.alpha.-(Ureidomethylene)lactones and derived 5-(hyroxyalkyl)uracils

Denny, George H.; Ryder, M. A.

doi:10.1021/jm00257a021

Cited by 10 publications

(7 citation statements)

References 1 publication

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“…(C27H29N307) C, , N. Halogenation of la and 3a/9a. Triphenylphosphine (5.2 g, 20 mmol) was added to a solution of 10 mmol of the corresponding pyrimidine derivative in 50 mL of DMF. After the mixture was stirred for 10 min, 15 mmol of the halogenating agent (carbon tetrachloride/pyridine or N-bromosuccinimide (NBS)) were added, and the solution was kept at room temperature until no more starting material could be detected by TLC (usually 1.5 h).…”

Section: -Aminomentioning

confidence: 99%

5-(Haloalkyl)-2'-deoxyuridines: a novel type of potent antiviral nucleoside analog

Griengl¹,

Bodenteich²,

Hayden³

et al. 1985

J. Med. Chem.

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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).

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Section: -Aminomentioning

confidence: 99%

5-(Haloalkyl)-2'-deoxyuridines: a novel type of potent antiviral nucleoside analog

Griengl¹,

Bodenteich²,

Hayden³

et al. 1985

J. Med. Chem.

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“…The synthesis of compounds 10 and 14 – 16 , as precursors for N -alkylation, was performed in excellent yields (80–99%) ( Scheme 1 ). 5-(2-Hydroxyethyl)- and 5-(3-hydroxypropyl)-substituted uracils 1 and 2 served as starting materials and their syntheses were reported earlier [ 22 , 23 , 24 ]. The synthesis of 5-substituted 2,4-dimethoxypyrimidine derivatives 10 and 11 was carried out by acetylation, chlorination at the positions C-2 and C-4 with POCl 3 , methoxylation with sodium methoxide and repeated acetylation [ 25 ] ( Scheme 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…5-(2-Hydroxyethyl)pyrimidin-2,4-dione ( 1 ), 5-(3-hydroxypropyl)pyrimidin-2,4-dione ( 2 ), 5-(2- acetoxyethyl)pyrimidin-2,4-dione ( 3 ), 5-(2-acetoxyethyl)-2,4-dichloropyrimidine ( 5 ), 5-(2-hydroxy-ethyl)-2,4-dimethoxypyrimidine ( 8 ), 5-(2-acetoxyethyl)-2,4-dimethoxypyrimidine ( 10 ), 5-(2-acetoxy-ethyl)-4-methoxypyrimidin-2-one ( 14 ) and 5-(2-hydroxyethyl)-4-methoxypyrimidin-2-one ( 16 ) were synthesized in accord with original procedures given in the literature [ 22 , 23 , 24 , 25 , 26 ].…”

Section: Methodsmentioning

confidence: 99%

C-5 Hydroxyethyl and Hydroxypropyl Acyclonucleosides as Substrates for Thymidine Kinase of Herpes Simplex Virus Type 1 (HSV-1 TK): Syntheses and Biological Evaluation

et al. 2013

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The efficient syntheses of 5-(2-hydroxyethyl)- and 5-(3-hydroxypropyl)-substituted pyrimidine derivatives bearing 2,3-dihydroxypropyl, acyclovir-, ganciclovir- and penciclovir-like side chains are reported. A synthetic approach that included the alkylation of an N-anionic-5-substituted pyrimidine intermediate (method A) provided the target acyclonucleosides in significantly higher overall yields in comparison to those obtained by method B using sylilation reaction. The phosphorylation assays of novel compounds as potential substrates for thymidine kinase of herpes simplex virus type 1 (HSV-1 TK) showed that solely pyrimidine 5-substituted acyclonucleosides with a penciclovir-like side chain acted as a fraudulent substrates of HSV-1 TK. Moreover, the uracil derivative with penciclovir-like side chain with less bulky 2-hydroxyethyl substituent at C-5 proved to be a better substrate than the corresponding one with a 3-hydroxypropyl substituent. Therefore, this acyclonucleoside was selected as a lead compound for the development of a positron emission tomography HSV-1 TK activity imaging agent.

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“…DNA alkylating agents have played an important part in cancer chemotherapy since the introduction of nitrogen mustards more than fifty years ago. Examples of these drugs include bis(benzimidazoles), pyrrolizidines and pyrrolobenzodiazepines [19], see Figure 1.…”

Section: Alkylatorsmentioning

confidence: 99%

Nanomaterial‐based Sensors for the Study of DNA Interaction with Drugs

2019

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The interaction of drugs with DNA has been searched thoroughly giving rise to an endless number of findings of undoubted importance, such as a prompt alert to harmful substances, ability to explain most of the biological mechanisms, or provision of important clues in targeted development of novel chemotherapeutics. The existence of some drugs that induce oxidative damage is an increasing point of concern as they can cause cellular death, aging, and are closely related to the development of many diseases. Because of a direct correlation between the response, strength/ nature of the interaction and the pharmaceutical action of DNA‐targeted drugs, the electrochemical analysis is based on the signals of DNA before and after the interaction with the DNA‐targeted drug. Nowadays, nanoscale materials are used extensively for offering fascinating characteristics that can be used in designing new strategies for drug‐DNA interaction detection. This work presents a review of nanomaterials (NMs) for the study of drug‐nucleic acid interaction. We summarize types of drug‐DNA interactions, electroanalytical techniques for evidencing these interactions and quantification of drug and/or DNA monitoring.

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.alpha.-(Ureidomethylene)lactones and derived 5-(hyroxyalkyl)uracils

Cited by 10 publications

References 1 publication

5-(Haloalkyl)-2'-deoxyuridines: a novel type of potent antiviral nucleoside analog

5-(Haloalkyl)-2'-deoxyuridines: a novel type of potent antiviral nucleoside analog

C-5 Hydroxyethyl and Hydroxypropyl Acyclonucleosides as Substrates for Thymidine Kinase of Herpes Simplex Virus Type 1 (HSV-1 TK): Syntheses and Biological Evaluation

Nanomaterial‐based Sensors for the Study of DNA Interaction with Drugs

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