TG6-10-1 Chemical Properties

Boiling point:

631.8±55.0 °C(Predicted)

Density 

1.24±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMF: 50 mg/ml; DMSO: 30 mg/ml; Ethanol: 5 mg/ml

form 

A crystalline solid

pka

13.84±0.46(Predicted)

color 

White to off-white

TG6-10-1 Usage And Synthesis

Uses

TG6-10-1 is an EP2 antagonist, shows low-nanomolar antagonist activity against only EP2, >300-fold selectivity over human EP3, EP4, and IP receptors, 100-fold selectivity over EP1 receptors[1].

Biological Activity

Primary Target
EP2', 'Reversible: yes

Synthesis

General procedure for the synthesis of (E)-N-(2-(2-(2-(trifluoromethyl)-1H-indol-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide (15d): Compound 13b (480 mg, 2.1 mmol) was dissolved in dichloromethane (10 mL) at room temperature, and sequentially added (E)-3-(3,4,5-trimethoxyphenyl ) acrylic acid (14a) (504 mg, 2.1 mmol), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDCI) (523 mg, 2.73 mmol) and N,N-dimethylaminopyridine (DMAP) (10 mg). The reaction mixture was stirred at room temperature for 8 hours. Upon completion of the reaction, the reaction was quenched with water (10 mL) and the product was extracted with ethyl acetate (20 mL × 3). The organic phases were combined and washed sequentially with 1% HCl (10 mL), saturated NaHCO3 solution (10 mL), water (20 mL), and brine (20 mL), then dried with anhydrous Na2SO4. After concentration under reduced pressure, the crude product was purified by silica gel column chromatography with the eluent being a hexane solution of 0-35% ethyl acetate to give the target product 15d (700 mg, 74% yield). The 1H NMR (CDCl3) data of product 15d: δ 7.59 (d, J = 8 Hz, 1H), 7.54 (d, J = 8.4 Hz, 1H), 7.50 (d, J = 15.2 Hz, 1H), 7.27 (q, J = 7.2 Hz, 1H), 7.1 (t, J = 7.2 Hz, 1H), 6.89 (s, 1H), 6.63 (s, 2H), 6.4 (t, J = 6 Hz, 1H), 6.25 (d, J = 15.2 Hz, 1H), 4.4 (t, J = 6.4 Hz, 1H), 3.8 (s, 3H), 3.76 (s, 6H), 3.69 (q, J = 6.4 Hz, 2H). lCMS (ESI) analysis: λ254 nm, MS purity > 95%; m /z 449 [M + H]+. Calculated elemental analysis (C23H23F3N2O4): C, 61.60; H, 5.17; N, 6.25; measured values: C, 61.34; H, 5.10; N, 6.16.

in vivo

References

[1] Jiang J, et al. Inhibition of the prostaglandin receptor EP2 following status epilepticus reduces delayed mortality and brain inflammation. Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3591-3596. DOI:10.1073/pnas.1218498110
[2] Kang X, et al. Cyclooxygenase-2 contributes to oxidopamine-mediated neuronal inflammation and injury via the prostaglandin E2 receptor EP2 subtype. Sci Rep. 2017 Aug 25;7(1):9459. DOI:10.1038/s41598-017-09528-z

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