Adenosine Deaminase Inhibitors. Synthesis and Biological Evaluation of Putative Metabolites of (+)-erythro-9-(2S-Hydroxy-3R-nonyl)adenine
| Autor: | Johanna D. Stoeckler, Mallela S. P. Sarma, Palle V. P. Pragnacharyulu, Elie Abushanab, Shih-Ying Li, Chandra Vargeese |
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| Rok vydání: | 1994 |
| Předmět: |
biology
Chemistry Stereochemistry Adenine Deamination Diastereomer AMP deaminase In Vitro Techniques Adenosine Affinities Adenosine deaminase Drug Discovery Adenosine Deaminase Inhibitors biology.protein medicine Animals Molecular Medicine Cattle Binding site Adenosine Deaminase Inhibitor medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 37:3844-3849 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00048a020 |
| Popis: | The synthesis and biological evaluation of three chain-hydroxylated (+)-erythro-9-(2S-hydroxy-3R-nonyl)adenine [(+)-EHNA] derivatives are reported. Hydroxy groups at positions 9', 8', and 8',9' (12, 25, and 16) were introduced by either epoxidation or hydroboration of a terminal olefinic intermediate. Affinities for calf intestinal adenosine deaminase (ADA) were determined from the steady-state inhibition of adenosine deamination. Ki values of 0.82, 3.8, 6.4, and 15.8 nM were estimated for (+)-EHNA, 9'-hydroxy-(+)-EHNA (12), 8'-hydroxy-(+)-EHNA (25), and 8',9'-dihydroxy-(+)-EHNA (16), respectively, by assuming a single class of binding sites. However, the data for all inhibitors conformed more closely to the kinetics of a heterogeneous system with different affinities for two or more binding sites. The fairly high potencies of 12 and 25 suggest that other substitutions at the terminal position of the nonyl chain could yield useful ADA inhibitors. |
| Databáze: | OpenAIRE |
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