2827. Darunavir

Nomenclature

CAS number: 206361-99-1
N-[(1S,2R)-3-[[(4-Aminophenyl)sulfonyl] (2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester; (1S,2R,3′R,3′aS,6′aR)-[3′-hexahydrofuro[2,3-b]furanyl-[3-(4-aminobenzenesulfonyl)isobutylamino]-1-benzyl-2-hydroxypropyl]carbamate; TMC-114; UIC-94017.
C27H37N3O7S; mol wt 547.66.
C 59.21%, H 6.81%, N 7.67%, O 20.45%, S 5.85%.

Description and references

Peptidomimetic HIV-1 protease inhibitor. Prepn: A. K. Ghosh et al., Bioorg. Med. Chem. Lett. 8, 687 (1998); idem et al., J. Org. Chem. 69, 7822 (2004). Prepn of solvated crystalline forms: H. W. P. Vermeersch et al., WO 03106461, eidem, US 050250845 (2003, 2005 both to Tibotec). In vitro activity vs multidrug resistant HIV isolates: Y. Koh et al., Antimicrob. Agents Chemother. 47, 3123 (2003). Crystal structures of complex with protease variants: Y. Tie et al., J. Mol. Biol. 338, 341 (2004). Clinical trial of combination with ritonavir: B. Clotet et al., Lancet 369, 1169 (2007). Reviews: J.-M. Molina, A. Hill, Expert Opin. Pharmacother. 8, 1951-1964 (2007); K. H. S. Busse, S. R. Penzak, Am. J. Health Syst. Pharm. 64, 1593-1602 (2007).

Chemical structure

Properties

White amorphous solid, mp 74° (dec). Sol in DMSO.

Derivative

Monoethanolate.

Nomenclature

CAS number: 635728-49-3
Prezista (Tibotec).
C27H37N3O7S.C2H5OH; mol wt 593.73.
C 58.66%, H 7.30%, N 7.08%, O 21.56%, S 5.40%.

Properties

White to off-white powder. d 1.248. Soly in water (20°): 0.15 mg/ml. Sol in acetone, dicloromethane, ethyl acetate, THF.

Therapeutic Category

Antiretroviral.

Keywords

HIV Protease Inhibitor; Antiretroviral; Protease Inhibitors