Piperazino-derivatives and their use as PDE4 inhibitor
First Claim
Patent Images
1. A compound of formula I in whichR1 and R2 are both hydrogen or together form an additional bond,R3 represents a benzene derivative of formula (a) or (b) whereinR4 is 1–
- 4C-alkoxy or 1–
4C-alkoxy which is completely or predominantly substituted by fluorine,R5 is 1–
8C-alkoxy, 3–
7C-cycloalkoxy, 3–
7C-cycloalkylmethoxy, or 1–
4C-alkoxy which is completely or predominantly substituted by fluorine,R6 is 1–
4C-alkoxy, 3–
5C-cycloalkoxy, 3–
5C-cycloalkylmethoxy, or 1–
4C-alkoxy which is completely or predominantly substituted by fluorine,R7 is 1–
4C-alkyl andR8 is hydrogen or 1–
4C-alkyl,or whereinR7 and R8 together and with inclusion of the two carbon atoms, to which they are bonded, form a spiro-linked 5-, 6- or 7-membered hydrocarbon ring, optionally interrupted by an oxygen or sulphur atom,A is a bond or methylene (—
CH2—
),R9 is —
C(O)R10, —
(CH2)m—
C(O)R11, —
(CH2)nR12, Aryl, Hetaryl, phenylprop-1-en-3-yl or 1-methyl-piperidin-4-yl,R10 hydrogen, 1–
4C-alkyl, —
OR13, furanyl, indolyl, phenyl, pyridyl, phenyl substituted by R16 and/or R17 or pyridyl substituted by R18 and/or R19,R11 is —
N(R14)R15,R12 is —
N(R14)R15, tetrahydrofuranyl or pyridinyl,R13 is 1–
4C-alkyl,R14 is hydrogen, 1–
4C-alkyl, 3–
7C-cycloalkyl or 3–
7C-cycloalkylmethyl,R15 is hydrogen, 1–
4C-alkyl, 3–
7C-cycloalkyl or 3–
7C-cycloalkylmethyl,or R14 and R15 together and with inclusion of the nitrogen atom to which they are bonded, form a 4-morpholinyl-, 1-pyrrolidinyl-, 1-piperidinyl- or 1-hexahydroazepinyl-ring,Aryl is phenyl, pyridyl, pyrimidinyl, phenyl substituted by R16 and/or R17, pyridyl substituted by R18 and/or R19,R16 is halogen, nitro, 1–
4C-alkyl, trifluoromethyl or 1–
4C-alkoxy,R17 is halogen or 1–
4C-alkyl,R18 is halogen, nitro, 1–
4C-alkyl, trifluoromethyl or 1–
4C-alkoxy,R19 is halogen or 1–
4C-alkyl,Hetaryl is indol-4-yl, 2-methyl-quinolin-4-yl, 5-chloro-6-oxo-1-phenyl-1,6-dihydro-pyridazin-4-yl, 3-phenyl-1,2,4-thiadiazol-5-yl or 3-o-tolyl-1,2,4-thiadiazol-5-yl,n is an integer from 1 to 4,m is an integer from 1 to 4,s is an integer from 1 to 2,X is —
C(O)—
or —
S(O)2—
,or a hydrate, salt, or hydrate of a salt thereof.
1 Assignment
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Accused Products
Abstract
The compounds of formula I
in which R1, R2, R3, A, X, s and R9 have the meanings as given in the description are novel effective PDE4 inhibitors.
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Citations
14 Claims
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1. A compound of formula I
in which R1 and R2 are both hydrogen or together form an additional bond, R3 represents a benzene derivative of formula (a) or (b) wherein R4 is 1– - 4C-alkoxy or 1–
4C-alkoxy which is completely or predominantly substituted by fluorine,R5 is 1–
8C-alkoxy, 3–
7C-cycloalkoxy, 3–
7C-cycloalkylmethoxy, or 1–
4C-alkoxy which is completely or predominantly substituted by fluorine,R6 is 1–
4C-alkoxy, 3–
5C-cycloalkoxy, 3–
5C-cycloalkylmethoxy, or 1–
4C-alkoxy which is completely or predominantly substituted by fluorine,R7 is 1–
4C-alkyl andR8 is hydrogen or 1–
4C-alkyl,or wherein R7 and R8 together and with inclusion of the two carbon atoms, to which they are bonded, form a spiro-linked 5-, 6- or 7-membered hydrocarbon ring, optionally interrupted by an oxygen or sulphur atom, A is a bond or methylene (—
CH2—
),R9 is —
C(O)R10, —
(CH2)m—
C(O)R11, —
(CH2)nR12, Aryl, Hetaryl, phenylprop-1-en-3-yl or 1-methyl-piperidin-4-yl,R10 hydrogen, 1–
4C-alkyl, —
OR13, furanyl, indolyl, phenyl, pyridyl, phenyl substituted by R16 and/or R17 or pyridyl substituted by R18 and/or R19,R11 is —
N(R14)R15,R12 is —
N(R14)R15, tetrahydrofuranyl or pyridinyl,R13 is 1–
4C-alkyl,R14 is hydrogen, 1–
4C-alkyl, 3–
7C-cycloalkyl or 3–
7C-cycloalkylmethyl,R15 is hydrogen, 1–
4C-alkyl, 3–
7C-cycloalkyl or 3–
7C-cycloalkylmethyl,or R14 and R15 together and with inclusion of the nitrogen atom to which they are bonded, form a 4-morpholinyl-, 1-pyrrolidinyl-, 1-piperidinyl- or 1-hexahydroazepinyl-ring, Aryl is phenyl, pyridyl, pyrimidinyl, phenyl substituted by R16 and/or R17, pyridyl substituted by R18 and/or R19, R16 is halogen, nitro, 1–
4C-alkyl, trifluoromethyl or 1–
4C-alkoxy,R17 is halogen or 1–
4C-alkyl,R18 is halogen, nitro, 1–
4C-alkyl, trifluoromethyl or 1–
4C-alkoxy,R19 is halogen or 1–
4C-alkyl,Hetaryl is indol-4-yl, 2-methyl-quinolin-4-yl, 5-chloro-6-oxo-1-phenyl-1,6-dihydro-pyridazin-4-yl, 3-phenyl-1,2,4-thiadiazol-5-yl or 3-o-tolyl-1,2,4-thiadiazol-5-yl, n is an integer from 1 to 4, m is an integer from 1 to 4, s is an integer from 1 to 2, X is —
C(O)—
or —
S(O)2—
,or a hydrate, salt, or hydrate of a salt thereof. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
- 4C-alkoxy or 1–
Specification