Indane compounds and their pharmaceutical use

Details Indane compounds and their pharmaceutical use Indane compounds and their pharmaceutical use

1999-12-03

2002-08-13

Siegel, Alan (Department: 1621)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Ketone doai

C514S681000, C514S727000, C514S728000, C514S730000, C514S732000, C562S433000, C562S427000, C562S462000, C562S466000, C564S440000, C564S443000, C564S434000, C568S327000, C568S715000

Reexamination Certificate

active

06433021

ABSTRACT:

The invention relates to indane compounds, process for their production, compositions containing them and their pharmacological use. More particularly, the invention relates to 2-[2-indenyl]indanones and 2-cyclopentenyl compounds as anti-inflammatory agents and mast cell stabilisation agents. According to the invention, there is provided a compound of any of the formulae 1-4.
wherein R
2
to R
7
are selected from the group consisting of:
hydrogen; hydroxy; cyclopentyl; alkyl carbonyl; hydro carbonyl; amino; amido; alkylamino; hydroxyamino; amine oxide groups; cyano; indane; indene; oxime; heterocyclic groups containing hetero atoms selected from one or more of N, 0 or S; aralkyl groups; aryl groups; mono and polybenzoid aryl groups; substituted aryl groups; thiol; thioureyl; phenylthiol groups; sulphonic acid groups; sulphoxide groups; sulphone groups; carboxylic acid groups of Cl to C
10
which may be substituted or unsubstituted; alkyl; substituted alkyl groups; acyl groups; and substituted acyl groups;
where R
1
and R
3
may together represent a double bond and wherein in (CH
2
)
n
, n is 0 to 8.
Preferred because of solubility salt formation, pharmacological activity and/or ease of production are the following subsets.
In one embodiment of the invention the compound is of the formula 2 as defined in claim
1
.
In a further embodiment of the invention the compound is of the formula 3 as defined in claim
1
.
In a preferred embodiment of the invention R
1
to R
7
are selected from one or more of the same or different of:
hydroxy, alkyl of C
1
to C
10
, aryl, substituted aryl, cyclopentyl, alkyl carbonyl, hydro carbonyl, amimo, amido, alkalamnino, hydroxyamino, amide oxide groups, cyano, indane, indene, oxime, sulphonic acid groups, sulphoxide groups, sulphone groups, or heterocyclic groups containing hetero atoms selected form one or more of N, O.
Preferably R
4
to R
7
are hydrogen.
In one preferred embodiment of the invention R
1
is cyclopentyl.
In this case preferably R
1
is cyclopenryenyl.
In one preferred aspect R
1
is indane.
In another preferred aspect R
1
is indene.
In one arrangement R
2
is acyl containing 1 to 10 carbon atoms.
Alternatively, R
2
is alkyl containing 1 to 10 carbon atoms, preferably, C
1
alkyl.
In another embodiment of the invention R
2
is substituted alkyl.
In a further embodiment of the invention R
2
is aryl having 4 to 8 carbon atoms, especially C
1
aryl.
The invention especially provides the following specific compounds:
1-phenyl-2-((2′-iidenyl)-indan-2-onyl)ethan-1-one (Compound I)
1-phenyl-2-((2′-iindenyl)-indan-2-ol)ethan-1-ol (Compound II)
1-phenyl-2-((2′-iidenyl)-indan-2-ol)ethan-1-one (Compound III)
1-phenyl-2-((2′-iidenyl)-indan-2-one)ethan-1-ol (Compound IV)
1-phenyl-2-((2′-cyclopent-1-enyl)indan-1-one)ethan-1-one (Compound V)
1-((2′-iindenyl)-indan-2-one)propan-2-one (Compound VI)
1-((2′-iindenyl)-indan-2-ol)propan-2-ol (Compound VII)
1-((2′-iindenyl)-indan-2-one)propan-2-ol (Compound VIII)
1-((2′-iindenyl)-indan-2-ol)propan-2-one (Compound IX)
The compounds may be used particularly to achieve mast cell stabilising and/or anti-inflammatory activity.
The invention also provides processes for preparing the compounds as defined in claims
33
to
42
.
It will be appreciated that the compounds include pharmacologically acceptable salts, esters, amides, isomers and solvates thereof.
It will also be appreciated that if the compounds have one or more chiral centres they may exist as a pair of enantiomers or as a mixture of diastereomers. This may have an effect on pharmacological properties.
It will further be appreciated that for pharmaceutical purposes the active compounds may be formulated in any desired form using any suitable excipients and/or carriers. For example, particularly in the case for use to achieve anti-inflammatory activity the compound may be formulated in a pharmaceutical composition suitable for topical/transdermal application.
The invention will be more clearly understood from the following description thereof, given by way of example only.
DETAILED DESCRIPTION OF THE INVENTION
In the preparation of some of the compounds of the invention are described in detail below. Some of the starting materials used are described in our earlier applications PCT/IE96/00080, PCT/IE96/00081 and PCT/IE96/00082 the contents of which are incorporated herein for reference. Other compounds within the scope of the claims can be prepared by analogy.


REFERENCES:
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patent: 1380089 (1975-01-01), None
patent: WO92/21641 (1992-12-01), None
patent: WO97/20802 (1997-06-01), None
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Herman et al, “Polymergebundene Cinchonaalkaloide als . . . ”, Helv. Chim. Acta, vol. 60, pp. 2208-2212, 1977.
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