| Synthesis of some 1, 8- and 2, 8-disubstituted derivatives of adenosine cyclic 3', 5'-phosphate and their interaction with some enzymes of cAMP metabolism. | |
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MedLine Citation:
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PMID: 176360 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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1, 8-Disubstituted derivatives of adenosine cyclic 3', 5'-phosphate (cAMP) were synthesized by N-oxidation or N-methylation of previously reported 8-substituted cAMP derivatives to yield 8-bromoadenosine cyclic 3', 5'-phosphate 1-oxide and 8-(benzylthio)-1-methyladenosine cyclic 3', 5'-phosphate. Substituents were introduced into the 8 position of 2-methyladenosine cyclic 3', 5'-phosphate and 2-butyladenosine cyclic 3', 5'-phosphate by bromination, followed by treatment with sodium benzylmercaptide, sodium p-chlorothiophenolate, or, in the former case, sodium azide. Each of the 1,8- and 2,8-disubstituted derivatives of cAMP was tested as activators of cAMP-dependent protein kinase and as substrates for the inhibitors of cyclic nucleotide phosphodiesterases. Depending on the substitutions, examples were found where the disubstituted derivatives were either more active, equally as active or less active than the monosubstituted parent compounds as protein kinase activators. For the compounds reported, 8-substitution completely or substantially eliminated the ability of 1- or 2-substituted derivatives of cAMP to serve as substrates for phosphodiesterase and diminished the ability of these latter derivatives to inhibit cAMP hydrolysis. |
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Authors:
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H Uno; R B Meyer; D A Shuman; R K Robins; L N Simon; J P Miller |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 19 ISSN: 0022-2623 ISO Abbreviation: J. Med. Chem. Publication Date: 1976 Mar |
Date Detail:
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Created Date: 1976-05-25 Completed Date: 1976-05-25 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 419-22 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3',5'-Cyclic-AMP Phosphodiesterases
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metabolism Animals Brain / enzymology Cattle Cyclic AMP / analogs & derivatives*, chemical synthesis, metabolism, pharmacology Enzyme Activation / drug effects Kidney / enzymology Lung / enzymology Myocardium / enzymology Protein Kinases / metabolism Rabbits |
| Chemical | |
Reg. No./Substance:
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60-92-4/Cyclic AMP; EC 2.7.-/Protein Kinases; EC 3.1.4.17/3',5'-Cyclic-AMP Phosphodiesterases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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