10267. Rilpivirine

Nomenclature

CAS number: 500287-72-9
4-[[4-[[4-[(1E)-2-Cyanoethenyl]-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile; R-278474; TMC-278.
C22H18N6; mol wt 366.42.
C 72.11%, H 4.95%, N 22.94%.

Description and references

Diarylpyrimidine (DAPY) nonnucleoside reverse transcriptase inhibitor (NNRTI). Prepn: J. E. G. Guillemont et al., WO 03016306; eidem, US 7125879 (2003, 2006 both to Janssen). Crystal structure in complexes with wild-type and mutant HIV-1 reverse transcriptase: K. Das et al., Proc. Natl. Acad. Sci. USA 105, 1466 (2008) DOI PubMed; and 2D-IR spectroscopy: C. Fang et al., ibid., 1472 DOI PubMed. Clinical pharmacokinetics and antiviral activity: F. Goebel et al., AIDS 20, 1721 (2006) DOI PubMed. Review of discovery and development: P. A. J. Janssen et al., J. Med. Chem. 48, 1901-1909 (2005) DOI PubMed.

Chemical structure

Properties

Slightly yellow crystalline powder, mp 242°. pKa 5.6. log P (pH 8): 4.8. Readily sol in DMSO (>50 mg/ml); moderately sol in PEG 400 (40 mg/ml). Practically insol in water (20 ng/ml, pH 7.0).

Therapeutic Category

Antiretroviral.

Keywords

Antiretroviral; Reverse Transcriptase Inhibitors; Nonnucleosides; Reverse Transcriptase Inhibitor