1,2-Benzothiazines. II. The Preparation and Sodium Borohydride Reduction of 3-Acyl-2H-1,2-benzothiazin-4(3H)-one 1,1-Dioxides<sup>1</sup>

Zinnes, Harold; Comes, Roger A.; Zuleski, Francis R.; Albert, N. Erick; Shavel, John

doi:10.1021/jo01018a029

Cited by 38 publications

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“…The synthetic pathways utilized in the preparation of the pyrazolobenzothiazines 1a , 1b – k , 2a , 2b – k , and 4 – 6 are outlined in Schemes and , while compounds belonging to the subset 3 (Table ) were already described and prepared according to the literature . N‐1 phenylpyrazolobenzothiazines 1a and 1b – i were obtained through a regioselective condensation of appropriate phenylhydrazine hydrochloride with the key synthon 7 (Scheme ). Initially, this reaction step was carried out employing the procedure described for the preparation of compounds belonging to the subset 3 .…”

Section: Resultsmentioning

confidence: 99%

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The Pyrazolobenzothiazine Core as a New Chemotype of p38 Alpha Mitogen‐Activated Protein Kinase Inhibitors

et al. 2015

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The identification, synthesis, biological activity, and binding mode prediction of a series of pyrazolobenzothiazines as novel p38α MAPK inhibitors are reported. Some of these compounds showed interesting activity in both p38α MAPK and TNF-α release assays. Derivative 6 emerged as the most interesting compound with IC50 (p38α) = 0.457 μm, IC50 (TNF-α) = 0.5 μm and a promising kinase selectivity profile. The obtained results strongly indicate the pyrazolobenzothiazine core as a new p38α inhibitor chemotype worthy of future chemical optimization efforts directed toward identifying a new generation of anti-inflammatory agents.

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Section: Resultsmentioning

confidence: 99%

“…In a microwave oven tube, the key synthon 7 (1 mmol) was dissolved in DMF (2.5 mL) and the appropriate phenylhydrazine hydrochloride (1.5 mmol) was added. The solution was irradiated at 100 °C from 5 to 75 min, employing the following experimental parameters: pressure 5 bar, cooling on, FHT on, prestirring 30 seconds, very high absorption.…”

Section: Methodsmentioning

confidence: 99%

The Pyrazolobenzothiazine Core as a New Chemotype of p38 Alpha Mitogen‐Activated Protein Kinase Inhibitors

et al. 2015

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“…-The ring-enlargement procedure [3], when applied directly to the precursors 18a, 20a, and 21 (Schemes 3 and 4 ) , does not give satisfactory results. It can be assumed that the reaction involves opening of the 'saccharin ring' to a diester [26], which then undergoes a Dieckmann cyclization to the p-keto-ester 6 (Scheme 1). We have found that superior yields are obtained by advancing stepwise, i.e.…”

Section: Transformation Intomentioning

confidence: 99%

Tilcotil^® Studies [3+2] additions with isothiazol‐3(2H)‐one 1,1‐dioxide

Burri

1989

Helvetica Chimica Acta

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Derivatives of isothiazolL3(2H)-one 1,l -dioxide react regiospecifically with 1,3-dipolar agents. The main regiocontrolling factor is ascertained to be the C=O group of the dipolarophile. The topology of the adducts is also in general agreement with predictions based on perturbation theory. Several adducts can be aromatized to heterocyclic equivalents of saccharin, and may then be elaborated into structural analogs of tenoxicam (Tilcotil") and piroxicam (Feldene'"').1. Introduction. -The widely used anti-inflammatory drug Feldene@ (Piroxicam, 1; Scheme I ) and the more recently introduced TilcotiP (Tenoxicam, 2) are the two bestknown representatives of a new class of antirheumatic agents referred to as oxicams [ 11. A valuable synthetic approach to oxicams results from an observation by Abe et al. [ 2 ] , i.e. that the saccharin derivative 3 (Scheme I) undergoes a methoxide-induced ring enlargement to the thiazinone 4; the procedure has subsequently been extended [3] to the rearrangement of 5, which similarly yields 6. Piroxicam 1 is then obtained from 6 by a chemoselective methylation, affording 7, followed by aminolysis with 2-aminopyridine [4].

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“…Pyrazolobenzothiazine 5,5-dioxide precursor 1 was prepared from sodium saccharine as a starting material, 5,24 and thence to the target compounds 6a-i and 7a-f, as previously reported (Scheme 1). 15…”

mentioning

confidence: 99%

Molecular docking and antiviral activity of N-substituted benzyl/phenyl-2-(3,4-dimethyl-5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin-2(4H)-yl)acetamides

Ahmad

Aslam

Rizvi

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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Two series of fifteen N-substituted benzyl/phenyl-2-(3,4-dimethyl-5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin-2(4H)-yl)acetamides were screened for anti-HIV-1 activity and cytotoxicity. The compounds 6a, 6d, 6e, 6g and 6i from the series 6a-i of benzylamides and 7a, 7b, 7c, 7d and 7e from the series 7a-f of anilides were identified as effective anti-HIV-1 agents with EC50 values <20μM. Among these compounds that displayed anti-HIV-1 activity, 6a, 6e, 6g and 6i showed no toxicity in human PBM, CEM and Vero cells, with the exception of 6a which displayed toxicity in Vero cells. Molecular docking of these compounds provided insight into the molecular mechanism and it was found that 6e, 6g and 6i bound deeply in the NNRTI binding pocket of the HIV-1 reverse transcriptase, using RT-bound nevirapine X-ray data and molecular docking for validation, showing the potential of these new structures as inhibitors of this viral enzyme.

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1,2-Benzothiazines. II. The Preparation and Sodium Borohydride Reduction of 3-Acyl-2H-1,2-benzothiazin-4(3H)-one 1,1-Dioxides¹

Cited by 38 publications

References 0 publications

The Pyrazolobenzothiazine Core as a New Chemotype of p38 Alpha Mitogen‐Activated Protein Kinase Inhibitors

The Pyrazolobenzothiazine Core as a New Chemotype of p38 Alpha Mitogen‐Activated Protein Kinase Inhibitors

Tilcotil^® Studies [3+2] additions with isothiazol‐3(2H)‐one 1,1‐dioxide

Molecular docking and antiviral activity of N-substituted benzyl/phenyl-2-(3,4-dimethyl-5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin-2(4H)-yl)acetamides

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1,2-Benzothiazines. II. The Preparation and Sodium Borohydride Reduction of 3-Acyl-2H-1,2-benzothiazin-4(3H)-one 1,1-Dioxides1

Cited by 38 publications

References 0 publications

The Pyrazolobenzothiazine Core as a New Chemotype of p38 Alpha Mitogen‐Activated Protein Kinase Inhibitors

The Pyrazolobenzothiazine Core as a New Chemotype of p38 Alpha Mitogen‐Activated Protein Kinase Inhibitors

Tilcotil® Studies [3+2] additions with isothiazol‐3(2H)‐one 1,1‐dioxide

Molecular docking and antiviral activity of N-substituted benzyl/phenyl-2-(3,4-dimethyl-5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin-2(4H)-yl)acetamides

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1,2-Benzothiazines. II. The Preparation and Sodium Borohydride Reduction of 3-Acyl-2H-1,2-benzothiazin-4(3H)-one 1,1-Dioxides¹

Tilcotil^® Studies [3+2] additions with isothiazol‐3(2H)‐one 1,1‐dioxide