Oxime ether derivatives, a new class of nonsteroidal antiinflammatory compounds

Abstract

A series of new 2-hydroxyethyl and carboxyalkyl ethers of aromatic oximes was found to possess pronounced antiinflammatory activity in the carrageenan-induced edema test in the rat. The activity was limited mainly to derivatives of p-haloacetophenone oxime and of p-halobenzaldehyde oxime. Nevertheless, the hydroxyethyl and carboxyalkyl groups may be converted into many derivatives with maintenance of activity. Some structure-activity relationships are in contrast to those of the well-known antiinflammatory arylacetic acids. The activity is limited to the E stereoisomers. The hydrochloride of 2-(dimethylamino)ethyl (E)-[[(p-chloro-alpha-methylbenzylidene)-amino[oxy]acetate (36, INN name Cloximate) was chosen for clinical evaluation. The first results agree with the pharmacological prospects.

Anti-inflammatory Properties of New Adamantane Derivatives. Design, Synthesis, and Biological Evaluation

“…The common feature of these compounds is that two lipophilic regions are linked by different bridges. These linkages retain a distance between the adamantane and a phenyl ring ranging from 3 to 4 atoms, structural characteristics that make them potential inhibitors of the enzymes which participate in the inflammatory response [3] . We estimated that the diversity of the functional groups at the linkage site would generate alterations, crucial for the activity parameters, of the molecule, relating for example to electrostatic potential and lipophilicity, and would therefore provide valuable information for the structure activity relationships (SAR) of this category of active molecules.…”

“…Carrageenin type K100 (Agno, Co., Greece), Concanavalin A (Con A, Sigma), Baker's dry yeast (Zanae Co., Greece), and Nystatin (Mycostatin, Serva) were used as phlogistics suspended in saline. [3.3.1.1 3,7 ]decan-2-one oxime (3a) To 1.65 g (0.01 mol) 2-adamantanone oxime (2) in 20 ml of dry DMF was added under nitrogen 1.3 g (0.026 mol) of sodium hydride (60% in paraffin oil). The reaction mixture was stirred at room temp.…”

“…IR ]dec-2-yl)-1,3-diamino-2-propanol (15) A mixture of 3 g (0.02 mol) 2-adamantanone in 50 ml anhydrous benzene and 0.9 g (0.01 mol) of 1,3-diamino-2-propanol in 50 ml anhydrous benzene was refluxed in a Dean-Stark apparatus for 40 h. The solvent was evaporated in reduced pressure and 3.35 g of crude residue [N, N′-bis(tricyclo[3.3.1.1 3,7 ]dec-2-ylidene)-1,3-diamino-2-propanol (14)] was obtained. Subsequently, a solution of 1.77 g (0.005 mol) of the crude double Schiff base (14) in 20 ml methanol was hydrogenated in the presence of 0.5 g 10% Pt-C as a catalyst under a pressure of 45 psi at 28 °C for 42 h. The suspension was filtered to remove the catalyst and the filtrate was evaporated under reduced pressure to afford 1.55 g of the diamine as a viscous oil.…”

“…Adamantane derivatives have been found to interfere with various enzymes and possess a variety of therapeutic activities, as anti-inflammatory [3] , anti-viral [4] , anti-Parkinson [5] , and antimicrobial-anticancer DHFR inhibitors [6][7][8] . In this work, in an attempt to develop safer therapeutic agents controlling inflammation, we have designed and synthesized adamantane-containing compounds as described in Tables 1 A series of adamantane-containing molecules consisting of two lipophilic centers which are linked by different bridges (oxime esters, oxime ethers, amides, and symmetric alcohols), were designed and synthesized as anti-inflammatory agents.…”

Novel cholinesterase modulators and their ability to interact with DNA

“…Pyridinium oximes are used mainly as antidotes for poisoning by organophosphorus compounds [23]. Other oximes can also act as agents with positive effect on the cardiovascular system [24] or for their an anti-inflammatory [25], anti-viral [26,27], antibacterial and antifungal activity [28,29]. The cholinesterase modulators have been only little studied as cytotoxic agents.…”