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We report on the synthesis and the antimicrobial activity of 9-cyclopropyl-4-fluoro-6-oxo[1,2,5]thiadiazolo[3,4-h]quinoline-5-carboxylic acid (16), representative of a new class of antibacterial agents structurally related to the clinically successful fluoroquinolones. The novel 6-fluoroquinolone (16) is herein prepared, in good yield, by thermal cyclocondensation of ethyl 7,8-diamino-9-cyclopropyl-4-fluoro-6-oxoquinoxaline-7-carboxylate with thionyl chloride, followed by acid-catalysed hydrolysis of the ester intermediate (15). Their structures were characterized by IR, MS, 1H- and 13C NMR spectra and X-ray crystal structure of 16 is presented. The antimicrobial evaluation against a broad panel of wild and resistant Gram-positive and Gram-negative bacteria and fungal species demonstrated the high antibacterial activity of 16, even at the concentration of 0.015 μg mL-1. [ABSTRACT FROM AUTHOR]

In the title mol-ecule, C(14)H(12)N(2)O(3)S(2), the benzisothia-zolone ring system is essentially planar and forms a dihedral angle of 67.37 (6)° with the plane of the benzene ring. In the crystal structure, mol-ecules are linked via inter-molecular N-H⋯O and C-H⋯O hydrogen bonds to form chains parallel to the b axis.

In the title compound, C(19)H(12)Cl(2)N(2)O(5)S(3), the benzene rings of the chloro-phenyl-sulfonyl groups form a dihedral angle of 35.85 (8)° and are inclined at angles of 23.51 (6) and 59.22 (6)° with respect to the essentially planar benzisothia-zole ring system [maximum deviation = 0.030 (2) Å]. The mol-ecular conformation is stabilized by an intra-molecular C-H⋯O hydrogen bond. In the crystal packing, mol-ecules are linked into chains parallel to the a axis by inter-molecular C-H⋯O hydrogen bonds and π-π stacking inter-actions, with centroid-centroid distances of 3.592 (5) Å.

The complete (1)H and (13)C NMR assignments of the novel compound methyl 2-amino-3-(benzo[d]isothiazol-3-yl)propanoate (1), of 3-amino-5-methylbenzo[d]isothiazole (2) and N-(t-butyloxycarbonyl)-2-aminobenzo[d]isothiazol-3(2H)-one (3) and of the desulfurated isostere of 3, N-(t-butyloxycarbonyl)-2-aminoisoindolin-1-one (4), using 1D and 2D NMR techniques, including COSY, INADEQUATE, HSQC, and HMBC experiments are reported., (Copyright (c) 2008 John Wiley & Sons, Ltd.)

New derivatives of N-benzo[d]isothiazol-3-yl-benzamidine 6 a were synthesized as nonacidic anti-inflammatory/antidegenerative agents. We investigated the influence of the amidines 6 a-j on the production of NO, PGE(2), MMP-3, COX-2, ROS, and GAGs, key molecules involved in cartilage destruction in osteoarthritic diseases. The antidegenerative properties of the novel designed derivatives 6 b-j were improved with respect to N-benzo[d]isothiazol-3-yl-benzamidine 6 a. All of the compounds 6 a-j promoted the reduction of most of the IL-1beta-induced harmful effects. Derivatives 6 d, 6 h, and 6 j were the most potent of all the tested compounds, particularly in the human chondrocyte culture model.

To date, the application of physiologically based pharmacokinetic (PBPK) models in support of drug discovery remains limited, in part due to information deficit and uncertainty regarding model parameters. Fuzzy set theory provides a suitable way to objectively account for parameter uncertainty in models. Here, we present a fuzzy set-based PBPK modeling framework and demonstrate its utility in predicting diazepam pharmacokinetics in human plasma, following intravenous dosing, from available animal in vivo and literature data. For computationally expensive PBPK models, the sparse grid method is proposed as an efficient alternative to commonly used fuzzy arithmetic algorithms for function simulation.

Several thiazolyl/benzothiazolyl/benzo[d]isothiazolyl Schiff bases and hydrazones have been tested as anti-inflammatory agents and five new compounds have been synthesized. The anti-inflammatory activity was examined in vivo using the carrageenin induced mice paw edema test (inhibition 16.3-64%). The compounds were tested for antioxidant activity as hydroxyl scavengers and for their ability to interact with the stable free radical 1,1-diphenyl-2-picryl-hydrazyl (DPPH). Both anti-inflammatory and antioxidant activities depended on some structural characteristics of the synthesized compounds.