870. Atrasentan

Nomenclature

CAS number: 173937-91-2
(2R,3R,4S)-4-(1,3-Benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-methoxyphenyl)-3-pyrrolidinecarboxylic acid; trans,trans-2-(4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)-1-[[(dibutylamino)carbonyl]methyl]pyrrolidine-3-carboxylic acid; (+)-A-127722.
C29H38N2O6; mol wt 510.62.
C 68.21%, H 7.50%, N 5.49%, O 18.80%.

Description and references

Endothelin (ET) antagonist with selectivity for the ETA subtype. Prepn: M. Winn et al., WO 9606905; eidem, US 5767144 (1996, 1998 both to Abbott); eidem, J. Med. Chem. 39, 1039 (1996). Synthesis: S. J. Wittenberger, M. A. McLaughlin, Tetrahedron Lett. 40, 7175 (1999). HPLC determn in pharmaceutical formulations: J. A. Morley et al., J. Pharm. Biomed. Anal. 19, 777 (1999); in plasma: P. D. Bryan et al., Biomed. Chromatogr. 15, 525 (2001). In vitro inhibition of ovarian carcinoma: D. Salani et al., Clin. Sci. 103, Suppl. 48, 318S (2002). Clinical pharmacokinetics and dynamics: M. C. Verhaar et al., Br. J. Clin. Pharmacol. 49, 562 (2000); and safety: M. A. Carducci et al., J. Clin. Oncol. 20, 2171 (2002). Clinical evaluation in prostate cancer: M. Fisher, Clin. Prostate Cancer 1, 79 (2002). Review of clinical development in prostate cancer: A. Jimeno, M. Carducci, Expert Opin. Invest. Drugs 13, 1631-1640 (2004).

Chemical structure

Properties

mp 122-124°.

Derivative

Hydrochloride.

Nomenclature

CAS number: 195733-43-8
ABT-627; A-147627.1; Xinlay (Abbott).
C29H38N2O6.HCl; mol wt 547.08.
C 63.67%, H 7.19%, N 5.12%, O 17.55%, Cl 6.48%.

Properties

Crystalline, non-hygroscopic solid. Readily sol in water.

Therapeutic Category

Antineoplastic.

Keywords

Antineoplastic; Endothelin Receptor Antagonist