Synthesis, anti-inflammatory, analgesic and kinase (CDK-1, CDK-5 and GSK-3) inhibition activity evaluation of benzimidazole/benzoxazole derivatives and some Schiff's bases.
A series of N-(acridin-9-yl)-4-(benzo[d]imidazol/oxazol-2-yl) benzamides has been synthesized by the condensation of 9-aminoacridine derivatives with benzimidazole or benzoxazole derivatives. Condensation of 2-hydroxy naphthaldehyde with functionalized diamines leads to the formation of Schiff's bases and not imidazole derivatives. All these compounds were characterized by correct FT-IR, (1)H NMR, MS and elemental analyses. These compounds were screened for anti-inflammatory, analgesic and kinase (CDK-1, CDK-5 and GSK-3) inhibition activities. Compounds 11 and 7e(f) showed good anti-inflammatory (35.8% at 50 mg/kg po) activity and good analgesic activity (60% at 50 mg/kg po), respectively. Compound 3b showed significant in vitro activity against CDK-5 (IC(50)=4.6 microM) and CDK-1(IC(50)=7.4 microM) and compound 3a showed moderate CDK-5 inhibitory activity (IC(50)=7.5 microM). The other compounds showed moderate anti-inflammatory and analgesic activities.
Department of Chemistry, Indian Institute of Technology Roorkee (IIT R), Roorkee-247 667, UA, India. sondifcy@iitr.ernet.in
Sham M
SM
Sondhi
Nirupma
N
Singh
Ashok
A
Kumar
Olivier
O
Lozach
Laurent
L
Meijer
D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016203:CDC2 Protein Kinase / Q000187:drug effects; D051360:Cyclin-Dependent Kinase 5 / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000187:drug effects; D051379:Mice; D011494:Protein Kinases / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012545:Schiff Bases / Q000737:chemistry; D013329:Structure-Activity Relationship
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001562:Benzimidazoles; D001583:Benzoxazoles; D012545:Schiff Bases; C031000:benzimidazole; D011494:Protein Kinases; D051360:Cyclin-Dependent Kinase 5; D016203:CDC2 Protein Kinase; D038362:Glycogen Synthase Kinase 3