181486-57-7Relevant articles and documents
IMIDAZO[2,1-B]THIAZOLE AND 5,6-DIHYDROIMIDAZO[2,1-B]THIAZOLE DERIVATIVES USEFUL AS S100-INHIBITORS
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Page/Page column 118; 119, (2016/04/09)
A compound of formula (I) or a pharmaceutically acceptable salt thereof. The compound is useful for use in the treatment of cancer, an inflammatory disorder,an autoimmunity disorder or a neurodegenerative disorder.
Tricyclic 6-alkylidene-penems as class-D beta-lactamases inhibitors
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Page/Page column 19, (2010/11/25)
This invention relates to certain tricyclic 6-alkylidene penems which act as a inhibitor of class-D enzymes. β-Lactamases hydrolyze β-lactam antibiotics, and as such serve as the primary cause of bacterial resistance. The compounds of the present inventio
Structure-activity relationship of 6-methylidene penems bearing tricyclic heterocycles as broad-spectrum β-lactamase inhibitors: Crystallographic structures show unexpected binding of 1,4-thiazepine intermediates
Venkatesan, Aranapakam M.,Gu, Yansong,Santos, Osvaldo Dos,Abe, Takao,Agarwal, Atul,Yang, Youjun,Petersen, Peter J.,Weiss, William J.,Mansour, Tarek S.,Nukaga, Michiyoshi,Hujer, Andrea M.,Bonomo, Robert A.,Knox, James R.
, p. 6556 - 6568 (2007/10/03)
The design and synthesis of a series of seven tricyclic 6-methylidene penems as novel class A and C serine β-lactamase inhibitors is described. These compounds proved to be very potent inhibitors of the TEM-1 and AmpC β-lactamases and less so against the class B metallo-β-lactamase CcrA. In combination with piperacillin, their in vitro activities enhanced susceptibility of all class C resistant strains from various bacteria. Crystallographic structures of a serine-bound reaction intermediate of 17 with the class A SHV-1 and class C GC1 enzymes have been established to resolutions of 2.0 and 1.4 A?, respectively, and refined to R-factors equal 0.163 and 0.145. In both β-lactamases, a seven-membered 1,4-thiazepine ring has formed. The stereogenic C7 atom in the ring has the R configuration in the SHV-1 intermediate and has both R and S configurations in the GC1 intermediate. Hydrophobic stacking interactions between the tricyclic C7 substituent and a tyrosine side chain, rather than electrostatic or hydrogen bonding by the C3 carboxylic acid group, dominate in both complexes. The formation of the 1,4- thiazepine ring structures is proposed based on a 7-endo-trig cyclization.
HETEROTRICYCLYL 6-ALKYLIDENE-PENEMS AS ΒΕΤΑ-LACTAMASE INHIBITORS
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Page/Page column 123, (2008/06/13)
The present invention provides a compound of formula I, pharmaceutical compositions and the use thereof for the treatment of bacterial infection or disease in a patient in need thereof.
Synthesis, in vitro and in vivo cytotoxicity, and prediction of the intestinal absorption of substituted 2-ethoxycarbonyl-imidazo[2,1-b]benzothiazoles
Trapani, Giuseppe,Franco, Massimo,Latrofa, Andrea,Reho, Antonia,Liso, Gaetano
, p. 209 - 216 (2007/10/03)
The imidazobenzothiazole compounds 3-17 together with the imidazobenzoxazole 18, and the imidazobenzoimidazole 19 were prepared and their cytotoxic activity evaluated at the National Cancer Institute (NCI) for testing against a panel of approximately 60 tumor cell lines. Compounds 5, 7, 8, and 16 exhibited interesting in vitro cytotoxic activity. The most active imidazobenzothiazole derivative 8 was further evaluated as a cytotoxic agent in the hollow fiber assay and showed a score greater than the minimum values for xenograft testing together with a net cell kill. Comparison with the results displayed in the in vivo assay by standard antitumor drugs in clinical use revealed a significant in vivo activity of the benzothiazole compound. COMPARE analyses for compounds 4-19 against the NCI's standard agent database show poor or no correlation, and it might suggest for these compounds a mechanism of action unrelated to that of any known drug. Furthermore, the benzothiazole 8 did not show significant antitumor activity in a panel of two xenotransplanted tumors (i.e. colon and non-small cell lung tumors). By computing the polar surface area of compounds 3-19 with the MAREA computer program it was established that the most active compounds 5, 7, 8, and 16 should experience good intestinal permeability. Copyright
Synthesis and benzodiazepine receptor binding of some imidazo- and pyrimido[2,1-b]benzothiazoles
Trapani,Franco,Latrofa,Carotti,Genchi,Serra,Biggio,Liso
, p. 575 - 587 (2007/10/03)
A series of substituted imidazo[2,1-b]benzothiazoles 2a-u was synthesized and the compounds evaluated for their affinity at the central benzodiazepine receptors. Substitution at the 7-position generally resulted in a decreased ligand affinity whereas a significant increase was observed for 5-substituted compounds. The intrinsic efficacy of selected high-affinity ligands 2j,k,q, as well as some previously reported pyrimido[2,1-b]benzothiazoles 1, was measured in vitro through the determination of the GABA ratio and [35S]TBPS displacement. Consistent with a partial inverse agonist profile, the benzothiazole derivatives 2j,k,q increased [35S]TBPS binding. For compounds 1c and 1d, a discrepancy between GABA ratio and [35S]TBPS binding data was observed. Only the latter assay was in full agreement with the pharmacological data, which indicated an inverse agonist and a partial agonist profile for 2k,q and 1c,d respectively. The affinity and intrinsic activity data of compounds 1c,d and 2j,k,q are discussed in the light of the recently proposed pharmacophore model by Skolnick/Cook; in particular, the agonistic activity of 1c,d is interpreted on the basis of a possible interaction of substitutents in position 6 with the receptors lipophilic area L3 of Skolnick/Cook, whereas the observed inverse agonist profile of 2j,k,q is explained taking into account their structural analogy with the well known proconvulsant β-CCE.
