8552. Sitagliptin

Nomenclature

CAS number: 486460-32-6
(3R)-3-Amino-1-[5,6-dihydro-3-(trifluoromethyl)-1,2,4-triazolo[4,3-a]pyrazin-7(8H)-yl]-4-(2,4,5-trifluorophenyl)-1-butanone; (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine; 7-[(3R)-3-Amino-1-oxo-4-(2,4,5-trifluorophenyl)butyl]-5,6,7,8-tetrahydro-3-(trifluoromethyl)-1,2,4-triazolo[4,3-a]pyrazine.
C16H15F6N5O; mol wt 407.31.
C 47.18%, H 3.71%, F 27.99%, N 17.19%, O 3.93%.

Description and references

Selective inhibitor of dipeptidyl peptidase IV (DPP-IV). Prepn: S. D. Edmondson et al., WO 03004498; eidem, US 6699871 (2003, 2004 both to Merck & Co.); and enzyme inhibitory profile: D. Kim et al., J. Med. Chem. 48, 141 (2005). Improved process: K. B. Hansen et al., Org. Process Res. Dev. 9, 634 (2005). Discovery and characterization: N. A. Thornberry, A. E. Weber, Curr. Top. Med. Chem. 7, 557 (2007). HTLC determn in plasma: W. Zeng et al., Rapid Commun. Mass Spectrom. 20, 1169 (2006). Clinical pharmacokinetics and pharmacodynamics: G. A. Herman et al., Clin. Pharmacol. Ther. 78, 675 (2005). Review: C. F. Deacon, Curr. Opin. Investig. Drugs 6, 419-426 (2005). Review of pharmacology and clinical experience: M. Choy, S. Lam, Cardiology Rev. 15, 264-271 (2007).

Chemical structure

Properties

Viscous oil.

Derivative

Monophosphate monohydrate.

Nomenclature

CAS number: 654671-77-9; 654671-78-0 (anhydrous)
Sitagliptin phosphate; MK-0431; Januvia (Merck & Co.).
C16H15F6N5O.H3PO4.H2O; mol wt 523.32.
C 36.72%, H 3.85%, F 21.78%, N 13.38%, O 18.34%, P 5.92%.

Properties

White to off-white, crystalline, nonhygroscopic powder, mp 215-217°. [α]D -74.4° (c = 1.0 in water). Sol in water, DMF; slightly sol in methanol; very slightly sol in ethanol, acetone, acetonitrile. Insol in isopropanol, isopropyl acetate.

Therapeutic Category

Antidiabetic.

Keywords

Antidiabetic; Dipeptidyl Peptidase IV Inhibitor