| Autor: |
Michael P.L. Caton, Keith Crowshaw |
| Rok vydání: |
1977 |
| Předmět: |
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| DOI: |
10.1016/b978-0-12-405850-7.50011-4 |
| Popis: |
(±)-11-Deoxyprostaglandins of the E 1 series are synthesised by elaboration of the aldehyde (vii) which is prepared from the enone (iv) via thenitrile (vi) or nitromethyl compound (xii). The stereochemistry of the intermediates is discussed and evidence presented thatnitrile and nitromethyl compounds are cis/trans mixtures and that most of the cis is converted to the trans form at the aldehyde stage.11-Deoxy-PGF 1 analogues are prepared directly from the nitrile (v) via the aldehyde (xvi). The synthesis has also been adapted to give 15- and 16-methyl analogues, and the finding that epoxides of 2-alkylcyclopent-2-enones react with acetic acid to give 5-acetoxy-2-alkylcyclopent-2-enones affords an approach to10-hydroxyprostenoic acids. A large number of the 11-deoxypros-taglandin E 1 analogues have been screened for bronchodilator and anti-secretory activity. Numerous side effects have been observed in animals and in man after treatment with both natural and synthetic analogues of PGE 1 and PGE 2 . We have designed new screening tests in an effort to detect these side effects in animals during the routine evaluation of the pharmacological properties ofour analogues. This has enabled us to derive an index of selectivity for each compound, and the pharmacological profiles of the more selective analogues are described in this paper. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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