- 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 63
(2008/06/13)
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- An Improved Total Synthesis of PET HSV-tk Gene Expression Imaging Agent 9-[(3-[18F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine ([ 18F]FHPG)
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An improved total synthesis of [18F]FHPG starting from 1,3-dibenzyloxy-2-propanol and guanine has been developed. [18F]FHPG was prepared by nucleophilic substitution of the appropriate precursor with [18F]KF/ Kryptofix 2.2.2 followed by a quick deprotection reaction and purification with a simplified Silica Sep-Pak solid-phase extraction (SPE) method in 10-15% radiochemical yield, and 70 min synthesis time from end of bombardment (EOB).
- Wang, Ji-Quan,Zheng, Qi-Huang,Fei, Xiangshu,Liu, Xuan,Gardner, Thomas A.,Kao, Chinghai,Raikwar, Sudhanshu P.,Glick-Wilson, Barbara E.,Sullivan, Michael L.,Mock, Bruce H.,Hutchins, Gary D.
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p. 917 - 932
(2007/10/03)
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- Novel radiosynthesis of PET HSV-tk gene reporter probes [ 18F]FHPG and [18F]FHBG employing dual Sep-Pak SPE techniques
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Positron emission tomography (PET) herpes simplex virus thymidine kinase (HSV-tk) gene reporter probes 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy) methyl]guanine ([18F]FHPG) and 9-(4-[18F]fluoro-3- hydroxymethylbutyl)guanine ([18F]FHBG) were prepared by nucleophilic substitution of the appropriate tosylated precursors with [18F]KF/ Kryptofix 2.2.2 followed by a quick deprotection reaction and purification with a simplified dual Silica Sep-Pak solid-phase extraction (SPE) method in 15-30% radiochemical yield.
- Wang, Ji-Quan,Zheng, Qi-Huang,Fei, Xiangshu,Mock, Bruce H.,Hutchins, Gary D.
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p. 3933 - 3938
(2007/10/03)
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- Substituted 9-(1 or 3-monoacyloxy or 1,3-diacyloxy-2-propoxymethyl) purines as antiviral agent
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Compounds useful as antiviral agents are defined by the following formula: STR1 and the pharmaceutically acceptable acid addition salts thereof wherein R1 is hydrogen or --C(O)R7 wherein R7 is hydrogen, alkyl of one to nineteen carbon atoms, hydroxyalkyl of one to eight carbon atoms, alkoxyalkyl of two to nine carbon atoms, alkenyl of two to nineteen carbon atoms, phenyl, 1-adamantyl or 2-carboxyethyl and the pharmaceutically acceptable alkali metal salts thereof; R2 is --C(O)R7 wherein R7 is as defined above; R3 is hydrogen, halo, thio, lower alkylthio of one to six carbon atoms, azido, NR9 R10 wherein R9 and R10 are independently hydrogen or lower alkyl of one to six carbon atoms or --NHC(O)R8 wherein R8 is hydrogen, alkyl of one to nineteen carbon atoms or 1-adamantyl; and (a) R6 is hydrogen, halo, lower alkoxy of one to six carbon atoms, azido, thio, lower alkylthio of one to six carbon atoms, --NR9 R10 wherein R9 and R10 are as defined above or --NHC(O)R8 wherein R8 is as defined above and R4 together with R5 is a bond; or (b) R5 together with R6 is a keto group and R4 is hydrogen.
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- SYNTHESIS AND ANTIVIRAL ACTIVITY OF 1,2,3-TRIAZOLE AND 8-AZAPURINE DERIVATIVES BEARING ACYCLIC SUGARS
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A variety of 1,2,3-triazole and 8-azapurine derivatives bearing acyclic sugar moieties were synthesized by the reaction of acyclic sugar azides with α-cyanoacetamide, norbornadiene, and acetylene derivatives, respectively.Antiviral tests of these compound
- Yokoyama, Masataka,Nakao, Eiko,Sujino, Keiko,Watanabe, Satoshi,Togo, Hideo
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p. 1669 - 1685
(2007/10/02)
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- Effect of Acyclic Pyrimidines Related to 9-guanine on Herpesviruses
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A series of pyrimidines related to the potent antiherpetic agent 9-guanine (1, BW B759U), all containing the same acyclic chain, have been synthesized.Some of the compounds were derivatives of the naturally occuring bases, cytosine, uracil, and thymine; others included compounds in which the 5-position of the cytosine and uracil moieties were substituted by bromo, iodo, fluoro, methyl, and amino groups.Other variations of the cytosine derivatives were the 5-aza, 2-mercapto, 4-methylamino, 4-dimethylamino, and isocytosine congeners.A 4-aminopyrimidine adduct was also made.Antiviral testing showed that 1-cytosine (18, BW A1117U) was equivalent to the guanine analogue in the potency against human cytomegalovirus and Epstein Barr virus.Other compounds in the series were largely inactive in antiviral screening against the herpesviruses.
- Beauchamp, Lilia M.,Serling, Barbara L.,Kelsey, John E.,Biron, Karen K.,Collins, Peter,et al.
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p. 144 - 149
(2007/10/02)
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- TWO ACYCLIC ANALOGUES OF 2-β-D-RIBOFURANOSYL THIAZOLE-4-CARBOXAMIDE (TIAZOFURIN)
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Two different synthetic strategies have been elaborated for the synthesis of 2-thiazole-4-carboxamide (4) and 2-methyl>thiazole-4-carboxamide (5).
- Kovacs, Lajos,Herczegh, Pal,Batta, Gyula,Farkas, Istvan
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p. 947 - 960
(2007/10/02)
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- Process for preparing guanine derivatives
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1-Monophosphate esters, 1,3-bisphosphate esters and cyclic phosphate esters of 9-(1,3-dihydroxy-2-propoxymethyl)guanine are useful as antiviral agents.
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- Studies on Nucleosides: Part XIII - Synthesis and Antiviral Activity of Acyclic Analogues of Spongosine
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6-Amino-9--2-methoxypurine (9), 6-amino-2-ethoxy-9-purine (10) and 6-amino-9-(2-hydroxyethoxymethyl)-2-methoxypurine (17) have been synthesized.Condensation of 2,6-dichloropurine (4) with 2-O-chloromethyl-1,3-di-O-benzylglycerol (5) furnishes the protected acyclic nucleosides 8 (yield 50percent) and 7 (yield 7percent).Amination of 7 and 8 affords 6 and 13 respectively.Treatment of 13 with sodium methoxide and ethoxide gives 11 and 12 respectively.Deblocking of 11 and 12 with Pd-C/H2 finally produces 9 and 10 respectively.Condensation of 4 with 1-O-benzyl-2-O-chloromethylethanediol gives 19 (yield 55percent) and 15 (yield 5percent).Amination of 19 affords 18 which on treatment with sodium methoxide furnishes 16.Deblocking of 16 with Pd-C/H2 gives 17.Compounds 9, 10, 11, 13 and 17 in combination with interferon inducer, mycoviral ds RNA, exhibit 16, 0, 16, 40 and 40percent enhancement of protection respectively against the semliki forest virus in Swiss albino mice.
- Singh, P. K.,Saluja, Sunita,Pratap, Ram,George, C. X.,Bhakuni, D. S.
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p. 823 - 827
(2007/10/02)
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- Uracil analogues of the acylonucleoside 9--methyl>guanine (BIOLF-62)
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A series of substituted uracil analogues of the antiviral agent 9-methyl>guanine (BIOL-62) has been synthesized and characterized.The uracil analogues show little activity against herpesviruses.
- Ogilvie, Kelvin K.,Hamilton, Raymond G.,Gillen, Michael F.,Radatus, Bruno K.,Smith, Kendall O.,Galloway, Karen S.
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- 9-(1,3-Dihydroxy-2-propoxymethyl)guanine as antiviral agent
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The compound 9-(1,3-dihydroxy-2-propoxymethyl)guanine and the pharmaceutically acceptable salts thereof are useful as antiviral agents.
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- 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine: A new potent and selective antiherpes agent
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The synthesis of a new acyclic analogue of deoxyguanosine, 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG, 1) is described starting from epichlorohydrin via condensation of 2-O-(acetoxymethyl)-1,3-di-O-benzylglycerol (5) with N2,9-diacetylguanine (6). In vitro studies indicate that DHPG is a potent and broad-acting (herpes simplex virus types 1 and 2, cytomegalovirus, and Epstein-Barr virus) antiherpetic agent. In vivo studies indicate its lack of toxicity [LD50 (mice) = 1-2 g/kg, ip] and its superiority over acyclovir [oral ED50 = 7 (mg/kg)/day vs. 550 (mg/kg)/day in HSV-2 infected mice].
- Martin,Dvorak,Smee,Matthews,Verheyden
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p. 759 - 761
(2007/10/02)
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- 9-(1,3-Dihydroxy-2-propoxymethyl)guanine as antiviral agent
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The compound 9-(1,3-dihydroxy-2-propoxymethyl)guanine and the pharmaceutically acceptable salts thereof are useful as antiviral agents.
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- RING OPEN ANALOGUES OF DEOXYNUCLEOTIDES
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The synthesis of acyclic analogues of 2'-deoxyadenosine and 2'-deoxythymidine which lack only the 2'-CH2 of the sugar is described.The synthesis of dinucleotides from these analogues is also described.
- Ogilvie, Kelvin K.,Gillen, Michael F.
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p. 327 - 330
(2007/10/02)
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