4945. Indinavir

Nomenclature

CAS number: 150378-17-9
2,3,5-Trideoxy-N-[(1S,2R)-2,3-dihydro-2-hydroxy-1H-inden-1-yl]-5-[(2S)-2-[[(1,1-dimethylethyl)amino]carbonyl]-4-(3-pyridinylmethyl)-1-piperazinyl]-2-(phenylmethyl)-d-erythro-pentonamide; (αR,γS,2S)-α-benzyl-2-(tert-butylcarbamoyl)-γ-hydroxy-N-[(1S,2R)-2-hydroxy-1-indanyl]-4-(3-pyridylmethyl)-1-piperazinevaleramide; N-(2(R)-hydroxy-1(S)-indanyl)-2(R)-(phenylmethyl)-4(S)-hydroxy-5-[1-[4-(3-pyridylmethyl)-2(S)-(N-tert-butylcarbamoyl)piperazinyl]]pentanamide.
C36H47N5O4; mol wt 613.79.
C 70.45%, H 7.72%, N 11.41%, O 10.43%.

Description and references

Member of the novel hydroxyaminopentane amide class of HIV-1 protease inhibitors. Prepn: J. P. Vacca et al., EP 541168; eidem, US 5413999 (1993, 1995 both to Merck & Co.); B. D. Dorsey et al., J. Med. Chem. 37, 3443 (1994). Diastereoselective synthesis: D. Askin et al., Tetrahedron Lett. 35, 673 (1994); P. E. Maligres et al., ibid. 36, 2195 (1995). Crystal structure of HIV-II protease complex: Z. Chen et al., J. Biol. Chem. 269, 26344 (1994). Antiviral activity and pharmacokinetics: J. P. Vacca et al., Proc. Natl. Acad. Sci. USA 91, 4096 (1994). HPLC determn in plasma and urine: E. Woolf et al., J. Chromatogr. A 692, 45 (1995). Metabolism in humans: S. K. Balani et al., Drug Metab. Dispos. 23, 266 (1995). Review of clinical pharmacology and therapeutic efficacy: G. L. Plosker, S. Noble, Drugs 58, 1165-1203 (1999).

Chemical structure

Properties

Occurs as monohydrate, crystals from wet ethyl or isopropyl acetate, loss of water below 100° followed by recrystallization of anhydrous form with mp 153-154°; second anhydrous form, mp 167.5-168°. Soly in water (mg/ml): 0.015 (unbuffered), >1.5 (pH 4.0). [α]D22 +24.1° (c = 0.0133 in chloroform).

Derivative

Sulfate.

Nomenclature

CAS number: 157810-81-6
MK-639; Crixivan (Merck & Co.).
C36H47N5O4.H2SO4; mol wt 711.87.
C 60.74%, H 6.94%, N 9.84%, O 17.98%, S 4.50%.

Properties

White to off-white, hygroscopic, crystalline powder. Occurs as the monoethanolate, crystals from absolute ethanol, softens at 135°, mp 150-153° (dec). Converts to hydrate upon loss of ethanol and exposure to moist air. Sol in water and methanol.

Therapeutic Category

Antiretroviral.

Keywords

HIV Protease Inhibitor; Antiretroviral; Protease Inhibitors