Gültaze Çapan

Synthesis and hypnotic activity of new 4-thiazolidinone and 2-thioxo-4,5-imidazolidinedione derivatives.

Conveniently accessible 4‐[(2‐(3,4‐dimethoxyphenyl)ethyl]‐3‐thiosemicarbazide (2) was converted to new 1‐substituted benzylidene/furfurylidene‐4‐[2‐(3,4‐dimethoxyphenyl)ethyl]‐3‐thiosemicarbazides (3) which furnished 2‐(substituted benzylidene/furfurylidene)hydrazono‐3‐[2‐(3,4‐dimethoxyphenyl)ethyl]thiaz‐olidin‐4‐ones (4) and 1‐(substituted benzylidene/furfurylidene)‐amino‐3‐[2‐(3,4‐dimethoxyphenyl)ethyl]‐2‐thioxo‐4,5‐imidazol‐idinediones (5) on reaction with chloroacetic acid and oxalyl chloride, respectively. The structure of 5 was confirmed by X‐ray diffraction studies performed on 5a. 4 and 5 were evaluated for their potentiating effects on pentobarbital induced hypnosis. Most of the compounds caused remarkable increases in pentobarbital sleeping time.

5-Nitroimidazole derivatives as possible antibacterial and antifungal agents

Some novel 1-[2-[[5-(2-furanyl)-4-substituted 4H-1,2,4-triazol-3-yl[thio[ethyl[-2-methyl-5-nitro-1H-imidazoles (3), 1-[3-[[5-(2-furanyl/2-thienyl)-4-substituted 4H-1,2,4-triazol-3-yl[-thio]-2-hydroxypropyl[-2-methyl-5-nitro-1H- imidazoles (5) and 1-[3-[(N,N-disubstituted thiocarbamoyl)-thio[-2-hydroxypropyl]-2-methyl-5-nitro-1H-imidazoles (7) were synthesized and evaluated for in vitro antibacterial and antifungal activity. Some of 5 were found to be effective against bacteria and fungi (minimum inhibitory concentration (MIC) 7.3-125 micrograms/ml), whereas 7 were found to be effective against fungi (MIC 3-25 micrograms/ml).

Synthesis, structure, and antifungal evaluation of some novel 1,2,4-triazolylmercaptoacetylthiosemicarbazide and 1,2,4-triazolylmercaptomethyl-1,3,4-thiadiazole analogs

Novel 1-[[4-(4-bromophenyl)-5-(2-furyl)-4H-1,2,4-triazole-3-yl]mercaptoacetyl]-4-alkyl/aryl-3-thiosemicarbazides (5–12) were synthesized by the reaction of 4-(4-bromophenyl)-5-(2-furyl)-4H-1,2,4-triazole-3-ylmercaptoacetylhydrazide (4) with substituted isothiocyanates. Cyclodehydration of thiosemicarbazides with concentrated sulfuric acid yielded 2-[4-(4-bromophenyl)-5-(2-furyl)-4H-1,2,4-triazole-3-yl]mercaptomethyl-5-alkyl/arylamino-1,3, 4-thiadiazoles (13–17). The new compounds were evaluated for in vitro antifungal activity using the microdilution method. The tested compounds showed varying degrees of activity against Microsporum gypseum NCPF-580, Microsporum canis, Trichophyton mentagrophytes, Trichophyton rubrum, and Candida albicans ATCC 10231 (MIC 8–4 μg/mL).

Synthesis and antiviral properties of novel indole-based thiosemicarbazides and 4-thiazolidinones

Abstract A novel series of indolylthiosemicarbazides (6a–6g) and their cyclization products, 4-thiazolidinones (7a–7g), have been designed, synthesized and evaluated, in vitro, for their antiviral activity against a wide range of DNA and RNA viruses. Compounds 6a, 6b, 6c and 6d exhibited notable antiviral activity against Coxsackie B4 virus, at EC50 values ranging from 0.4 to 2.1μg/mL. The selectivity index (ratio of cytotoxic to antivirally effective concentration) values of these compounds were between 9 and 56. Besides, 6b, 6c and 6d also inhibited the replication of two other RNA viruses, Sindbis virus and respiratory syncytial virus, although these EC50 values were higher compared to those noted for Coxsackie B4 virus. The SAR analysis indicated that keeping the free thiosemicarbazide moiety is crucial to obtain this antiviral activity, since the cyclization products (7a–7g) did not produce any antiviral effect.

Indole-based hydrazide-hydrazones and 4-thiazolidinones: synthesis and evaluation as antitubercular and anticancer agents

Abstract A new series of indolylhydrazones (6) and indole-based 4-thiazolidinones (7, 8) have been designed, synthesized and screened for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. 4-Thiazolidinone derivatives 7g–7j, 8g, 8h and 8j displayed notable antituberculosis (anti-TB) activity showing 99% inhibition at MIC values ranging from 6.25 to 25.0 µg/ml. Compounds 7g, 7h, 7i, 8h and 8j demonstrated anti-TB activity at concentrations 10-fold lower than those cytotoxic for the mammalian cell lines. The indolylhydrazone derivative 6b has also been evaluated for antiproliferative activity against human cancer cell lines at the National Cancer Institute (USA). Compound 6b showed an interesting anticancer profile against different human tumor-derived cell lines at sub-micromolar concentrations with obvious selectivity toward colon cancer cell line COLO 205.

5-Fluoro-N′-[(E)-4-methoxy­benzyl­idene]-3-phenyl-1H-indole-2-carbohydrazide

In the title molecule, C23H18FN3O2, the mean plane of the indole system forms dihedral angles of 44.23 (8) and 14.54 (7)°, respectively, with the phenyl and benzene rings. In the crystal, intermolecular N—H⋯O hydrogen bonds link molecules into two-layer ribbons extended along the b axis. The crystal packing also exhibits weak intermolecular C—H⋯O, C—H⋯F and C—H⋯π interactions.

N'-[(2Z)-3-Allyl-4-oxo-1,3-thia-zolidin-2-yl-idene]-5-fluoro-3-phenyl-1H-indole-2-carbohydrazide.

In the title compound, C21H17FN4O2S, the planar indole fused-ring [maximum deviation 0.009 (1) Å] makes dihedral angles of 54.75 (9) and 14.90 (9)°, respectively, with the phenyl ring and the dihydrothiazolyl ring. The –CH2CH=CH2 substituent is disordered over two positions in a 0.51 (1):0.49 (1) ratio. An intramolecular N—H⋯S hydrogen bond generates an S(5) ring motif. The two independent molecules are linked into a dimer by two N—H⋯O hydrogen bonds, forming an R 2 2(10) ring motif. The crystal structure features intermolecular C—H⋯π and π–π stacking [centroid–centroid distance = 3.679 (1) Å] interactions. C—H⋯O and C—H⋯F interactions are also present.

5-Fluoro-N′-(4-methyl­cyclo­hexyl­idene)-3-phenyl-1H-indole-2-carbohydrazide

The title compound, C22H22FN3O, crystallized with two independent molecules (A and B) in the asymmetric unit; these are linked by a pair of N—H⋯O hydrogen bonds, forming a pseudo-centrosymmetric dimer with an R 2 2(10) motif. In addition, a number of C—H⋯π interactions are also observed. The 1H-indole ring systems in molecules A and B are essentially planar [maximum deviations of 0.019 (2) and 0.014 (2) Å, respectively] and make dihedral angles of 77.64 (10) and 69.50 (9)°, respectively, with thephenyl rings.

5-Chloro-N′-cyclo­hexyl­idene-3-methyl-1H-indole-2-carbohydrazide

In the title compound, C16H18ClN3O, the cyclohexane ring adopts a distorted chair conformation. In the crystal, pairs of molecules are linked by N—H⋯O hydrogen bonds into inversion dimers, forming R 2 2(10) ring motifs. These dimers are connected through C—H⋯N hydrogen bonds into chains along the a axis, forming layers parallel to (101).

4-{3-[Hydr­oxy(phen­yl)meth­yl]-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-4-yl}benzene­sulfonamide

In the title compound, C15H14N4O3S2, the hydroxy group is disordered over two positions with occupancies of 0.619 (5) and 0.381 (5). The benzene ring attached to the heterocycle makes a dihedral angle of 86.92 (9)° with respect to the best plane through the five-membered ring. The crystal packing is stabilized by intermolecular O—H⋯O, N—H⋯S, N—H⋯N, C—H⋯O and C—H⋯N hydrogen bonds, and N—H⋯π and C—H⋯π interactions.