Synthesis and characterization of 3-ketohexadecanoic acid-1-14-C, DL-3-hydroxyhexadecanoic acid-1-14-C, and trans-2-hexadecenoic acid-1-14-C

The chemical synthesis and characterization of three intermediates in the Beta oxidation of palmitic acid-1-(14)C by rat liver mitochondria, namely, 3-ketohexadecanoic acid-1-(14)C, DL-3-hydroxyhexadecanoic acid-1-(14)C, and trans-2-hexadecenoic acid-1-(14)C, are described.     

Aromatic amide derivatives of 5,6-dimethoxy-2,3-dihydro-1H-inden(-1-yl)acetic acid as anti-inflammatory agents free of ulcerogenic liability

Amide derivatives of 5,6-dimethoxy-2,3-dihydro-1H-inden(-1-yl)acetic acid were synthesized and evaluated for their anti-inflammatory and analgesic activity. Few selected compounds were also screened for their antipyretic, anti-arthritic, and ulcerogenic potential. Most of the compounds exhibited good activity profile and were free of gastrointestinal toxicity of common NSAIDs. However these compounds failed to decrease secondary lesions of adjuvant induced arthritis and also did not inhibit TNF- in lipopolysaccharide induced pyresis.     

Synthesis and cyclooxygenase inhibition of various (aryl-1,2,3-triazole-1-yl)-methanesulfonylphenyl derivatives

A series of 1,4- and 1,5-diaryl substituted 1,2,3-triazoles was synthesized by either Cu(I)-catalyzed or Ru(II)-catalyzed 1,3-dipolar cycloaddition reactions between 1-azido-4-methane-sulfonylbenzene 9 and a panel of various para-substituted phenyl acetylenes (4-H, 4-Me, 4-OMe, 4-NMe₂, 4-Cl, 4-F). All compounds were used in in vitro cyclooxygenase (COX) assays to determine the combined electronic and steric effects upon COX-1 and COX-2 inhibitory potency and selectivity. Structure-activity relationship studies showed that compounds having a vicinal diaryl substitution pattern showed more potent COX-2 inhibition (IC₅₀ = 0.03–0.36 μM) compared to their corresponding 1,3-diaryl-substituted counterparts (IC₅₀ = 0.15 to >10.0 μM). In both series, compounds possessing an electron-withdrawing group (Cl and F) at the para-position of one of the aryl rings displayed higher COX-2 inhibition potency and selectivity as determined for compounds containing electron-donating groups (Me, OMe, NMe₂). The obtained data show, that the central carbocyclic or heterocyclic ring system as found in many COX-2 inhibitors can be replaced by a central 1,2,3-triazole unit without losing COX-2 inhibition potency and selectivity. The high COX-2 inhibition potency of some 1,2,3-triazoles having a vicinal diaryl substitution pattern along with their ease in synthesis through versatile Ru(II)-catalyzed click chemistry make this class of compounds interesting candidates for further design and synthesis of highly selective and potent COX-2 inhibitors.