Ritonavir

Names

[ Name ]:
Ritonavir

[Synonym ]:
[5S-(5R*,8R*,10R*,11R*)]-10-Hydroxy-2-methyl-5-(1-methylethyl)-1-[2-(1-methylethyl)-4-thiazolyl]-3,6-dioxo-8,11-bis(phenylmethyl)-2,4,7,12-tetraazatridecan-13-oic acid 5-thiazolylmethyl ester
Norvir
Ritonavir
EINECS 208-127-9
N-[(2S,4S,5S)-4-Hydroxy-1,6-diphenyl-5-{[(1,3-thiazol-5-ylmethoxy)carbonyl]amino}hexan-2-yl]-N-{[(2-isopropyl-1,3-thiazol-4-yl)methyl](methyl)carbamoyl}-L-valinamide
Ritonavi
Carbamic acid, N-[(1S,2S,4S)-2-hydroxy-4-[[(2S)-3-methyl-2-[[[methyl[[2-(1-methylethyl)-4-thiazolyl]methyl]amino]carbonyl]amino]-1-oxobutyl]amino]-5-phenyl-1-(phenylmethyl)pentyl]-, 5-thiazolylmethyl ester
ABT-538
(1E,2S)-N-[(2S,4S,5S)-4-Hydroxy-5-{(E)-[hydroxy(1,3-thiazol-5-ylmethoxy)methylene]amino}-1,6-diphenyl-2-hexanyl]-2-[(E)-(hydroxy{[(2-isopropyl-1,3-thiazol-4-yl)methyl](methyl)amino}methylene)amino]-3-methylbutanimidic acid
1,3-Thiazol-5-ylmethyl-[(1S,2S,4S)-1-benzyl-2-hydroxy-4-({(2S)-3-methyl-2-[(methyl{[2-(1-methylethyl)-1,3-thiazol-4-yl]methyl}carbamoyl)amino]butanoyl}amino)-5-phenylpentyl]carbamat
N-[(1S,3S,4S)-1-benzyl-3-hydroxy-5-phenyl-4-{[(1,3-thiazol-5-ylmethoxy)carbonyl]amino}pentyl]-N-(methyl{[2-(1-methylethyl)-1,3-thiazol-4-yl]methyl}carbamoyl)-L-valinamide
[(1S,2S,4S)-1-benzyl-2-hydroxy-4-({(2S)-3-méthyl-2-[(méthyl{[2-(1-méthyléthyl)-1,3-thiazol-4-yl]méthyl}carbamoyl)amino]butanoyl}amino)-5-phénylpentyl]carbamate de 1,3-thiazol-5-ylméthyle
Butanimidic acid, N-[(1S,3S,4S)-3-hydroxy-4-[[(1E)-hydroxy(5-thiazolylmethoxy)methylene]amino]-5-phenyl-1-(phenylmethyl)pentyl]-2-[[(1E)-hydroxy[methyl[[2-(1-methylethyl)-4-thiazolyl]methyl]amino]methylene]amino]-3-methyl-, (1E,2S)-
N-[(2S,4S,5S)-4-Hydroxy-1,6-diphenyl-5-{[(1,3-thiazol-5-ylmethoxy)carbonyl]amino}-2-hexanyl]-N-{[(2-isopropyl-1,3-thiazol-4-yl)methyl](methyl)carbamoyl}-L-valinamide
carbamic acid, [(1S,2S,4S)-2-hydroxy-4-[[(2S)-3-methyl-2-[[[methyl[[2-(1-methylethyl)-4-thiazolyl]methyl]amino]carbonyl]amino]-1-oxobutyl]amino]-5-phenyl-1-(phenylmethyl)pentyl]-, 5-thiazolylmethyl es
N-[(2S,4S,5S)-4-hydroxy-1,6-diphenyl-5-{[(1,3-thiazol-5-ylmethoxy)carbonyl]amino}hexan-2-yl]-N2-(methyl{[2-(propan-2-yl)-1,3-thiazol-4-yl]methyl}carbamoyl)-L-valinamide
Liponavir Core
1,3-thiazol-5-ylmethyl [(1S,2S,4S)-1-benzyl-2-hydroxy-4-({(2S)-3-methyl-2-[(methyl{[2-(1-methylethyl)-1,3-thiazol-4-yl]methyl}carbamoyl)amino]butanoyl}amino)-5-phenylpentyl]carbamate
A-84538 ABT-538 Abbott 84538
Norvi
(2S,3S,5S)-5-[N-[N-[[N-methyl-N-[(2-isopropyl-4-thiazolyl)methyl]amino]carbonyl]valinyl]amino]-2-[N-[(5-thiazolyl)methoxycarbonyl]amino]-1,6-diphenyl-3-hydroxyhexane
RITONA
MFCD04115732
carbamic acid, [(1S,2S,4S)-2-hydroxy-4-[[(2S)-3-methyl-2-[[[methyl[[2-(1-methylethyl)-4-thiazolyl]methyl]amino]carbonyl]amino]-1-oxobutyl]amino]-5-phenyl-1-(phenylmethyl)pentyl]-, 5-thiazolylmethyl ester

Biological Activity

[Description]:

Ritonavir is an inhibitor of HIV protease used to treat HIV infection and AIDS.

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> HIV Protease

Signaling Pathways >> Anti-infection >> HIV

Research Areas >> Infection

[In Vitro]

Ritonavir is an inhibitor of CYP3A4 mediated testosterone 6β-hydroxylation with mean Ki of 19 nM and also inhibits tolbutamide hydroxylation with IC50 of 4.2 μM[1]. Ritonavir is found to be a potent inhibitor of CYP3A-mediated biotransformations (nifedipine oxidation with IC50 of 0.07 mM, 17alpha-ethynylestradiol 2-hydroxylation with IC50 of 2 mM; terfenadine hydroxylation with IC50 of 0.14 mM). Ritonavir is also an inhibitor of the reactions mediated by CYP2D6 (IC50=2.5 mM) and CYP2C9/10 (IC50=8.0 mM)[2]. Ritonavir results in an increase in cell viability in uninfected human PBMC cultures. Ritonavir markedly decreases the susceptibility of PBMCs to apoptosis correlated with lower levels of caspase-1 expression, decreases in annexin V staining, and reduces caspase-3 activity in uninfected human PBMC cultures. Ritonavir inhibits induction of tumor necrosis factor (TNF) production by PBMCs and monocytes in a time- and dose-dependent manner at nontoxic concentrations[3]. Ritonavir inhibits p-glycoprotein-mediated extrusion of saquinavir with an IC50 of 0.2 μM, indicating a high affinity of ritonavir for p-glycoprotein[4]. Ritonavir inhibits human liver microsomal metabolism of ABT-378 potently with Ki of 13 nM. Ritonavir combined with ABT-378 (at 3:1 and 29:1 ratios) inhibits CYP3A (IC50=1.1 and 4.6 μM), albeit less potently than Ritonavir (IC50=0.14 μM)[5].

[References]

[1]. Eagling VA, et al. Differential inhibition of cytochrome P450 isoforms by the protease inhibitors, ritonavir, saquinavir and indinavir. Br J Clin Pharmacol. 1997 Aug;44(2):190-4.

[2]. Kumar GN, et al. Cytochrome P450-mediated metabolism of the HIV-1 protease inhibitor ritonavir (ABT-538) in human liver microsomes. J Pharmacol Exp Ther. 1996 Apr;277(1):423-31.

[3]. Weichold FF, et al. HIV-1 protease inhibitor ritonavir modulates susceptibility to apoptosis of uninfected T cells. J Hum Virol. 1999 Sep-Oct;2(5):261-9.

[4]. Drewe J, et al. HIV protease inhibitor ritonavir: a more potent inhibitor of P-glycoprotein than the cyclosporine analog SDZ PSC 833. Biochem Pharmacol. 1999 May 15;57(10):1147-52.

[5]. Kumar GN, et al. Potent inhibition of the cytochrome P-450 3A-mediated human liver microsomal metabolism of a novel HIV protease inhibitor by ritonavir: A positive drug-drug interaction. Drug Metab Dispos. 1999 Aug;27(8):902-8.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
947.0±65.0 °C at 760 mmHg

[ Melting Point ]:
120-122°C

[ Molecular Formula ]:
C₃₇H₄₈N₆O₅S₂

[ Molecular Weight ]:
720.944

[ Flash Point ]:
526.6±34.3 °C

[ Exact Mass ]:
720.312744

[ PSA ]:
202.26000

[ LogP ]:
5.28

[ Vapour Pressure ]:
0.0±0.3 mmHg at 25°C

[ Index of Refraction ]:
1.600

[ Storage condition ]:
-20°C Freezer

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302 + H312 + H332

[ Precautionary Statements ]:
P261-P280-P301 + P312 + P330

[ Hazard Codes ]:
Xi

[ Risk Phrases ]:
R36/38:Irritating to eyes and skin .

[ Safety Phrases ]:
26-37/39

[ RIDADR ]:
NONH for all modes of transport

[ RTECS ]:
XA5310000

[ HS Code ]:
2942000000

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2942000000

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Related Compounds

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