Thioflosulide (L-745337) (Synonyms: L-745337)

Thioflosulide (L-745337) is a selective cyclooxygenase-2 (COX2) inhibitor, with an IC50 of 2.3 nM, and shows anti-inflammatory activity.

In a rat model of postoperative pain, Thioflosulide (L-745337) (40-80 μg, intrathecal) coadministered with intrathecal morphine (0.5 nmol) increases the withdrawal thresholds in a dose-dependent manner. Adding 80 μg Thioflosulide (L-745337) to 1 nmol morphine produces an antiallodynic effect greater than that of morphine at twice the dose. Thioflosulide (L-745337) (0-30 mg/kg, s.c.) combined with intrathecal morphine results in the same antiallodynic response as morphine alone[1]. Thioflosulide (L-745337) shows anti-inflammatory activity, with the effective-dose of 0.4 mg/kg, and the maximal anti-inflammation dose of 5 mg/kg in arthritic rats[2].

[1]. Kroin JS, et al. Cyclooxygenase-2 inhibition potentiates morphine antinociception at the spinal level in a postoperative pain model. Reg Anesth Pain Med. 2002 Sep-Oct;27(5):451-5. [2]. Turull N, et al. Effect of the COX-2 selective inhibitor l-745,337 on inflammation and organ prostaglandin E2 (PGE2) levels in adjuvant arthritic rats. Inflammation. 2000 Dec;24(6):533-45. [3]. Li CS, et al. Cyclooxygenase-2 inhibitors. Synthesis and pharmacological activities of 5-methanesulfonamido-1-indanone derivatives. J Med Chem. 1995 Dec 8;38(25):4897-905.