Claims
- 1. A compound of formula I ##STR7## in which R1 is 1-4C-alkoxy or 1-4C-alkoxy which is completely or predominantly substituted by fluorine,
- R2 is 1-8C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy or 1-4C-alkoxy which is completely or predominantly substituted by fluorine,
- R3 and R4 are both hydrogen or together form an additional bond,
- R5 is R6, --C.sub.m H.sub.2m --R7, --C.sub.n H.sub.2n --C(O)R8, --CH(R9).sub.2 --C.sub.p H.sub.2p --Ar, in which
- R6 is hydrogen (H), 1-8C-alkyl, 3-10C-cycloalkyl, 3-7C-cycloalkylmethyl, 3-7C-alkenyl, 3-7C-alkynyl, phenyl-3-4C-alkenyl, 7-10C-polycycloalkyl, naphthyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidyl, quinazolinyl, quinoxalinyl, cinnolinyl, isoquinolyl, quinolyl, indanyl, benzoxazolyl, benzothiazolyl, oxazolyl, thiazolyl, N-methylpiperidyl, tetrahydropyranyl, tetrahydrothiapyranyl, or an unsubstituted or by R61 and/or R62 substituted phenyl radical, in which
- R61 is 1-4C-alkyl, 1-4C-alkoxy, nitro, halogen, carboxyl, carboxy-1-4C-alkyl, 1-4C-alkoxycarbonyl, hydroxy-1-4C-alkyl, amino, mono- or di-1-4C-alkylamino, 1-4C-alkylcarbonylamino, aminocarbonyl, mono- or di-1-4C-alkylaminocarbonyl, aminosulfonyl, mono- or di-1-4C-alkylaminosulfonyl, 4-methylphenylsulfonamido, tetrazol-5-yl, 2-(1-4C-alkyl)tetrazol-5-yl or 2-benzyl-tetrazol-5-yl and
- R62 is 1-4C-alkyl, 1-4C-alkoxy, nitro or halogen,
- R7 is hydroxyl, halogen, cyano, nitro, nitroxy(-O--NO.sub.2), carboxyl, carboxyphenyloxy, phenoxy, 1-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, 1-4C-alkylcarbonyl, 1-4C-alkylcarbonyloxy, 1-4C-alkylcarbonylamino, 1-4C-alkoxycarbonyl, aminocarbonyl, mono- or di-1-4C-alkylaminocarbonyl, amino, mono- or di-1-4C-alkylamino, or an unsubstituted or by R71 and/or R72 substituted piperidyl, piperazinyl, pyrrolidinyl or morpholinyl radical, where
- R71 is hydroxyl, 1-4C-alkyl, hydroxy-1-4C-alkyl or 1-4C-alkoxycarbonyl, and
- R72 is 1-4C-alkyl, carboxyl, aminocarbonyl or 1-4C-alkoxycarbonyl,
- R8 is an unsubstituted or by R81 and/or R82 substituted phenyl, naphthyl, phenanthrenyl or anthracenyl radical, in which
- R81 is hydroxyl, halogen, cyano, 1-4C-alkyl, 1-4C-alkoxy, carboxyl, aminocarbonyl, mono- or di-1-4C-alkylaminocarbonyl, 1-4C-alkylcarbonyloxy, 1-4C-alkoxycarbonyl, amino, mono- or di-1-4C-alkylamino, 1-4C-alkylcarbonylamino, or 1-4C-alkoxy which is completely or predominantly substituted by fluorine, and
- R82 is hydroxyl, halogen, 1-4C-alkyl, 1-4C-alkoxy or 1-4C-alkoxy which is completely or predominantly substituted by fluorine,
- R9 is --C.sub.q H.sub.2q -phenyl,
- Ar is an unsubstituted phenyl, naphthyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, quinazolinyl, quinoxalinyl, cinnolinyl, isoquinolyl, quinolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzotriazolyl, N-benzosuccinimidyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, furyl, thienyl, pyrrolyl, a 2-(1-4C-alkyl)-thiazol-4-yl radical, or a phenyl radical substituted by R10 and/or R11, in which
- R10 is hydroxyl, halogen, nitro, 1-4C-alkyl, trifluoromethyl, 1-4C-alkoxy, carboxyl, carboxy-4-4-C-alkyl, 1-4C-alkylcarbonyloxy, 1-4C-alkoxycarbonyl, amino, mono- or di-1-4C-alkyl-amino, 1-4-C-alkylcarbonylamino, aminocarbonyl or mono- or di-1-4C-alkylamino-carbonyl, and
- R11 is hydroxyl, halogen, nitro, 1-4C-alkyl or 1-4C-alkoxy,
- m is an integer from 1 to 8,
- n is an integer from 1 to 4,
- p is an integer from 1 to 6,
- q is an integer from 0 to 2,
- or a salt thereof.
- 2. A compound of formula I according to claim 1, in which
- R1 is 1-4C-alkoxy or 1-4C-alkoxy which is completely or predominantly substituted by fluorine,
- R2 is 1-8C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy or 1-4C-alkoxy which is completely or predominantly substituted by fluorine,
- R3 and R4 are both hydrogen or together form an additional bond,
- R5 is R6, --C.sub.m H.sub.2m --R7, --C.sub.n H.sub.2n --C(O)R8, --CH(R9).sub.2 --C.sub.p H.sub.2p --Ar, in which
- R6 is hydrogen (H), 1-8C-alkyl, 3-10C-cycloalkyl, 3-7C-cycloalkylmethyl, 3-7C-alkenyl, 3-7C-alkynyl, phenyl-3-4C-alkenyl, bornyl, norbornyl, adamantyl or an unsubstituted or by R61 and/or R62 substituted phenyl radical, in which
- R61 is 1-4-C-alkyl, 1-4C-alkoxy, nitro or halogen, and
- R62 is 1-4C-alkyl, nitro or halogen,
- R7 is hydroxyl, halogen, cyano, nitro, carboxyl, phenoxy, 1-4-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, 1-4C-alkylcarbonyl, 1-4C-alkylcarbonyloxy, 1-4C-alkylcarbonylamino, 1-4C-alkoxycarbonyl, aminocarbonyl, mono- or di-1-4C-alkylaminocarbonyl, amino, mono- or di-1-4C-alkylamino, or an unsubstituted or by R71 and/or R72 substituted piperidyl, piperazinyl, pyrrolidinyl or morpholinyl radical, where
- R71 is hydroxyl, 1-4C-alkyl, 1-4C-hydroxyalkyl or 1-4C-alkoxycarbonyl, and
- R72 is 1-4C-alkyl, carboxyl, aminocarbonyl or 1-4C-alkoxycarbonyl,
- R8 is an unsubstituted or by R81 and/or R82 substituted phenyl, naphthyl, phenanthrenyl or anthracenyl radical, in which
- R81 is hydroxyl, halogen, cyano, 1-4C-alkyl, 1-4C-alkoxy, carboxyl, aminocarbonyl, mono- or di-1-4C-alkylaminocarbonyl, 1-4C-alkylcarbonyloxy, 1-4C-alkoxycarbonyl, amino, mono- or di-1-4C-alkylamino, 1-4C-alkylcarbonylamino, or 1-4C-alkoxy which is completely or predominantly substituted by fluorine, and
- R82 is hydroxyl, halogen, 1-4C-alkyl, 1-4C-alkoxy or 1-4C-alkoxy which is completely or predominantly substituted by fluorine,
- R9 is --C.sub.q H.sub.2q -phenyl,
- Ar is an unsubstituted phenyl, naphthyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, quinazolinyl, quinoxalinyl, cinnolinyl, isoquinolyl, quinolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzotriazolyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, furyl, thienyl, pyrrolyl, a 2-(1-4C-alkyl)-thiazol-4-yl radical, or a phenyl radical substituted by R10 and/or R11, in which
- R10 is hydroxyl, halogen, nitro, 1-4C-alkyl, trifluoromethyl, 1-4C-alkoxy, carboxyl, carboxy-1-4C-alkyl, 1-4C-alkylcarbonyloxy, 1-4C-alkoxycarbonyl, amino, mono- or di-1-4C-alkylamino, 1-4C-alkylcarbonylamino, aminocarbonyl or mono- or di-1-4C-alkylaminocarbonyl, and
- R11 is hydroxyl, halogen, nitro, 1-4C-alkyl or 1-4C-alkoxy,
- m is an integer from 1 to 8,
- n is an integer from 1 to 4,
- p is an integer from 1 to 4,
- q is an integer from 0 to 2,
- or a salt thereof.
- 3. A compound of formula I according to claim 1, in which
- R1 is 1-4C-alkoxy or 1-2C-alkoxy which is completely or predominantly substituted by fluorine,
- R2 is 1-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy or 1-2C-alkoxy which is completely or predominantly substituted by fluorine,
- R3 and R4 are both hydrogen or together form an additional bond,
- R5 is R6, --C.sub.m H.sub.2m --R7, --C.sub.n H.sub.2n --C(O)R8, --CH(R9).sub.2 or --C.sub.p H.sub.2p --Ar, in which
- R6 is hydrogen, 1-8C-alkyl, 3-8C-cycloalkyl, 3-7C-cycloalkylmethyl, 3-7C-alkenyl, 3-7C-alkynyl, phenyl-3-4C-alkenyl, bornyl, norbornyl, adamantyl, naphthyl, pyridyl, quinoxalinyl, indanyl, benzothiazolyl, N-methylpiperidyl, tetrahydropyranyl, tetrahydrothiopyranyl, or an unsubstituted or by R61 and/or R62 substituted phenyl radical, in which
- R61 is 1-2-C-alkyl, 1-2C-alkoxy, nitro, halogen, carboxyl, carboxy-1-4C-alkyl, 1-4C-alkoxycarbonyl, hydroxy-1-4C-alkyl, amino, mono- or di-1-4C-alkylamino, aminocarbonyl, aminosulfonyl, mono- or di-1-4C-alkylaminosulfonyl, 4-methylphenylsulfonamido, tetrazol-5-yl, 2-(1-4C-alkyl)tetrazol-5-yl or 2-benzyltetrazol-5-yl, and
- R62 is 1-2C-alkyl, 1-2C-alkoxy, nitro, or halogen,
- R7 is hydroxyl, halogen, carboxyl, nitroxy (--O--NO.sub.s), phenoxy, carboxyphenyloxy, 1-4C-alkoxy, 1-4C-alkylcarbonyl, 1-4C-alkylcarbonyloxy, 1-4C-alkylcarbonylamino, 1-4C-alkoxycarbonyl, aminocarbonyl, mono- or di-1-4-C-alkylaminocarbonyl, amino, mono- or di-1-4C-alkylamino, or an unsubstituted or by R71 and/or R72 substituted piperidyl, piperazinyl or morpholinyl radical, where
- R71 is hydroxyl, 1-4C-alkyl, 1-4C-hydroxyalkyl or 1-4C-alkoxycarbonyl, and
- R72 is 1-4-alkyl, carboxyl, aminocarbonyl or 1-4C-alkoxycarbonyl,
- R8 is an unsubstituted or by R81 and/or R82 substituted phenyl or naphthyl radical, where
- R8 1is hydroxyl, halogen, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy, 1-4C-alkylcarbonylamino, or 1-2C-alkoxy which is completely or predominantly substituted by fluorine, and
- R82 is halogen, 1-4C-alkyl or 1-4C-alkoxy,
- R9 is --C.sub.q H.sub.2q -phenyl,
- Ar is an unsubstituted phenyl, naphthyl, pyridyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzotriazolyl, N-benzosuccinimidyl, imidazolyl, oxazolyl, thiazolyl, a 2-(1-2C-alkyl)-thiazol-4-yl radical, or a phenyl radical substituted by R10 and/or R11, in which
- R10 is hydroxyl, halogen, 1-4C-alkyl, trifluoromethyl, 1-4C-alkoxy, carboxyl, carboxy-1-4C-alkyl, 1-4C-alkylcarbonyloxy, 1-4C-alkoxycarbonyl and
- R11 is hydroxyl, halogen, 1-4C-alkyl or 1-4C-alkoxy,
- m is an integer from 1 to 8,
- n is an integer from 1 to 4,
- p is an integer from 1 to 6,
- q is an integer from 0 to 1,
- or a salt thereof.
- 4. A compound of formula I according to claim 1 in which
- R1 is methoxy, ethoxy or difluoromethoxy,
- R2 is 1-4C-alkoxy, difluoromethoxy, 3-5C-cycloalkoxy or 3-5C-cycloalkylmethoxy,
- R3 and R4 are both hydrogen or together form an additional bond,
- R5 is R4, --C.sub.m H.sub.2m --R7, --C.sub.n H.sub.2n --C(O)R8, --CH(R9).sub.2 or --C.sub.p H.sub.2p --Ar, in which
- R6 is hydrogen, 1-8C-alkyl, 3-8C-cycloalkyl, 3-7C-cycloalkylmethyl, 3-4C-alkenyl, 3-4C-alkynyl, phenyl-3-4C-alkenyl, adamantyl, pyridyl, quinoxalinyl, indanyl, benzothiazolyl, N-methylpiperidyl, tetrahydropyranyl, tetrahydrothiopyranyl, or an unsubstituted or by R61 and/or R62 substituted phenyl radical, in which
- R61 is 1-2C-alkyl, 1-2C-alkoxy, nitro, halogen, carboxyl, carboxy-1-2C-alkyl, 1-4C-alkoxycarbonyl, hydroxy-1-2C-alkyl, amino, aminosulfonyl, 4-methylphenylsulfonamido, 2-(1-2C-alkyl)tetrazol-5-yl or 2-benzyltetrazol-5-yl, and
- R62 is 1-2C-alkyl or halogen,
- R7 is hydroxyl, halogen, carboxyl, nitroxy (--O--NO.sub.2), phenoxy, carboxyphenyloxy, 1-4C-alkoxycarbonyl, aminocarbonyl, mono- or di-1-4C-alkylaminocarbonyl, amino, mono- or di-1-4C-alkylamino, or an unsubstituted or by R71 and/or R72 substituted piperidyl, piperazinyl or morpholinyl radical, where
- R71 is hydroxyl, 1-4C-alkyl, 1-4C-hydroxyalkyl or 1-4C-alkoxycarbonyl, and
- R72 is 1-4C-alkyl, carboxyl, aminocarbonyl or 1-4C-alkoxycarbonyl,
- R8 is an unsubstituted or by R81 substituted phenyl or naphthyl radical where
- R81 is halogen or 1-4C-alkoxy,
- R9 is --C.sub.q H.sub.2q -phenyl,
- Ar is an unsubstituted phenyl, naphthyl, pyridyl, benzimidazolyl, benzotriazolyl, N-benzosuccinimidyl, imidazolyl, thiazolyl, a 2-(1-2C-alkyl)-thiazol-4-yl-radical, or a phenyl radical substituted by R10 and/or R11, in which
- R10 is hydroxyl, halogen, 1-2C-alkyl, trifluoromethyl, 1-2C-alkoxy, carboxyl, carboxy-1-2C-alkyl or 1-2C-alkoxycarbonyl, and
- R11 is halogen, 1-2C-alkyl or 1-2C-alkoxy,
- m is an integer from 1 to 8,
- n is an integer from 1 to 6,
- p is 1 or 2,
- q is 0 or 1,
- or a salt thereof.
- 5. A compound of formula I according to claim 1, in which
- R1 is methoxy or ethoxy,
- R2 is methoxy, ethoxy, difluoromethoxy, cyclopropylmethoxy or cyclopentyloxy,
- R3 and R4 are both hydrogen or together form an additional bond,
- R5 is R6, --C.sub.m H.sub.2m --R7, --C.sub.n H.sub.2n --C(O)R8, --CH(R9).sub.2 or --C.sub.p H.sub.2p --Ar, in which
- R6 is hydrogen, 1-8C-alkyl, 3-8C-cycloalkyl, 3-7C-cycloalkylmethyl, allyl, 2-propinyl, phenyl-trans-prop-1-en-3-yl, adamantyl, pyridyl, quinoxalinyl, indanyl, benzothiazolyl, N-methylpiperidyl, tetrahydropyranyl, tetrahydrothiopyranyl, or an unsubstituted or by R61 substituted phenyl radical, in which
- R61 is 1-4C-alkyl, nitro, halogen, carboxyl, carboxymethyl, hydroxy-1-2C-alkyl, amino, aminosulfonyl, 4-methylphenylsulfonamido, 2-ethyltetrazol-5-yl or 2-benzyltetrazol-5-yl,
- R7 is hydroxyl, halogen, carboxyl, nitroxy (--O--NO.sub.2), phenoxy, carboxyphenyloxy, 1-4C-alkoxycarbonyl, amino, methylamino, dimethylamino, dimethylaminocarbonyl, 1-piperidyl or N-methyl-4-piperidyl,
- R8 is phenyl, 2-methoxyphenyl, 4-chlorophenyl or 2-naphthyl,
- R9 is --C.sub.q H.sub.2q -phenyl,
- Ar is an unsubstituted phenyl, pyridyl, benzimidazolyl, benzotriazolyl, N-benzosuccinimidyl, imidazolyl, a 2-methyl-thiazol-4-yl radical, or a phenyl radical substitued by R10 and/or R11, in which
- R10 is hydroxyl, halogen, methoxy, trifluoromethyl, carboxyl, carboxymethyl or methoxycarbonyl, and
- R11 is methoxy,
- m is an integer from 1 to 8,
- n is 1,
- p is an integer from 1 to 6,
- q is 0,
- or a salt thereof.
- 6. Compounds of the formula I according to claim 1, in which
- R1 is methoxy,
- R2 is methoxy, ethoxy, difluoromethoxy, cyclopropylmethoxy or cyclopentyloxy,
- R3 and R4 are both hydrogen or together form an additional bond,
- R5 is R6, --C.sub.n H.sub.2n --C(O)R8 or --C.sub.p H.sub.2p --Ar, in which
- R6 is 3-8C-alkyl, 5-8C-cycloalkyl, 3-7C-cycloalkylmethyl, adamantyl, quinoxalinyl, indanyl, benzothiazolyl, tetrahydropyranyl, tetrahydrothiopyranyl, or an unsubstituted or by R61 substituted phenyl radical, in which
- R61 is 1-4C-alkyl, nitro, halogen, carboxyl, carboxymethyl, hydroxy-1-2C-alkyl, aminosulfonyl, 4-methylphenylsulfonamido, 2-ethyltetrazol-5-yl or 2-benzyltetrazol-5-yl,
- R8 is phenyl or 2-naphthyl,
- Ar is an unsubstituted phenyl, benzimidazolyl, N-benzosuccinimidyl, imidazolyl, or a phenyl radical substituted by R10, in which
- R10 is hydroxyl, halogen, methoxy, trifluoromethyl or carboxyl,
- n is 1,
- p is an integer from 1 to 6,
- or a salt thereof.
- 7. A compound of formula I according to claim 1, in which
- R1 is methoxy or ethoxy,
- R2 is methoxy, ethoxy or cyclopentyloxy,
- R3 and R4 are both hydrogen or together form an additional bond,
- R5 is R6, --C.sub.m H.sub.2m --R7, --C.sub.n H.sub.2n --C(O)R8, --CH(R9).sub.2 or --C.sub.p H.sub.2p --Ar, in which
- R6 is 1-6C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkylmethyl, allyl, 2-propinyl, phenyl or phenyl-trans-prop-1-en-3-yl,
- R7 is hydroxyl, carboxyl or phenoxy,
- R8 is phenyl, 2-methoxyphenyl, 4-chlorophenyl or 2-naphthyl,
- R9 is --C.sub.q H.sub.2q -phenyl,
- Ar is an unsubstituted phenyl, pyridyl, benzotriazolyl, a 2-methyl-thiazol-4-yl radical, or a phenyl radical substituted by R10 and/or R11, in which
- R10 is hydroxyl, halogen, methoxy, trifluoromethyl, carboxyl, carboxymethyl or methoxycarbonyl, and
- R11 is methoxy,
- m is an integer from 1 to 6,
- n is 1,
- p is 1 or 2,
- q is 0,
- or a salt thereof.
- 8. A medicament composition which comprises an effective amount of a compound of claim 1 or a pharmaceutically-acceptable salt thereof together with a suitable pharmaceutical auxiliary or carrier.
- 9. A method for treating a subject afflicted with a condition amenable to treatment with a PDE inhibitor which comprises administering an effective amount of the PDE inhibitor to the subject and wherein the PDE inhibitor is a compound of claim 1 or a pharmaceutically-acceptable salt thereof.
- 10. A method of claim 9 wherein the condition is an airway disorder.
- 11. In a method for compounding a medicament composition, having an active ingredient for treating an airway disorder, by combining the active ingredient with a suitable pharmaceutical auxiliary or carrier, the improvement wherein said active ingredient is a compound of claim 1 or a pharmaceutically-acceptable salt thereof.
Priority Claims (1)
Number |
Date |
Country |
Kind |
97100488 |
Jan 1997 |
EPX |
|
Parent Case Info
This application is a 371 of PCT/EP98/00124 filed Jan. 12, 1998.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/EP98/00124 |
1/12/1998 |
|
|
7/14/1999 |
7/14/1999 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO98/31674 |
7/23/1998 |
|
|
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
4289774 |
Schacht et al. |
Sep 1981 |
|
5849741 |
Watanable et al. |
Dec 1998 |
|
Foreign Referenced Citations (2)
Number |
Date |
Country |
WO 9412461 |
Jun 1994 |
EPX |
634404 |
Jan 1995 |
EPX |