393105-53-8

Tiplaxtinin(393105-53-8) is an inhibitor of plasminogen activator inhibitor 1 (PAI-1; IC₅₀ = 2.7 μM for the human enzyme). It inhibits differentiation of human adipocytes when used at a concentration of 5 μM. Tiplaxtinin (5 and 20 mg/kg) reduces tumor growth and microvessel density in a T24 bladder cancer mouse xenograft model. It prevents carotid artery occlusion, increases the time to occlusive thrombosis, and decreases the thrombus size in a rat model of ferric chloride-induced arterial thrombosis when administered at a dose of 1 mg/kg.

Tiplaxtinin inhibits smooth muscle cells (SMC) migration and intimal hyperplasia. A novel therapeutic agent to improve diabetic wound.

ChEBI: Tiplasinin is a member of indole-3-acetic acids. It is a potent and selective PAI-1 inhibitor. Tiplaxtinin demonstrated efficacy in vivo in multiple models of acute arterial thrombosis and has been shown to reduce physiologic PAI-1 activity.

Tiplaxtinin has high oral bioavailability. It is metabolically stable and shows large safety multiples in animal toxicology studies. Tiplaxtinin can be easily synthesized in bulk quantities. This drug also reduces diet-induced obesity in mice.

General procedure for the synthesis of 2-(1-benzyl-5-(4-(trifluoromethoxy)phenyl)-1H-indol-3-yl)-2-oxoacetic acid from compound (CAS: 481630-47-1): ethyl 2-{1-benzyl-5-[4-(trifluoromethoxy)phenyl]-1H-indol-3-yl}-2-oxoacetate (0.463 g, 0.991 mmol) was stirred with potassium hydroxide (0.224 g, 3.99 mmol) in a mixture of tetrahydrofuran (5 mL) and water (5 mL) at 50 °C for 40 min. After completion of the reaction, the mixture was cooled to room temperature, poured into excess water, acidified with 2N hydrochloric acid and extracted with ethyl acetate. The organic phase was washed sequentially with water and brine, dried over anhydrous magnesium sulfate and subsequently concentrated to dryness under reduced pressure. The residue was dried at 80 °C for 15 h to give 2-(1-benzyl-5-(4-(trifluoromethoxy)phenyl)-1H-indol-3-yl)-2-oxoacetic acid as a light yellow solid (0.314 g, 78%) with melting point 169-171 °C. For analysis, the sample was recrystallized from acetonitrile. Mass spectrum (+APCI, [M+H]+) m/z 440; 1H NMR (400 MHz, DMSO-d6): δ 13.8-14.2 (br, 1H), 8.75 (s, 1H), 8.45 (d, 1H, J=1.5 Hz), 7.75-7.8 (m, 2H), 7.7 (d, 1H, J=8.5 Hz), 7.6 ( dd, 1H, J=8.7 Hz), 7.45 (d, 2H, J=8.8 Hz), 7.25-7.35 (m, 5H), 5.65 ppm (s, 2H). Elemental analysis C24H16F3NO4: calculated values: C, 65.61; H, 3.67; N, 3.19. measured values: C, 65.59; H, 3.54; N, 3.17.

Store at -20°C

[1] Patent: US2004/116504, 2004, A1. Location in patent: Page 9
[2] Patent: US2003/125371, 2003, A1