5-(2-chloroethyl)-2--deoxyuridine and brivudine

5-(2-chloroethyl)-2--deoxyuridine has been researched along with brivudine* in 7 studies

Other Studies

7 other study(ies) available for 5-(2-chloroethyl)-2--deoxyuridine and brivudine

ArticleYear
Analysis of the thymidine kinase of a herpes simplex virus type 1 isolate that exhibits resistance to (E)-5-(2-bromovinyl)-2'-deoxyuridine.
    The Journal of general virology, 1994, Volume: 75 ( Pt 7)

    The mechanism responsible for the decreased sensitivity of a clinical herpes simplex virus type 1 (HSV-1) isolate, HSV-145, to (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) was examined. Measurements of 50% inhibitory doses of several drugs demonstrated that although HSV-145 was sensitive to phosphonoacetic acid, adenine arabinoside and acyclovir, its sensitivity to BVDU and 5-(2-chloroethyl)-2'-deoxyuridine was significantly less than that normally observed for HSV-1. Analysis of the thymidylate kinase (TMP-K) activity of HSV-145 thymidine kinase (TK) demonstrated a decreased level of TMP-K activity when compared to HSV-1 TK. The TMP-K activity of HSV-145 resembled that observed for HSV-2 and the TK-deficient strain HSV-1 TK-7. When the nucleotide sequence of the HSV-145 TK gene was compared to that of the HSV-1 strains C1(101) and SC16 a single nucleotide substitution (G changed to A at base position 502) was detected which would result in the substitution of threonine at amino acid position 168 for alanine. The substitution is the same as that for the laboratory-derived BVDU-resistant virus HSV-1 SC16B3. Collectively, these studies highlight the importance of amino acid conservation at position 168 of the HSV-1 TK in conferring efficient TMP-K activity and BVDU sensitivity.

    Topics: Acyclovir; Amino Acid Sequence; Antiviral Agents; Base Sequence; Binding Sites; Bromodeoxyuridine; Deoxyuridine; Drug Resistance, Microbial; Herpesvirus 1, Human; Humans; Kinetics; Molecular Sequence Data; Phosphonoacetic Acid; Phosphorylation; Point Mutation; Sequence Analysis, DNA; Thymidine; Thymidine Kinase; Vidarabine

1994
Phosphonoformate and phosphonoacetate derivatives of 5-substituted 2'-deoxyuridines: synthesis and antiviral activity.
    Journal of medicinal chemistry, 1988, Volume: 31, Issue:9

    The synthesis of potential "combined prodrugs" wherein phosphonoformate or phosphonoacetate was attached to the 5'-position of 2'-deoxyuridine, 2'-deoxythymidine, 5-iodo-2'-deoxyuridine (IDU), 5-(2-chloroethyl)-2'-deoxyuridine (CEDU), or 5-(2-bromovinyl)-2'-deoxyuridine (BVDU) or to the 3'-position of CEDU is described. The antiviral activities of these derivatives and of reference compounds were compared in Vero, HEp-2, and primary rabbit kidney cells against herpes simplex virus types 1 and 2 (HSV-1 and -2). The CEDU and BVDU analogues were also evaluated against systemic and intracutaneous HSV-1 infection in mice. The nature of the 5-substituent proved critical for antiviral activity, since only the 5-iodo-, 5-(2-bromovinyl)-, and 5-(2-chloroethyl)-substituted derivatives were inhibitory to the herpesviruses. Furthermore, the type specificity is determined by the nature of the 5-substituent: the IDU analogues were similarly inhibitory to HSV-1 and -2 whereas the CEDU and BVDU analogues inhibited HSV-2 replication only at considerably higher concentrations than HSV-1. In vivo, several derivatives were shown to possess significant antiviral activity; however, none surpassed its respective parent compound, CEDU or BVDU, in potency. It seems improbable, therefore, that a synergistic effect between PFA or PAA and the nucleoside analogue occurred. The extent of in vitro and in vivo activity of the CEDU and BVDU 5'-phosphonoformates and 5'-phosphonoacetates is most plausibly explained by the ease by which the "combined prodrugs" are hydrolyzed and the parent compound, CEDU and BVDU, respectively, is released.

    Topics: Animals; Antiviral Agents; Bromodeoxyuridine; Cell Line; Chemical Phenomena; Chemistry; Deoxyuridine; Foscarnet; Herpes Simplex; Mice; Organophosphorus Compounds; Pharmaceutical Preparations; Phosphonoacetic Acid; Prodrugs; Rabbits; Simplexvirus; Thymidine; Vero Cells

1988
2'-Fluorinated arabinonucleosides of 5-(2-haloalkyl)uracil: synthesis and antiviral activity.
    Journal of medicinal chemistry, 1987, Volume: 30, Issue:7

    The synthesis of 5-(2-fluoroethyl)-2'-deoxyuridine (FEDU, 4b), its 2'-fluoro analogue 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-(2-fluoroethyl)-1H,3H- pyrimidine-2,4-dione (FEFAU, 4k), and the 2'-fluoro analogue of the potent antiherpes virus compound 5-(2-chloroethyl)-2'-deoxyuridine (CEDU), 5-(2-chloroethyl)-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-1H,3H-pyr imidine - 2,4-dione (CEFAU, 4i), is described. The antiviral activities of these compounds were determined in cell culture against herpes simplex virus (HSV) types 1 and 2 and varicella zoster virus (VZV). All compounds were shown to possess significant and selective antiviral activity. FEDU proved less potent than CEDU against VZV replication; however, it was more active against HSV-2. CEFAU showed marked activity against HSV-1, HSV-2, and VZV. The compound containing fluorine at both positions, FEFAU, exhibited the strongest antiviral potency against HSV-1, HSV-2, and VZV. It inhibited HSV-1 at a concentration of 0.03-0.2 microgram/mL, HSV-2 at 0.1-0.3 microgram/mL, and VZV at 0.03 microgram/mL. Neither FEDU nor CEFAU or FEFAU exerted a significant inhibitory effect on cell proliferation at a concentration of 100 micrograms/mL. Thus, the cytotoxicity of these compounds is as low as that of CEDU and compares favorably to that of previously described 2'-fluoroarabinosyl nucleoside analogues.

    Topics: Antiviral Agents; Bromodeoxyuridine; Deoxyuridine; Floxuridine; Simplexvirus; Structure-Activity Relationship

1987
Efficacy of (S)-HPMPA against thymidine kinase-deficient herpes simplex virus-keratitis.
    Investigative ophthalmology & visual science, 1987, Volume: 28, Issue:2

    A new acyclic adenosine analogue, (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], was evaluated for its efficacy in the topical treatment of experimental keratitis caused by the thymidine kinase-positive (TK+) and thymidine kinase-deficient (TK-) herpes simplex virus type 1 (HSV-1) strains. In the treatment of TK+ HSV-1 keratitis, 0.2% (S)-HPMPA eyedrops were as effective as the reference compounds, 0.2% (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and 0.2% 5-(2-chloroethyl)-2'-deoxy-uridine (CEDU) eyedrops. The three compounds produced a statistically significant healing effect, as compared with placebo eyedrops. In the treatment of keratitis caused by the TK- HSV-1 strain, 0.2%BVDU and 0.2% CEDU eyedrops did not differ from placebo eyedrops, whereas 0.2% (S)-HPMPA eyedrops exerted a highly significant healing effect.

    Topics: Adenine; Administration, Topical; Animals; Antiviral Agents; Bromodeoxyuridine; Deoxyuridine; Herpesvirus 1, Human; Keratitis, Herpetic; Ophthalmic Solutions; Organophosphonates; Organophosphorus Compounds; Rabbits; Thymidine Kinase

1987
Deoxyribosyl exchange reactions leading to the in vivo generation and regeneration of the antiviral agents (E)-5-(2-bromovinyl)-2'-deoxyuridine, 5-ethyl-2'-deoxyuridine and 5-(2-chloroethyl)-2'-deoxyuridine.
    Biochemical pharmacology, 1986, May-15, Volume: 35, Issue:10

    In the rat, the highly potent anti-herpes drug (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVdUrd) is rapidly converted to its base (E)-5-(2-bromovinyl)uracil (BVUra) through the action of pyrimidine nucleoside phosphorylases. However, BVdUrd can be regenerated or even generated de novo from BVUra by a pentosyl transfer reaction upon the administration of 2'-deoxythymidine (dThd), 2'-deoxyuridine (dUrd) or 5-ethyl-2'-deoxyuridine (EtdUrd). The antiherpetic drugs EtdUrd and 5-(2-chloroethyl)-2'-deoxyuridine (ClEtdUrd) can also be regenerated or generated de novo from their respective bases 5-ethyluracil (EtUra) and 5-(2-chloroethyl)uracil (ClEtUra), by a pentosyl transfer mediated by the administration of dThd or dUrd as deoxyribosyl donor. The generation or regeneration of BVdUrd, EtdUrd and ClEtdUrd from their bases (BVUra, EtUra and ClEtUra, respectively) is readily achieved because the latter have long half-lifes. Thus, the active anti-herpes drugs can be (re)generated repeatedly after a single administration of these nucleosides or their bases, followed by repeated administrations of dUrd.

    Topics: Animals; Antiviral Agents; Bromodeoxyuridine; Bromouracil; Deoxyuridine; Half-Life; Humans; Male; Rabbits; Rats; Rats, Inbred Strains; Simplexvirus; Uracil

1986
Ocular penetration and efficacy of chloroethyldeoxyuridine against herpetic keratouveitis.
    Investigative ophthalmology & visual science, 1986, Volume: 27, Issue:10

    Topical administration of 0.1% or 1% chloroethyldeoxyuridine eyedrops caused a significant reduction in the severity of experimental herpes simplex iritis and stromal keratitis in rabbits. The healing effect caused by chloroethyldeoxyuridine was comparable to that obtained with 0.1% and 0.5% bromovinylde-oxyuridine eyedrops. The drug levels achieved in the anterior chamber fluid following topical application of 1% eyedrops of [2-14C]CEDU, a radiolabelled analogue of chloroethyldeoxyuridine, were well above the minimum concentration (0.1 microgram/mL) required for inhibition of herpes simplex virus type 1 replication. The beneficial effects of chloroethyldeoxyuridine on stomal keratitis and iritis appear consistent with its efficient penetration through the cornea.

    Topics: Animals; Anterior Chamber; Antiviral Agents; Bromodeoxyuridine; Deoxyuridine; Iritis; Keratitis, Dendritic; Ophthalmic Solutions; Rabbits

1986
5-(Haloalkyl)-2'-deoxyuridines: a novel type of potent antiviral nucleoside analogue.
    Journal of medicinal chemistry, 1985, Volume: 28, Issue:11

    Syntheses of 5-(2-haloethyl)-2'-deoxyuridines, 5-(3-chloropropyl)-2'-deoxyuridines, and 5-(2-chloroethyl)-2'-deoxycytidine are described. The antiviral activities of these compounds were determined in cell culture against herpes simplex virus types 1 and 2. All compounds were shown to possess significant and selective antiviral activity. The most potent derivative, 5-(2-chloroethyl)-2'-deoxyuridine (CEDU), inhibited HSV-1 at concentrations below 0.1 microgram/mL. It exerted measurable inhibitory effects on cell proliferation only at concentrations higher than 100 micrograms/mL. In vivo CEDU reduced the mortality rate of HSV-1-infected mice at concentrations lower than 5 mg/kg per day when given intraperitoneally and orally. Thus, it proved to be more effective in this in vivo model than the reference compounds (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and 9-[(2-hydroxyethoxy)methyl]guanine (ACV).

    Topics: Animals; Bromodeoxyuridine; Chemical Phenomena; Chemistry; Deoxyuridine; Dose-Response Relationship, Drug; Halogens; Herpes Simplex; Mice; Rats

1985