Synthesis and D₂-like binding affinity of new derivatives of N3-[(1- ethyltetrahydro-1H-2-pyrrolyl)methyl]-4,5-dihydrobenzo[g]indole-3- carboxamide and related compounds

In previous papers 4a,b we have reported the syntheses and structure-activity relationships of a series of 5-phenyl-3-pyrrole carboxamide and related 4,5-dihydrobenzo[g]indole-3-carboxamide analogues whose most representative terms were 1a and 2a respectively. Encouraged by these results we carried out several modifications of 2a

Synthesis and solid state structures of Chalcogenide compounds of Imidazolin-2-ylidene-1,1-Diphenyl-phosphinamine

We report the synthesis and solid state structures of 1,3-di-aryl-imidazolin-2-ylidine-1,1-diphenylphosphinamine [(aryl = mesityl (1a) and aryl = 2,6-diisopripyl (1b)] and their chalcogenide compounds 1, 3-di-aryl-imidazolin-2-ylidine- P,P-diphenylphosphinicamide (2a,b), 1,3-di-aryl-imidazolin-2-ylidine-P,P-diphenyl-phosphinothioicamide (3a,b) and 1,3-diaryl-imidazolin-2-ylidine- P,P-diphenyl-phosphinoselenoic-amide (4a,b). The compounds 1a,b were prepared in good yield by the reaction of 1,3-di-aryl-imidazolin-2-imine and chlorodiphenylphosphine in the presence of triethylamine in toluene. The reactions of 1a,b with elemental sulphur and selenium afforded the corresponding chalcogenide compounds 3a,b and 4a,b respectively. The corresponding oxo- derivative (2a,b) was obtained by reacting compound 1a,b with 30% aqueous hydrogen peroxide in THF. The molecular structures of 1a, 2a, 3a and 4a,b have been established by single crystal X-ray diffraction analyses. The molecular structures reveal that even C1–N1–P1 angle (124.62 ∘) in compound 1a is less obtuse compared to the corresponding C1–N1–Si1 angles (157.8 ∘) observed in related N-silylated 2-iminoimidazolines and trimethylsilyl iminophosphoranes. C1–N1–P1 angles are further widened in compounds 2a, 3a, and 4a,b due to the attachment of chalcogen atoms onto phosphorus atom

SYNTHESIS OF SOME NEW HETEROCYCLIC COMPOUNDS DERIVED FROM N-(Ñ-PHENYL GLYCYL) SACCHARIN AND STUDY THEIR BIOLOGICAL ACTIVITY

Objective: In the present work, a variety of new heterocyclic compounds namely aza-β- lactam, cyclicimides, 1,3-thiazole, and 1,2,4-triazole.Methods: Procedure includes the synthesis of aza-β- lactam, cyclic imides, 1,3-thiazole, and 1,2,4-triazole. The synthesis was carried out in eleven steps using N-(Ñ-substituted phenylglycyl) saccharin derivatives (1a,b) as a starting material and converted to benzoic acid derivatives (2a,b) and then to ester derivatives (3a,b), which finally convers to benzohydrazide derivatives (4a,b). The cyclization of (4a,b) with carbon disulfide and hydrazine hydrate (80%) in the presence of potassium hydroxide gives 1,2,4-triazole compounds (5a,b), and subsequently (5a,b) derivatives reacted with different aromatic aldehydes in the presence of few drops of glacial acetic acid to give Schiff bases (6a-f). Compounds (7a-b) was prepared by the reaction of compounds (4a,b) with chloroacetyl chloride. 1,3-thiazole derivatives (8a,b) were synthesized through the cyclization of compounds (7a,b) with thiourea. Schiff bases (9a-f) were obtained by condensation of (4a,b) with different aromatic aldehydes in the presence of few drops of glacial acetic acid. Aza-β-lactam compounds (10a-f) were prepared by the cycloaddition of Schiff-bases (9a-f) with phenyl isocyanate through [2+2] cycloaddition reaction. Reaction (4a,b) with various acid anhydrides in presence of acetic acid gave the corresponding cyclic imide (11a-f). The newly prepared.Results: The results showed that compounds (5a) and (10e) have a good activity against Gram-positive bacterium and no activity against Gram-negative bacterium, compared to standard drugs (ciprofloxacin and amoxicillin), while compounds (8a) and (6b) have a high activity against fungi, compared to standard drugs (metronidazole benzoate), and the other tested compounds have low-to-moderate activity.Conclusion: 1,2,4-triazole is a most potent assemblage of Gram-positive bacterium retardants and cyclic imides are a most potent assemblage of fungi retardants

Synthesis of New 2H-Pyrano[3,2-h]quinolines With Potential Biological Activity

5-Halo-8-hydroxyquinoline-7-carboxaldehyde 1a,b reacted with diethyl malonate to afford ethyl 6-halo-2-oxo-2H-pyrano[3,2-h]quinoline-3-carboxylates  2a,b. Michael addition followed by cyclisation of acetyl  acetone with 2a,b gave 1-acetyl-11-halo-2-methyl-4H,5H,4,5-dioxo-dipyrano[3,4-c,3`,2`-h]quinoline derivatives 3a,b. Compounds 2a,b were converted into their acid hydrazide 4a,b. Reaction of 4a,b with acetyl acetone produced 6-halo-3-(3`,5`-dimethyl-1H-pyrazole-1-carbonyl)-2H-pyrano[3,2-h]quinolin-2-ones 5a,b. Treatment of acid hydrazides 4a,b with isatin yielded 1H,2H-3-(2H-6-halo-2-oxo-pyrano[3,2-h]quinolin-3-carboxyhydrazono)-2-indolinones 6a,b which on cyclisation with Conc. H2SO4 afforded 3-[1,3,4-oxadiazino(5,6-b)indol-2-yl]-6-halo-2H-pyrano[3,2-h]quinolin-2-ones 7a,b. The biological screening was showed that pyrano[3,2-h] quinoline derivatives which containing pyrazole and indoline moieties have excellent antibacterial and antifungal activities.   Keywords: Quinoline, 2H-pyrano[3,2-h]quinoline, 8-hydroxyquinoline,microbial activity

Microwave-assisted and conventional synthesis of novel antimicrobial 1,2,4-triazole derivatives containing nalidixic acid skeleton

Carbothioamides 4a,b, obtained from nalidixic acid, were converted to the corresponding 1,3-thiazolidine derivatives 5a,b by cyclocondensation with 2-bromo-1-(4-chlorophenyl)ethanone. Treatment of 4a,b with base afforded 1,2,4-triazoles 6a,b. The synthesis of 1,3-oxazolidine 7 was performed by the reaction of compound 4a with ethyl bromoacetate. Treatment of 4a with acid produced 1,3,4-thiadiazole 8. The reaction of compounds 6a and 6b with several heterocyclic amines in the presence of formaldehyde gave the corresponding Mannich bases 9–15 containing various pharmacophore groups. Conventional and microwave-assisted methods were used for the synthesis. The effect of an acid catalyst on Mannich reactions was investigated. The structures of the newly synthesized compounds were elucidated on the basis of 1H NMR, 13C NMR, FTIR, EIMS techniques, and elemental analysis. All compounds were screened for their antimicrobial activity

The old metal-poor open cluster ESO 92-SC05: accreted from a dwarf galaxy?

The study of old open clusters outside the solar circle can bring constraints on formation scenarios of the outer disk. In particular, accretion of dwarf galaxies has been proposed as a likely mechanism in the area. We use BVI photometry for determining fundamental parameters of the faint open cluster ESO 92-SC05. Colour-Magnitude Diagrams are compared with Padova isochrones, in order to derive age, reddening and distance. We derive a reddening E(B-V)= 0.17, and an old age of $\sim$6.0 Gyr. It is one of the rare open clusters known to be older than 5 Gyr. A metallicity of Z$\sim$0.004 or [M/H]$\sim$-0.7 is found. The rather low metallicity suggests that this cluster might be the result of an accretion episode of a dwarf galaxy.Comment: 11 figures: 1, 2a,b,c, 3a,b, 4a,b, 5, 6, 7 6 pages to compile with mn2e.cls. Monthly Notices of the Royal Astronomical Society, in pres

An NOS3 Haplotype is Protective against Hypertension in a Caucasian Population

The endothelial nitric oxide synthase gene (NOS3) has been implicated in the development of hypertension, although the specific role of variants and haplotypes has not been clarified. In this study, the association of three polymorphisms (promoter T786C, intronic 4a/b, and nonsynonymous G894T) was tested in a case-control sample of 230 patients with essential hypertension and 306 healthy controls. Haplotype analysis was also performed. The mutant allele a∗ of the 4a/b polymorphism showed a protective effect against hypertension under a dominant model (odds ratio = 0.64, 95% confidence interval (0.44–0.93)), although this effect was not significant after the adjustment for covariates (P = 0.06). The estimated frequency of the haplotype composed of the T786∗, 4a∗, and G894∗ alleles was significantly higher in controls (5.5%) compared to cases (2%). These results indicate that although individual NOS3 polymorphisms are not associated with hypertension, a rare haplotype of the gene might be protective against the development of hypertension

Author Correction:Charge disproportionate molecular redox for discrete memristive and memcapacitive switching (Nature Nanotechnology, (2020), 15, 5, (380-389), 10.1038/s41565-020-0653-1)

Correction to: Nature Nanotechnology. Published online 23 March 2020. In the version of this article initially published, there were presentation errors in the range of y-axis values displayed in Extended Data Figure 4a,b, and Extended Data Figure 5b. The errors have been corrected in the HTML and PDF versions of the article.</p