Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
|
| pubmed:dateCreated |
1993-6-9
|
| pubmed:abstractText |
A series of branched-chain sugar isonucleosides was synthesized and evaluated for antiviral activity against herpesviruses. The preparation of homochiral [3S-(3 alpha, 4 beta, 5 alpha)]-2-amino-1, 9-dihydro-9-[tetrahydro-4,5-bis(hydroxymethyl)-3-furanyl]-6H-purin-6-one (7, BMS-181,164) and related compounds was stereospecifically achieved starting from 1,2-isopropylidene-D-xylofuranose (10). An efficient two-step reduction of the anomeric center of bis-acetate 18 involved formation of the chloride intermediate 19, followed by diisobutylaluminum hydride reduction. Tosylation of the resulting alcohol 20 provided the key intermediate 21, which was coupled with a variety of nucleobase anions. Several members of this new class of compounds possess activity against herpes simplex virus types 1 and 2 (HSV-1 and -2), varicella-zoster virus (VZV), and human cytomegalovirus (HCMV). Compound 7 exhibits potent and selective activity against thymidine kinase encoding herpesviruses, in particular, HSV-1 and HSV-2. Evaluation of compound 7 for inhibition of WI-38 cell growth indicated an ID50 of > 700 microM. Although the antiherpetic activity in vitro of 7 is less than that of acyclovir (1), compound 7 displays superior efficacy in mouse model infections. The (bromovinyl)uridine analog 8 (BMS-181,165) also exhibits selective activity against HSV-1 and VZV, with no cytostatic effect on WI-38 cell growth at > 800 microM. Compound 8 is active against simian varicella virus and is efficacious in the corresponding monkey model.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
0022-2623
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
30
|
| pubmed:volume |
36
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
N
|
| pubmed:pagination |
1221-9
|
| pubmed:dateRevised |
2011-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:8387600-Animals,
pubmed-meshheading:8387600-Antiviral Agents,
pubmed-meshheading:8387600-Cell Line,
pubmed-meshheading:8387600-Chickenpox,
pubmed-meshheading:8387600-Cytomegalovirus,
pubmed-meshheading:8387600-Female,
pubmed-meshheading:8387600-Guanosine,
pubmed-meshheading:8387600-Herpes Simplex,
pubmed-meshheading:8387600-Herpesviridae,
pubmed-meshheading:8387600-Herpesvirus 3, Human,
pubmed-meshheading:8387600-Mice,
pubmed-meshheading:8387600-Molecular Structure,
pubmed-meshheading:8387600-Simplexvirus,
pubmed-meshheading:8387600-Structure-Activity Relationship,
pubmed-meshheading:8387600-Thymidine Kinase,
pubmed-meshheading:8387600-Uridine,
pubmed-meshheading:8387600-Vaccinia virus,
pubmed-meshheading:8387600-Viral Plaque Assay
|
| pubmed:year |
1993
|
| pubmed:articleTitle |
Synthesis and antiviral activity of novel isonucleoside analogs.
|
| pubmed:affiliation |
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.
|
| pubmed:publicationType |
Journal Article
|