Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai
Patent
1997-01-24
1998-12-22
Clardy, S. Mark
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Cyclopentanohydrophenanthrene ring system doai
552502, C07J 900, C07J 100, A61K 31565, A61K 31575
Patent
active
058520058
DESCRIPTION:
BRIEF SUMMARY
This application has been filed under 35 USC 371 as a national stage application of PCT/EP95/02913 filed Jul. 24, 1995 published as WO96/03419 Feb. 8, 1996. The present invention relates to dammara compounds and to pharmaceutical uses thereof. The dammara compounds comprise a recognized compound group of the triterpene class and are characterised by a tetracyclic core structure of formula I. ##STR1##
In the known dammara compounds this core structure is commonly substituted, generally mono-substituted, at the 3-position, e.g. by hydroxy (dammar-3-ols) or oxo (dammar-3-ones). Dammara compounds are also commonly substituted, generally mono-substituted, at the 17-position, e.g. as in the case of the dammarenes which are found in Ginseng root and other plant material and in which the 17-position commonly bears a hydrocarbyl residue comprising one or more, e.g. 1 or 2, alkene (--C.dbd.C--) linkages. Most typically in the case of the dammarenes, the 17-hydrocarbyl substituent comprises a C.sub.8 -alkenyl or -alkadienyl residue which may be further substituted, e.g. by one or more hydroxy groups. Dammara compounds may also bear one or more further substituents, commonly hydroxy groups, at other positions on the core structure or may incorporate one or more unsaturated linkages, e.g. double bonds, within the core structure. In the dammara compounds, however, the cyclic structure, stereochemical configuration as well as distribution of methyl groups at the 4-, 10-, 8- and - 14 positions shown in formula I remains unaltered.
In accordance with the present invention it has now been found that dammara compounds have desirable pharmaceutical, in particular immunosuppressive and antiinflammatory, properties.
Accordingly the invention provides in a first aspect: immunosuppressant or an antiinflammatory agent; therapeutic application as an immunosuppressant or an antiinflammatory agent; and/or antiinflammatory therapy which comprises administering an effective amount of a dammara compound to said subject.
Specific immunosuppressive and/or antiinflammatory indications or conditions comprised in the above definitions a.sup.1) to a.sup.3) include, in particular, any of those hereinafter specifically set forth.
By the term "dammara compound" as used herein is meant a compound comprising the characteristic core structure of formula I as herein above illustrated, i.e. having the particular cyclic structure, stereochemical configuration and distribution of methyl substituents shown in formula I. To the extent that stereochemical configuration shown in formula I remains unaltered, the term is to be understood as embracing compounds in which the formula I core structure bears one or more additional substituents, in particular at the 3- and/or 17-position, as well as compounds in which one or more of the carbon-carbon linkages comprising the core structure is/are unsaturated, e.g. ethylenically unsaturated. The term is thus to be understood as embracing, e.g., both dammar-3-ols and dammar-3-ones.
The term dammara compound as used herein is in particular to be understood as including 17C-dammara compounds, i.e. dammara compounds which are substituted at the 17-position by a group attached to the 17-position via a carbon atom. Such 17C-dammara compounds may be mono- or di-substituted, more conventionally mono-substituted, at the 17-position.
Preferred dammara compounds for use in accordance with the present invention are dammar-3-ols and physiologically hydrolysable and acceptable esters thereof and darnmar-3-ones and, in particular, 17C-dammara compounds. Especially preferred compounds for use in accordance with the invention are thus 17C-dammar-3-ols and physiologically hydrolysable and acceptable esters thereof and 17C-dammar-3-ones, for example compounds of formula IA ##STR2## in which a is >CH--OR.sub.1, in which R.sub.1 is hydrogen or a physiologically cleavable and acceptable acyl residue, or >C.dbd.O atom.
By the term "physiologically hydrolysable and acceptable ester" as used herein is meant any ester which is cleavabl
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Hiestand Peter
Naef Reto
Naegeli Hans-Ulrich
Oberer Lukas
Revesz Laszlo
Clardy S. Mark
Loeschorn Carol A.
Novartis AG
Qazi Sabiha N.
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