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US 5,684,205 AGranted
Use of substituted cyclopentane- di- and -triones
AssigneeBayer Aktiengesellschaft
InventorsPeter Norman, Roderick L. Hall, Graham A. Place, Graham Holmwood, Gabriele Braunlich
Life of this patent
Estimating the term…
Abstract
The invention relates to the use of substituted cyclopentane-diones and cyclopentane-triones for the preparation of medicaments which as chloride channel blockers are suitable for controlling airway diseases, secretory diarrhea and inflammatory diseases.
Claims10
Substituted cyclopentane- di- and -triones of the general formula ##STR30## in which A and D are identical or different and represent hydrogen, halogen, nitro, phenyl or straigth-chain or branched alkyl having up to 8 carbon atoms or represent a group of the formula --NR.sup.11 R.sup.12,--CO.sub.2 R.sup.13 or --O(CH.sub.2).sub.a (CO.sub.2).sub.b R.sup.14
- in which
- R.sup.11 and R.sup.12 are identical or different and denote hydrogen, phenyl or straight-chain or branched alkyl having up to 6 carbon atoms,
- denotes hydrogen or straight-chain or branched alkyl having up to 8 carbon atoms,
- a denotes a number 0, 1,2, 3 or 4,
- b denotes a number 0 or 1,
- R.sup.14 has the abovementioned meaning of R.sup.13 and is identical or different to that or denotes phenyl,
- R.sup.1 represents hydrogen,
- R.sup.2 and R.sup.3, R.sup.4 and R.sup.5 and/or R.sup.6 and R.sup.7 represent a residue of the formula .dbd.O, or two of the pairs have the abovementioned meaning and both substituents of the remaining pair,
- R.sup.2 and R.sup.3 or R.sup.4 and R.sup.5 or R.sup.6 and R.sup.7 represent hydrogen,
- or
- R.sup.1 and R.sup.2 or R.sup.1 and R.sup.7 or R.sup.2 and R.sup.4 together represent a double bond and in these cases,
- R.sup.3,R.sup.5 and R.sup.6 respectively represent hydrogen hydroxyl or a straight-chain or branched alkoxy having up to 6 carbon atoms,
- R.sup.8 and R.sup.9 represent hydrogen,
- or
- R.sup.8 and R.sup.9 together represent a double bond,
- R.sup.10 has the abovementioned meaning of A or D and is identical or different to that,
- E represents a 5 to 7 membered, aromatic heterocycle having up to 3 heteroatoms from the series comprising N, S and O and to which a phenyl ring can be fused, or
- represents aryl having up to 6 to 10 carbon atoms and wherein all rings are optionally monosubstituted to trisubstituted by identical or different substitutents from the series comprising halogen, nitro, trifluoromethyl, phenyl or straight-chain or branched alkyl having up to 6 carbon atoms or by a group of the formula --NR.sup.15 R.sup.16, --CO.sub.2 R.sup.17 or --O(CH.sub.2).sub.d' --(CO.sub.2).sub.e' R.sup.18,
- in which
- R.sup.15 and R.sup.16 have the abovementioned meaning of R.sup.11 and R.sup.12 and are identical or different to that,
- R.sup.17 has the abovementioned meaning of R.sup.13 and is identical or different to that
- R.sup.18 has the above mentioned meaning of R.sup.14 and is identical or different to that,
- d denotes a number 0, 1, 2, 3 or 4,
- e denotes a number 0 or 1,
- and their tautomers, racemates, enantiomers, diastereomers and salts,
- with the exception of
- 1. 2,4-cyclopentanetrione, 3-(4-chlorophenyl)methyl!-5-phenyl, 1,2,4-cyclopentanetrione, 3-(4-chloro-3-nitrophenyl)methyl!-5-phenyl, 1,2,4-cyclopentanetrione, 3-(4-chlorophenyl)methylene!-5-phenyl, 4-cyclopentene-1,3-dione, 4-ethoxy-5-phenyl-2-(phenylmethylene)-(Z) and (E) 4-cyclopentene-1,3-dione, 2-(4-chlorophenyl)methyl!-4-hydroxy-5-phenyl 4-cyclopentene-1,3-dione, 2-4-(chlorphenyl)methylene)-4-hydroxy-5-phenyl 2- (4-chloro-3-nitrobenzyliden)-4-hydroxy-5-phenyl-cyclopent-4-ene- 1,3-dion 3-(4-nitro-benzylidene)-5-phenyl-cyclopentane-1,2,4-trione 3-(4-methyl-benzylidene)-5-phenyl-4-cyclopentane-1,2,4-trione 3-benzylidene-5-phenyl-cyclopentane-1,2,4-trione.
24 more elements
A process for the preparation of substituted cyclopentane- di- and -triones according to claim 5 characterized in that
- A! compounds of the general formula (II) ##STR31## in which A and D have the meaning already given,
- and
- L stands for the residue ##STR32## are reacted with compounds of the general formulae (III) or (IIIa) ##STR33## in which E has the meaning given,
- and
- T denotes halogen,
- in the presence of an inert solvent and optionally in presence of a base or an auxiliary,
- or
- B! in the case of the triones and their tautomers compounds of the general formula (IV) ##STR34## in which A, D and E have the abovementioned meaning,
- are reacted with diethyloxalate/NaOC.sub.2 H.sub.5 by cyclisation after decarboxylation,
- and
- if appropriate in the case of R.sup.8 /R.sup.9 =hydrogen,
- compounds of the general formulae (I) with a corresponding double bond are hydrogenated
- and in the case of R.sup.3, R.sup.5 or R.sup.6 .noteq.OH, the corresponding hydroxyl compounds are etherified.
10 more elements
A method for controlling airway disease, secretory diarrhoea and inflammatory diseases which comprises administering to a host in need thereof an effective amount of a substituted cyclopentane- di- and -trione of the formula ##STR35## in which A and D are identical or different and represent hydrogen, halogen, nitro, phenyl or straigth-chain or branched alkyl having up to 8 carbon atoms or represent a group of the formula --NR.sup.11 R.sup.12, --CO.sub.2 R.sup.13 or
- --O(CH.sub.2).sub.a (CO.sub.2).sub.b R.sup.14
- in which
- R.sup.11 and R.sup.12 are identical or different and denote hydrogen, phenyl or straight-chain or branched alkyl having up to 6 carbon atoms,
- R.sup.13 denotes hydrogen or straight-chain or branched alkyl having up to 8 carbon atoms,
- a denotes a number 0, 1,2, 3 or 4,
- b denotes a number 0 or 1,
- R.sup.14 has the abovementioned meaning of R.sup.13 and is identical or different to that or denotes phenyl,
- R.sup.1 represents hydrogen,
- R.sup.2 and R.sup.3, and R.sup.5 and/or R.sup.6 and R.sup.7 represent a residue of the formula .dbd.O,
- or two of the pairs have the abovementioned meaning and both substitutents of the remaining pair;
- R.sup.2 and R.sup.3 or R.sup.4 and R.sup.5 or R.sup.6 and R.sup.7 represent hydrogen,
- or
- R.sup.1 and R.sup.2 or R.sup.1 and R.sup.7 or R.sup.2 and R.sup.4 together represent a double bond and in these cases,
- R.sup.3, R.sup.5 and R.sup.6 respectively represent hydrogen, hydroxyl or a straight-chain or branched alkoxy having up to 6 carbon atoms,
- R.sup.8 and R.sup.9 represent hydrogen,
- or
- R.sup.8 and R.sup.9 together represent a double bond,
- R.sup.10 has the abovementioned meaning of A or D and is identical or different to that,
- E represents a 5 to 7 membered, aromatic heterocycle having up to 3 heteroatoms from the series comprising N, S and O and to which a phenyl ring can be fused, or
- represents aryl having up to 6 to 10 carbon atoms
- and wherein all rings are optionally monosubstituted to trisubstituted by identical or different substitutents from the series comprising halogen, nitro, trifluoromethyl, phenyl or straight-chain or branched alkyl having up to 6 carbon atoms or by a group of the formula --NR.sup.15 R.sup.16, --CO.sub.2 R.sup.17 or
- --O(CH.sub.2).sub.d --(CO.sub.2).sub.e R.sup.18
- in which
- R.sup.15 and R.sup.16 have the abovementioned meaning of R.sup.11 and R.sup.12 and are identical or different to that,
- R.sup.17 has the abovementioned meaning of R.sup.13 and is identical or different to that
- R.sup.18 has the above mentioned meaning of R.sup.14 and is identical or different to that,
- d denotes a number 0, 1, 2, 3 or 4,
- e denotes a number 0 or 1,
- or an isomer or salt thereof.
26 more elements
Dependencies are inferred from the claim text.