Novel 3, 3a, 4, 5, 6, 7-Hexahydroindazole and Arylthiazolylpyrazoline derivatives as Anti-inflammatory Agents

• Published in: Archiv der Pharmazie (Weinheim) Vol. 336; no. 12; pp. 551 - 559
• Main Authors: Nasr, Magda N. A., Said, Shehta A.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.12.2003; WILEY‐VCH Verlag; Wiley-VCH
• Subjects: Administration, Oral; Animals; Anti-inflammatory activity; Arylthiazolylpyrazoline; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Carrageenan; Cyclooxygenase Inhibitors - chemical synthesis; Cyclooxygenase Inhibitors - pharmacology; Cyclooxygenase-2-inhibitor; Edema - chemically induced; Edema - drug therapy; Hexahydroindazole; Indazoles - adverse effects; Indazoles - chemical synthesis; Indazoles - pharmacology; Male; Medical sciences; Pharmacology. Drug treatments; Pyrazoles - adverse effects; Pyrazoles - chemical synthesis; Pyrazoles - pharmacology; Rats; Structure-Activity Relationship; Technology, Pharmaceutical; Thiazoles - adverse effects; Thiazoles - chemical synthesis; Thiazoles - pharmacology; Ulcer - chemically induced; Five membered ring; Rat; Nitrogen heterocycle; Toxicity; Cyclooxygenase 2; Thiazole derivatives; Furan derivatives; Selectivity; Cyclooxygenase-2-inhibitor; Thiophene derivatives; Gastroduodenal; Structure activity relation; Arylthiazolylpyrazoline; Bicyclic compound; Pyrazole derivatives; Ulcer; Aromatic compound; Chemical synthesis; Sulfur nitrogen heterocycle; Hexahydroindazole; Enzyme; Rodentia; Benzene derivatives; Oral administration; Enzyme inhibitor; Tricyclic compound; Indazole derivatives; Non steroidal antiinflammatory agent; Vertebrata; Mammalia; Animal; Anti-inflammatory activity; Oxidoreductases
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.200300796

A novel series of 7‐benzylidene‐3, 3a, 4, 5, 6, 7‐hexahydro‐3‐phenyl‐2H‐indazole substituted at the 2‐position were synthesized. The reaction of 2, 6‐bis‐benzylidenecyclohexanone (1) with thiosemicarbazide in the presence of NaOH afforded a mixture of the 3‐H, 3a‐H trans 2 and cis 2a diastereoisomers which have been separated by fractional recrystallization. Interaction of the first intermediate 2 with substituted phenacyl bromides, aromatic aldehydes and chloroacetic acid in presence of a mixture of acetic acid and acetic anhydride, and 2, 3‐dichloroquinoxaline yielded the corresponding 7‐benzylidene‐3, 3a, 4, 5, 6, 7‐hexahydro‐3‐phenyl‐2H‐indazole derivatives substituted at the 2‐position with 4‐aryl‐2‐thiazolyl 3a, b, 5‐arylidene‐4, 5‐dihydro‐4‐oxo‐2‐thiazolyl 4a, b and thiazolo[4, 5‐b]quinoxalin‐2‐yl 5, respectively. Moreover, the other intermediates 3, 5‐diaryl‐1‐thiocarbamoyl‐2‐pyrazolines 7a—d were reacted with the previously‐mentioned reagents and gave the corresponding 3, 5‐diaryl‐1‐(4‐aryl‐2‐thiazolyl)‐2‐pyrazolines 8a—h, 3, 5‐diaryl‐1‐(5‐arylidene‐4, 5‐dihydro‐4‐oxo‐2‐thiazolyl)‐2‐pyrazolines 9a—d and 3, 5‐diaryl‐1‐(thiazolo[4, 5‐b]quinoxalin‐2‐yl)‐2‐pyrazoline derivatives 10a, b, respectively. Some of the newly prepared compounds were subjected to evaluation for their anti‐inflammatory activity. The structures of the new compounds were confirmed by elemental analyses as well as 1H‐NMR, IR, and MS data.