216
9.2.2.5 Synthetic Inhibitors of Cyclooxygenase
Methane Sulphonanilide Inhibitors These are alkylsulphonanilide derivatives and
Nimesulide is the best example under this category. Their structural analogues have
also better inhibitory potential. Nimesulide has IC 50 of 10 μM for COX 1 and 1.9
μM for COX 2 (Leone et al. 2007) (Fig. 9.16).
Diarylheterocycles-Derived Inhibitors Most of the COX 2 inhibitors come under
these groups and DuP-697 is the first member in this group. This compound has a
thiophene 5-membered ring in the tricyclic group and 1,2- diaryl substitution in that
thiophene ring. -SO 2 Me, or a -SO 2 NH 2 group at para position of phenyl ring
increases the inhibitory effect. A para-F- substitution at non-sulphonyl vicinal phenyl ring also increases the activity. Due to long unusual plasma half-life this drug
become clinically unfit and removed. Diphenyl cyclopentenes and cyclopentenone
derivatives of DuP-697 were developed and SC57666 is the first compound in this
category which does not have any gastric complications. -SO 2 NH 2 and -SO 2 Me at
para position lead to another molecule with increased oral bioactivity (Fig. 9.17).
Diarylheterocycles Have Central 5-Membered Pyrazole Ring 1,5-Diarylpyrazole
group of compounds were found to be significant cyclooxygenase inhibitors. In that
Fig. 9.15 Crystal structure
of COX 1 in complex with
celecoxib. (PDB ID 3KK6)
O
Nimesulide
NS- 398
O
NO 2
NO2
NHSO2Me
NHSO2Me
Fig. 9.16 Methanesulphonanilide inhibitors
C.S. Sharanya and M. Haridas
9.2.2.5 Synthetic Inhibitors of Cyclooxygenase
Methane Sulphonanilide Inhibitors These are alkylsulphonanilide derivatives and
Nimesulide is the best example under this category. Their structural analogues have
also better inhibitory potential. Nimesulide has IC 50 of 10 μM for COX 1 and 1.9
μM for COX 2 (Leone et al. 2007) (Fig. 9.16).
Diarylheterocycles-Derived Inhibitors Most of the COX 2 inhibitors come under
these groups and DuP-697 is the first member in this group. This compound has a
thiophene 5-membered ring in the tricyclic group and 1,2- diaryl substitution in that
thiophene ring. -SO 2 Me, or a -SO 2 NH 2 group at para position of phenyl ring
increases the inhibitory effect. A para-F- substitution at non-sulphonyl vicinal phenyl ring also increases the activity. Due to long unusual plasma half-life this drug
become clinically unfit and removed. Diphenyl cyclopentenes and cyclopentenone
derivatives of DuP-697 were developed and SC57666 is the first compound in this
category which does not have any gastric complications. -SO 2 NH 2 and -SO 2 Me at
para position lead to another molecule with increased oral bioactivity (Fig. 9.17).
Diarylheterocycles Have Central 5-Membered Pyrazole Ring 1,5-Diarylpyrazole
group of compounds were found to be significant cyclooxygenase inhibitors. In that
Fig. 9.15 Crystal structure
of COX 1 in complex with
celecoxib. (PDB ID 3KK6)
O
Nimesulide
NS- 398
O
NO 2
NO2
NHSO2Me
NHSO2Me
Fig. 9.16 Methanesulphonanilide inhibitors
C.S. Sharanya and M. Haridas