Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Bacterium or component thereof or substance produced by said...
Patent
1982-05-17
1984-08-21
Jiles, Henry R.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Bacterium or component thereof or substance produced by said...
424274, 424275, 424285, 546269, 548525, 549 60, 549415, 549465, A61K 31557, C07D307935
Patent
active
044669690
DESCRIPTION:
BRIEF SUMMARY
The invention relates to prostacyclin derivatives, a process for their manufacture and their use as medicaments.
Prostacyclin (PGI.sub.2), one of the main factors in blood platelet aggregation, has a dilating effect on various blood vessels (Science 196, 1072) and could therefore come into consideration as an agent for reducing blood pressure. PGI.sub.2 does not, however, possess the stability necessary for use as a medicament. For example, its half life at physiological pH values and at room temperature is only a few minutes.
We have now found that the introduction of an oxo group in the 7-position of the prostacyclin results in stabilisation of the prostacyclin molecule whilst retaining the pharmacological range of action and the duration of action of these prostacyclins is distinctly prolonged.
The compounds according to the present invention have a hypotensive and bronchodilative action. They are also suitable for inhibiting thrombocyte aggregation, vasoconstriction and gastric acid secretion.
The present invention provides a 7-oxoprostacyclin of the general formula ##STR3## in which R.sub.1 represents the radical OR.sub.3 wherein unsubstituted or substituted, alkyl radical having from 1 to 10 carbon atoms, an unsubstituted or substituted aryl radical, an unsubstituted or substituted cycloalkyl radical, or an unsubstituted or substituted heterocyclic radical or or saturated, unsubstituted or substituted, organic carboxylic or sulphonic acid having from 1 to 15 carbon atoms, --CH.dbd.CH-- group, ##STR4## group, the hydroxy group of which may be free or functionally modified and may be in the .alpha.- or .beta.-position, unsubstituted or substituted alkylene radical having from 1 to 10 carbon atoms, and substituted, alkyl radical having from 1 to 10 carbon atoms, a straight-chain or branched-chain, unsubstituted or substituted, alkenyl radical having from 2 to 10 carbon atoms, or, where D and E together represent a direct bond, a straight-chain or branched-chain, unsubstituted or substituted, alkynyl radical having from 2 to 6 carbon atoms,
As alkyl groups represented by R.sub.3, there come into consideration straight-chain or branched alkyl groups having from 1 to 10 carbon atoms, such as, for example, methyl, ethyl, propyl, butyl, isobutyl, tert.-butyl, pentyl, neopentyl, heptyl, hexyl or decyl radicals. The alkyl groups R.sub.3 may optionally be substituted by one or more of the same or different substituents selected from halogen atoms, alkoxy radicals having from 1 to 4 carbon atoms, optionally substituted aryl groups, dialkylamines and trialkylammonium radicals each having from 1 to 4 carbon atoms in each alkyl radical. Those alkyl groups which are mono-substituted are preferred. Examples of substituents that may be mentioned are fluorine, chlorine and bromine atoms and phenyl, dimethylamine, methoxy and ethoxy radicals. As preferred alkyl groups R.sub.3 are those having from 1 to 4 carbon atoms, such as, for example, methyl, ethyl, propyl, dimethylaminopropyl, isobutyl and butyl radicals.
As aryl groups represented by R.sub.3, there come into consideration both substituted and unsubstituted aryl groups, such as, for example, phenyl, 1-naphthyl and 2-naphthyl radicals which may each be substituted by from 1 to 3 halogen atoms, a phenyl group, from 1 to 3 alkyl radicals each having from 1 to 4 carbon atoms, a chloromethyl, fluoromethyl, trifluoromethyl, carboxy or hydroxy radical or an alkoxy radical having from 1 to 4 carbon atoms. Preferably, the substituents are in the 3- and 4-positions on the phenyl ring, for example fluorine, chlorine, alkoxy or trifluoromethyl radicals or, in the 4-position, hydroxy radicals.
A cycloalkyl group represented by R.sub.3 may contain from 4 to 10, preferably 5 and 6, carbon atoms in the ring. The rings may be substituted by alkyl radicals having from 1 to 4 carbon atoms. There may be mentioned, for example, cyclopentyl, cyclohexyl, methylcyclohexyl and adamantyl radicals.
As heterocyclic groups represented by R.sub.3, there come into consideration 5- and 6-membere
REFERENCES:
patent: 4330553 (1982-05-01), Simonidesz et al.
Casals-Stenzel Jorge
Mannesmann Gerda
Nikolson Robert C.
Vorbruggen Helmut
Dentz Bernard
Jiles Henry R.
Schering Aktiengesellschaft
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