1,2-Benzothiazines. 6. 3-Carbamoyl-4-hydroxy-2H-1,2-benzothiazine 1,1-dioxides as antiinflammatory agents

Abstract

A variety of new 3-carbamoyl-4-hydroxy-2//-l,2-benzothiazine 1,1-dioxides of structure II was prepared and evaluated an antiinflammatory agents. Three synthetic methods were employed. Method A, consisting of base-catalyzed carbamoylation of ketone I by isocyanates, and method B, involving aminolysis of j3-keto ester III, are modifications of previously described processes. In the completely new method C, the enamine IV, derived from ketone I, is reacted with phosgene to give the acid chloride V. The latter reacts with an amine to give enamine-amide VI which can be hydrolyzed to II. The prototype compound 2 has the same order of activity as phenylbutazone when evaluated against adjuvant-induced polyarthritis as well as carrageenin-induced edema. Its acute toxicity is less than that of phenylbutazone. The structural modifications described herein all resulted in decreased or complete loss of activity in the carrageenin test.Our continuing studies1 in 1,2-benzothiazine chemistry as

2-(3,4-Dimethyl-5,5-dioxo-2H,4H-pyrazolo[4,3-c][1,2]benzothiazin-2-yl)acetic acid

“…For the biological activity of benzothiazine derivatives, see: Turck et al (1996); Silverstein et al (2000); Lombardino et al (1973); Zinnes et al (1973); Ahmad et al (2010). For related structures, see: Siddiqui et al (2008Siddiqui et al ( , 2009.…”

“…Meloxicam and Celecoxib are well known for their selective inhibition of the cox-2 enzyme that is responsible for inflammation (Turck et al, 1996;Silverstein et al, 2000). Though a number of benzothiazine based compounds have shown anti-inflammatory and analgesic character, yet there is a huge scope for selective cox-2 inhibitors in this family of heterocyclic compounds (Lombardino et al, 1973;Zinnes et al, 1973). In continuing the pursuit of potential drugs in this category, we have fused benzothiazine and pyrazole heterocycles that are core nuclei of meoxicam and celecoxib, respectively (Ahmad et al, 2010), we have synthesized and determined the crystal structure of the title compound which is presented in this paper.…”

2-(3,4-Dimethyl-5,5-dioxo-2H,4H-pyrazolo[4,3-c][1,2]benzothiazin-2-yl)-N-(2-fluorobenzyl)acetamide

“…For biological activities of benzothiazine derivatives, see: Turck et al (1996); Silverstein et al (2000); Lombardino et al (1973); Zinnes et al (1973); ; Ahmad, Siddiqui, Zia-ur-Rehman & Parvez (2010). For related crystal structures, see: Siddiqui et al (2008Siddiqui et al ( , 2009.…”

“…Data collection: APEX2 (Bruker, 2004); cell refinement: SAINT (Bruker, 2004); data reduction: SAINT and XPREP (Bruker, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: SHELXL97. Oxicam drugs are benzothiazine based carboxamides which are well known for their potent anti-inflammatory and analgesic actions (Turck et al, 1996;Lombardino et al, 1973;Zinnes et al, 1973). On the other hand, celecoxib, a pyrazole compound is an anti-inflammatory drug and a selective inhibitor of the cox-2 enzyme (Silverstein et al, 2000).…”

Sulfonilamidometilación intramolecular de 2-naftilmetan y 2-(2-naftil)etansulfonamidas

“…Estos métodos fueron aplicados en trabajos posteriores para la preparación de otras carboxamido-sultamas, en algunos casos con modificaciones novedosas. (63,66,115,149,(166)(167)(168)(169)(170)(171)(172) Otro método de síntesis de sultamas utilizando ciclización promovida por bases fue desarrollada por Proudfoot y colaboradores (173) quienes utilizaron sacarinas sustituidas como precursores que fueron sometidas a expansión de anillo. La síntesis de los derivados de sacarina comienza con la introducción de un grupo dimetilcarbamoil en posición 2 de la N-metilbencensulfonamida (152).…”