喷昔洛韦, Penciclovir

Penciclovir is an antiviral agent and acyclic guanine derivative. Penciclovir has proven efficient in the treatment of Herpes Simplex type 1 and 2 (HSV1 and HSV2) infection. Penciclovir is transformed by the virus into an active derivative able to block the deoxyguanosine triphosphate substrate binding site of the HSV polymerase.

Purine acyclic nucleoside analogue. Shows antiviral activity. Induces apoptosis without causing genotoxicity.

Penciclovir is a guanosine analog with antiviral activity. It has activity against multiple laboratory and clinical isolate strains of herpes simplex virus 1 (HSV-1), HSV-2, and varicella zoster virus (VZV) in a plaque reduction assay (IC50s = 0.4-3.1 μg/ml). Penciclovir inhibits HSV-1 and HSV-2 replication (IC99s = 0.4 and 0.7 μg/ml, respectively) and DNA synthesis (IC50 = 0.04 μg/ml) in MRC-5 cells. In vivo, topical and systemic administration of penciclovir reduces the severity of skin lesions caused by HSV-1 in guinea pigs and mice. It also prevents development of HSV-2-induced genital lesions in guinea pigs infected intravaginally.

Penciclovir, also known as BRL-39123, is a guanosine analogue antiviral drug used for the treatment of various herpesvirus infections. It is a nucleoside analogue which exhibits low toxicity and good selectivity. Because penciclovir is absorbed poorly when given orally it is used more as a topical treatment, and is the active ingredient in the cold sore medications Denavir, Vectavir and Fenivir.

Title: Penciclovir

CAS Registry Number: 39809-25-1

CAS Name: 2-Amino-1,9-dihydro-9-[4-hydroxy-3-(hydroxymethyl)butyl]-6H-purin-6-one

Additional Names: 9-[4-hydroxy-3-(hydroxymethyl)but-1-yl]guanine; PCV

Manufacturers' Codes: BRL-39123

Trademarks: Denavir (SKB); Vectavir (SKB)

Molecular Formula: C10H15N5O3

Molecular Weight: 253.26

Percent Composition: C 47.42%, H 5.97%, N 27.65%, O 18.95%

Literature References: Carba analog of ganciclovir, q.v., active against several herpes viruses. Prepn: U. K. Pandit et al., Synth. Commun. 2, 345 (1972); R. L. Jarvest, M. R. Harnden, US 5075445 (1991 to Beecham). Synthesis: M. R. Harnden et al., J. Med. Chem. 30, 1636 (1987); J. Hannah et al., J. Heterocycl. Chem. 26, 1261 (1989). Crystal and molecular structures: M. R. Harnden et al., Nucleosides Nucleotides 9, 499 (1990). In vitro activity of enantiomers in comparison with acyclovir, q.v.: G. Abele et al., Antiviral Chem. Chemother. 2, 163 (1991); against herpes simplex viruses: A. Weinberg et al., Antimicrob. Agents Chemother. 36, 2037 (1992). Clinical pharmacokinetics: S. E. Fowles et al., Eur. J. Clin. Pharmacol. 43, 513 (1992). HPLC determn in plasma and urine: J. R. McMeekin et al., Anal. Proc. 29, 178 (1992). Review of development and antiviral activity: M. R. Harnden, Drugs Future 14, 347-358 (1989).

Properties: White crystalline solid from water, (monohydrate), mp 275-277°; also reported as colorless matted needles, mp 272-275°. uv max (in water): 253 nm (e 11500). uv max (aq 0.01N NaOH): 215, 268 nm (e 18140, 10710). Sol in water (20°): 1.7 mg/ml, pH 7.

Melting point: mp 275-277°; mp 272-275°

Absorption maximum: uv max (in water): 253 nm (e 11500); uv max (aq 0.01N NaOH): 215, 268 nm (e 18140, 10710)

Derivative Type: Sodium salt

Manufacturers' Codes: BRL-39123A

Properties: Occurs as monohydrate, stable crystalline solid. Sol in water (20°): >200 mg/ml. 30 mg/ml soln has pH 11.

Therap-Cat: Antiviral.

Keywords: Antiviral; Purines/Pyrimidinones.