• 한국식품영양학회지
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• 제10권1호
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• pp.53-59
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• 1997

Aspergillus fumigatus IFO 5840이 생산하는 cytosine deaminase에 미치는 cytosine analogue의 영향을 조사하여 다음의 결과를 얻었다. 1. Cytosine deaminase의 강한 저해를 나타내는 cytosine analogue는 2-thiouracil, 2-thiocytosine, 2-mercaptopyrimidine, 및 6-azacytosine이었다. 2. 본 효소에 대한 2-thiocytosine 및 6-azacytosine의 50% 효소활성 저해농도(HIC)는 각각 0.80mM과 1.15mM이었다. 3. 2-thiocytosine은 일정한 수준에서 본 효소의 반응을 정지시키는 반면, 6-azacytosine은 반응시간에 비례하여 일정한 비율로 저해하였다. 4. 2-thiocytosine과 6-azacytosine은 cytosine이나 5-fluorocytosine의 기질 종류에 관계없이 본 효소의 저해제로 작용하였으며 2-thiocytosine이 6-azacytosine보다 약 2배 정도의 높은 저해를 나타내었다. 5. cytosine을 기질로 하였을 경우, 2-thiocytosine과 6-azacytosine에 의해 경쟁적 저해를 나타내며 이들에 대한 Ki값은 각각 4.5$\times$10-4M과 1.756$\times$10-3M이었으며 cytosine, 2-thiocytosine 및 6-azacytosine에 대한 Hill 계수(Hn)는 각각 1.80, 1.81, 2.45로 나타났다.

• Bulletin of the Korean Chemical Society
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• 제32권6호
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• pp.1931-1935
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• 2011

The synthesis of carbocyclic analogues of normal nucleosides has grown exclusively since they have shown potential antiviral and antitumor activities. Radiolabeled cis-1-[4-(hydroxy-methyl)-cyclopent-2-enyl]-5-$[^{124}I]$-iodocytosine (carbocyclic d4IC) and cis-1-[4-(hydroxy-methyl)-cyclopent-2-enyl]-5-(2-$[^{124}I]$iodovinyl)cytosine(carbocyclic d4IVC) were synthesized. The synthetic route employed Pd(0)-catalyzed coupling reaction together with organotin and exchange reaction for radioiodination as key reactions. Carbocyclic $[^{124}I]$d4IC gave more than 75% radiochemical yield with greater than 95% radiochemical purity. Carbocyclic $[^{124}I]$d4IVC gave more than 80% radiochemical yield with greater than 95% radiochemical purity.

• Bulletin of the Korean Chemical Society
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• 제26권10호
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• pp.1520-1524
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• 2005

This paper describes the racemic and stereoselective synthetic route for a novel 4'$\alpha$-phenyl and 6'$\alpha$-methyl doubly branched carbocyclic nucleosides from an acyclic 2-hydroxy acetophenone. The installation of phenyl group at the 4'-position of carbocyclic nucleoside was successfully accomplished via a sequential [3,3]-sigmatropic rearrangement. The stereoselective introduction of a methyl group in the 6'$\alpha$-position was accomplished by Felkin-Anh controlled alkylation. Bis-vinyl 11 compound was successfully cyclized using a Grubbs’ catalyst II to desired carbocycles. The natural bases (adenine and cytosine) were efficiently coupled using a Pd(0) catalyst. Although all the synthesized compounds were examined for their activity against several viruses such as HIV-1, HSV-1, HSV-2 and HCMV, only cytosine analogues 17 exhibited weak antiviral activity against HCMV.

• Bulletin of the Korean Chemical Society
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• 제32권4호
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• pp.1146-1152
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• 2011

The discovery of 2'-spirocyclopropyl-ribocytidine (J. Med. Chem. 2010, 53, 8150-8160) as a potent inhibitor of RNA synthesis by NS5B ($IC_{50}=7.3{\mu}M$), the RNA polymerase encoded by hepatitis C Virus (HCV), has led to the synthesis and biological evaluation of several carbocyclic versions of 2'-spiropropyl-nucleosides. The cyclopentenol intermediate 7 was successfully constructed via ring-closing metathesis (RCM) from divinyl 6. Spirocyclopropanation of enone 8 was effected by using (2-chloroethyl)-dimethylsulfonium iodide and potassium tert-butoxide to form the desired intermediate 9. The synthesized nucleoside analogues 21-24 were assayed for their ability to inhibit HCV RNA replication in a subgenomic replicon Huh7 cell line. Among them, the cytosine nucleoside analogue 22 exhibited significant anti-HCV activity ($EC_{50}= 8.2{\mu}M$).

• 통합자연과학논문집
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• 제8권3호
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• pp.153-163
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• 2015

Racemic synthesis of novel 5',5'-difluoro-2'-methyl-apiose nucleoside phosphonic acid analogs was achieved as potent antiviral agents. Phosphonation was performed by direct displacement of triflate intermediate with diethyl (lithiodifluoromethyl) phosphonate to give the corresponding (${\alpha},{\alpha}$-difluoroalkyl) phosphonate. Condensation successfully proceeded from a glycosyl donor with persilylated bases to yield the nucleoside phosphonate analogs. Deprotection of diethyl phosphonates provided the target nucleoside analogs. An antiviral evaluation of the synthesized compounds against various viruses such as HIV, HSV-1, HSV-2 and HCMV revealed that the pyrimidine analogs (cytosine, uracil, and thymine) have weak anti-HIV or HCMV activity.

• 약학회지
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• 제51권2호
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• pp.103-107
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• 2007

In these study novel 1,4-disubstituted carbocyclic nucleoside analogues were synthesized as potential antiviral agents. The coupling reaction of the alcohol 8${\alpha}$ with natural bases using Mitsunobu reaction afforded the target nucleosides 13, 14. The synthesized compounds were evaluated for their antiviral activity against various viruses such as HIV-1, HSV-1, HSV-2 and HCMV. Cytosine derivative 13 exhibited moderate antiviral activity against HIV-1 (EC$_{50}$=16.4 ${\mu}$M).