Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai
Patent
1998-06-24
2000-09-05
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Cyclopentanohydrophenanthrene ring system doai
540 65, 540 67, C07J 7100, A61K 31565
Patent
active
061143189
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to novel anti-inflammatory and anti-allergic compounds of the androstane series and to processes for their preparation. The present invention also relates to pharmaceutical formulations containing the compounds and to therapeutic uses thereof, particularly for the treatment of inflammatory and allergic conditions.
Glucocorticosteroids which have-anti-inflammatory properties are known and are widely used for the treatment of inflammatory disorders or diseases such as asthma and rhinitis. However, such glucocorticosteroids may suffer from the disadvantage of causing unwanted systemic effects following administration. WO94/13690, WO94/14834, WO92/13873 and WO92/13872 all disclose glucocorticosteroides which are alleged to possess anti-inflammatory activity coupled with reduced systemic potency.
The present invention provides a novel group of compounds which possess useful anti-inflammatory activity whilst having little or no systemic activity. Thus, the compounds of the present invention represent a safer alternative to those known glucocorticoids which have poor side-effect profiles.
Thus, according to one aspect of the invention, there is provided a compound of formula (I) ##STR2## and solvates thereof in which
R.sub.1 and R.sub.2 are the same or different and each represents hydrogen or C.sub.1-6 alkyl;
R.sub.3 and R.sub.4 are the same or different and each represents hydrogen or halogen; and ##STR3## represents a single or a double bond.
In the above definitions, the term "alkyl" as a group or part of a group means a straight chain or, where available, a branched chain alkyl moiety. For example, it may represent a C.sub.1-4 alkyl function as represented by methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl and t-butyl.
The solvates may, for example, be hydrates.
References hereinafter to a compound according to the invention includes both compounds of formula (I) and their solvates, particularly pharmaceutically acceptable solvates.
It will be appreciated that the invention includes within its scope all stereoisomers of the compounds of formula (I) and mixtures thereof.
In particular the compounds of formula (I) contain an asymmetric centre at the point of attachment of the lactone moiety. Thus, the invention includes within its scope both diastereoisomers at this asymmetric centre and mixtures thereof.
Diastereoisomers and mixtures thereof at the asymmetric centre ##STR4## when R.sub.1 and R.sub.2 are different are also included within the scope of the present invention.
The sulphur linkage may be to the alpha, beta or gamma carbon atoms of the lactone group, ##STR5## however, compounds of formula (I) in which S is bonded to the alpha atom are generally preferred.
A preferred group of compounds are compounds of formula (I) in which R.sub.1 and R.sub.2 which may be the same or different each represents hydrogen or C.sub.1-3 alkyl, particularly hydrogen, methyl or n-propyl.
Compounds of formula (I) in which R.sub.3 and R.sub.4, which can be the same or different, each represents hydrogen, fluorine or chlorine, particularly hydrogen or fluorine, are preferred. Especially preferred are compounds in which both R.sub.3 and R.sub.4 are fluorine.
A particularly preferred group of compounds of the invention are compounds of formula (I) in which R.sub.1 and R.sub.2 are the same or different and each represents hydrogen or C.sub.1-3 alkyl, especially hydrogen, methyl or n-propyl; R.sub.3 and R.sub.4 which can be the same or different each represents hydrogen or fluorine, especially fluorine; and ##STR6## represents a single or a double bond. The R-isomers of compounds within this group in which R.sub.1 and R.sub.2 are different are particularly preferred.
It is to be understood that the present invention covers all combinations of particularly and preferred groups referred to hereinabove.
Compounds of formula (I) include: enedioxy-17.beta.-(2-oxo-tetrahydro-furan-3-yl-sulfanyl)-androst-4-en-3-one ; enedioxy-17.beta.-(2-oxo-tetrahydro-furan-3-yl-sulfanyl)-androsta-1,4-dien- 3-one; -hyd
REFERENCES:
patent: 4481144 (1984-11-01), Varma
Biggadike Keith
Procopiou Panayiotis Alexandrou
Coleman Brenda
Glaxo Group Limited
Shah Mukund J.
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