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.     

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.     

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 of 2,5-bis(2-aminothiazol-5-yl)-3,6-dichloro-1,4-benzoquinones

A series of 2-(2-aminothiazol-5-yl)-3,6-dichloro-5-diethylaminoethenyl-1,4-benzoquinones was synthesized from 2-(2-aminothiazol-5-yl)-3,5,6-trichloro-1,4-benzoquinones using acetaldehyde and diethylamine in toluene solution. Refluxing these compounds with substituted thioureas in acetonitrile in the presence of hydrochloric acid gives the corresponding 2,5-bis(2-aminothiazol-5-yl)-3,6-dichlorohydroquinones which can be oxidized to the target products with ferric chloride in aqueous DMF.Riga Technical University, Riga LV-1048, LatviaTranslated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 835–839, June, 2000     

Synthesis of Some Novel 5-(Arylidene)-2-imino-3(pyridin-2-yl)thiazolidin-4-one Derivatives

Treatment of 2-aminopyridine ( 1 ) with chloroacetyl chloride in dry benzene gave 2-chloro-N-(pyridin-2-yl)acetamide ( 3 ), which on further reaction with potassium thiocyanate gave 2-imino-3-(pyridin-2-yl)thiazolidin-4-one ( 4 ) as an intermediate compound for the synthesis of pyridin-2-yl substituted 2-imino-thiazolidine-4-one derivatives. Cyclocondensation reaction of ( 4 ) with a series of aromatic aldehydes gave 5-arylidene derivatives of pyridin-2-yl substituted 2-imino-thiazolidine-4-ones 5a–j . ¹ H and ¹³C NMR spectroscopy, as well as elemental analyses, were used for the identification of these new compounds.     

Synthesis of Novel New 2-(2-(4-((3,4-Dihydro-4-oxo-3-aryl quinazolin-2-yl)methyl)piperazin-1-yl)acetoyloxy)-2-phenyl Acetic Acid Esters

Stereoselective diazotization of (S)-2-amino-2-phenyl acetic acid (L-phenyl glycine) (4) with NaNO₂ in 6% H₂SO₄ in a mixture of acetone and water gave optically pure (S)-2-hydroxy-2-phenyl acetic acid (L-mandelic acid) (5). Esterification, gave (S)-2-hydroxy-2-phenyl acetic acid esters (6). The latter was treated with chloroacetyl chloride in the presence of triethylamine (TEA) in dichloromethane (DCM) to yield (S)-2-chloroacetyloxy phenyl acetic acid ester (2). In another sequence, the reaction of 2-(chloromethyl)-3-arylquinazolin-4(3H)-one (9) treated with N-Boc piperazine, followed by deprotection of the Boc group, to obtain 3-aryl-2-((piperazin-1-yl)methyl) quinazolin-4(3H)-one (3). Reaction of 2 with 3 in the presence of K₂CO₃ and KI gave the title compound, 2-(2-(4-((3,4-dihydro-4-oxo-3-arylquinazolin-2-yl)methyl)piperazin-1-yl) acetoyloxy)-2-phenyl acetic acid esters (1). The structures of all the new compounds obtained in the present work are supported by spectral and analytical data.     

Hydrothermal synthesis method of 5-(4'-methylbiphenyl-2-yl)-1H-tetrazole

A clean and safe synthesis method of 5-(4’-methylbiphenyl-2-yl)-1H-tetrazole was found:under hydrothermal conditions,1.2 equiv.of 4’-methylbiphenyl-2-carbonitrile react with 1 equiv.of sodium azide in a mixed solvent of propane-1,2-diol/H2O,with 1.5 equiv.of ammonium chloride and 0.2 equiv.of ammonium fluoride as catalyst.After simple post-processing,the yield can be improved to 95%,and the purity of the product is 99%without further recrystallization.     

Synthesis and Reactions of 5-Amino-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-7-phenyl-7 H -thiazolo[3,2- a ]pyrimidine-6-carbonitrile

5-Amino-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-7-phenyl-7H-thiazolo[3,2-a]pyrimidine-6-carbonitrile was synthesized via the reaction of 4-(2-aminothiazol-4-yl)-3-methyl-1-phenyl-2-pyrazolin-5-one with benzylidene malononitrile and was then transformed to related fused heterocyclic systems. The antifungal and antibacterial studies revealed in some cases excellent biocidal properties.     

Novel Synthesis of 1-(1,2,3,5,6,7-Hexahydro- s-indacen-4-yl)-3-[4-(1-hydroxy-1-methyl-ethyl)-furan-2-sulfonyl]urea,an Anti-inflammatory Agent

Abstract

A novel synthesis of the anti-inflammatory agent 1-(1,2,3,5,6,7- hexahydro-s-indacen-4-yl)-3-[4-(1-hydroxy-1-methyl-ethyl)-furan-2-sulfonyl] urea 1 is described. Sulfonamide 5 was prepared starting from ethyl 3-furoate 2. Key steps were a one-pot sulfonylation with chlorosulfonic acid in methylene chloride followed by pyridinium salt formation and reaction with phosphorus pentachloride to provide ethyl 2-(chlorosulfonyl)-4-furoate 7. This sulfonyl chloride was treated with ammonium bicarbonate to form sulfonamide 8, followed by treatment with excess methyl magnesium chloride to provide 4-(1-hydroxy-1-methyl-ethyl)-furan-2-sulfonamide 5. 4-Isocyanato-1,2,3,5,6,7-hexahydro-s-indacene 16 was prepared from indan in five steps. The formation of the desired sulfonyl urea was carried out both with the isolated isocyanate 16 and via an in situ method.     

Synthesis of 3-[4-(1-Benzofuran-2-yl)-1,3-thiazol-2-yl]-2-(4-aryl)-1,3-thiazolidin-4-one Derivatives as Biological Agents

A protocol for the synthesis of 3-[4-(1-benzofuran-2-yl)-1,3-thiazol-2-yl]-2-(4-aryl)-1,3-thiazolidin-4-one derivatives (5a–e) has been developed from 1-(1-benzofuran-2-yl)-2-bromoethanone (2),which served as a key intermediate for the synthesis of the title compounds. The reaction of compound 2 with thiourea furnished 4-(1-benzofuran-2-yl)-1,3-thiazol-2-amine 3, which upon further reaction with various aromatic aldehydes, gave Schiff bases 4a–e. These Schiff bases, when treated with thioacetic acid in the presence of catalytic amount of anhydrous ZnCl₂, yielded thiazolidinone derivatives 5a–e. All the newly synthesized compounds have been characterized by analytical and spectral data and screened for their antimicrobial and analgesic activity.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Structure of 3-(2-aminothiazol-4-yl)coumarin

The structure of 3-(2-aminothiazol-4-yl)coumarin has been established by X-ray structural analysis. The data obtained were compared with the results of molecular mechanics calculations.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 492–494, March, 1995.     

Preparation of leukotriene B(4) inhibitory active 2- and 3-(2-aminothiazol-4-yl)benzo[b]furan derivatives and their growth inhibitory activity on human pancreatic cancer cells

A series of 2-(2-aminothiazol-4-yl)benzo[b]furan and 3-(2-aminothiazol-4-yl)benzo[b]furan derivatives were prepared, and their leukotriene B(4) inhibitory activity and growth inhibitory activity in cancer cell lines were evaluated. Several compounds showed strong inhibition of calcium mobilization in CHO cells overexpressing human BLT(1) and BLT(2) receptors and growth inhibition to human pancreatic cancer cells MIA PaCa-2. 3-(4-Chlorophenyl)-2-[5-formyl-2-[(dimethylamino)methyleneamino]thiazol-4-yl]-5-methoxybenzo[b]furan 8b 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. 3-(4-Chlorophenyl)-2-[2-[(dimethylamino)methyleneamino]-5-(2-hydroxyethyliminomethyl)thiazol-4-yl]-5-methoxybenzo[b]furan 9a displayed growth inhibitory activity towards MIA PaCa-2.     

Synthesis and Transformations of 2-Hydroxy-2-(benzotriazol-1-yl)-1,4-naphthoquinone

2-Hydroxy-3-(benzotriazol-1-yl)-1,4-naphthoquinone reacts with o-phenylenediamine and 4-chloro-2-aminophenol to give cyclization products: 5-oxo-6-(benzotriazol-1-yl)-5,6H-benzo[a]phenazine and 5-oxo-6-(benzotriazol-1-yl)-10-chlorobenzo[a]phenoxazine; the reaction with aniline yields the quaternary anilinium salt, and benzoyl chloride and benzenesulfonyl chloride acylate the nitrogen atom of the benzotriazolyl moiety.     

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.     

Facile and Green Syntheses of 2-(N-Methylindole-3-carbonyl)-3-(N-methylpyrrol-2-yl)acrylonitriles and a Study of Their Antimicrobial Activities

Facile and green syntheses of substituted-2-(N-methylindole-3-carbonyl)-3-(N-methyl pyrrol-2-yl) acrylonitriles 6a–d are being reported. L-Proline has been utilized as an efficient and ecofriendly catalyst in aqueous medium for Knoevenagel condensation of pyrrole-2-carboxyaldehyde (1) and its N-methyl derivative (2) with the active methylene compounds 3-cyanoacetylindoles 3a–d at room temperature to afford substituted-2-(1H-indole-3-carbonyl)-3-(1H-pyrrol-2-yl)acrylonitriles 4a–d and substituted-2-(1H-indole-3-carbonyl)-3-(N-methylpyrrol-2-yl) acrylonitriles 5a–d respectively. Subsequently these products were treated with dimethyl sulfate (DMS) in polythylene glycol (PEG)–600 as an efficient and green solvent to afford the corresponding substituted-2-(N-methylindole-3-carbonyl)-3-(N-methylpyrrol-2-yl)acrylonitriles 6a–d. The antibacterial and antifungal activities of 4a–d, 5a–d, and 6a–d have been studied.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource: Full experimental and spectral details.]     

(E)- and (Z)-1-benzenesulfonyl-4-trimethylsilyl-2-butenes as (E)-1-(1,3-butadienyl) synthons

(E)- and (Z)-1-benzenesulfonyl-4-trimethylsilyl-2-butenes (E/Z=9), prepared from 4-trimethylsilyl-1-buten-3-ol, $\text{n}$-butyllithium and benzenesulfenyl chloride and oxidation of the intermediate (E)- and (Z)-1-benzenesulfinyl-4-trimethylsilyl-2-butenes with hydrogen peroxide, react with $\text{n}$-butyllithium and then primary halides to give 4-benzenesulfonyl-1-trimethylsilyl-2-alkenes which are rapidly 1,4-debenzenesulfonyltrimethylsilated to (E)-1,3-alkadienes by tetra-$\text{n}$-butylammonium fluoride at O°C.     

Efficient Synthesis of Novel 3-[5-(1H-Benzimidazol-2-Ylmethanesulfonyl)-4-Phenyl-4H-(1,2,4)Triazol-3-Yl]-1H-(1,8)Naphthyridin-4-One Derivatives

Abstract

of 1,4-dihydro-4-oxo-1,8-naphthyridine-3-carbohydrazide (4) with substituted phenyl isothiocyanates (5) in ethanol under reflux for 30 min gave thiosemicarbazide derivatives 6, which on cyclization in 2N NaOH under refluxing conditions for 1 h resulted in 3-(5-mercapto- 4-phenyl-4H-1,2,4-triazol-3-yl)-1,8-naphthyridin-4(1H)-one (7). Alternatively, 7 could also be prepared from following sequence of reactions, i.e., 4 → 8 → 7. In another sequence of reactions, condensation of 7 with chloroacetic acid in dimethylformamide (DMF) and K₂CO₃ as a mild base at 120 °C for 2 h resulted in 2-((5-(1,4-dihydro-4-oxo-1,8-naphthyridin-3-yl)-4-phenyl-4H-1,2,4-triazol-3-yl)sulfanyl)acetic acid (10). The latter, on reaction with substituted o-phenylenediamine (11) in 6N HCl for 4 h yielded 3-(5-((1H-benzo[d]imidazol-2-yl)methylthio)-4-phenyl-4H-1,2,4-triazol-3-yl)-1,8-naphthyridin-4(1H)-one (12). Alternatively, 12 could also be prepared by reacting 7 with 13 in DMF and K₂CO₃ as a mild base at 120 °C for 2 h, followed by oxidation with H₂O₂ resulting in the corresponding sulfonyl derivatives 14.     

Unexpected product distributions in the synthesis of 2,6-bis-(indazolyl)pyridine and 2-(pyrazol-1-yl)-6-(indazolyl)pyridine

Reaction of 2-bromopyridine with 2 equiv of sodium indazolide in diglyme at 140 °C affords 2,6-bis-(indazol-1-yl)pyridine and 2-(indazol-1-yl)-6-(indazol-2-yl)pyridine in purified yields of 24% and 68% respectively. A similar reaction, using 1 equiv of sodium indazolide at 70 °C, gives a low-yield mixture of 2-(indazol-1-yl)-6-bromopyridine and 2-(indazol-2-yl)-6-bromopyridine. Both these intermediates are transformed into 2-(pyrazol-1-yl)-6-(indazol-1-yl)pyridine and 2,6-di(pyrazol-1-yl)pyridine upon treatment with 1 equiv of sodium pyrazolide in diglyme at 140 °C. These observations imply that the indazolyl group is a leaving group comparable to a bromo substituent under nucleophilic attack by pyrazolide or indazolide ions under these conditions. No reaction was observed between 2-(pyrazol-1-yl)-6-bromopyridine and 1 equiv of sodium indazolide under the same conditions. A single crystal structure of its iron(II) complex confirmed the regiochemistry of 2,6-bis-(indazol-1-yl)pyridine, and revealed significant conformational flexibility in the distal ligand indazolyl groups.     

Synthesis,characterisation and structural aspects of some symmetrical organotellurium halides based on Bis(2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)telluride

Bis(2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)telluride (2) has been synthesised in good yield by reacting 1-(2-chloroethyl)-3,5-dimethylpyrazole with in situ prepared sodium telluride, Na₂Te in an aqueous solution. A number of new organotellurium halides from bis(2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)telluride have been synthesised by using different halogenating reagents. Reaction of 2 with bromine gave bis(2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)telluride dibromide (5a) in addition to unexpected product bis(2-(4-bromo-3,5-dimethyl-1H-pyrazol-1-yl)ethyl)telluride dibromide (5b). All compounds were characterized by different spectroscopic techniques viz., ¹H, ¹³C, ¹²⁵Te NMR, Mass spectroscopy, IR and CHN analysis. EDXRF studies have also been employed to confirm the identity of 5a and 5b. Thermal gravimetric analysis of bis(2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)telluride (IV) chloride (4) and bis(2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)telluride (IV) iodide (5c) reveals the thermal stability of these molecules above 100°C. The X-ray studies of 5c shows trigonal bipyramidal geometry around tellurium atom and intermolecular secondary interaction viz., C-H π stacking between H23A and C22 showing a supramolecular packing between two molecules.     

A New 2-((Z)-Thiosemicarbazidomethyl)- Quinolin-8-YL Acetate Ligand and its Cu(II) Complex: Syntheses,Structures, and Characterizations

Abstract

A new ligand, 2-((Z)-thiosemicarbazidomethyl)-quinolin-8-yl acetate (C₁₃H₁₂ N₄O₂S) (L) and its Cu(II) coordination complex, [Cu(L₁)] [HL₁ = (Z)-1-((8-hyd- roxyquinolin-2-yl)methylene)thiosemicarbazide], have been synthesized, and characterized by IR, elemental analysis, ¹H NMR, MS, and X-ray single-crystal diffraction. L shows a stable three-dimensional supramolecular structure through hydrogen bonds and π-π stacking interactions. [Cu(L₁)] shows a three-dimensional network structure formed only by hydrogen bonds. In addition, the fluorescence spectra of L were measured.