Tenidap

Tenidap, a non-steroidal anti-inflammatory drug, is a selective COX-1 inhibitor, with IC50 values of 0.03 µM and 1.2 µM for COX-1 and COX-2, respectively. Tenidap has anti-inflammatory and antirheumatic properties[1][2].

Tenidap is a member of indoles, a member of ureas, a member of thiophenes and an organochlorine compound. It has a role as a non-steroidal anti-inflammatory drug and an EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor.

Chloroaldehyde hydrate, water, anhydrous sodium sulfate and p-chloroaniline are mixed, soluble in 3mol/L. Hydrochloric acid and 20% hydroxylamine hydrochloride solution, gradually heated to boiling. After cooling to room temperature, the solid was collected by filtration and recrystallized from absolute ethanol to obtain compound (I) with a yield of 95.5%. At 50°C, compound (I) slowly dissolves in concentrated sulfuric acid, maintaining the temperature at 60-70°C. Raise to 80 ℃ to keep warm. Cool to 30°C and pour into water to hydrolyze. The solid was collected by filtration, washed with cold water until neutral, and dried at 100°C to obtain compound (II) with a yield of 93.6%. Compound (II), potassium hydroxide, polyethylene glycol 400 and 80% hydrazine hydrate are mixed, slowly raised to 110°C, and kept warm. Distill the water, raise to 180 ℃, keep warm until no nitrogen is released. Cool to room temperature, adjust to Ph value 1 with 10% hydrochloric acid, and extract with ether. The extract was dried, filtered, concentrated, and dried in the air to obtain compound (III) in 63.8% yield. Compound (III), toluene and pyridine were mixed, and methyl chloroformate was added dropwise at room temperature. Add it and stir. Nitrogen was expelled from the remaining methyl chloroformate, and toluene was recovered under reduced pressure. The residue was washed with water and filtered to obtain a solid. Add methanol, vent ammonia gas, and react at 30～38℃. Methanol was distilled off under reduced pressure and recrystallized by adding ethanol to obtain compound (IV) as white crystals with a yield of 79.8%. Compound (IV), dimethylformamide and N-methylmorpholine were mixed, and a solution of thienyl chloride in dimethylformamide was slowly added dropwise. Add it and stir. Concentrate, wash the residue with water, and then wash with 5% sodium bicarbonate solution. Filter and recrystallize with acetone to obtain white crystalline tenidap, yield 85%, melting point 223-224°C (decomposition).

Anti-inflammatory (osteoarthritis and rheumatoid arthritis).NSAID that preferentially inhibits COX-1 (IC 50 values are < 0.03, 1.2 and > 30 μ M for COX-1, COX-2 and 5-lipoxygenase respectively). Inhibits formation of pro-inflammatory arachidonic acid metabolites in isolated human peripheral polymorphonuclear leukocytes. Opener of inward rectifying hK IR 2.3 channel (EC 50 = 402 nM).

Molecular Weight:320.8
XLogP3:3.8
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:320.0022410
Monoisotopic Mass:320.0022410
Topological Polar Surface Area:114
Heavy Atom Count:21
Complexity:450
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes