- A direct method for the preparation of 2-hydroxyethoxymethyl derivatives of guanine, adenine, and cytosine
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Alkylation of 2-chloro-6-iodopurine with iodomethyl [(trimethylsilyl)oxy]ethyl ether at -63°C and subsequent treatment of the 9-substituted chloroiodopurine with K2CO3 in aqueous dioxane at 25°C and then with NH3 under pressure at 150°C provided 9-[(2-hydroxyethoxy)methyl]guanine (1a), a potent antiviral agent against Herpes simplex virus type 1, in excellent yield. Its monophosphate (1g), which is enzymatically produced from 1a in the virus-infected cell, was also synthesized. 6-Chloropurine and 4-(methylthio)pyrimidin-2-one anions were similarly alkylated with iodomethyl [(trimethylsilyl)oxy]ethyl ether, and the products were transformed by treatment with methanolic NH3 at 110°C into 9-[(2-hydroxyethoxy)methyl]adenine and 1-[(2-hydroxyethoxy)methyl]cytosine respectively. The synthesis of these analogues, heretofore difficult to prepare by a simple procedure, has been conveniently accomplished.
- Barrio,Bryant,Keyser
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Read Online
- An acyl-SAM analog as an affinity ligand for identifying quorum sensing signal synthases
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N-Acylhomoserine lactones (AHLs) are quorum sensing signals produced by Gram-negative bacteria. We here report the affinity purification of AHL synthases using beads conjugated with an enzyme inhibitor, which was designed based on the catalytic intermediate acyl-SAM. the Partner Organisations 2014.
- Kai, Kenji,Fujii, Hiroki,Ikenaka, Rui,Akagawa, Mitsugu,Hayashi, Hideo
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supporting information
p. 8586 - 8589
(2014/07/22)
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- Synthesis and in vitro stability of nucleoside 5′-phosphonate derivatives
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Nucleoside derivatives are largely synthesized and tested to investigate their influence on platelet aggregation. It's well known that P2Y receptors play an important role in the regulation of platelet function and, as consequence, in controlling atherothrombotic events. The research of compounds that antagonize P2Y1 and, in particular, P2Y12 receptors is of great interest in the aim to obtain platelet aggregation inhibitors that are effective in the prevention and treatment of arterial thrombosis. In this study we present the synthesis and in vitro metabolic stability in human blood and rat liver homogenate of a new class of nucleoside derivatives, in particular 5′-phosphonate adenosine, inosine, guanosine and thioadenosine analogues also modified at the ribose moiety. On the basis of the results obtained we can hypothesize compounds 4 and 18 to have in vivo a relatively high stability.
- Vertuani, Silvia,Baldisserotto, Anna,Varani, Katia,Borea, Pier Andrea,De Marcos Maria Cruz, Bonache,Ferraro, Luca,Manfredini, Stefano,Dalpiaz, Alessandro
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supporting information; experimental part
p. 202 - 209
(2012/09/07)
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- Novel trypanocidal analogs of 5′-(methylthio)-adenosine
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The purine nucleoside 5′-deoxy-5′-(hydroxyethylthio)-adenosine (HETA) is an analog of the polyamine pathway metabolite 5′-deoxy-5′- (methylthio)-adenosine (MTA). HETA is a lead structure for the ongoing development of selectively targeted trypanocidal agents. Thirteen novel HETA analogs were synthesized and examined for their in vitro trypanocidal activities against bloodstream forms of Trypanosoma brucei brucei LAB 110 EATRO and at least one drug-resistant Trypanosoma brucei rhodesiense clinical isolate. New compounds were also assessed in a cell-free assay for their activities as substrates of trypanosome MTA phosphorylase. The most potent analog in this group was 5′-deoxy-5′-(hydroxyethylthio)-tubercidin, whose in vitro cytotoxicity (50% inhibitory concentration [IC50], 10 nM) is 45 times greater than that of HETA (IC50, 450 nM) against pentamidine-resistant clinical isolate KETRI 269. Structure-activity analyses indicate that the enzymatic cleavage of HETA analogs by trypanosome MTA phosphorylase is not an absolute requirement for trypanocidal activity. This suggests that additional biochemical mechanisms are associated with the trypanocidal effects of HETA and its analogs. Copyright
- Sufrin, Janice R.,Spiess, Arthur J.,Marasco Jr., Canio J.,Rattendi, Donna,Bacchi, Cyrus J.
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p. 211 - 219
(2008/03/14)
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- PREVENTION AND TREATMENT OF CANCER AND OTHER DISEASES
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Nucleoside chemical compounds, which interact with specific structures of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) are disclosed. The compounds interfere with the activities of telomerase and reverse transcriptase, and are useful as antivirals, antibacterials and anticancer agents. Methods of treating or preventing cancers in patients involving administration of a therapeutically effective amount of a composition having an inhibitor or antagonist of the reverse transcriptases (RTs) expressed in cells of the patients are also disclosed. Method of using nucleoside analogs and other inhibitors of RTs in conjunction with DNA damaging agents such as genotoxic agents or radiation or photodynamic therapy or combinations these for the treatment of various cancers are also disclosed.
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Page/Page column 61-62
(2008/06/13)
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- Antiviral compounds
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This invention relates to purine compounds of formula (I): R1 is NH2 or OH; R2 is H or NH2; R3 is H or alkyl; each of m and n, independently, is 1, 2, 3, or 4; X is O, S, or NH; and Y is H, halogen, ORa, P(O)(ORa)2, or P(O)(ORa)(ORb), in which Ra is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, and Rb is wherein A is adenine, guanine, cytosine, uracil, or thymine; Rc is H or OH; Rd is H or alkyl; Re is H, alkyl, or 5-ethylidene-(3,4-dialkoxyl)-furan-2-one; provided that if R1 is NH2, R2 is H; and if R1 is OH, R2 is NH2.
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- Synthesis and evaluation of analogues of 5′-([(Z)-4-amino-2-butenyl]methylamino)-5′-deoxyadenosine as inhibitors of tumor cell growth, trypanosomal growth, and HIV-1 infectivity
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A well-defined series of 5′-([(Z)-4-amino-2-butenyl]methylamino)-5′-deoxyadenosine analogues was designed and synthesized in order to further ascertain the optimal structural requirements for S-adenosylmethionine decarboxylase inhibition and potentially t
- Marasco Jr., Canio J.,Kramer, Debora L.,Miller, John,Porter, Carl W.,Bacchi, Cyrus J.,Rattendi, Donna,Kucera, Louis,Iyer, Nathan,Bernacki, Ralph,Pera, Paula,Sufrin, Janice R.
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p. 5112 - 5122
(2007/10/03)
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- Process for producing acyclic nucleosides and process for separating purine nucleosides
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Herein is disclosed a novel and industrially advantageous process for synthesizing acyclic nucleosides such as acyclovir and ganciclovir from ribonucleosides, which process comprises adding an acid catalyst and an acid anhydride to a solution of a ribonucleoside such as guanosine and an ester derivative of an acyclic sugar, and heating the mixture, whereby a transglycosilation reaction takes place between the ribose moiety of the ribonucleoside and the ester derivative of the acyclic sugar. Herein is also disclosed an industrially favorable method for the separation of 9-substituted purine nucleosides which are important intermediates for the synthesis of acyclic nucleosides such as acyclovir, ganciclovir, and the like from ribonucleosides, which method comprises crystallizing only the 9-isomer from a solution or suspension containing both a 9-substituted purine nucleoside and a 7-substituted purine nucleoside by cooling the solution or/and by adding a crystallizing solvent thereto.
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- Preparation of a Novel Potent Inhibitor of Methylthioadenosine Nucleosidase
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9-(4-Methylthiobutyl)adenine 7 has been prepared and shown to be a potent inhibitor of the enzyme methylthioadenosine nucleosidase.
- Hendry, David,Hutchinson, Edward J.,Roberts, Stanley M.,Dunn, Steven M.,Bryant, John A.
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p. 1109 - 1112
(2007/10/02)
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- 2-Amido-9-(2-acyloxyethoxymethyl)hypoxanthines
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Method of preparing 9-(2-hydroxyethoxymethyl)guanine which comprises preparing the compound STR1 wherein R and R1 are hydrogen, lower alkyl and phenyl and then hydrolyzing same. 9-(2-hydroxyethoxymethyl)guanine is useful as an antiviral.
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