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A new approach was recently introduced to improve the structure elucidation power of tandem mass spectrometry simulating the MS(3) of ion trap mass spectrometry system overcoming the different drawbacks of the latter. The fact that collision induced dissociation in the triple quadrupole mass spectrometer system provides richer fragment ions compared to those achieved in the ion trap mass spectrometer system utilizing resonance excitation. Moreover, extracting comprehensive spectra in the ion trap needs multistage fragmentation, whereas similar fragment ions may be acquired from one stage product ion scan using the triple quadrupole mass spectrometer. The new strategy was proven to enhance the qualitative performance of tandem mass spectrometry for structural elucidation of different chemical entities. In the current study we are endeavoring to prove our hypothesis of the efficiency of the new pseudo-MS(3) technique via its comparison with the MS(3) mode of ion trap mass spectrometry system. Ten pharmacologically and synthetically important (E)-3-(dimethylamino)-1-arylprop-2-en-1-ones (enaminones 4a-j) were chosen as model compounds for this study. This strategy permitted rigorous identification of all fragment ions using triple quadrupole mass spectrometer with sufficient specificity. It can be used to elucidate structures of different unknown components. The data presented in this paper provide clear evidence that our new pseudo-MS(3) may simulate the MS(3) of ion trap spectrometry system.

The asymmetric unit of the title compound, C(13)H(11)BrN(2)OS, consists of two crystallographically independent mol-ecules (A and B). In each mol-ecule, the pyrrolidine ring adopts an envelope conformation with a methyl-ene C atom as the flap atom. In mol-ecule A, the central thia-zole ring makes a dihedral angle of 36.69 (11)° with the adjacent phenyl ring, whereas the corresponding angle is 36.85 (12)° in mol-ecule B. The pyrrolidine ring is slightly twisted from the thia-zole ring, with C-N-C-N torsion angles of 4.8 (3) and 3.0 (4)° in mol-ecules A and B, respectively. In the crystal, C-H⋯π and π-π [centroid-to-centroid distance = 3.7539 (14) Å] inter-actions are observed. The crystal studied was a pseudo-merohedral twin with twin law (-100 0-10 101) and a refined component ratio of 0.7188 (5):0.2812 (5).

In the title compound, C(18)H(22)BrN(3)OS, the piperidine ring adopts a chair conformation. The mean plane of the thia-zole ring forms dihedral angles of 23.97 (10) and 75.82 (10)° with the mean planes of its adjacent benzene and piperidine rings, respectively. An intra-molecular N-H⋯N hydrogen bond generates an S(7) ring motif in the mol-ecule. In the crystal, no significant inter-moelcular hydrogen bonds are observed, but a weak π-π inter-action with a centroid-centroid distance of 3.8855 (13) Å occurs.

The title mol-ecule, C(18)H(19)N(3)O(3), lies on a mirror plane that bis-ects the adamantyl group. In the crystal, C-H⋯O and C-H⋯N inter-actions lead to supra-molecular chains along [100]. These assemble into layers in the ab plane via π-π inter-actions [centroid-centroid distance = 3.6548 (7) Å] between the oxadiazole and benzene rings.

In the title compound, C(12)H(8)F(2)N(2)OS, the thienyl ring is disordered over two positions, with the S atom of the major component [occupancy = 75.03 (18)%] oriented away from an ortho-F atom of the benzene ring. The mol-ecule is nearly planar, the dihedral angle between the thio-phene and benzene rings being 6.19 (18) (in the major component) or 3.5 (6)° (in the minor component). The azomethine C=N double-bond in the mol-ecule is of an E configuration. In the crystal, mol-ecules are linked by pairs of N-H⋯O hydrogen bonds, generating inversion dimers.

In the title mol-ecule, C(15)H(18)N(2)OS, a small twist is noted, with the dihedral angle between the central carbohydrazone residue (r.m.s. deviation = 0.029 Å) and the thio-phene ring being 12.47 (10)°. The syn arrangement of the amide H and carbonyl O atoms allows for the formation of centrosymmetric dimers via N-H⋯O hydrogen bonds. These are linked in the three-dimensional structure by C-H⋯π inter-actions. The thio-phene ring is disordered over two co-planar orientations, the major component having a site-occupancy factor of 0.833 (2).

A simple, sensitive and accurate stability-indicating HPLC method has been developed and validated for determination of varenicline (VRC) in its bulk form and pharmaceutical tablets. Chromatographic separation was achieved on a Zorbax Eclipse XDB-C8 column (150 mm × 4.6 mm i.d., particle size 5 μm, maintained at ambient temperature) by a mobile phase consisted of acetonitrile and 50 mM potassium dihydrogen phosphate buffer (10:90, v/v) with apparent pH of 3.5 ± 0.1 and a flow rate of 1.0 ml/min. The detection wavelength was set at 235 nm. VRC was subjected to different accelerated stress conditions. The degradation products, when any, were well resolved from the pure drug with significantly different retention time values. The method was linear (r = 0.9998) at a concentration range of 2 - 14 μg/ml. The limit of detection and limit of quantitation were 0.38 and 1.11 μg/ml, respectively. The intra- and inter-assay precisions were satisfactory; the relative standard deviations did not exceed 2%. The accuracy of the method was proved; the mean recovery of VRC was 100.10 ± 1.08%. The proposed method has high throughput as the analysis involved short run-time (~ 6 min). The method met the ICH/FDA regulatory requirements. The proposed method was successfully applied for the determination of VRC in bulk and tablets with acceptable accuracy and precisions; the label claim percentages were 99.65 ± 0.32%. The results demonstrated that the method would have a great value when applied in quality control and stability studies for VRC.

New 1-adamanyl-1,3,4-thiadiazole derivatives namely, 5-(1-adamantyl)-1,3,4-thiadiazoline-2-thione 3, 5-(1-adamantyl)-3-(benzyl- or 4-substituted benzyl)-1,3,4-thiadiazoline-2-thione 4a-d, 5-(1-adamantyl)-3-(4-substituted-1-piperazinylmethyl)-1,3,4-thiadiazoline-2-thiones 5a-c, 2-[5-(1-adamantyl)-2-thioxo-1,3,4-thiadiazolin-3-yl]acetic acid 7, (±)-2-[5-(1-adamantyl)-2-thioxo-1,3,4-thiadiazolin-3-yl]propionic acid 9, 3-[5-(1-adamantyl)-2-thioxo-1,3,4-thiadiazolin-3-yl]propionic acid 11, N-[5-(1-adamantyl)-1,3,4-thiadiazol-2-yl]-N'-arylthioureas 15a-c and 5-(1-adamantyl)-1,3,4-thiadiazoline-2-one 16, were synthesized and tested for in vitro activities against a panel of gram-positive and gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compounds 7, 9, 15b and 15c displayed marked activity against the tested gram-positive bacteria, while compound 3 was highly active against the tested gram-negative bacteria. Compounds 4b, 7 and 15c were weakly or moderately active against C. albicans. In addition, the in vivo anti-inflammatory activity of the synthesized compounds was determined using the carrageenan-induced paw oedema method in rats. The propionic acid derivative 9 produced good dose-dependent anti-inflammatory activity., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Two series of some new 2,4,6-trisubstituted-quinazoline derivatives were prepared and screened for their analgesic, anti-inflammatory activity and acute toxicity. Four compounds were more potent analgesic agents than the reference drug Indomethacin and thirteen compounds showed significant anti-inflammatory activity. Seven compounds showed combined ability to inhibit both pain and inflammation. Compounds tested for acute toxicity showed no toxic symptoms or mortality rates 24 h post-administration implying their good safety margin., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Reaction of 1-adamantanecarbonyl chloride with certain carboxylic acid hydrazides in pyridine yielded the corresponding N-acyl adamantane-1-carbohydrazide derivatives 3a-j, which were cyclized to the corresponding 2-(1-adamantyl)-5-substituted-1,3,4-oxadiazoles 4a-j via heating with phosphorus oxychloride. Treatment of 1-adamantylisothiocyanate with some carboxylic acid hydrazides in ethanol yielded the corresponding 1-acyl-4-(1-adamantyl)-3-thiosemicarbazides 7a-g, which were cyclized to the corresponding 2-(1-adamantylamino)-5-substituted-1,3,4-thiadiazole derivatives 8a-g. Compounds 4a-j, 7a-g, and 8a-g were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Several derivatives produced good or moderate activities particularly against the tested Gram-positive bacteria Bacillus subtilis. Meanwhile, compounds 4i and 8g displayed marked antifungal activity against C. albicans. In addition, the in vivo anti-inflammatory activity of the synthesized compounds was determined using the carrageenin-induced paw oedema method in rats. The oxadiazole derivatives 4c, 4g, 4i and 4j produced good dose-dependent anti-inflammatory activity.