19406-49-6Relevant articles and documents
Synthesis and properties of arsenic(III)-reactive coumarin-appended benzothiazolines: A new approach for inorganic arsenic detection
Ezeh, Vivian C.,Harrop, Todd C.
, p. 2323 - 2334 (2013/04/10)
The EPA has established a maximum contaminant level (MCL) of 10 ppb for arsenic (As) in drinking water requiring sensitive and selective detection methodologies. To tackle this challenge, we have been active in constructing small molecules that react specifically with As3+ to furnish a new fluorescent species (termed a chemodosimeter). We report in this contribution, the synthesis and spectroscopy of two small-molecule fluorescent probes that we term ArsenoFluors (or AFs) as As-specific chemodosimeters. The AFs (AF1 and AF2) incorporate a coumarin fluorescent reporter coupled with an As-reactive benzothiazoline functional group. AFs react with As3+ to yield the highly fluorescent coumarin-6 dye (C6) resulting in a 20-25-fold fluorescence enhancement at λem ～ 500 nm with detection limits of 0.14-0.23 ppb in tetrahydrofuran (THF) at 298 K. The AFs also react with common environmental As3+ sources such as sodium arsenite in a THF/CHES (N-cyclohexyl-2-aminoethanesulfonic acid) (1:1, pH 9, 298 K) mixture resulting in a modest fluorescence turn-ON (1.5- to 3-fold) due to the quenched nature of coumarin-6 derivatives in high polarity solvents. Bulk analysis of the reaction of the AFs with As3+ revealed that the C6 derivatives and the Schiff-base disulfide of the AFs (SB1 and SB2) are the ultimate end-products of this chemistry with the formation of C6 being the principle photoproduct responsible for the As3+-specific turn-ON. It appears that a likely species that is traversed in the reaction path is an As-hydride-ligand complex that is a putative intermediate in the proposed reaction path.
Identification of a novel series of tetrahydrodibenzazocines as inhibitors of 17β-hydroxysteroid dehydrogenase type 3
Fink, Brian E.,Gavai, Ashvinikumar V.,Tokarski, John S.,Goyal, Bindu,Misra, Raj,Xiao, Hai-Yun,Kimball, S. David,Han, Wen-Ching,Norris, Derek,Spires, Thomas E.,You, Dan,Gottardis, Marco M.,Lorenzi, Matthew V.,Vite, Gregory D.
, p. 1532 - 1536 (2007/10/03)
A novel series of 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) inhibitors has been identified. These inhibitors, based on a dibenzazocine core, exhibited picomolar to low nanomolar inhibition of 17β-HSD3 in cell-free enzymatic as well as in cell-based transcriptional reporter assays.
Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications
Van Zandt, Michael C.,Jones, Michael L.,Gunn, David E.,Geraci, Leo S.,Jones, J. Howard,Sawicki, Diane R.,Sredy, Janet,Jacot, Jorge L.,DiCioccio, A. Thomas,Petrova, Tatiana,Mitschler, Andre,Podjarny, Alberto D.
, p. 3141 - 3152 (2007/10/03)
Recent efforts to identify treatments for chronic diabetic complications have resulted in the discovery of a novel series of highly potent and selective 3-[(benzothiazol-2-yl)methyl]indole-N-alkanoic acid aldose reductase inhibitors. The lead candidate, 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat, 9) inhibits aldose reductase with an IC50 of 5 nM, while being 5400 times less active against aldehyde reductase, a related enzyme involved in the detoxification of reactive aldehydes. It lowers nerve and lens sorbitol levels with ED50's of 1.9 and 4.5 mg/kg/d po, respectively, in the 5-day STZ-induced diabetic rat model. In a 3-month diabetic intervention model (1 month of diabetes followed by 2 months of drug treatment at 5 mg/kg/d po), it normalizes polyols and reduces the motor nerve conduction velocity deficit by 59% relative to diabetic controls. It has a favorable pharmacokinetic profile (F, 82%; t1/2, 5.6 h; Vd, 0.694 L/kg) with good drug penetration in target tissues (Cmax in sciatic nerve and eye are 2.36 and 1.45 μg equiv/g, respectively, when dosed with [14C] lidorestat at 10 mg/kg po).
Synthesis and structure-activity relationship studies of conformationally restricted, analogs of 2-chloro-4-trifluoromethylpyrimidine- 5-[N-(3',5'-bis(trifluoromethyl)phenyl)]carboxamide
Palanki, Moorthy S.S.,Erdman, Paul E.,Goldman, Mark E.,Suto, Carla,Suto, Mark J.
, p. 19 - 29 (2007/10/03)
2-Chloro-4-trifluoromethylpyrimidine-5-N[(3,5- bis(trifluoromethyl)phenyl] carboxamide (1) was identified as an inhibitor of AP-1 and NF-κB mediated transcriptional activation. In an effort to identify novel compounds that contain less number of trifluoromethyl groups with comparable potency as 1, several conformationally restricted analogs of I were synthesized in which the pyrimidine ring and the aniline ring were connected through a second 'bridge'. The 7-membered sulfur bridged analog was the most potent in this series, and comparable to 1 in activity.
PYRIMIDO-BENZOTHIAZINES
-
, (2008/06/13)
This invention relates to novel pyrimido-benzothiazine derivative compounds. The compounds of the present invention inhibit the action of the lipoxygenase enzyme and are useful in the treatment or alleviation of inflammatory diseases, allergy and cardiovascular diseases in mammals. this invention also relates to pharmaceutical compositions comprising such compounds.
Synthesis and pharmacologic properties of 2 chloro and 2 trifluoromethyl 5a,6,7,8,9,10,10a,11 octahydrobenzo[b]cyclohepta[e][1,4]thiazine derivatives. II
Cardellini,Claudi,Gulini,et al.
, p. 513 - 518 (2007/10/05)
Dialkylaminoalkyl derivatives of 2 chloro and 2 trifluoromethyl 5α,6,7,8,9,10,10α,11 octahydrobenzo [b]cyclohepta [e] [1,4]thiazine were synthesized and their activities on central nervous system, and in vitro on smooth muscle, were tested. They have little antiserotonin or antihistamine activity but their effects on the CNS are considerable.
