Stavudine, 司他夫定

2',3'-Didehydro-2',3'-dideoxythymidine

Used as an antiviral. A reverse transcriptase inhibitor.

Stavudine is a nucleoside reverse transcriptase inhibitor analog of thymidine. Stavudine has been recommended to undergo phase-out management due to its long-term, irreversible side-effects.

Stavudine is a first generation nucleoside analogue and reverse transcriptase inhibitor used in combination with other agents in the therapy of human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). Stavudine is an uncommon, but well established cause of clinically apparent acute and chronic liver injury.

Stavudine, also known as zerit or D4T, belongs to the class of organic compounds known as nucleoside and nucleotide analogues. These are analogues of nucleosides and nucleotides. These include phosphonated nucleosides, C-glycosylated nucleoside bases, analogues where the sugar unit is a pyranose, and carbocyclic nucleosides, among others. Stavudine is a drug which is used for the treatment of human immunovirus (hiv) infections. Stavudine exists as a solid, soluble (in water), and a very weakly acidic compound (based on its pKa). Stavudine has been detected in multiple biofluids, such as urine and blood. In humans, stavudine is involved in the stavudine action pathway. Stavudine is a potentially toxic compound.

Title: Stavudine

CAS Registry Number: 3056-17-5

CAS Name: 2',3'-Didehydro-3'-deoxythymidine

Additional Names: 1-(2,3-dideoxy-b-glycero-pent-2-enofuranosyl)thymine; 3'-deoxy-2'-thymidinene; D4T

Manufacturers' Codes: BMY-27857

Trademarks: Zerit (BMS)

Molecular Formula: C10H12N2O4

Molecular Weight: 224.21

Percent Composition: C 53.57%, H 5.39%, N 12.49%, O 28.54%

Literature References: Analog of thymidine, q.v.; reverse transcriptase inhibitor. Prepn: J. P. Horwitz et al., J. Org. Chem. 31, 205 (1966); J. W. Beach et al., ibid. 57, 3887 (1992). Large scale production: J. E. Starrett et al., EP 334368; eidem, US 5130421 (1989, 1992 both to Bristol-Myers). In vitro activity against HIV and toxicology: M. M. Mansuri et al., Antimicrob. Agents Chemother. 34, 637 (1990). Mechanism of action study: H.-T. Ho, M. J. M. Hitchcock, ibid. 33, 844 (1989). Disposition and metabolism: E. M. Cretton et al., ibid. 37, 1816 (1993). Clinical pharmacokinetics: M. N. Dudley et al., J. Infect. Dis. 166, 480 (1992). HPLC determn in plasma and urine: J. S. Janiszewski et al., J. Chromatogr. 577, 151 (1992). Clinical evaluation in AIDS and ARC: M. J. Browne et al., J. Infect. Dis. 167, 21 (1993).

Properties: Colorless, granular solid from ethanol/benzene, mp 165-166° (Horwitz). Also reported as crystals from ethanol-ether, mp 174° (Beach). uv max (water): 266 nm (e 10149). [a]D25 -39.4° (c = 0.701 in water); [a]D20 -46.1° (c = 0.7 in water).

Melting point: mp 165-166° (Horwitz); mp 174° (Beach)

Optical Rotation: [a]D25 -39.4° (c = 0.701 in water); [a]D20 -46.1° (c = 0.7 in water)

Absorption maximum: uv max (water): 266 nm (e 10149)

Therap-Cat: Antiviral.

Keywords: Antiviral; Purines/Pyrimidinones; Reverse Transcriptase Inhibitor.