Rilpivirine  (Synonyms: 利匹韦林; R278474; TMC278; DB08864)

Rilpivirine (R278474) is a potent and specific diarylpyrimidine (DAPY) non-nucleoside reverse transcriptase inhibitor (NNRTI). Rilpivirine has high antiviral activity against wild-type HIV (EC₅₀=0.4 nM) and mutant viruses (EC₅₀=0.1-2.0 nM). Rilpivirine has a high genetic barrier to resistance development of HIV^[1][2].

R278474 is active against wild-type HIV-1 (EC₅₀=0.4 nM) and all single and double mutants tested (EC₅₀=0.1-2.0 nM)^[1].
R278474 (10-5000 nM; 30 d) does not observe the sign of wild-type HIV-1 breakthrough at 1 μM within 30 days^[1].
R278474 inhibits 81% of clinical isolates (about 1200 recombinant clinical isolates) at a 50% inhibitory concentration (EC₅₀) less than 1 nM, and inhibits 94% at EC₅₀ less than 10 nM^[1].
TMC278 shows subnanomolar EC₅₀s against wild-type HIV-1 group M isolates (0.07-1.01 nM) and nanomolar EC₅₀s against group O isolates (2.88-8.45 nM) in MT4 T-cells^[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

R278474 (10-160 mg/kg; p.o. for 1 month) does not produce abnormal effects in rat, apart from liver weight increase and species-specific thyroid hypertrophy, both at the higher dose levels^[1].
R278474 (i.v.) exhibits elimination half-life ranges from 4.4 h in rat to 31 h in dog, and exposure (AUC_inf) amounts to 3.1 μg•h/mL (4 mg/kg) in rat, 8.7 μg•h/mL (1.25 mg/kg) in dog, 1.4 μg•h/mL (1.25 mg/ kg) in monkey, and 44•μg h/mL (1.25 mg/kg) in rabbit^[1].
R278474 (p.o.) exhibits half-life ranges between 2.8 h in rat and 39 h in dog, and oral bioavailability of 32% and 31% in rat and dog^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

366.42

C₂₂H₁₈N₆

500287-72-9

固体

Light yellow to yellow

利匹韦林；利吡韦林

Room temperature in continental US; may vary elsewhere.

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• [1]. Janssen PAJ, et, al. In search of a novel anti-HIV drug: multidisciplinary coordination in the discovery of 4-[[4-[[4-[(1E)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]-2- pyrimidinyl]amino]benzonitrile (R278474, rilpivirine). J Med Chem. 2005 Mar 24;48(6):1901-9.  [Content Brief]

  [2]. Azijn H, et, al. TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1. Antimicrob Agents Chemother. 2010 Feb;54(2):718-27.  [Content Brief]