219
Diarylheterocycles with a Central 6-Membered Pyridazinone Ring Pyridazinone
ring-based designed compounds are excellent COX 2 inhibitors (Li et al. 2003)
(Fig. 9.22).
COX 2 IC 50 –0.08 μM; COX 1 IC 50 > 10 μM; COX 2 IC 50 –0.02 μM; COX 1 IC 50
> 10 μM.
Central 6-Membered Pyranone Ring in Diarylheterocycles Central 6-membered
lactone on tricyclic class serves as an excellent template for COX 2 inhibitors. Other
designed 3,4-diphenylpyran-2-ones with a central six-membered lactone ring has an
IC 50 of 3 nM for COX 2 and 386 μM for COX 1 (a) (Rao et al. 2003). But this compound has lesser anti-inflammatory activity, hence a new compound was designed
with increased anti-inflammatory potential in vitro and in vivo (COX 2 IC 50 = 0.10
μM; COX 1 IC 50 = 288 μM) (b) (Rao et al. 2003). Regioisomeric molecule with
3,4,6-triphenylpyrones substituents were designed and exhibited increased potency
(COX 2 IC 50 = 0.02 μM; COX 1 IC 50 > 100 μM) (c) (Rao et al. 2004). This compound is more potent than celecoxib and rofecoxib (Fig. 9.23).
N
N
N
N
O
O
O
Me
Me
SO 2 Me
SO 2 Me
Fig. 9.22 Chemical
structure of COX inhibitors
with a central 6-membered
pyridazinone ring
O
a
b
c
F
SO 2 Me
SO 2 Me
SO 2 Me
O
O
O
O
O
EtS
EtO
MeO
Fig. 9.23 Chemical structure of COX inhibitors with a central 6-membered pyranone ring
9 Anti-inflammatory Molecules: Enzyme Inhibitors