133044-35-6Relevant academic research and scientific papers
Synthesis and characterization of [3H]-SN56, a novel radioligand for the σ1 receptor
Fishback, James A.,Mesangeau, Christophe,Poupaert, Jacques H.,McCurdy, Christopher R.,Matsumoto, Rae R.
, p. 1 - 7 (2011)
The study of the binding characteristics of σ ligands in vivo and in vitro requires radiolabeled probes with high affinity and selectivity. The radioligand presently used for in vitro studies of the σ1 receptor, [3H](+)-pentazocine, has significant limitations; it is difficult to synthesize, has limited chemical stability, and can be problematic to obtain. Evaluation of a series of novel 2(3H)-benzothiazolone compounds revealed SN56 to have sub-nanomolar and preferential affinity for the σ1 subtype, relative to σ2 and non-sigma, binding sites. The goal of this study was to characterize the binding of [ 3H]-SN56 to σ1 receptors isolated from rat brain. Standard in vitro binding techniques were utilized to 1) determine the specificity and affinity of binding to σ1 receptors, 2) confirm that [3H]-SN56 labels sites previously identified as σ1 by comparing binding to sites labeled by [ 3H](+)-pentazocine, and 3) characterize the kinetics of binding. The results indicate that [3H]-SN56 exhibits 1) specific, saturable, and reversible binding to the σ1 receptor, with Bmax = 340 ± 10 fmol/mg and Kd = 0.069 ± 0.0074 nM, 2) competitive displacement by classical sigma compounds, yielding σ1 Ki values consistent with those reported in the literature, and 3) binding kinetics compatible with a 90 min incubation, and filtration for separation of free and bound radioligand. The results of these studies suggest that [3H]-SN56 may serve as a viable alternative to [3H](+)-pentazocine in radioligand binding assays.
Structure activity relationship study of benzo[d]thiazol-2(3H)one based σ receptor ligands
Bhat, Rohit,Fishback, James A.,Matsumoto, Rae R.,Poupaert, Jacques H.,McCurdy, Christopher R.
, p. 5011 - 5013 (2013)
Herein we report the SAR study which involved structural modifications to the linker length, aryl substitution and alkylamine ring size of the benzo[d]thiazol-2(3H)one based sigma receptor (σ) ligands. Many compounds in this series displayed low nanomolar affinity for the σ receptor subtypes. In particular, 8a showed high affinity (σ-1 Ki = 4.5 nM) for σ-1 receptors and moderately high selectivity (483-fold) over σ-2 receptors.
Design and synthesis of 3-acyl-2(3H)-benzoxazolone and 3-acyl-2(3H)- benzothiazolone derivatives
Guenadil, Faouzi,Aichaoui, Hocine,Kapanda, Coco N.,Lambert, Didier M.,McCurdy, Christopher R.,Poupaert, Jacques H.
experimental part, p. 67 - 80 (2011/09/20)
A simpler and efficient "green" method using solid sodium hydroxide in a solvent mixture of acetone/water was found to catalyze N-acylation of 2(3H)-benzoxazolones and 2(3H)-benzothiazolones for facile and rapid synthesis of N-acyl derivatives in excellent yields. This method was applied to the synthesis of a series of 132 compounds employing a variety of acyl chlorides. Graphical abstract: [Figure not available: see fulltext.]
Application of the "fries like" rearrangement using ZnCL 2 for the synthesis of 6-acyl-2(3H)-benzothiazolones
Guenadil, Faouzi,Aichaoui, Hocine
, p. 1703 - 1708 (2007/10/03)
In this work we report another method of acylation on the 6-position of the 2(3H)-benzothiazolone ring with Fries-like rearrangement catalyzed by zinc chloride instead of aluminium chloride and 3-acyl-2(3H)-benzothiazolones derivatives as starting materia
Study of the acylation reaction of 2(3H)-benzothiazolones in the mixture of ZnCl2-DMF
Guenadil, Faouzi,Aichaoui, Houcine
, p. 2633 - 2638 (2007/10/03)
The use of polyphosphoric acid and the complex AlCl3-DMF in 6-acylation of 2(3H)-benzothiazolones previously have been reported. Instead of the frequently used AlCl3 as a catalyst in the Friedl-Crafts reactions, we conducted the acyl
'Fries like' rearrangement: A novel and efficient method for the synthesis of 6-acyl-2(3H)-benzoxazolones and 6-acyl-2(3H)-benzothiazolones
Ucar, Huseyin,Van Derpoorten, Kim,Depovere, Paul,Lesieur, Daniel,Isa, Majed,Masereel, Bernard,Delarge, Jacques,Poupaert, Jacques H.
, p. 1763 - 1772 (2007/10/03)
6-Acyl-2(3H)-benzoxazolone and 6-acyl-2(3H)-benzothiazolone derivatives have particularly interesting anti-inflammatory, antiepileptic, analgesic and antiviral properties. In this study, we report an original method of acylation on the 6-position of 2(3H)-banzoxazolone and 2(3H)benzothiazolone which consists in a two-step procedure involving migration of the acyl group from the N-position to the 6-position of the hetexocycle, at 165 °C and catalyzed by AlCl3. This new procedure was found to be more efficient with regard to the consumption of AICI3 and the yield (76-90%) than other acylation methods previously described.
Synthesis and anticonvulsant activity of 2(3H)-benzoxazolone and 2(3H)- benzothiazolone derivatives
Ucar, Huseyin,Van Derpoorten, Kim,Cacciaguerra, Silvia,Spampinato, Santi,Stables, James P.,Depovere, Paul,Isa, Majed,Masereel, Bernard,Delarge, Jacques,Poupaert, Jacques H.
, p. 1138 - 1145 (2007/10/03)
A series of 2(3H)-benzoxazolone and 2(3H)-benzothiazolone derivatives were synthesized and evaluated for anticonvulsant activity. The compounds were assayed, intraperitoneally in mice and per os in rats, against seizures induced by maximal electroshock (MES) and pentylene-tetrazole (scMet). Neurologic deficity was evaluated by the rotarod test. The compounds were prepared to determine the relationship between the 2(3H)-benzoxazolone and 2(3H)-benzothiazolone derivatives' structures and anticonvulsant activity. Several of these compounds showed significant anticonvulsant activity. Compounds 43 and 45 were the most active of the series against MES-induced seizures with ED50 values of 8.7 and 7.6 mg/kg, respectively. Compound 45 displayed good protection against MES-induced seizures and low toxicity in rats with an oral ED50 of 18.6 mg/kg and a protective index (PI = TD50/ED50) of 1 receptors with nanomolar affinities.
Benzothiazolinone compounds
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, (2008/06/13)
Compounds of general formula (I): STR1 in which: R1 represents a hydrogen atom or a lower alkyl group, R2 represents a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstitute
