Sumru Özkırımlı

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.

Synthesis of new triazolyl-N,N-dialkyldithiocarbamates as antifungal agents.

N,N-Dialkylditihiocarbamate derivatives have been well known as broad-range fungicides. In this study, the triazole derivatives of ten newN,N- disubstituted dithiocarbamates (3a-j) were synthesized and their structures were identified by spectral and elemental analysis. Results of the antifungal activity studies showed that some of the compounds tested were active againstM. canis, M. gypseum, andT. rubrum at the concentration of 12.5 μg/mL when clotrimazol was used as a standard.

Synthesis, antibacterial and antifungal activities of 3-(1,2,4-triazol-3-yl)-4-thiazolidinones

A new series of 3-(1,2,4-triazol-3-yl)-4-thiazolidinone derivatives has been synthesized by the reaction of Schiff bases of 3-amino-1,2,4-triazoles with mercaptoacetic acid and 2-mercaptopropionic acid. Their antibacterial and antifungal activities were evaluated against S. aureus, S. epidermidis, C. albicans and C. glabrata

Synthesis and pharmacology of new dithiocarbamic acid esters derived from phenothiazine and diphenylamine

2‐Methylthio‐10‐[(N,N‐disubstituted‐thiocarbamoylthio)acetyl]‐phenothiazines (4a—g) and N‐(3‐methylthiophenyl)‐N‐[(N,N‐disubstituted‐ thiocarbamoylthio)acetyl]phenylamines (5a—g) were synthesized by subsequent treatment of 2‐methylthio‐10‐chloroacetylphenothiazines (1) and N‐(3‐methylthiophenyl)‐N‐chloroacetylphenylamine (2) with potas sium salts of N,N‐disubstituted dithiocarbamic acid derivatives (3a—i). The structures of the compounds were determined by analytical and spectral (IR, 1H NMR, 13C NMR, EIMS) methods. The antihistaminic and anticholinergic activities of 4a, 4c, 4e g, 5a c, 5e, and 5g were evaluated in comparison with H1‐receptor antagonist mepyramine and nonselective cholinergic antagonist atropine. In the first series of experiments, the cumulative concentration‐response curves to histamine (10‐8‐10‐4M) and acetylcholine (10‐8‐10‐4M) were constructed in seperate fundus strips. The test compounds exhibited marked antihistaminic activity at 10‐6M concentration but compounds did not influence acetylcholine induced contractions. Concentration‐related experiments carried out on 4g and 5g revealed that a moderate antihistaminic activity was present at 10‐7M concentration of the compounds and became strong at higher concentrations. In the second series of experiments, the cumulative concentration‐response curve to histamine (10‐9‐10‐4M) was constructed in guinea‐pig ileum segments. Maximal responses were obtained by 10‐6‐3×10‐6M concentrations of histamine in ileum segments. Similar inhibitions of histamine contractions were also obtained with the test compounds. Their inhibitory effectiveness was evaluated by comparing the pA2 values.

Synthesis and Preliminary CNS Depressant Activity Evaluation of New 3-[(3-Substituted-5-methyl-4-thiazolidinon-2-ylidene)hydrazono]-1H-2-indolinones and 3-[(2-Thioxo-3-substituted-4,5-imidazolidine-dion-1-yl)imino] - 1H-2-indolinones

A series of (+) 3‐[(3‐substituted‐5‐methyl‐4‐thiazolidinon‐2‐ylidene)hydrazono]‐1H‐2‐indolinones (2a–h) and 3‐[(2‐thioxo‐3‐substituted‐4,5‐imidazolidinedion‐1‐yl)imino]‐1H‐2‐indolinones (3a–g) were synthesized by the cyclization of 3‐(4‐substituted‐thiosemicarbazono)‐1H‐2‐indolinones (1a–h) with ethyl 2‐bromopropionate in anhydrous ethanolic medium and oxalyl chloride in anhydrous diethyl ether, respectively. The structures of 2 and 3 were confirmed by analytical and spectral data (IR, 1H NMR, 13C NMR, and EIMS). The configuration of 3 was assigned on the basis of 1H NMR and 13C NMR data. 2c, 2d, 2g, 2h, and 3a–g were evaluated for anticonvulsant activity against maximal electroshock (MES) and subcutaneous pentylenetetrazol (ScMet) induced seizures. Among the compounds tested, only 2d exhibited some activity in anticonvulsant identification (Phase I) trials in mice. 2a, 2b, 2d, 2g, 2h, and 3a–g were additionally tested for potentiating effects on pentobarbital induced hypnosis in mice. All of the test compounds increased the sleeping time of pentobarbital significantly (p < 0.05) and the most potent compound was found to be 3a.

Simultaneous determination of medazepam and hyoscine butylbromide in tablets by second-derivative ultraviolet spectrometry

Abstract A second-derivative UV spectrophotometric method for the simultaneous determination of medazepam and hyoscine butylbromide in sugar-coated tablets without prior separation is described. In the derivative spectrophotometric determination of these drugs, calibration graphs were obtained by plotting peak-trough amplitudes at 252.6 and 264.8 run versus concentration of medazepam and zero-crossing amplitude at 212.5 nm versus concentration of hyoscine butylbromide. The relative standard deviation of the method was found to be ±0.56% for medazepam and ±0.08% for hyoscine butylbromide. This method has been successfully applied to tablets containing medazepam and hyoscine butylbromide.

LC determination of aminoglutethimide enantiomers as dansyl and fluorescamine derivatives in tablet formulations.

Determination of dansyl (AG-DNS) and fluorescamine (AG-F) derivatives of rac-aminoglutethimide in tablet formulation by HPLC has been achieved on a cellulose tris-(3,5-dimethylphenyl carbamate), known as Chiralcel OD and OD-R under normal and reversed phase columns, respectively, using a fluorescence detector (lambda(ex), 360 nm; lambda(em), 530 nm for AG-DNS derivatives; lambda(ex), 395 nm, lambda(em), 495 nm for fluorescamine derivatives (AG-F)). The best results were obtained with mobile phase ethanol:cyclohexane:methanol (95:5:2 v/v/v) for AG-DNS derivatives and acetonitrile:0.5% ortho-phosphoric acid (85:15 v/v) containing 0.26 mM 1-hexanesulfonic acid sodium salt (HSA) for AG-F, respectively. The lower limit of detection (signal to noise ratio of 3:1) were found to be 20 ng ml(-1) for each enantiomer for AG-DNS and 20.5 ng ml(-1) for each diastreoisomer for AG-F.

Determination of aminoglutethimide enantiomers as dansyl derivative in human plasma by HPLC with fluorescence detection.

Determination of aminoglutethimide enantiomers as a dansyl derivative in plasma by HPLC has been achieved using cellulose tris(3,5‐dimethylphenyl carbamate) chiral stationary phase known as Chiralcel OD, and a mobile phase consisted of ethanol‐cyclo‐hexane‐methanol (95:5:2 v/v/v). The limit of detection for each enantiomer of aminoglutethimide using fluorescence detector was 20 ng ml‐1.

ENANTIOSELECTIVE QUANTIFICATION OF DOXYLAMINE IN HUMAN PLASMA BY HPLC

A high pressure liquid chromatography-diode array detector (HPLC-DAD) method using amylose tris(3,5-dimethylphenyl carbamate) chiral stationary phase (Chiralpak AD-H) is described for the determination of doxylamine enantiomers in human plasma. Doxylamine enantiomers were separated on a Chiralpak AD-H column using a mobile phase composed of n-hexane-2-propanol-diethylamine (98:2:0.025, v/v/v). Diphenhydramine was used as an internal Standard (IS). Doxylamine was extracted from plasma samples using dichloromethane:hexane (1:2 v/v), which yielded high extraction yields (87%), satisfactory precision (RSD < 1.05%), and good selectivity. Linearity was found in the 8–40 µg · mL−1 range with the limits of detection 0.13 µg · mL−1. Doxylamine enantiomers were well separated with no interference from endogenous plasma constituents. The method developed, showed a good linearity, sensitivity, and repeatability.

N-[2-(4-Chloro-phen-yl)-5-methyl-4-oxo-1,3-thia-zolidin-3-yl]pyridine-3-carboxamide.

The title compound, C16H14ClN3O2S, crystallizes with two molecules in the asymmetric unit. In the 1,3-thiazolidine rings, the carbonyl O atoms, the S atoms, the methyl groups and the ring carbon attached to the methyl groups are disordered with occupancy ratios of 0.509 (7):0.491 (7) in one molecule and 0.464 (14):0.536 (14) in the other. The crystal structure is stabilized by intermolecular N—H⋯N, C—H⋯O hydrogen bonds and C—H⋯Cl interactions. In addition, there is a π–π stacking interaction [centroid–centroid distance = 3.794 (3) Å] between the benzene and pyridine rings.