five new compounds) are synthesized and their structures are established by elemental analysis, IR, 1 H NMR and 1 3 C NMR spectral data.

Synthesis and antimicrobial activities of oxadiazoles, phthalazines and indolinones

Abstract: A series of oxadiazoles 5 phthalizines 6-8, and indolinones 9,10 have been synthesized from 2-[oxyacetyl hydrazine]ethyl benzenes 3. The compounds are characterized and screened for their antimicrobial activities.

Two new lipid constituents of Nigella sativa (Seeds)

Abstract: The hexane extract of Nigella saliva seeds yields two new aliphatic compounds. The compounds have been characterized as 16-triecosen-7-ol 1 and 6-nonadecanone 2 using IR, 1 H NMR, 1 3 C NMR, EIMS and chemical evidences.

Enantioselective synthesis of (S)-α-arylpropionic acids via Pd-catalyzed kinetic resolution of benzylic alcohols

Abstract: A convenient synthetic route for the synthesis of three (S)-α-propionic acids, (S)-naproxen (90% ee), (S)-ibuprofen (82% ee) and (S)-phenylpropionic acid (92% ee) is described. Pd-catalyzed oxidative kinetic resolution ofthe corresponding benzylic alcohols is used as a key step to introduce stereogenicity into the molecule.

Rapid and efficient synthesis of some biological active 2-azetidinones under microwave irradiation

Abstract: An efficient and extremely fast procedure for the synthesis of 4-aryl-3-chloro-1-[(2-benzothiazolylthio)acetamidyl]-2azetidinone 4 by the reaction of arylidene-[(2-benzothiazolylthio)acetamidyl] 3 with chloroacetylchloride in DMF in the presence of catalytic amount of triethylamine under microwave irradiation is described. A considerable increase in the reaction rate has been observed with better yield. All the compounds have been screened for their antifungal activity against Candida albicans and Aspergillus niger, and antibacterial activity against Escherchia coli, Staphylococcus aureus and Bacills substilis. In the primary screening, some of the compounds exhibit appreciable activity. The structures of the synthesised compounds 4a-j have been characterized on the basis of their elemental analysis and spectral data.

QSPR with TAU indices : Molar refractivity of diverse functional acyclic compounds

Abstract: Molar refractivity of diverse functional acyclic compounds (n = 166) has been correlated with first order TAU indices to unravel the diagnostic feature of the TAU scheme. It has been found that TAU relations could satisfactorily explain the variances of the molar refractivity values of diverse functional compounds (up to 98.6% predicted variance and explained variance for the composite set of 166 compounds), especially when the first order composite topochemical index is partitioned into different components. Moreover, specific contributions of functionality, branching, shape and size terms to the molar refractivity values could be found out from the relations involving TAU parameters. It is observed that molar refractivity increases with the rise in molecular bulk. Further, branching has specific contribution on molar refraction depending on the type of ramification: it has negative contribution to molar refractivity for compounds with same molecular bulk. Negative impact of hydroxy, amino and oxy groups and positive impact of bromo and iodo functionalities on molar refraction are also observed. The predicted MR values based on a selected TAU model are also compared with the calculated MR values according to the Crippen's fragmentation method.

Two new flavonoids from Andrographis macrobotrys

Abstract: Two new flavonoids, 5,7,8,2'-tetramethoxyflavanone 1 and 2'-hydroxy-2,3,4'-trimethoxychalcone 3, together with three known flavones, 5-hydroxy-7-methoxyflavone 2, 5,2',6'-trihydroxy-7-methoxyflavone 4 and 5,7,2',6'-tetrahydroxyflavone 5 have been isolated from the whole plant of Andrographis macrobotrys. The structures of the new compounds 1 and 3 have been established using extensive 2D NMR and ESI-MS/MS studies.