Cyclooxygenase-1-selective inhibitors are attractive candidates for analgesics that do not cause gastric damage. design and in vitro/in vivo evaluation of a benzamide-type cyclooxygenase-1 selective inhibitor.

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Kakuta H, Zheng X, Oda H, Harada S, Sugimoto Y, Sasaki K, Tai A

Cyclooxygenase-1-selective inhibitors are attractive candidates for analgesics that do not cause gastric damage. design and in vitro/in vivo evaluation of a benzamide-type cyclooxygenase-1 selective inhibitor.

J Med Chem. 2008 Apr 24;51(8):2400-11. doi: 10.1021/jm701191z. Epub 2008 Mar 26.

PubMed ID
18363350 [ View in PubMed
]
Abstract

Although cyclooxygenase-1 (COX-1) inhibition is thought to be a major mechanism of gastric damage by nonsteroidal anti-inflammatory drugs (NSAIDs), some COX-1-selective inhibitors exhibit strong analgesic effects without causing gastric damage. However, it is not clear whether their analgesic effects are attributable to COX-1-inhibitory activity or other bioactivities. Here, we report that N-(5-amino-2-pyridinyl)-4-(trifluoromethyl)benzamide ( 18f, TFAP), which has a structure clearly different from those of currently available COX-1-selective inhibitors, is a potent COX-1-selective inhibitor (COX-1 IC 50 = 0.80 +/- 0.05 microM, COX-2 IC 50 = 210 +/- 10 microM). This compound causes little gastric damage in rats even at an oral dose of 300 mg/kg, though it has an analgesic effect at as low a dose as 10 mg/kg. Our results show that COX-1-selective inhibitors can be analgesic agents without causing gastric damage.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
Acetylsalicylic acidProstaglandin G/H synthase 1IC 50 (nM)100000N/AN/ADetails
Acetylsalicylic acidProstaglandin G/H synthase 2IC 50 (nM)710000N/AN/ADetails
IndomethacinProstaglandin G/H synthase 1IC 50 (nM)100N/AN/ADetails
IndomethacinProstaglandin G/H synthase 2IC 50 (nM)11000N/AN/ADetails