Palladium‐mediated synthesis of novel nimesulide derivatives

Abstract

Synthesis of a series of compounds structurally related to the anti-inflammatory agent nimesulide has been accomplished via Pd-catalyzed C-C bond forming reactions. Thus 4-iodo derivative, prepared from nimesulide, participated in Sonogashira (copper-free), Heck and Suzuki coupling reactions to afford the corresponding alkynyl, alkenyl and aryl substituted products. Some of the compounds synthesized were tested for anti-inflammatory activities in vivo.

Nonsteroidal Anti‐inflammatory Drug‐based N‐Allylidene Benzohydrazides and 1‐Acyl‐2‐pyrazolines: Their Synthesis as Potential Cytotoxic Agents In Vitro

“…Thus, a combination of A and an appropriate NSAID in a single molecule is expected to provide a new template E (Figure ) for the design and identification of novel anticancer agents. Prompted by this idea and because of our longstanding interest in the chemical modification of NSAIDs , we became interested in the synthesis and pharmacological evaluation of a library of compounds based on E . Herein, we report in vitro cytotoxic activities of novel 1‐acyl‐2‐pyrazoline derivatives based on E incorporating the structural features of known NSAIDs, for example, mefenamic acid and ibuprofen.…”

“…Thus, a combination of A and an appropriate NSAID in a single molecule is expected to provide a new template E (Figure 2) for the design and identification of novel anticancer agents. Prompted by this idea and because of our longstanding interest in the chemical modification of NSAIDs [13][14][15][16][17][18][19], we became interested in the synthesis and pharmacological evaluation of a library of compounds based on E. Herein, we report in vitro cytotoxic activities of novel 1-acyl-2pyrazoline derivatives based on E incorporating the structural features of known NSAIDs, for example, mefenamic acid and ibuprofen. Because the free carboxylic acid moiety of these NSAIDs are known to be partially responsible for their increased risk of stomach ulcers and gastrointestinal bleeding [20], hence, new compounds were designed by linking the carboxylic acid moiety of mefenamic acid/ibuprofen to the NH group of 2-pyrazoline in the form of an amide bond.…”

Nimesulide Based Novel Glycolamide Esters: Their Design, Synthesis, and Pharmacological Evaluation

“…The design of our target molecules A was based on the structural modifications of nimesulide [14][15][16][17][18][19][20]. We anticipated that combining the structural features of nimesulide and glycolamide esters in a single molecule may afford novel template for the design and synthesis of new anticancer agents.…”

N-{2-[3-(3-Formyl-2-oxoquinolin-1(2H)-yl)prop-1-ynyl]phenyl}acetamide

“…The alkynylation of iodoarenes via C-C bond forming reaction under Pd-Cu catalysis (the Sonogashira coupling) [9] was used in our earlier synthesis [8]. The methodology offered a very convenient, mild and one-step process for the direct coupling of terminal alkynes with iodoarene to provide the desired internal alkynes of medicinal value [10]. We adopted the OPEN ACCESS…”