JP2007537187A5

JP2007537187A5 -

Info

Publication number: JP2007537187A5
Application number: JP2007512067A
Authority: JP
Filing date: 2005-05-10
Publication date: 2008-06-26

Claims

It may optionally be in the form of individual enantiomers, individual enantiomers or racemic mixtures, optionally in the form of acid addition salts with pharmacologically acceptable acids, or in some cases Compounds of general formula 1 which may be in the form of solvates and / or hydrates:

(Wherein n represents 1 or 2;
A represents a double bond group selected from — (C═O) —, —S (═O) —, —S (═O) ₂ — and —C (R ⁴ R ⁵ ) —;
B represents —O—, —NR ⁶ — , —CH ₂ —, —S—CR ⁷ R ⁸ —, —NR ⁶ —CR ⁷ R ⁸ —, —CH ₂ —CR ⁷ R ⁸ —, —O—CR. ⁹ represents a double bond group selected from R ¹⁰ -and -CH = CH-;
R ¹ and R ² may be the same or different and each represents hydrogen, C _1-4 alkyl, halogen, OH or —O—C _1-4 alkyl;
R ³ is hydrogen, C _1-4 alkyl, OH, halogen, —O—C _1-4 alkyl, —COOH, —COO—C _1-4 alkyl, —O—C _1-4 alkylene-COOH or —O. -C _1-4 alkylene-CO-O-C _1-4 alkyl is shown;
R ⁴ and R ⁵ may be the same or different and are hydrogen, C _1-4 alkyl, OH, halogen, —O—C _1-4 alkyl, —COOH or —COO—C _1-4 alkyl. Indicates;
R ⁶ represents hydrogen or C _1-4 alkyl;
R ⁷ and R ⁸ may be the same or different and each represents hydrogen or C _1-4 alkyl; R ⁹ and R ¹⁰ may be the same or different, and C _1-4 Represents alkyl).

n represents 1 or 2;
A represents a double bond group selected from — (C═O) —, —S (═O) ₂ —, and —C (R ⁴ R ⁵ ) —;
B represents —O—, —NR ⁶ —, —CH ₂ —, —S—CR ⁷ R ⁸ —, —NR ⁶ —CR ⁷ R ⁸ —, —CH ₂ —CR ⁷ R ⁸ —, —O—CR. ⁹ represents a double bond group selected from R ¹⁰ -and -CH = CH-;
R ¹ and R ² may be the same or different and represent hydrogen, methyl, ethyl, propyl, fluorine, chlorine, bromine, OH, methoxy or ethoxy;
R ³ is hydrogen, methyl, ethyl, propyl, fluorine, chlorine, bromine, OH, methoxy, ethoxy, —COOH, —COO methyl, —COO ethyl, —O—CH ₂ —COOH, —O—CH ₂ —COO. - methyl, -O-CH ₂ -COO- _{_{ethyl, -O-CH 2 -CH 2 -COOH}} , -O-CH 2 -CH 2 -COO- methyl, -O-CH _₂ -CH ₂ -COO- ethyl, Represents —O—CH ₂ —CH ₂ —CH ₂ —COOH, —O—CH ₂ —CH ₂ —CH ₂ —COO-methyl or —O—CH ₂ —CH ₂ —CH ₂ —COO-ethyl;
R ⁴ and R ⁵ may be the same or different and represent hydrogen, methyl, ethyl, OH, fluorine, chlorine, —COOH, —COO methyl or —COO ethyl;
R ⁶ represents hydrogen, methyl, ethyl or propyl, preferably hydrogen;
R ⁷ and R ⁸ may be the same or different and represent hydrogen, methyl, ethyl or propyl;
R ⁹ and R ¹⁰ may be the same or different and represent methyl, ethyl or propyl,
It may optionally be in the form of individual enantiomers, individual enantiomers or racemic mixtures, optionally in the form of acid addition salts with pharmacologically acceptable acids, or in some cases The compound of formula 1 according to claim 1, which may be in the form of a solvate and / or a hydrate.

n represents 1 or 2;
A represents a double bond group selected from — (C═O) —, —S (═O) ₂ —, and —C (R ⁴ R ⁵ ) —;
B represents —O—, —NR ⁶ —, —CH ₂ —, —S—CR ⁷ R ⁸ —, —NR ⁶ —CR ⁷ R ⁸ —, —CH ₂ —CR ⁷ R ⁸ —, —O—CR. ⁹ represents a double bond group selected from R ¹⁰ -and -CH = CH-;
R ¹ and R ² may be the same or different and represent hydrogen, methyl, ethyl, fluorine, chlorine, OH, methoxy or ethoxy;
R ³ is hydrogen, methyl, ethyl, fluorine, chlorine, OH, methoxy, ethoxy, —COOH, —COO methyl, —COO ethyl, —O—CH ₂ —COOH, —O—CH ₂ —COO-methyl, — O-CH ₂ -COO- _{_{ethyl, -O-CH 2 -CH 2 -COOH}} , -O-CH 2 -CH 2 -COO- methyl or -O-CH _₂ -CH ₂ -COO- ethyl;
R ⁴ and R ⁵ may be the same or different and represent hydrogen, methyl, ethyl, —COOH, —COO methyl or —COO ethyl;
R ⁶ represents hydrogen, methyl or ethyl;
R ⁷ and R ⁸ may be the same or different and represent hydrogen, methyl or ethyl, preferably hydrogen or methyl;
R ⁹ and R ¹⁰ may be the same or different and represent methyl or ethyl, preferably methyl,
It may optionally be in the form of individual enantiomers, individual enantiomers or racemic mixtures, optionally in the form of acid addition salts with pharmacologically acceptable acids, or in some cases 3. A compound of formula 1 according to claim 1 or 2 which may be in the form of a solvate and / or hydrate.

n represents 1 or 2;
A represents a double bond group selected from — (C═O) —, —S (═O) ₂ —, and —C (R ⁴ R ⁵ ) —;
B is, -O -, - NH -, - CH 2 -, - S-CH 2 -, - NH-CH 2 -, - CH 2 -CH 2 -, - O-CR 9 R 10 - and -CH = A double bond group selected from CH-;
R ¹ and R ² may be the same or different and represent hydrogen, methyl, ethyl, fluorine, chlorine, OH, methoxy or ethoxy;
R ³ is hydrogen, methyl, ethyl, fluorine, chlorine, OH, methoxy, ethoxy, —COOH, —COO methyl, —COO ethyl, —O—CH ₂ —COOH, —O—CH ₂ —COO-methyl, — O-CH ₂ -COO- _{_{ethyl, -O-CH 2 -CH 2 -COOH}} , -O-CH 2 -CH 2 -COO- methyl or -O-CH _₂ -CH ₂ -COO- ethyl;
R ⁴ and R ⁵ may be the same or different and represent hydrogen, methyl, ethyl, —COOH, —COO methyl or —COO ethyl;
R ⁹ and R ¹⁰ may be the same or different and are preferably the same and represent methyl or ethyl, preferably methyl,
It may optionally be in the form of individual enantiomers, individual enantiomers or racemic mixtures, optionally in the form of acid addition salts with pharmacologically acceptable acids, or in some cases The compound of formula 1 according to any one of claims 1 to 3, which may be in the form of a solvate and / or a hydrate.

n represents 1 or 2;
A represents a double bond group selected from — (C═O) — and —S (═O) ₂ —;
B is, -O -, - NH -, - CH 2 -, - S-CH 2 -, - NH-CH 2 -, - CH 2 -CH 2 -, - O-CR 9 R 10 - and -CH = A double bond group selected from CH-;
R ¹ and R ² may be the same or different and represent hydrogen, methyl, ethyl, fluorine, chlorine, OH, methoxy or ethoxy;
R ³ is hydrogen, methyl, ethyl, fluorine, chlorine, OH, methoxy, ethoxy, —COOH, —COO methyl, —COO ethyl, —O—CH ₂ —COOH, —O—CH ₂ —COO-methyl, — O-CH ₂ -COO- _{_{ethyl, -O-CH 2 -CH 2 -COOH}} , -O-CH 2 -CH 2 -COO- methyl or -O-CH _₂ -CH ₂ -COO- ethyl;
R ⁹ and R ¹⁰ may be the same or different and are preferably the same and represent methyl or ethyl, preferably methyl,
It may optionally be in the form of individual enantiomers, individual enantiomers or racemic mixtures, optionally in the form of acid addition salts with pharmacologically acceptable acids, or in some cases The compound of formula 1 according to any one of claims 1 to 4, which may be in the form of a solvate and / or a hydrate.

R ¹ and R ² may be the same or different and represent hydrogen, methyl, ethyl, fluorine, chlorine, OH, methoxy or ethoxy;
R ³ represents hydrogen,
It may optionally be in the form of individual enantiomers, individual enantiomers or racemic mixtures, optionally in the form of acid addition salts with pharmacologically acceptable acids, or in some cases 6. The compound of formula 1 according to any one of claims 1 to 5, which may be in the form of a solvate and / or a hydrate.

R ¹ and R ² may be the same or different and represent hydrogen, methyl, fluorine, chlorine or methoxy;
R ³ may be the same or different and represents hydrogen, methyl, fluorine, chlorine or methoxy;
It may optionally be in the form of individual enantiomers, individual enantiomers or racemic mixtures, optionally in the form of acid addition salts with pharmacologically acceptable acids, or in some cases 6. The compound of formula 1 according to any one of claims 1 to 5, which may be in the form of a solvate and / or a hydrate.

R ³ is methyl, ethyl, fluorine, chlorine, OH, methoxy, ethoxy, —COOH, —COO methyl, —COO ethyl, —O—CH ₂ —COOH, —O—CH ₂ —COO-methyl, —O—. CH ₂ -COO- _{_{ethyl, -O-CH 2 -CH 2 -COOH}} , a -O-CH _₂ -CH ₂ -COO- methyl or -O-CH _₂ -CH ₂ -COO- ethyl shown,
It may optionally be in the form of individual enantiomers, individual enantiomers or racemic mixtures, optionally in the form of acid addition salts with pharmacologically acceptable acids, or in some cases 6. The compound of formula 1 according to any one of claims 1 to 5, which may be in the form of a solvate and / or a hydrate.

R ³ is methyl, ethyl, OH, methoxy, ethoxy, —O—CH ₂ —COOH, —O—CH ₂ —COO-methyl or —O—CH ₂ —COO-ethyl, preferably OH, methoxy or ethoxy Showing,
It may optionally be in the form of individual enantiomers, individual enantiomers or racemic mixtures, optionally in the form of acid addition salts with pharmacologically acceptable acids, or in some cases 6. The compound of formula 1 according to any one of claims 1 to 5, which may be in the form of a solvate and / or a hydrate.

Hydrochloride, hydrobromide, hydroiodide, hydrosulfate, hydrophosphate, hydromethanesulfonate, hydronitrate, hydromaleate, hydroacetate, hydrobenzoate, hydrocitrate, hydrofumarate, hydrotartrate, 10. The form of any of the acid addition salts with pharmacologically acceptable acids selected from hydrooxalates, hydrosuccinates, hydrobenzoates and hydro-p-toluenesulfonates. A compound of formula 1 as described in

General formula R-1:

11. The compound of formula 1 according to any one of claims 1 to 10, in the form of the R-enantiomer of

The compound of general formula 1 according to any one of claims 1 to 11 as a pharmaceutical composition.

Use of a compound of general formula 1 according to any one of claims 1 to 12 for the manufacture of a pharmaceutical composition for the treatment of respiratory diseases.

A pharmaceutical formulation comprising a compound of formula 1 according to any one of claims 1-12.