Synthesis of new bridgehead substituted azabicyclo-[2.2.1]heptane and -[3.3.1]nonane derivatives as potent and selective α7 nicotinic ligands

New azabicyclo[2.2.1]heptane and -[3.3.1]nonane derivatives containing a pyridinyl substituent at the bridgehead position have been synthesized via an efficient ten chemical steps pathway. Both chemical series were then evaluated in vitro for their affinity at α7 nicotinic receptors revealing nanomolar potency with notably excellent selectivity over the α4β2 nicotinic subtype.     

Synthesis and discovery of N-(1-methyl-4-oxo-4,5-dihydro-1H-imidazol-2-yl)-[1,1′-biphenyl]-2-carboxamide derivatives as antimicrobial agents

Novel dihydro-1H-imidazole-2-yl)-[1,1′-biphenyl]-2-carboxamides ( 4a-l ) was achieved using a three-step synthesis process and evaluated as antimicrobial agents. These compounds were characterized through FTIR, NMR, LCMS and evaluated for DNA gyrase inhibition potentials and antimicrobial properties against Gram-negative bacteria Escherichia coli (MTCC 443), Pseudomonas aeruginosa (MTCC 424), Klebsiella pneumoniae MTCC 530 and Gram-positive bacteria Staphylococcus aureus (MTCC 3160), Corynebacterium diphtheriae (MTCC 116) and Streptococcus pyogenes (MTCC 442). Excellent DNA gyrase inhibition exhibited by compound 4f (IC₅₀ 0.2 μM and relative percentage activity 96.24%). A broad spectrum of antimicrobial activity showed by compounds 4d , 4f and 4 k with a Minimal Inhibitory Constant (MIC) of 1.05, 1.35 and 1.25 μg mL⁻¹, respectively.     

Synthesis, activity evaluation and 3D-QSAR study of some novel derivatives of 4, 5, 6, 7-tetrahydrothieno [3,2-c] pyridine

A series of novel derivatives of 4, 5, 6, 7-tetrahydrothieno [3,2-c] pyridine were synthesized and structurally characterized by 1H NMR and MS. Their in vivo anti-platelet aggregation activities were evaluated. A 3D-QSAR was performed using the CoMFA and the CoMSIA. This model provided useful guidelines for novel anti-platelet thienopyridines design.     

Synthesis of substituted pyrido[3´,2´:4,5]thieno[3,2-c]isoquinolin-5(6H)-ones and their sulfinyl and sulfonyl derivatives

A method for the synthesis of previously unknown pyrido[3´,2´:4,5]thieno[3,2-c]isoquinolin-5(6H)-ones was suggested, which includes a condensation reaction of substituted 3-cyanopyridine-2(1H)-thiones with methyl 2-(chloromethyl)benzoate and subsequent treatment of the condensation products with potassium tert-butoxide. The oxidation of the condensation products to sulfoxides or sulfones and subsequent treatment of these compounds with potassium tert-butoxide led to substituted pyrido[3´,2´:4,5]thieno[3,2-c]isoquinolin-5(6H)-one 11-oxides or substituted pyrido[3´,2´:4,5]thieno[3,2-c]isoquinolin-5(6H)-one 11,11-dioxides.

     

An Efficient Synthesis of Ethyl 7-Chloro-6-fluoro-1-methyl-4-oxo-1,4-dihydro-[1, 3]thiazeto[3, 2-a]quinoline-3-carboxylate as Intermediate of the Prulifloxacin Containing Tricyclic Fluoroquinolone

The fluoroquinolones such as ciprofloxacin and sparfloxacin have been widely used for the treatment of various bacterial infections1. Their mechanism of action is believed to be associated with inhibition of bacterial DNA gyrase2. Moreover, recent studies…     

Synthesis,docking and ADMET prediction of novel 5-（（5-substituted- 1 -H- 1,2,4-triazol-3-yl ） methyl ）-4, 5,6,7-tetrahydrothieno [ 3,2-c ] pyri- dine as antifungal agents

A novel series of 5-((5-substituted-1H-1,2,4-triazol-3-yl)methyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridines 5(a–i) has been synthesized from thienopyridine hydrazide, substituted aromatic nitriles using 4-dimethylaminopyridine(DMAP) as a catalyst under microwave irradiation and evaluated for their in vitro antifungal activity. Compound 5g is found to be more potent against Candida albicans when compared with miconazole. Docking study of the newly synthesized compounds was performed, and results showed good binding mode in the active site of fungal enzyme P450 cytochrome lanosterol 14 ademethylase. ADMET properties of synthesized compounds were also analyzed and showed good drug like properties. The results of in vitro antifungal activity, docking study and ADMET prediction revealed that the synthesized compounds have potential antifungal activity and can be further optimized and developed as a lead compound.     

Synthesis and pharmacological evaluation of 5-[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine derivatives as platelet aggregation inhibitors

One pot synthesis and characterization of new 5-[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-4,5,6,7-tetrahydro-thieno[3,2-c]pyridines (3a–k) using amides (2a–k) were reported. The prepared 5-[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine (3a) is a bioisostere of 4′-(6,7-dihydro-4H-thieno [3,2-c]pyridin-5-ylmethyl)-biphenyl-2-carboxylic acid (1), having good in vivo antithrombotic activity compared with Clopidogrel. The new tetrazole derivatives (3a–k) were screened for their in vitro activity as platelet aggregation inhibitors.     

Synthesis of derivatives of the new condensed system 4H,7H-furo[3′,4′:6,7]cyclohepta[1,2-<Emphasis Type="Italic">b</Emphasis>]pyran

8-Hydroxy-1,3-dimethyl-4H-cyclohepta[c]furan-4-one reacts with arylidenemalononitriles and, like 1,3-oxo enols, forms the corresponding condensed 2-amino-4H-pyrans. The analogous reaction with 3-(dicyanomethylene)indolin-2-ones give spirocyclic 2-amino-4H-pyrans. The 4-aminopyrimidine ring is formed on the basis of the enamino nitrile fragment of the new pyrans by successive reaction with triethoxymethane and then with aqueous ammonia. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 188–195, February, 2008.     

Rapid synthesis of new 2-methyl-7-nitro-5-substituted-2,3-dihydroimidazo[5,1-b]oxazole as potential antibacterial drugs through one-pot cyclization and Suzuki–Miyaura coupling

Original 2-methyl-7-nitro-5-substituted-2,3-dihydroimidazo[5,1-b]oxazoles were prepared by reacting 1-(2,5-dibromo-4-nitro-1H-imidazol-1-yl)propan-2-ol and various arylboronic acids through “one-pot” cyclization and Suzuki–Miyaura reactions under microwave irradiation.     

Synthesis and Crystal Structure of 3′-Ethyl 5′-Methyl 1-Benzyl-4′-methyl-2-oxo-3′,4′-dihydrospiro-[indoline-3,2′-pyrrole]-3′,5′-dicarboxylate

The crystal structure of the title compound(C24H24N2O5, Mr = 420.45) has been determined by single-crystal X-ray diffraction. The crystal is of triclinic, space group P1 with a = 8.991(1), b = 11.166(1), c = 11.169(1) , α = 91.413(2), β = 105.887(2), γ = 90.992(2)°, V = 1077.8(2) 3, Z = 2, Dc = 1.296 g/cm3, F(000) = 444, μ(MoKα) = 0.091 mm-1, the final R = 0.0466 and wR = 0.1507 for 4185 observed reflections(I 2σ(I)). The single-crystal X-ray diffraction data indicated intermolecular C(17)–H(17)O(4), C(5)–H(5)… O(4) hydrogen bonds and C–H…π interaction in the structure.     

Central-to-axial chirality transfer and induced circular dichroism in 6,7-dihydro-5H-dibenz[c,e]azepine derivatives of α- and β-amino esters

DAZ-Xaa^∗-OMe amino ester derivatives with Xaa^∗ = d/l-Ala, d/l-Val, l-Leu, l-Ile, l-Ser, l-β³-HAla, l-β³-HVal, l-β³-HLeu, (1S,2S)/(1R,2R)-ACHC (2-aminocyclohexanecarboxylic acid) and (1S,2S)/(1R,2R)-ACPC (2-aminocyclopentanecarboxylic acid), N-blocked as 6,7-dihydro-5H-dibenz[c,e]azepines (DAZ), have been synthesized and evaluated for the determination of the absolute configuration of α- and β-amino esters through the induced circular dichroism of the biphenyl chromophore.     

Synthesis and Crystal Structure of Ethyl 3-（4-Chlorophenyl）-3,4-dihydro-6-methyl-4-oxo-2- （pyrrolidin-1-yl）furo[2,3-d]pyrimidine-5-carboxylate

The crystal structure of the title compound ethyl 3-（4-chlorophenyl）-3,4-dihydro-6- methyl-4-oxo-2-（pyrrolidin-1-yl）furo[2,3-d]pyrimidine-5-carboxylate （C20H20ClN3O4, Mr= 401.84） has been prepared and determined by single-crystal X-ray diffraction. The crystal is of monoclinic, space group P21/n with a = 20.6215（9）, b = 8.5311（4）, c = 21.6886（9） A^°, β = 91.607（1）°, V = 3814.0（3）A^°^3, Z = 8, Dc = 1.400 g/cm^3, F（000） = 1680, μ = 0.233 mm^-1, R = 0.0718 and wR = 0.1545 for 6717 observed reflections with I 〉 2σ（I）. X-ray diffraction analysis reveals two crystallographically independent molecules in the asymmetric unit.     

Three-component condensation of 3-aminothiophene derivatives with isatines and Meldrum’s acid. Synthesis of 2,5′-dioxo-3′-phenyl-5′,6′-dihydro-4′H-spiro[indoline-3,7′-thieno[3,2-b]pyridine]-2′-carboxylic acids

A method for the synthesis of 2,5′-dioxo-3′-phenyl-5′,6′-dihydro-4′H-spiro[indoline-3,7′-thieno[3,2-b]pyridine]-2′-carboxylic acids was elaborated based on the three-component condensation of 3-aminothiophenes, Meldrum’s acid, and isatines.     

Synthesis of new substituted acetamide derivatives of 6′,7′-dimethoxy-2′,3′-dihydro-1′<Emphasis Type="Italic">H</Emphasis>-spiro[isoquinoline-1,4′-cyclopentane]-1′-carboxamide

Reaction of ethyl 6′,7′-dimethoxy-3′Н-spiro[isoquinoline-1,4′-cyclopentane]-1′-carboxylate with ammonia and isopropylamine afforded dihydroisoquinoline carboxamides that were reduced with NaBH₄ in amides of 6,7-dimethoxy-4-spirocyclopentane-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid. The reaction of unsubstituted carboxamide with chloroacetyl chloride led to chloroamide that reacted with versatile secondary amines and heterylthiols providing the corresponding substituted amino- and sulfanylamides of tetrahydroisoquinoline series.     

Triheterocyclic Thiadiazepine Derivatives of Pharmacological Interest: Synthesis of 2-Aryl-4-[p-(2,3-dihydro-5-methyl-2-oxo-1,3,4-oxadiazol-3-yl)phenyl]-6-(un)substituent-1",2",4"-triazolo[3",4"-b]-1',3',4'-thiadiazepine

Synthesis of novel thiadiazepine derivatives based on the reactivity of 4-acetylphenylsydnone (1) was reported. The structures of the newly synthesized compounds have been proved by their physical, analytical, IR, ¹H NMR, ¹³C NMR and mass spectral data.     

Triheterocyclic Thiadiazepine Derivatives of Pharmacological Interest： Synthesis of 2-Aryl-4-[ρ-（2,3-dihydro-5-methyl-2-oxo-1,3,4-oxadiazol-3-yl）phenyl]-6-（u n）su bstituent-1 ＂,2＂ ,4＂- triazolo[3＂,4＂-b]-1 ＇,3＇,4＇-thiadiazepine

Synthesis of novel thiadiazepine derivatives based on the reactivity of 4-acetylphenylsydnone （1） was reported. The structures of the newly synthesized compounds have been proved by their physical, analytical, IR, 1^H NMR, 13^C NMR and mass spectral data.