1,2,3-Dithiazoles and new routes to 3,1-benzoxazin-4-ones, 3,1-benzothiazin-4-ones and N-arylcyanothioformamides

Moussa

2013

Archiv der Pharmazie

A series of 15 novel symmetrical and non-symmetrical bis-imidazolidineiminothiones (6a-g, 7a-e, 8a,b, and 9) with various substituents at N-(1) (p-tolyl, p-methoxyphenyl, p-ethoxyphenyl, p-chlorophenyl, p-bromophenyl, p-iodophenyl, and 3,5-dichlorophenyl) and different linkers between the N-(3) atoms [4,4'-oxybis(4,1-phenylene), 2,2'-dimethoxybiphenyl, and (1,3,3-trimethylcyclohexyl)methyl)] were prepared in 65-75% yields from substituted N-arylcyanothioformanilides and various bis-isocyanates. Screening for cytotoxicity against the HEPG2, HEP2, MCF7, and HCT116 tumor cell lines gave IC50 values ranging from 6.3 to 84.6 µM, where compounds 6b,d,e,g and 7a were markedly active against a least one cell line, underlining the matching effect of properly positioned substituents on N-(1) and the appropriate N-(3)-N-(3) linker. Likewise, all heterocyles were tested against microbial organisms (Pseudomonas aeruginosa, Sarcina lutea, Bacillus pumilus, and Micrococcus luteus) and fungal strains (Candida albicans and Penicilium chrysogenum). Most compounds showed significant antibacterial and antifungal activities, reaching in certain cases the same level of antimicrobial activity as the standard antibacterial agent erythromycin and the antifungal agent metronidazole. The antimicrobial activity was further supported by quantitative assessment of susceptibilities of a selection of the preceding microorganisms using minimum inhibitory concentration and minimum bactericidal concentration techniques. Finally, the antiviral properties of all compounds were investigated against the viral strains HAV, HSV1, and CoxB4, where 6c,d,f and 7a,c,e were markedly active against one or two viral strains, reducing the virus plaque count of various viral strains by 66 to 88%. Structure activity relationship studies revealed several matching pairs of aromatic substituents on N-(1) and the N-(3)-N-(3) linkers, which could serve to optimize structural features for high activity to eventually render such compounds clinically useful drug agents.

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Bis‐Imidazolidineiminothiones: A Comparative Study

Moussa

2013

Archiv der Pharmazie

“…For example the thermolysis of N -aryldithiazolimines can afford benzothiazoles [ 10 , 11 ], benzimidazoles [ 12 ], thiazolopyridines [ 13 ] and benzoxazines [ 14 ]. Moreover, N -aryldithiazolimines can also be transformed into useful acyclic functionalities such as cyanothio-formanilides [ 15 , 16 , 17 ], N -arylcyanoformimidoyl chlorides [ 10 , 18 ] and N -arylisothiocyanates [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of [(4-Chloro-5H-1,2,3-dithiazol-5-ylidene)amino]azines

2011

The reactions of 2-, 3- and 4-aminopyridines with 4,5-dichloro-1,2,3-dithiazol-ium chloride (Appel salt) 4 to give N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)pyridin-X-amines 1a (X = 2), 1g (X = 3) and 1k (X = 4) were optimized with respect to base, temperature and reaction time. Based on these conditions a total of thirteen [(dithiazol-ylidene)amino]azines 1a-m were prepared and fully characterized.

“…On the other hand, the benzothiazinone 5i was the main product of the reaction of 4i with TFAA while the corresponding benzoxazinone 9i was only formed in traces. The formation of 8h is envisaged to occur by a nucleophilic attack of the carboxyl oxygen at the activated thiocarbonyl carbon [ 31 , 32 , 33 , 34 , 35 , 36 ]. Further investigations are needed to clarify the mechanism of this desulphurisation-cyclisation.…”

Section: Resultsmentioning

confidence: 99%

2-Amino- and 2-Alkylthio-4H-3,1-benzothiazin-4-ones: Synthesis, Interconversion and Enzyme Inhibitory Activities

et al. 2009

The synthetic access to 2-sec-amino-4H-3,1-benzothiazin-4-ones 2 was explored. Compounds 2 were available from methyl 2-thioureidobenzoates 1, 2-thioureidobenzoic acids 3, and novel 2-thioureidobenzamides 6, respectively, under different conditions. 2-Alkylthio-4H-3,1-benzothiazin-4-ones 5 have been prepared from anthranilic acid following a two step route. Both, benzothiazinones 2 and 5 underwent ring cleavage reactions to produce thioureas 1 and 6, respectively. Twelve benzothiazinones were evaluated as inhibitors against a panel of eight proteases and esterases to identify one selective inhibitor of human cathepsin L, 2b, and one selective inhibitor of human leukocyte elastase, 5i.