2′-Amino-2′-deoxy-N6-(1-naphthylmethyl)adenosine as Novel Scaffold for a Polymer-Assisted Amidation Protocol

Golisade, Abolfasl; Calenbergh, Serge Van; Link, Andreas

doi:10.1016/s0040-4020(00)00228-3

Cited by 15 publications

(9 citation statements)

References 19 publications

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“…28 Route 1 suffers from poor yields of the alkylation and rearrangement steps and is limited in scope to the availability, either commercially or synthetically, of activated halide alkylating agents. Routes 2 and 3 both suffer from poor yields at the diazotization-halogenation step.…”

Section: Chemistrymentioning

confidence: 99%

“…There are three reported methods for the synthesis of N 6 -(substituted)-2′-deoxy-2′-(benzamido)adenosine analogues: (1) acylation of 2′-amino-2′-deoxy-3′,5′-O-(1,1,3,3tetraisopropyldisiloxane-1,3-diyl)adenosine 20,26 followed by N1 alkylation with subsequent Dimroth rearrangement and removal of the Markiewicz protecting group; 23,27 (2) acylation of 2′-amino-2′-deoxy-3′,5′-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)adenosine followed by diazotization-iodination of N 6 , C6 amination, and removal of the Markiewicz protecting group; 24 (3) diazotizationchlorination of 2′-azido-2′-deoxy-3′,5′-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)adenosine, removal of the Markiewicz protecting group, amination of the C6 position, reduction of the C2′ azide, and polymerassisted amidation. 28 Route 1 suffers from poor yields of the alkylation and rearrangement steps and is limited in scope to the availability, either commercially or synthetically, of activated halide alkylating agents. Routes 2 and 3 both suffer from poor yields at the diazotization-halogenation step.…”

Section: Chemistrymentioning

confidence: 99%

“…Regioselective acylation of the 5′ amine is accomplished with the use of the appropriately acylated safety-catch resin at ambient temperature to give 2′,5′-dideoxy-2′-amino-5′-(cyclohexylacetamido)adenosine (46) and 2′,5′-dideoxy-2′-amino-5′-(diphenylacetamido)adenosine (47) ing the appropriately acetylated safety-catch resin at elevated temperatures. 28,33,34 2-Naphthalenemethylamine hydrochloride (51), 4methoxy-1-naphthalenemethylamine hydrochloride (55), and 3-methoxy-1-naphthalenemethylamine hydrochloride (57) were prepared by LiAlH 4 reduction of 2-naphthonitrile (50), 35 4-methoxy-1-naphthonitrile (54), and 3-methoxy-1-naphthonitrile (56), 36 respectively. By use of the methodology of Deana et al 37,38 for the synthesis of 2-hydroxy-1-naphthalenemethylamine, 2-methoxy-1naphthalenemethylamine (53) was prepared by treatment of 2-methoxynaphthalene (52) with 2-chloro-N-(hydroxymethyl)acetamide and hydrochloric acid.…”

Section: Chemistrymentioning

confidence: 99%

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Adenosine Analogues as Selective Inhibitors of Glyceraldehyde-3-phosphate Dehydrogenase of Trypanosomatidae via Structure-Based Drug Design

et al. 2001

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In our continuation of the structure-based design of anti-trypanosomatid drugs, parasite-selective adenosine analogues were identified as low micromolar inhibitors of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Crystal structures of Trypanosoma brucei, Trypanosoma cruzi, Leishmania mexicana, and human GAPDH's provided details of how the adenosyl moiety of NAD + interacts with the proteins, and this facilitated the understanding of the relative affinities of a series of adenosine analogues for the various GAPDH's. From exploration of modifications of the naphthalenemethyl and benzamide substituents of a lead compound, N 6 -(1-naphthalenemethyl)-2′-deoxy-2′-(3-methoxybenzamido)adenosine (6e), N 6 -(substituted-naphthalenemethyl)-2′-deoxy-2′-(substituted-benzamido)adenosine analogues were investigated. N 6 -(1-Naphthalenemethyl)-2′-deoxy-2′-(3,5-dimethoxybenzamido)adenosine (6m), N 6 -[1-(3-hydroxy-naphthalene)methyl]-2′-deoxy-2′-(3,5-dimethoxybenzamido)adenosine (7m), N 6 -[1-(3-methoxy-naphthalene)methyl]-2′-deoxy-2′-(3,5-dimethoxybenzamido)adenosine (9m), N 6 -(2-naphthalene-methyl)-2′-deoxy-2′-(3-methoxybenzamido)adenosine (11e), and N 6 -(2-naphthalenemethyl)-2′-deoxy-2′-(3,5-dimethoxybenzamido)adenosine (11m) demonstrated a 2-to 3-fold improvement over 6e and a 7100-to 25000-fold improvement over the adenosine template. IC 50 's of these compounds were in the range 2-12 μM for T. brucei, T. cruzi, and L. mexicana GAPDH's, and these compounds did not inhibit mammalian GAPDH when tested at their solubility limit. To explore more thoroughly the structure-activity relationships of this class of compounds, a library of 240 N 6 -(substituted)-2′-deoxy-2′-(amido)adenosine analogues was generated using parallel solution-phase synthesis with N 6 and C2′ substituents chosen on the basis of computational docking scores. This resulted in the identification of 40 additional compounds that inhibit parasite GAPDH's in the low micromolar range. We also explored adenosine analogues containing 5′-amido substituents and found that 2′,5′-

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Section: Chemistrymentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

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Adenosine Analogues as Selective Inhibitors of Glyceraldehyde-3-phosphate Dehydrogenase of Trypanosomatidae via Structure-Based Drug Design

et al. 2001

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“…2‘-Acylamidonucleotides have previously been employed in oligoribonucleotides and oligodeoxyribonucleotides to introduce new functionalities for cross-linking, to induce chemical cleavage of DNA, to render them fluorescent, and to obtain models for reporter group-bearing strands . The 2‘-acylated residues include adenosine derivatives with 2‘-acylamido substituents . Unacylated 2‘-amino-2‘-deoxyuridine residues have been used to modify hammerhead ribozymes , and to provide insight into the mechanism of RNA hydrolysis …”

mentioning

confidence: 99%

A 2‘-Acylamido Cap That Increases the Stability of Oligonucleotide Duplexes

et al. 2001

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Reported here is the synthesis of oligonucleotides containing a 2′-acylamido-2′-deoxyuridine residue at their 3′-terminus. Compared to control sequences bearing a thymidine residue, the quinolone-capped duplexes give higher UV melting points. In the case of (5′-ACGCGU-NA-2′) 2 , where NA denotes a nalidixic acid residue, the melting point increase is up to 22 °C over that of (ACGCGT) 2 .

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“…Fully silylated TBDMS derivative 20 was obtained according to the known synthetic methodology 34) (Chart 2). TIPDS derivatives (11,35) 12, 36) 36 37) ) were obtained apply- ing the synthetic strategy reported by Robins et al 38) (Charts 1, 2). In the case of araA the product of incomplete cyclization at the 3Ј-OH (35) was also isolated.…”

Section: - 53-o-and 52-o-substituted Adenine Nucleoside Analogsmentioning

confidence: 99%

Design, Synthesis and Anti Flaviviridae Activity of N6-, 5',3'-O- and 5',2'-O-Substituted Adenine Nucleoside Analogs

Angusti

Manfredini

Durini

et al. 2008

CHEMICAL & PHARMACEUTICAL BULLETIN

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The Flaviviridae virus family presents linear, plus sense, single-stranded RNA genome of 9.6 to 12.3-kilobases in length and is responsible for about seventy diseases, of which thirteen in humans. The viruses belonging to this family, are divided in three different genera, showing a great similarity in virion morphology, genome organization and replication strategy:1) Hepacivirus [Hepatitis C Virus (HCV)], Flavivirus [e.g. Yellow Fever Virus (YFV), Dengue Fever Virus (DFV), West Nile Virus (WNV)], and Pestivirus [Bovine Viral Diarrhea Virus (BVDV), Border Disease Virus (BDV)]. [2][3][4][5] Bovine viral diarrhea virus (BVDV), the prototype representative of the Pestivirus genus, is ubiquitous and causes a range of clinical manifestations, including abortion, teratogenesis, respiratory problems, chronic wasting syndrome, immune system dysfunction, and predisposition to secondary viral and bacterial infections. 5)Regardless of the availability of vaccines 6) against BVDV and the increasingly elaborate eradication or control of programs, BVDV continues to be a financial burden to the farming industry. An alternative approach against BVDV infections could be the use of antiviral agents that specifically inhibit the replication of the virus. Although not suited to treat large herds, it could be important to have selective anti-Pestivirus compounds on hand.Recently, a number of selective anti-BVDV compounds have been reported. These include the following: polymerase inhibitors i.e. N-propyl-N-[2-(2H-1,2,4-triazino[5,6-b]indol-3-ylthio)ethyl]-1-propanamine (VP32947), 7) a thiazole urea derivative, 8) a cyclic urea derivative 9) and inhibitors of the NS3/NS4A protease, for example, a boron-modified peptidyl mimetic.10) Aromatic cationic molecules have also been reported to inhibit BVDV replication, although the mechanism of action remains to be elucidated.11) Other BVDV inhibitors target cellular enzymes such as the a-glucosidase 12-14) and inosine monophosphate dehydrogenase (IMPDH).15) Recently, a new highly selective BVDV polymerase inhibitor of pestivirus replication, 5-[(4-bromophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (BPIP), was reported. 16)Like BVDV, HCV also belongs to the Flaviviridae family. It is an important cause of chronic hepatitis throughout the world and is the most common factor involved in the development of liver cirrhosis and hepatocellular carcinoma. 17,18) The licensed therapy based on the combination of pegylated interferon-a with the broad spectrum antiviral agent ribavirin, has a limited efficacy (about 60%) and there are important side effects associated with the therapy. Therefore, highly effective and selective inhibitors of HCV replication are urgently required. 19) BVDV is considered to be a valuable surrogate virus model for identifying and characterizing antiviral agents for use against HCV. 20) In some aspects of viral replication, BVDV is more advantageous than the currently used HCV replicon systems 21,22) because this latter does not present a complete replication cycle thus...

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2′-Amino-2′-deoxy-N6-(1-naphthylmethyl)adenosine as Novel Scaffold for a Polymer-Assisted Amidation Protocol

Cited by 15 publications

References 19 publications

Adenosine Analogues as Selective Inhibitors of Glyceraldehyde-3-phosphate Dehydrogenase of Trypanosomatidae via Structure-Based Drug Design

Adenosine Analogues as Selective Inhibitors of Glyceraldehyde-3-phosphate Dehydrogenase of Trypanosomatidae via Structure-Based Drug Design

A 2‘-Acylamido Cap That Increases the Stability of Oligonucleotide Duplexes

Design, Synthesis and Anti Flaviviridae Activity of N6-, 5',3'-O- and 5',2'-O-Substituted Adenine Nucleoside Analogs

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