Synthesis of acridinyl-thiazolino derivatives and their evaluation for anti-inflammatory, analgesic and kinase inhibition activities

Abstract

Variety of N-(4-phenyl-3-(2′,3′,4′(un)substituted phenyl)thiazol-2(3H)-ylidene)-2,4(un)substituted acridin-9-amine (4a–o) and 1-[(2,4-(un)substituted acridin-9-yl)-3-(4-phenyl-3-(2′,3′,4′(un)substituted phenyl)thiazol-2(3H)-ylidene)]isothiourea (5a–h) derivatives have been synthesized by condensation of 4-phenyl-3-(2′,3′,4′(un)substituted phenyl)thiazol-2(3H)-imine (3a–g) with 9-chloro-2,4-(un)substituted acridine (1a–c) and 9-isothiocyanato-2,4-(un)substituted acridine (2a–d), respectively. All these compounds were characterized by correct 1H NMR, FT-IR, MS and elemental analyses. These compounds were screened for anti-inflammatory, analgesic and kinase (CDK1, CDK5 and GSK3) inhibition activities. Some compounds exhibited good anti-inflammatory (25–32%) and potent analgesic (50–75%) activities, at 50 mg/kg p.o. A compound, 4o (R1 = H, R2 = OCH3, R3 = CH3, R4 = CH3, R5 = H) exhibited moderate CDK1 (IC50 = 8.5 μM) inhibition activity.