Relationships Between the Lipophilicity and Anticonvulsant Activity of N-Benzyl-2-azaspiro[4.4]nonane- and [4.5]decane-1,3-dione Derivatives

JPC – Journal of Planar Chromatography – Modern TLC - The lipophilicity of twenty-one N-benzyl-2-azaspiro[4.4]nonaneand [4.5]decane-1,3-dione derivatives, fifteen of which (1–15)...     

One-pot synthesis of 2-oxa-7-azaspiro[4.4]nonane-8,9-diones using Mn(III)-based oxidation of 4-acylpyrrolidine-2,3-diones

2-Oxa-7-azaspiro[4.4]nonane-8,9-diones were newly synthesized in good yields by the Mn(III)-based reaction of a mixture of 1,1-diarylethenes and 4-acylpyrrolidine-2,3-diones. Under the stated reaction conditions, the pyrrolidinedione ring remained intact and became one of the two rings of the 2-oxa-7-azaspiro[4.4]nonanedione scaffold. The procedure was simple and the product was easily separated. The structure determination and the mechanism for the formation of the 2-oxa-7-azaspiro[4.4]nonanediones were also discussed.     

Synthesis, spectroscopic characterization, X-ray structure and DFT studies on 4-(2-hydroxyphenyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-5-ium chloride hydrate

The title molecular salt, 4-(2-hydroxyphenyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-5-ium chloride hydrate (C₁₂H₁₄N₃O⁺·Clˉ·H₂O), was synthesized and characterized by IR-NMR spectroscopy and single-crystal X-ray diffraction. In addition to the molecular geometry from X-ray experiment, the molecular geometry, vibrational frequencies and gauge-independent atomic orbital (GIAO) ¹H and ¹³C NMR chemical shift values of the title compound in the ground state have been calculated using the density functional theory (DFT/B3LYP) method with the 6-31++G(d,p) and 6-311++G(d,p) basis sets, and compared with the experimental data. Besides, molecular electrostatic potential (MEP) distribution and non-linear optical properties of the title compound were investigated by theoretical calculations at the B3LYP/6-311++G(d,p) level.     

p-TSA-catalyzed one-pot synthesis and docking studies of some 5H-indeno[1,2-b]quinoline-9,11(6H,10H)-dione derivatives as anticonvulsant agents

The present work describes a facile, one-pot three component environment friendly, green synthesis of a series of 5-(4-methoxyphenyl)-7,7-dimethyl-10-phenyl-7,8-dihydro-5H-indeno[1,2-b]quinoline-9,11(6H,10H)-dione derivatives 8(a-n). 1,3-indanedione, aryl-aldehyde and enaminone was thoroughly ground in the presence of catalytic amount of p-toluene sulfonic acid (p-TSA) to give the titled compounds in good yields. All the synthesized derivatives were evaluated for their anticonvulsant activity using the maximal electroshock (MES) method with phenytoin as a standard drug along with their neurotoxicity effect. Derivatives 8b, 8e and 8k exhibited significant anticonvulsant activity (P<0.001). The neurotoxicity study clearly revealed that all the tested compounds are non-toxic at a dose of 40 mg/kg. The molecular modeling studies also predicted good binding interactions of most active molecules with the serotonin 5-HT_2A receptor. Therefore, it can be safely concluded that synthesized derivatives 8(a-n) would represent useful leads for further investigation in the development of a new class of anticonvulsant agents.     

Synthesis and Antimycobacterial Activity of New 2-Hydroxy-N-(3-oxo-1-thia-4-azaspiro[4.4]non-4-yl)/(3-oxo-1-thia-4-azaspiro[4.5]dec-4-yl)-2,2-diphenylacetamide Derivatives

Summary. 2-Hydroxy-2,2-diphenylacetohydrazide (2), cyclic ketones, and mercaptoalkanoic acids were converted into 2-hydroxy-N-(3-oxo-1-thia-4-azaspiro[4.4]non/[4.5]dec-4-yl)-2,2-diphenylacetamide derivatives (3, 4) in a one pot procedure. Compounds 3 and 4 were tested for in vitro antimycobacterial activity against M. tuberculosis H37Rv. The compounds were found to provide 0–86% inhibition of mycobacterial growth in the primary screen conducted at 6.25 μg/cm³.     

Synthesis of the end-capped 5-(N,N-dimethylamino)naphthyl-1-ethynyl derivatives and their 1,4-di[5-(N,N-dimethylamino)naphthyl]-1,3-butadiynes: anti rotamer structure

A new family of the end-capped 5-(N,N-dimethylamino)naphthylethynyl chains were synthesized, as terminal acetylenes or poly(yne) structures, by heterocoupling between 5-iodo-N,N-dimethylnaphthalen-1-amine and 2-methyl-3-butyn-2-ol or 4-(5-iodo-1-naphthyl)-2-methyl-3-butyn-2-ol, catalyzed by the palladium-copper system. Catalytic homocoupling of the terminal acetylenes, affords to 1,4-dinaphthyl-1,3-butadiyne nanostructures. X-ray diffraction analysis of 1,4-di(α-naphthyl)-1,3-butadiyne shows that the naphthalene rings are in the anti configuration along the acetylene axis. All the conjugated compounds show an important fluorescent emission radiation.     

Synthesis and conformational analysis of naphth[1′,2′:5,6][1,3]oxazino[3,2-c][1,3]benzoxazine and naphth[1′,2′:5,6][1,3]oxazino[3,4-c][1,3]benzoxazine derivatives

A new functional group, the hydroxy group, was inserted into a Betti base by reaction with salicylaldehyde, and the naphthoxazine derivatives thus obtained were converted by ring-closure reactions with formaldehyde, acetaldehyde, propionaldehyde or phosgene to the corresponding naphth[1′2′:5,6][1,3]oxazino[3,2-c][1,3]benzoxazine derivatives. Further, the conformational analysis of these polycyclic compounds by NMR spectroscopy and an accompanying molecular modelling are reported; especially, both quantitative anisotropic ring current effects of the aromatic moieties in these compounds and steric substituent effects were employed to determine the stereochemistry of the naphthoxazinobenzoxazine derivatives.     

Synthesis,characterization and biological activity of diorganotin dithioate derivatives

Reaction of dithioacid (ArCS₂CH₂CO₂H, Ar = phenyl, 2‐furyl or 2‐thienyl) with ⁿBu₂SnO gives monomeric (ArCS₂CH₂CO₂)₂Sn(Buⁿ)₂ in a 2:1 molar ratio, and dimeric {[(ArCS₂CH₂CO₂)Sn(Buⁿ)₂]₂O}₂ in a 1:1 molar ratio, respectively, which have been characterized by IR, NMR (¹H, ¹³C and ¹¹⁹Sn) spectra and elemental analyses. X‐ray crystal structure analyses indicate that the compound [(C₄H₃S)CS₂CH₂CO₂]₂Sn(Buⁿ)₂ is monomeric with the tin atom occupying a skew‐trapezoidal bipyramidal geometry. In addition, this compound forms a three‐dimensional structure through the weak intermolecular S^…S and Sn^…O interactions. Compound {[((C₄H₃S)CS₂CH₂CO₂)Sn(Buⁿ)₂]₂O}₂ is a centrosymmetric dimer with a cyclic Sn₂O₂ unit, in which the coordination modes of the two crystallographically unique carboxylic ligands are different. One acts as monodentate ligand by the carboxylate oxygen atom, the other bridges two tin atoms via only one carboxylate oxygen atom. Furthermore, each tin atom in this compound locates a distorted trigonal bipyramidal geometry. Biological activities of these organotin compounds show that they have hardly acaricidal activity, but display certain activities on fungi. In mononuclear tin compounds, the inhibition percentage of [(C₄H₃S)CS₂CH₂CO₂]₂Sn(Buⁿ)₂ in vitro for Alternaria solani and Physolospora piricola is 57.1% and 43.9%, respectively, while in dimers {[((C₄H₃O)CS₂CH₂CO₂)Sn(Buⁿ)₂]₂O}₂ shows high inhibition percentage for Gibbereila zeae (52.6%) and Physolospora piricola (50.0%), respectively. Copyright © 2006 John Wiley & Sons, Ltd.     

Synthesis and properties of new Mo(II) complexes with N-heterocyclic and ferrocenyl ligands

New Mo(II) complexes with 2,2′-dipyridylamine (L1), [Mo(CH₃CN)(η³-C₃H₅)(CO)₂(L1)]OTf (C1a) and [{MoBr(η³-C₃H₅)(CO)₂(L1)}₂(4,4′-bipy)](PF₆)₂ (C1b), with {[bis(2-pyridyl)amino]carbonyl}ferrocene (L2), [MoBr(η³-C₃H₅)(CO)₂(L2)] (C2), and with the new ligand N,N-bis(ferrocenecarbonyl)-2-aminopyridine (L3), [MoBr(η³-C₃H₅)(CO)₂(L3)] (C3), were prepared and characterized by FTIR and ¹H and ¹³C NMR spectroscopy. C1a, C1b, L3, and C2 were also structurally characterized by single crystal X-ray diffraction. The Mo(II) coordination sphere in all complexes features the facial arrangement of allyl and carbonyl ligands, with the axial isomer present in C1a and C2, and the equatorial in the binuclear C1b. In both C1a and C1b complexes, the L1 ligand is bonded to Mo(II) through the nitrogen atoms and the NH group is involved in hydrogen bonds. The X-ray single crystal structure of C2 shows that L2 is coordinated in a κ²-N,N-bidentate chelating fashion. Complex C3 was characterized as [MoBr(η³-C₃H₅)(CO)₂(L3)] with L3 acting as a κ²-N,O-bidentate ligand, based on the spectroscopic data, complemented by DFT calculations.The electrochemical behavior of the monoferrocenyl and diferrocenyl ligands L2 and L3 has been studied together with that of their Mo(II) complexes C2 and C3. As much as possible, the nature of the different redox changes has been confirmed by spectrophotometric measurements. The nature of the frontier orbitals, namely the localization of the HOMO in Mo for both in C2 and C3, was determined by DFT studies.     

Synthesis,antifungal and antibacterial activity of calix[4]arene-based 1,3,4-oxadiazole derivatives

We describe the synthesis of some novel p-tert-butylcalix[4]arene-based (5-aryl-1,3,4-oxadiazol-2-yl)2-chloroethanethioate derivatives ( 4a–e ). These compounds were synthesized by the reaction of tetra-tert-butyl calix[4]arene ( 1 ) with (5-aryl-1,3,4-oxadiazol-2-yl)2-chloroethanethioate ( 3a–e ) in the presence of potassium carbonate as a weak base and dry acetone as the solvent. All the newly synthesized calix[4]arene derivatives were characterized by elemental analysis and various spectroscopic methods such as FT-IR, ¹H NMR,¹³C NMR, DEPT, and ESI-MS. The synthesized compounds were tested in vitro for their antibacterial and antifungal activities against Escherichia coli and Aspergillus fumigates in comparison with enrofloxacin and amphotericin as reference drugs, which are normally used for treating such infections. The synthesized compounds showed different inhibition zones against the tested bacteria and fungi. Compound 4c was found to be most effective against A. fumigates, whereas compound 4e was found to be equally effective against E. coli and A. fumigates.     

2H-1，2，4-噻二唑并[2，3-a]嘧啶衍生物的合成及除草活性研究（Ⅲ）

合成了10个新的2-乙氧甲酰亚胺基-2H-1，2，4-噻二唑并[2，3，-a]嘧啶类化 合物，结构经IR，^1H NMR,MS和元素分析确证，除草活性测定结果表明，部分目标 化合物具有良好的除草性且选择性较好，对双子叶植物安全。     

Synthesis and biological activity of fluorinated 2-amino-4-aryl-3,4-dihydro[1,3,5]triazino[1,2-a]benzimidazoles

The heterocyclic nucleus s-triazino[1,2-a]benzimidazole has been reported to exhibit antibacterial activity. In this study, seven new 3,4-dihydro[1,3,5]triazino[1,2-a]benzimidazole derivatives were prepared via cyclocondensation between 2-guanidinobenzimidazole and fluorine substituted (including trifluoromethyl) benzaldehydes. The structures of all the compounds were confirmed by ¹H, ¹³C NMR and IR spectral data. Spectral data also suggested the existence of various tautomeric forms of the fluorine-containing s-triazino[1,2-a]benzimidazole compounds. The synthesized compounds were also screened for antibacterial and bovine dihydrofolate reductase (DHFR) inhibitory activities. The compound 3g substituted with a 3′,5′-bis(trifluoromethyl)phenyl moiety demonstrated the best antibacterial activity in the series. None of the tested compounds significantly inhibited bovine DHFR.     

Synthesis of novel fluorinated 4H-benzo[h]chromen-4-one and 4H-pyrano[3,2-h]quinolin-4-one derivatives

New fluorinated 4H-benzo[h]chromen-4-one and 4H-pyrano[3,2-h]quinolin-4-one derivatives are obtained in moderate to good yields, through a one-pot aldolization-intramolecular S_NAr process, from the tetrakis(dimethylamino)ethylene (TDAE) mediated reductive cleavage of two N,N-dimethylamino-bis-chlorodifluoroacetyl substrates in the presence of heteroaryl aldehydes.     

Synthesis and spectral characterization of mercury(II) complexes with the bidentate Schiff base ligand N,N′-bis(2,3-dimethoxybenzylidene)-1,2-diaminoethane: The crystal structures of [Hg((23-MeO-ba)2en)I2] and [Hg((23-MeO-ba)2en)Br2]

Three mercury(II) complexes, [Hg((23-MeO-ba)₂en)X₂] (X = I (1), Br (2) and Cl(3)), and the ligand (23-MeO-ba)₂en ((23-MeO-ba)₂en = N,N′-bis(2,3-dimethoxybenzylidene)-1,2-diaminoethane) have been synthesized and characterized by elemental analyses, FT-IR and ¹H NMR spectroscopy. The crystal and molecular structures of 1 and 2 were determined by X-ray crystallography from single-crystal data. The metal-to-ligand ratio was found to be 1:1. The mercury(II) center in 1 and 2 has a distorted tetrahedral geometry with HgN₂I₂ and HgN₂Br₂ chromophores, respectively. The Schiff base ligand (23-MeO-ba)₂en acts as a chelating ligand, coordinating via the two nitrogen atoms to the mercury(II) center, and it adopts an E,E conformation. The coordination sphere of the mercury(II) center in 1 and 2 is completed by the two I and Br atoms, respectively. In complex 1 an inter-molecular non-classical hydrogen bond of the type C-H?O was found, while in complex 2 inter- and intra-molecular non-classical hydrogen bonds of the type C-H?X (X = O and Br) were found. The ¹H NMR spectra of the complexes exhibit downfield as well as upfield shifts of the free ligand resonances, reflecting changes in the ligand’s geometry during its coordination.     

Synthesis and biological activity of fluorinated 7-aryl-2-pyridyl-6,7-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-amines

In our lead finding program, 12 new fluorinated 7-aryl-2-pyridyl-6,7-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-amines were prepared via a practical three-step procedure starting from (iso)nicotinic hydrazides. The fluorine substituted aryl fragment was introduced in the last step through cyclocondensation of N-(3-pyridyl-1,2,4-triazol-5-yl)guanidines and fluoro/trifluoromethyl substituted benzaldehydes. The structures of the compounds were confirmed by ¹H and ¹³C NMR spectral data. The tautomeric preferences for the compounds were established using 2D NOESY experiments. The antiproliferative activity of the synthesized 1,2,4-triazolo[1,5-a][1,3,5]triazines was evaluated against breast, colon and lung cancer cell lines. The highest antiproliferative activity in the series was found for 2-(pyridine-3-yl)-7-(4-trifluoromethylphenyl)-6,7-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-amine. The lack of inhibitory activity against bovine dihydrofolate reductase (DHFR) indicated that the antiproliferative activity was realized via other mechanisms.     

Synthesis and amination of 5- and 8-amino derivatives of 2-phenylnaphtho[2,3-d]-1,3-thiazole-4,9-dione

5- and 8-Amino-2-phenylnaphtho[2,3-d]-1,3-thiazole-4,9-diones were obtained by treatment of 3,5-diamino-2-chloro- and 2,5-diamino-3-chloro-1,4-naphthoquinones with sodium sulfide followed by condensation with benzaldehyde. Thermal and photochemical butylamination and CoCl{in2}-promoted arylamination of 5-amino-2-phenylnaphthothiazole-4,9-dione in position 8 was carried out.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2203–2206, December, 1994.     

Synthesis of novel triazolothione,thiadiazole, triazole-functionalized furo/thieno[2,3-b]pyridine derivatives and their antimicrobial activity

A series of novel triazolothione, thiadiazole, triazole-functionalized furo/thieno[2,3-b]pyridine derivatives 9a–l, respectively, were prepared starting from 2 (1H) pyridone 3 through selective O/S-alkylation followed by Thorpe–Ziegler cyclization to form furo/thieno[2,3-b]pyridine derivatives 6. Compounds 6 on reaction with hydrazine hydrate resulted carbohydrazide derivatives 7 and further reacted with diverse substituted phenyl isothiocyanates to form phenyl hydrazine carbothiamide derivatives 8. Each compound 8 is independently reacted in presence of NaOH, H₂SO₄, and N₂H₄.H₂O to form triazolothione, thiadiazole, triazole-functionalized furo/thieno[2,3-b]pyridine derivatives 9a–l, respectively. All the products 9a–l were screened against Gram +ve, Gram –ve bacteria and fungal strains. Compounds 9c–h showed high activity against Bacillus subtilis microbial-type culture collection (MTCC) 121 at <8.0 micromolar concentration. Promising compounds further screened for minimum bactericidal concentration against B. subtilis MTCC 121 using ciprofloxacin as standard and found to show very good activity. These compounds also screened for biofilm inhibition activity against B. subtilis MTCC 121 using erythromycin as standard and confirmed the high activity.     

Quantum-chemical,spectroscopic and X-ray diffraction studies on nickel complex of 2-hydroxyacetophenone thiosemicarbazone with triphenylphospine

Reaction of 2-hydroxyacetophenone thiosemicarbazone with [Ni(PPh₃)₂Cl₂] in optimized conditions afforded a mixed ligand complex with an isolated triphenylphosphine molecule. The structure was characterized by elemental analysis, IR, NMR and UV–Vis. spectroscopies and single crystal X-ray diffraction technique. In addition, the molecular geometry, vibrational frequencies and gauge including atomic orbital (GIAO) ¹H and ¹³C NMR chemical shift values of the title compound in the ground state have been calculated using the density functional theory (DFT/B3LYP) method with the 6-31G(d,p) basis set for the C, N, O, S, P, H atoms and LANL2DZ pseudo-potential for the Ni atom, and compared with the experimental data. Besides, atomic charge distributions, molecular electrostatic potential and frontier molecular orbitals (FMO) analysis of the title compound were investigated by theoretical calculations. The thermodynamic properties of the compound at different temperatures have been calculated and corresponding relations between the properties and temperature have also been obtained. Atomic charge distributions indicate that during forming the title compound, the free ligand of thiosemicarbazone ion transfers their negative charges to central Ni(II) ion. The effect of different solvents (chloroform, methanol and water) on the geometry, vibrational frequencies, total energies and dipole moments was studied using the density functional theory (DFT/B3LYP) method by applying the Onsager and the Polarizable Continuum Model (PCM).