2877. Delavirdine

Nomenclature

CAS number: 136817-59-9
1-[3-[(1-Methylethyl)amino]-2-pyridinyl]-4-[[5-[(methylsulfonyl)amino]-1H-indol-2-yl]carbonyl]piperazine; 1-(5-methanesulfonamido-1H-indol-2-ylcarbonyl)-4-[3-(1-methylethylamino)pyridinyl]piperazine; 1-[3-(isopropylamino)-2-pyridyl]-4-[(5-methanesulfonamidoindol-2-yl)carbonyl]piperazine; U-90152.
C22H28N6O3S; mol wt 456.56.
C 57.88%, H 6.18%, N 18.41%, O 10.51%, S 7.02%.

Description and references

Bisheteroarylpiperazine non-nucleoside reverse transcriptase inhibitor (NNRTI). Prepn: D. L. Romero et al., WO 9109849; J. R. Palmer et al., US 5563142 (1991, 1996 both to Upjohn). Structure-activity studies: D. L. Romero et al., J. Med. Chem. 36, 1505 (1993). In vitro activity vs HIV-1: T. J. Dueweke et al., Antimicrob. Agents Chemother. 37, 1127 (1993); P. J. Pagano, K.-T. Chong, J. Infect. Dis. 171, 61 (1995). Enzyme kinetic studies: I. W. Althaus et al., Biochem. Pharmacol. 47, 2017 (1994). NMR characterization of crystalline forms: P. Gao, Pharm. Res. 15, 1425 (1998). HPLC determn in plasma: C.-L. Cheng et al., J. Chromatogr. B 769, 297 (2002). Review of discovery and development: W. J. Adams et al., in Pharm. Biotechnol., R. T. Borchardt et al., Eds. (Plenum Press, New York, 1998) pp 285-312; of clinical use in HIV infection: L. J. Scott, C. M. Perry, Drugs 60, 1411-1444 (2000).

Chemical structure

Properties

Crystals from ethyl acetate + hexane, mp 226-228°. Aqueous soly at 23° (μg/ml): 2942 (pH 1.0); 295 (pH 2.0); 0.81 (pH 7.4). pKa1 4.56. pKa2 8.9. Log P (n-octanol/water): 2.84.

Derivative

Methanesulfonate.

Nomenclature

CAS number: 147221-93-0
Delavirdine mesylate; U-90152S; Rescriptor (Pharmacia & Upjohn).
C22H28N6O3S.CH3SO3H; mol wt 552.67.
C 49.98%, H 5.84%, N 15.21%, O 17.37%, S 11.60%.

Therapeutic Category

Antiretroviral.

Keywords

Reverse Transcriptase Inhibitor; Antiretroviral; Reverse Transcriptase Inhibitors; Nonnucleosides