US2010240669A1PendingUtilityA1
New compounds
Est. expiryFeb 26, 2029(~2.6 yrs left)· nominal 20-yr term from priority
Inventors:Norbert HauelAngelo CeciHenri DoodsIngo KonetzkiJuergen MackHenning PriepkeAnnette Schuler-MetzRainer WalterDieter Wiedenmayer
A61P 9/00A61P 37/02A61P 3/10A61P 35/00A61P 9/12A61P 37/08A61P 9/10A61P 43/00A61P 31/04A61P 25/00A61P 25/02A61P 25/16A61P 25/06A61P 29/00A61P 25/28A61P 25/04A61P 3/04A61P 25/08A61P 25/24A61P 17/02A61P 17/06A61P 17/04A61P 13/08A61P 11/14A61P 19/10A61P 13/00A61P 11/08A61P 21/00A61P 13/10A61P 19/02A61P 11/06A61P 1/00A61P 17/00C07D 401/12C07D 239/557C07D 233/90C07D 239/28C07D 271/10C07D 405/12C07D 261/18C07D 207/277C07D 211/62C07D 213/81C07C 237/24C07C 2601/02
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Claims
Abstract
The present invention relates to the compounds of general formula I wherein n, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 and X are defined as described hereinafter, the enantiomers, the diastereomers, the mixtures and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases, which have valuable properties, the preparation thereof, the medicaments containing the pharmacologically effective compounds, the preparation thereof and the use thereof.
Claims
exact text as granted — not AI-modified1 . A compound of the formula I
wherein
n denotes one of the numbers 0, 1 or 2,
R 1 denotes
(a) a C 1-6 -alkyl group optionally substituted by a group R 1.1 ,
(b) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
(c) a substituted C 3-6 -cycloalkyl group optionally substituted by a group R 1.2 wherein a —CH 2 — unit may be replaced by a —C(O)— group,
(d) an aryl-C 0-2 -alkylene group optionally substituted by 1, 2 or 3 groups R 1.3 ,
(e) a five-membered heteroaryl-C 0-2 -alkylene group optionally substituted by 1, 2 or 3 groups R 1.4 , which contains at least one N, O or S atom and which optionally additionally contains one, two or three further N-atoms and which may additionally be benzo-condensed,
(f) a six-membered heteroaryl-C 0-2 -alkylene group optionally substituted by 1 or 2 groups R 1.4 , which contains one, two or three N-atoms and which may additionally be benzo-condensed,
(g) a nine- or ten-membered heteroaryl group optionally substituted by 1 or 2 groups R 1.4 substituted, which contains one, two or three N-atoms,
(h) a 5- or 6-membered heterocyclic group optionally substituted by 1 or 2 groups R 1.4 , in which a —CH 2 — unit may be replaced by a —C(O)— group,
(i) —O—R 1.1.1 ,
(i) —NR 1.1.3 R 1.1.4 or
(k) —C(═NR 15 )—CN,
R 1.1 denotes halogen, —NO 2 , —CN, C 3-6 -cycloalkyl, —OR 1.1.1 , —SR 1.1.1 , —C(O)R 1.1.1 , —S(O) 2 —R 1.1.2 , —O—S(O) 2 —R 1.1.1 , —CO 2 R 1.1.1 , —O—C(O)—R 1.1.1 , —NR 1.1.3 R 1.1.4 , —NR 1.1,3- C(O)—R 1.1.1 , —NR 1.1,3- C(O)—R 1.1.1 , —NR 1.1,3- CO 2 —R 1.1.1 or —C(O)—NR 1.1.3 R 1.1.4 ,
R 1.1.1 denotes
(a) H,
(b) C 1-4 -alkyl,
(c) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
(d) a phenyl group optionally substituted by 1, 2 or 3 groups R 1.1.1.1 ,
(e) C 3-6 -cycloalkyl or
(f) a pyridyl group optionally substituted by 1, 2 or 3 groups R 1.1.1.2 ,
R 1.1.1.1 independently of one another denote
(a) halogen, —NO 2 , —CN, —OH, C 3-6 -cycloalkyl, C 1-4 -alkyl or
(b) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
R 1.1.1.2 independently of one another denote halogen or C 1-4 -alkyl,
R 1.1.2 denotes
(a) C 1-4 -alkyl,
(b) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
(c) —O—C 1-4 -alkyl or
(d) a phenyl group optionally substituted by 1, 2 or 3 groups R 1.1.1.1 substituted,
R 1.1.3 ,
R 1.1.4 independently of one another denote
(a) H,
(b) a C 1-4 -alkyl group optionally substituted by 1, 2 or 3 groups R 1.1.4.1 ,
(c) a phenyl group optionally substituted by 1, 2 or 3 groups R 1.1.1.1 ,
(d) C 3-6 -cycloalkyl, or
R 1.1.3 and R 1.1.4 together with the N atom to which they are attached form a 5- or 6-membered heterocyclic ring, which may additionally contain a further heteroatom selected from N, O and S, or
R 1.1.3 and R 1.1.4 together with the N atom to which they are attached, form a cyclic imide,
R 1.1.4.1 independently of one another halogen denote —NH 2 , —NH(C 1-4 -alkyl), —N(C 1-4 -alkyl) 2 or —SO 2 —R 1.1.1 ,
R 1.2 denotes halogen, —NO 2 , —CN, OH, —O—CH 3 or phenyl,
R 1.3 denotes
(a) halogen, —NO 2 , —CN, —OR 1.1.1 , —SR 1.1.1 , —CO 2 R 1.1.1 , C 1-6 -alkyl or
(b) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
R 1.4 independently of one another denote
(a) halogen, —NO 2 , —CN, —OR 1.1.1 , —SR 1.1.1 , —S(O)—R 1.1.2 , —S(O) 2 —R 1.1.2 , —NR1.1.3R 1.1.4 , —N(R) 1.4.1 )—C(O)—C 1-4 -alkyl, C 1-6 -alkyl,
(b) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms, or
(c) an oxo group,
R 1.4.1 denotes H or C 1-4 -alkyl,
R 1.5 denotes —OH or —O—C 1-3 -alkyl,
R 2 denotes
(a) H,
(b) C 1-4 -alkyl,
(c) C 1-4 -alkyl-C(O)—,
R 3 and R 4 together with the carbon atom to which they are bound denote a C 3-6 -cycloalkylene group optionally substituted by a group R 3.1 wherein a —CH 2 — unit may be replaced by a heteroatom O, N, S or by a group CO, SO or SO 2 ,
R 3.1 denotes H, —OH,
R 5 denotes
(a) H,
(b) C 1-4 -alkyl,
(c) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
R 6 independently of one another denote
(a) H, halogen, —CN, —OH, C 3-7 -cycloalkyl, —O—C 1-4 -alkyl, —O—CF 3 , —O—C 3-6 -cycloalkyl, —N(C 1-3 -alkyl) 2 , —C(O)—NH 2 , —(SO 2 )NH 2 , —SO 2 —C 1-3 -alkyl, or
(b) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
R 7 denotes
(a) H, halogen, —CN, —OH,
(b) C 1-6 -alkyl
(c) C 1-3 -alkyl or —O—C 1-3 -alkyl, wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms, (d) C 3-7 -cycloalkyl, (e) —O—C 1-6 -alkyl, (f) —O—C 3-7 -cycloalkyl, (g) —NH 2 , —NH(C 1-3 -alkyl), —N(C 1-3 -alkyl) 2 , (h) —C(O)—R 7.1 , (i) —S—C 1-4 -alkyl, —SO 2 —R 7.2 , (j) a five-membered heteroaryl group optionally substituted by one or two C 1-3 -alkyl groups which is selected from among pyrrolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, imidazolyl, pyrazolyl, triazolyl and tetrazolyl, or (k) a six-membered heteroaryl group optionally substituted by one or two C 1-3 -alkyl groups which is selected from among pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl and triazinyl,
R 7.1 denotes —NH 2 , —NH(C 1-6 -alkyl), —N(C 1-6 -alkyl) 2 , N-acetidinyl, N-pyrrolidinyl, N-piperidinyl, N-morpholinyl, —OH, —O—C 1-6 -alkyl or —O—C 3-7 -cycloalkyl,
R 7.2 denotes —NH 2 , —NH(C 1-6 -alkyl), —N(C 1-6 -alkyl) 2 , N-acetidinyl, N-pyrrolidinyl, N-piperidinyl or N-morpholinyl and
R 8 denotes H, halogen, C 1-4 -alkyl,
R 9 denotes
(a) H, halogen, —CN, —OH,
(b) C 1-6 -alkyl
(c) C 1-3 -alkyl or —O—C 1-3 -alkyl, wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
(d) C 3-7 -cycloalkyl,
(e) C 2-4 -alkynyl,
(f) —O—C 1-6 -alkyl,
(g) —O—C 3-7 -cycloalkyl,
(h) —NH 2 , —NH(C 1-3 -alkyl), —N(C 1-3 -alkyl) 2 ,
(i) —C(O)—R 9.1 ,
(j) —S—C 1-4 -alkyl, —SO—C 1-4 -alkyl, —SO 2 —C 1-4 -alkyl,
R 9.1 denotes —NH 2 , —NH(C 1-6 -alkyl), —N(C 1-6 -alkyl) 2 , N-acetidinyl, N-pyrrolidinyl, N-piperidinyl, N-morpholinyl, —OH, —O—C 1-6 -alkyl or —O—C 3-7 -cycloalkyl,
R 10 denotes H, halogen, C 1-4 -alkyl,
R 11 denotes
(a) H, halogen, —CN, —OH,
(b) C 1-6 -alkyl,
(c) C 1-3 -alkyl or —O—C 1-3 -alkyl, wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
(d) C 3-7 -cycloalkyl,
(e) —O—C 1-6 -alkyl,
(f) —O—C 3-7 -alkyl,
(g) —NH 2 , —NH(C 1-3 -alkyl), —N(C 1-3 -alkyl) 2 ,
(h) —C(O)—R 11.1 ,
(i) —S—C 1-3 -alkyl, —SO 2 —R 11.2 ,
(j) a five-membered heteroaryl group optionally substituted by one or two C 1-3 -alkyl groups which is selected from among pyrrolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, imidazolyl, pyrazolyl, triazolyl and tetrazolyl, or
(k) a six-membered heteroaryl group optionally substituted by one or two C 1-3 -alkyl groups which is selected from among pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl and triazinyl,
R 11.1 denotes —NH 2 , —NH(C 1-6 -alkyl), —N(C 1-6 -alkyl) 2 , N-acetidinyl, N-pyrrolidinyl, N-piperidinyl, N-morpholinyl, —OH, —O—C 1-8 -alkyl or —O—C 3-7 -cycloalkyl,
R 11.2 denotes —NH 2 , —NH(C 1-6 -alkyl), —N(C 1-6 -alkyl) 2 , N-acetidinyl, N-pyrrolidinyl, N-piperidinyl or N-morpholinyl and
X independently of one another denote C—R 6 or N,
or a salt thereof.
2 . A compound of the formula I according to claim 1 , wherein:
R 1 denotes
(a) a C 1-6 -alkyl group optionally substituted by a group R 1.1 ,
(b) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
(c) a C 3-6 -cycloalkyl group optionally substituted by a group R 1.2 wherein a —CH 2 -unit may be replaced by a —C(O)— group,
(d) a phenyl group optionally substituted by 1, 2 or 3 groups R 1.3 ,
(e) a five-membered heteroaryl group optionally substituted by 1, 2 or 3 groups R 1.4 , which contains at least one N, O or S atom and which optionally additionally contains one, two or three further N-atoms,
(f) a six-membered heteroaryl group optionally substituted by 1 or 2 groups R 1.4 , which contains one, two or three N-atoms,
(g) a nine- or ten-membered heteroaryl group optionally substituted by 1 or 2 groups R 1.4 , which contains one, two or three N-atoms,
(h) a 5- or 6-membered heterocyclic group optionally substituted by 1 or 2 groups R 1.4 , in which a —CH 2 — unit may be replaced by a —C(O)— group,
(i) —O—R 1.1.1 or
(j) —NR 1.1.3 R 1.1.4 ,
R 1.1 denotes —CN, C 3-6 -cycloalkyl, —OR 1.1.1 , —NR 1.1.3 R 1.1.4 , R 1.1.1 denotes
(a) H,
(b) C 1-4 -alkyl,
(c) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
R 1.1.3 , R 1.1.4 independently of one another denote
(a) H,
(b) C 1-4 -alkyl,
(c) C 3-6 -cycloalkyl, or
R 1.1.3 and R 1.1.4 together with the N atom to which they are attached form a 5- or 6-membered heterocyclic ring, which may additionally contain a further heteroatom selected from N, O and S, or R 1.2 denotes halogen, —NO 2 , —CN, —OH, —O—CH 3 or phenyl, R 1.3 independently of one another denote
(a) halogen, —NO 2 , —CN, —OR 1.1.1 , C 1-6 -alkyl or
(b) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
R 1.4 independently of one another denote
(a) halogen, —NO 2 , —CN, —NR 1.1.3 R 1.1.4 , —N(R 1.4.1 )—C(O)—C 1-4 -alkyl, C 1-6 -alkyl, or
(b) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms, and
R 1.4.1 denotes H or C 1-4 -alkyl, or a salt thereof.
3 . A compound of the formula I according to claim 1 , wherein:
R 1 denotes
(a) a C 1-6 -alkyl group optionally substituted by a group R 1.1 ,
(b) a phenyl group optionally substituted by 1, 2 or 3 groups R 1.3 ,
(c) a five-membered heteroaryl group optionally substituted by 1, 2 or 3 groups R 1.4 , which contains at least one N, O or S atom and which optionally additionally contains one, two or three further N-atoms,
(d) a six-membered heteroaryl group optionally substituted by 1 or 2 groups R 1.4 , which contains one, two or three N-atoms,
(e) a nine- or ten-membered heteroaryl group optionally substituted by 1 or 2 groups R 1.4 , which contains one, two or three N-atoms,
(f) a 5- or 6-membered heterocyclic group optionally substituted by 1 or 2 groups R 1.4 , in which a —CH 2 — unit may be replaced by a —C(O)— group,
R 1.1 denotes —CN, C 3-6 -cycloalkyl, —OH, —OCH 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 , R 1.3 independently of one another denote
(a) F, Cl, Br, —OH, —OCH 3 , C 1-6 -alkyl or
(b) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms, and
R 1.4 independently of one another denote
(a) F, Cl, Br, —OH, —OCH 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 , —N(C 2-3 -alkyl) 2 , —NH—C(O)—C 1-4 -alkyl, C 1-6 -alkyl, or
(b) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
or a salt thereof.
4 . A compound of the formula I according to claim 1 , wherein:
R 1 denotes
(a) a C 1-6 -alkyl group optionally substituted by a group R 1.1 ,
(b) a phenyl group optionally substituted by 1, 2 or 3 groups R 13 ,
(c) a five-membered heteroaryl group optionally substituted by 1, 2 or 3 groups R 1.4 , which is
(d) a six-membered heteroaryl group optionally substituted by 1 or 2 groups R 1.4 which is
(e) a nine-membered heteroaryl group optionally substituted by 1 or 2 groups R 1.4 , which is
(f) a 5- or 6-membered heterocyclic group optionally substituted by 1 or 2 groups R 1.4 , which is
R 1.1 denotes —CN, cyclopropyl, —OH, —OCH 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 ,
R 1.3 independently of one another denotes
(a) F, Cl, Br, —OH, —OCH 3 , —OCH 3 , C 1-4 -alkyl or
(b) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms, and
R 1.4 independently of one another denotes
(a) F, Cl, Br, —OH, —OCH 3 , —OCF 3 , —NH 2 , —NH—C 1-4 -alkyl, —N(C 1-4 -alkyl) 2 , —NH—C(O)—C 1-4 -alkyl, C 1-6 -alkyl, or
(b) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
or a salt thereof.
5 . A compound of the formula I according to claim 1 , wherein:
R 1 is
or a salt thereof.
6 . A compound of the formula I according to claim 1 , wherein:
R 1 is
or a salt thereof.
7 . A compound of the formula I according to claim 1 , wherein:
n denotes one of the numbers 0, 1 or 2, R 2 denotes
(a) H,
(b) C 1-4 -alkyl,
R 3 and R 4 together with the carbon atom to which they are bound denote a C 3-6 -cycloalkylene group optionally substituted by a group R 3.1 wherein a —CH 2 — unit may be replaced by a heteroatom O, N, S or by a group CO, SO or SO 2 , R 3.1 denotes H, —OH, R 5 denotes
(a) H,
(b) C 1-4 -alkyl,
(c) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
R 6 independently of one another denotes
(a) H, halogen, —CN, —OH, C 3-7 -cycloalkyl, —O—CF 3 , —O—C 3-6 -cycloalkyl, —N(C 1-3 -alkyl) 2 , —C(O)—NH 2 , —(SO 2 )NH 2 , —SO 2 —C 1-3 -alkyl, or
(a) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
R 7 denotes
(a) H, halogen, —CN, —OH,
(b) C 1-6 -alkyl,
(c) C 1-3 -alkyl or —O—C 1-3 -alkyl, wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
(d) C 3-7 -cycloalkyl,
(e) —O—C 1-6 -alkyl,
(f) —O—C 3-7 -alkyl,
(g) —NH 2 , —NH(C 1-3 -alkyl), —N(C 1-3 -alkyl) 2 ,
(h) —C(O)—R 7.1 ,
(i) —S—C 1-4 -alkyl,
R 7.1 denotes —NH 2 , —OH, —O—C 1-8 -alkyl, R 8 denotes H, halogen, C 1-4 -alkyl, R 9 denotes
(a) H, halogen, —CN, —OH,
(b) C 1-6 -alkyl,
(c) C 1-3 -alkyl or —O—C 1-3 -alkyl, wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
(d) C 3-7 -cycloalkyl,
(e) C 2-4 -alkynyl,
(f) —O—C 1-6 -alkyl,
(g) —O—C 3-7 -alkyl,
(h) —NH 2 , —NH(C 1-3 -alkyl), —N(C 1-3 -alkyl) 2 ,
(i) —C(O)—R 9.1 ,
(j) —S—C 1-4 -alkyl, —SO—C 1-4 -alkyl, —SO 2 —C 1-4 -alkyl,
R 9.1 denotes —NH 2 , —OH, —O—C 1-8 -alkyl, R 10 denotes H, halogen, C 1-4 -alkyl, R 11 denotes
(a) H, halogen, —CN, —OH,
(b) C 1-6 -alkyl,
(c) C 1-3 -alkyl or —O—C 1-3 -alkyl, wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
(d) C 3-7 -cycloalkyl,
(e) —O—C 1-6 -alkyl,
(f) —O—C 3-7 -alkyl,
(g) —NH 2 , —NH(O 1-3 -alkyl), —N(C 1-3 -alkyl) 2 ,
(h) —C(O)—R 11.1 ,
(i) —S—C 1-3 -alkyl,
R 11.1 denotes —NH 2 , —OH, —O—C 1-8 -alkyl, and X independently of one another represent C—R 6 or N,
or a salt thereof.
8 . A compound of the formula I according to claim 1 , wherein:
R 2 denotes H or CH 3 ,
or a salt thereof.
9 . A compound of the formula I according to claim 1 , wherein:
R 2 denotes H, or a salt thereof.
10 . A compound of the formula I according to claim 1 , wherein:
R 3 and R 4 together with the carbon atom to which they are bonded denote a C 3-6 -cycloalkylene group wherein a —CH 2 — unit may be replaced by an oxygen atom, or a salt thereof.
11 . A compound of the formula I according to claim 1 , wherein:
R 3 and R 4 together with the carbon atom to which they are bonded denote
or a salt thereof.
12 . A compound of the formula I according to claim 1 , wherein:
R 5 denotes H or CH 3 , or a salt thereof.
13 . A compound of the formula I according to claim 1 , wherein:
R 6 denotes H, F, Cl or methyl, or a salt thereof.
14 . A compound of the formula I according to claim 1 , wherein:
R 7 denotes H, F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 or CHF 2 , R 8 denotes H, R 9 denotes F, Cl, Br, C 1-4 -alkyl, —S—C 1-4 -alkyl, R 10 denotes H and R 11 denotes F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 or CHF 2 , or a salt thereof.
15 . A compound of the formula Ia,
wherein
R 1 denotes
(a) a C 1-6 -alkyl group optionally substituted by a group R 1.1 ,
(b) a phenyl group optionally substituted by 1, 2 or 3 groups R 1.3 ,
(c) a five-membered heteroaryl group optionally substituted by 1, 2 or 3 groups R 1.4 , which contains at least one N, O or S atom and which optionally additionally contains one, two or three further N-atoms,
(d) a six-membered heteroaryl group optionally substituted by 1 or 2 groups R 1.4 , which contains one, two or three N-atoms,
(e) a nine- or ten-membered heteroaryl group optionally substituted by 1 or 2 groups R 1.4 , which contains one, two or three N-atoms,
(f) a 5- or 6-membered heterocyclic group optionally substituted by 1 or 2 groups R 1.4 , in which a —CH 2 unit may be replaced by a —C(O) group,
R 1.1 denotes —CN, C 3-6 -cycloalkyl, —OH, —OCH 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 ,
R 13 independently of one another denotes
(a) F, Cl, Br, —OH, —OCH 3 , C 1-6 -alkyl or
(b) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms, and
R 1.4 independently of one another denotes
(a) F, Cl, Br, —OH, —OCH 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 , —NH—C(O)—C 1-4 -alkyl, C 1-6 -alkyl, or
(a) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
R 2 denotes H or CH 3 ,
R 3 and R 4 together with the carbon atom to which they are bonded denote a C 3-6 -cycloalkylene group wherein a —CH 2 — unit may be replaced by an oxygen atom,
R 5 denotes H or C 1-4 -alkyl,
R 6 denotes H, F, Cl, Br or C 1-4 -alkyl,
R 7 denotes H, F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 ,
R 9 denotes F, Cl, Br, C 1-4 -alkyl, —S—C 1-4 -alkyl,
R 11 denotes F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 , and
X denotes CH or N,
or a salt thereof.
16 . A compound of the formula Ia according to claim 14 , wherein
R 1 denotes
(a) a C 1-6 -alkyl group optionally substituted by a group R 1.1 ,
(b) a phenyl group optionally substituted by 1, 2 or 3 groups R 1.3 ,
(c) a five-membered heteroaryl group optionally substituted by 1, 2 or 3 groups R 1.4 , which is
(d) a six-membered heteroaryl group optionally substituted by 1 or 2 groups R 1.4 , which is
(e) a nine-membered heteroaryl group optionally substituted by 1 or 2 groups R 1.4 , which is
(f) a 5- or 6-membered heterocyclic group optionally substituted by 1 or 2 groups R 1.4 , which is
R 1.1 denotes —CN, cyclopropyl, —OH, —OCH 3 , —NH 2 , —NHCH 3 , or —N(CH 3 ) 2 ,
R 1.3 denotes independently of one another
(a) F, Cl, Br, —OH, —OCH 3 , —OCF 3 , or C 1-4 -alkyl or
(b) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms, and
R 1.4 denotes independently of one another
(a) F, Cl, Br, —OH, —OCH 3 , —OCF 3 , —NH 2 , —NH—C 1-4 -alkyl, —N(C 1-4 -alkyl) 2 , —NH—C(O)—C 1-4 -alkyl, or C 1-6 -alkyl, or
(a) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
R 2 denotes H or CH 3 ,
R 3 and R 4 together with the carbon atom to which they are bonded denote a C 3-6 -cycloalkylene group wherein a —CH 2 unit may be replaced by an oxygen atom,
R 5 denotes H or CH 3 ,
R 6 denotes H, F, Cl or methyl,
R 7 denotes H, F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 ,
R 9 denotes F, Cl, Br, C 1-4 -alkyl, —O—C 1-4 -alkyl, —S—C 1-4 -alkyl,
R 11 denotes F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 , and
X denotes CH or N,
or a salt thereof.
17 . A compound of the formula Ia according to claim 14 , wherein
R 1 denotes
R 2 denotes H or CH 3 ,
R 3 and R 4 together with the carbon atom to which they are bonded denote a C 3-6 -cycloalkylene group wherein a —CH 2 unit may be replaced by an oxygen atom,
R 5 denotes H or CH 3 ,
R 6 denotes H, F, Cl or methyl,
R 7 denotes H, F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 ,
R 9 denotes F, Cl, Br, C 1-4 -alkyl, —O—C 1-4 -alkyl, —S—C 1-4 -alkyl,
R 11 denotes F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 , and
X denotes CH or N,
or a salt thereof.
18 . A compound of the formula Ia according to claim 15 , wherein
R 1 denotes
R 2 denotes H or CH 3 ,
R 3 and R 4 together with the carbon atom to which they are attached denote a C 3-6 -cycloalkylene group wherein a —CH 2 — unit may be replaced by an oxygen atom,
R 5 denotes H or CH 3 ,
R 6 denotes H, F, Cl or methyl,
R 7 denotes H, F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 ,
R 9 denotes F, Cl, Br, C 1-4 -alkyl, —O—C 1-4 -alkyl, —S—C 1-4 -alkyl,
R 11 denotes F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 , and
X denotes CH or N,
or a salt thereof.
19 . A compounds of the formula Ib
wherein:
R 1 denotes
(a) a C 1-6 -alkyl group optionally substituted by a group R 1.1 ,
(b) a phenyl group optionally substituted by 1, 2 or 3 groups R 1.3 ,
(c) a five-membered heteroaryl group optionally substituted by 1, 2 or 3 groups R 1.4 , which contains at least one N, O or S atom and which optionally additionally contains one, two or three further N-atoms,
(d) a six-membered heteroaryl group optionally substituted by 1 or 2 groups R 1.4 , which contains one, two or three N-atoms,
(e) a nine- or ten-membered heteroaryl group optionally substituted by 1 or 2 groups R 1.4 , which contains one, two or three N-atoms,
(f) a 5- or 6-membered heterocyclic group optionally substituted by 1 or 2 groups R 1.4 , in which a —CH 2 — unit may be replaced by a —C(O)— group,
R 1.1 denotes —CN, C 3-6 -cycloalkyl, —OH, —OCH 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 ,
R 1.3 denotes independently of one another
(a) F, Cl, Br, —OH, —OCH 3 , C 1-6 -alkyl or
(b) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms, and
R 1.4 denotes independently of one another
(a) F, Cl, Br, —OH, —OCH 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 , —NH—C(O)—C 1-4 -alkyl, C 1-6 -alkyl, or
(a) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
R 2 denotes H or CH 3 ,
R 5 denotes H or C 1-4 -alkyl,
R 6 denotes H, F, Cl, Br or C 1-4 -alkyl,
R 7 denotes H, F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 ,
R 9 denotes F, Cl, Br, C 1-4 -alkyl, —O—C 1-4 -alkyl, —S—C 1-4 -alkyl,
R 11 denotes F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 , and
X denotes CH or N,
or a salt thereof.
20 . A compound of the formula Ib according to claim 17 , wherein
R 1 denotes
(a) a C 1-6 -alkyl group optionally substituted by a group R 1.1 ,
(b) a phenyl group optionally substituted by 1, 2 or 3 groups R 1.3 ,
(c) a five-membered heteroaryl group optionally substituted by 1, 2 or 3 groups R 1.4 , which is
(d) a six-membered heteroaryl group optionally substituted by 1 or 2 groups R 1.4 , which is
(e) a nine-membered heteroaryl group optionally substituted by 1 or 2 groups R 1.4 , which is
(f) a 5- or 6-membered heterocyclic group optionally substituted by 1 or 2 groups R 1.4 , which is
R 1.1 denotes —CN, cyclopropyl, —OH, —OCH 3 , —NH 2 , —NHCH 3 , or —N(CH 3 ) 2 ,
R 1.3 denotes independently of one another
(a) F, Cl, Br, —OH, —OCH 3 , —OCF 3 , C 1-4 -alkyl or
(b) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms, and
R 1.4 denotes independently of one another
(a) F, Cl, Br, —OH, —OCH 3 , —OCF 3 , —NH 2 , —NH—C 1-4 -alkyl, —N(C 1-4 -alkyl) 2 , —NH—C(O)—C 1-4 -alkyl, C 1-6 -alkyl, or
(a) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
R 2 denotes H or CH 3 ,
R 5 denotes H or CH 3 ,
R 6 denotes H, F, Cl or methyl,
R 7 denotes H, F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 ,
R 9 denotes F, Cl, Br, C 1-4 -alkyl, —O—C 1-4 -alkyl, —S—C 1-4 -alkyl,
R 11 denotes F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 , and
X denotes CH or N,
or a salt thereof.
21 . A compound of the formula Ib according to claim 17 , wherein
R 1 denotes
R 2 denotes H or CH 3 ,
R 5 denotes H or CH 3 ,
R 6 denotes H, F, Cl or methyl,
R 7 denotes H, F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 ,
R 9 denotes F, Cl, Br, C 1-4 -alkyl, —O—C 1-4 -alkyl, —S—C 1-4 -alkyl,
R 11 denotes F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 , and
X denotes CH or N,
or a salt thereof.
22 . A compound of the formula Ib according to claim 19 , wherein
R 1 denotes
R 2 denotes H,
R 5 denotes H or CH 3 ,
R 6 denotes H, F, Cl or methyl,
R 7 denotes H, F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 ,
R 9 denotes F, Cl, Br, C 1-4 -alkyl, —O—C 1-4 -alkyl, —S—C 1-4 -alkyl,
R 11 denotes F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 , and
X denotes CH or N,
or a salt thereof.
23 . A compound of the formula Ic,
wherein
R 1 denotes
(a) a C 1-6 -alkyl group optionally substituted by a group R 1.1 ,
(b) a phenyl group optionally substituted by 1, 2 or 3 groups R 1.3 ,
(c) a five-membered heteroaryl group optionally substituted by 1, 2 or 3 groups R 1.4 , which contains at least one N, O or S atom and which optionally additionally contains one, two or three further N-atoms,
(d) a six-membered heteroaryl group optionally substituted by 1 or 2 groups R 1.4 , which contains one, two or three N-atoms,
(e) a nine- or ten-membered heteroaryl group optionally substituted by 1 or 2 groups R 1.4 , which contains one, two or three N-atoms,
(f) a 5- or 6-membered heterocyclic group optionally substituted by 1 or 2 groups R 1.4 , in which a —CH 2 — unit may be replaced by a —C(O)— group,
R 1.1 denotes —CN, C 3-6 -cycloalkyl, —OH, —OCH 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 ,
R 1.3 denotes independently of one another
(a) F, Cl, Br, —OH, —OCH 3 , C 1-6 -alkyl or
(b) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms, and
R 1.4 denotes independently of one another
(a) F, Cl, Br, —OH, —OCH 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 , —NH—C(O)—C 1-4 -alkyl, or
(b) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
R 2 denotes H or CH 3 ,
R 5 denotes H or C 1-4 -alkyl,
R 6 denotes H, F, Cl, Br or C 1-4 -alkyl,
R 7 denotes H, F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 ,
R 9 denotes F, Cl, Br, C 1-4 -alkyl, —O—C 1-4 -alkyl, —S—C 1-4 -alkyl,
R 11 denotes F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 , and
X denotes CH or N,
or a salt thereof.
24 . A compound of the formula Ic according to claim 20 , wherein
R 1 denotes
(a) a C 1-6 -alkyl group optionally substituted by a group R 1.1 ,
(b) a phenyl group optionally substituted by 1, 2 or 3 groups R 1.3 ,
(c) a five-membered heteroaryl group optionally substituted by 1, 2 or 3 groups R 1.4 , which is
(d) a six-membered heteroaryl group optionally substituted by 1 or 2 groups R 1.4 , which is
(e) a nine-membered heteroaryl group optionally substituted by 1 or 2 groups R 1.4 , which is
(f) a 5- or 6-membered heterocyclic group optionally substituted by 1 or 2 groups R 1.4 , which is
R 1.1 denotes —CN, cyclopropyl, —OH, —OCH 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 ,
R 1.3 denotes independently of one another
(a) F, Cl, Br, —OH, —OCH 3 , —OCF 3 , C 1-4 -alkyl or
(b) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms, and
R 1.4 denotes independently of one another
(a) F, Cl, Br, —OH, —OCH 3 , —OCF 3 , —NH 2 , —NH—C 1-4 -alkyl, —N(C 1-4 -alkyl) 2 , —NH—C(O)—C 1-4 -alkyl, C 1-6 -alkyl, or
(a) a C 1-3 -alkyl group wherein each methylene group may be substituted by 1 or 2 fluorine atoms and each methyl group may be substituted by 1, 2 or 3 fluorine atoms,
R 2 denotes H or CH 3 ,
R 5 denotes H or CH 3 ,
R 6 denotes H, F, Cl or methyl,
R 7 denotes H, F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 ,
R 9 denotes F, Cl, Br, C 1-4 -alkyl, —O—C 1-4 -alkyl, —S—C 1-4 -alkyl,
R 11 denotes F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 , and
X denotes CH or N,
or a salt thereof.
25 . A compound of the formula Ic according to claim 20 , wherein
R 1 denotes
R 2 denotes H or CH 3 ,
R 5 denotes H or CH 3 ,
R 6 denotes H, F, Cl or methyl,
R 7 denotes H, F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 ,
R 9 denotes F, Cl, Br, C 1-4 -alkyl, —O—C 1-4 -alkyl, —S—C 1-4 -alkyl,
R 11 denotes F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 , and
X denotes CH or N,
or a salt thereof.
26 . A compound of the formula Ic according to claim 23 , wherein
R 1 denotes
R 2 denotes H or CH 3 ,
R 5 denotes H or CH 3 ,
R 6 denotes H, F, Cl or methyl,
R 7 denotes H, F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 ,
R 9 denotes F, Cl, Br, C 1-4 -alkyl, —O—C 1-4 -alkyl, —S—C 1-4 -alkyl,
R 11 denotes F, Cl, Br, —CN, C 1-4 -alkyl, CF 3 , CHF 2 , and
X denotes CH or N,
or a salt thereof.
27 . A compound of the formula Id,
wherein
R 1 denotes
R 3 and R 4 together with the carbon atom to which they are attached denote a C 3-6 -cycloalkylene group wherein a —CH 2 unit may be replaced by an oxygen atom,
R 5 denotes H or CH 3 ,
R 6 denotes C 1 or CH 3 ,
R 7 denotes H or F, and
X denotes CH or N,
or a salt thereof.
28 . A compound according to claim 1 selected from the group consisting of:
No.
Structure
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
(11)
(12)
(13)
(14)
(15)
(16)
(17)
(18)
(19)
(20)
(21)
(22)
(23)
(24)
(25)
(26)
(27)
(28)
(29)
(30)
(31)
(32)
(33)
(34)
(35)
(36)
(37)
(38)
(39)
(40)
(41)
(42)
(43)
(44)
(45)
(46)
(47)
(48)
(49)
(50)
(51)
(52)
(53)
(54)
(55)
(56)
(57)
(58)
(59)
(60)
(61)
(62)
(63)
(64)
(65)
(66)
(67)
(68)
(69)
(70)
(71)
(72)
(73)
(74)
(75)
(76)
(77)
(78)
(79)
(80)
(81)
(82)
(83)
(84)
(85)
(86)
(87)
(88)
(89)
(90)
(91)
(92)
(93)
(94)
(95)
(96)
(97)
(98)
(99)
(100)
(101)
(102)
(103)
(104)
(105)
(106)
(107)
(108)
(109)
(110)
(111)
(112)
(113)
(114)
(115)
(116)
(117)
(118)
(119)
(120)
(121)
(122)
(123)
(124)
(125)
(126)
(127)
(128)
(129)
(130)
(131)
(132)
(133)
(134)
(135)
(136)
(137)
(138)
(139)
(140)
(141)
(142)
(143)
(144)
(145)
(146)
(147)
(148)
(149)
(150)
(151)
(152)
(153)
(154)
(155)
(156)
(157)
(158)
(159)
(160)
(161)
(162)
(163)
(164)
(165)
(166)
(167)
(168)
(169)
(170)
(171)
(172)
(173)
(174)
(175)
(176)
(177)
(178)
(179)
(180)
(181)
(182)
(183)
(184)
(185)
(186)
(187)
(188)
(189)
(190)
(191)
(192)
(193)
(194)
(195)
(196)
(197)
(198)
(199)
(200)
(201)
(202)
(203)
(203a)
(203b)
(204)
(205)
(206)
(207)
(208)
(209)
(210)
(211)
(212)
(212a)
(212b)
(213)
(213a)
(213b)
(214)
(215)
(216)
(217)
(218)
(219)
(220)
(221)
(222)
(223)
(224)
(225)
(226)
(227)
(228)
(229)
(230)
(231)
(232)
(233)
(234)
(235)
(236)
(237)
(238)
(239)
(240)
(241)
(242)
(243)
(244)
(245)
(246)
(247)
(248)
(249)
(250)
(251)
(252)
(253)
(254)
(255)
(256)
(257)
(258)
(258)
(260)
(261)
(262)
(263)
(264)
(265)
(266)
(267)
(268)
(269)
(270)
(271)
(272)
(273)
(274)
(275)
(276)
(277)
(278)
(279)
(280)
(281)
(282)
(283)
(284)
(285)
(286)
(287)
(288)
(289)
(290)
(291)
(292)
(293)
(294)
(295)
(296)
(297)
(298)
(299)
(300)
(301)
(302)
(303)
(304)
(305)
(306)
(307)
(308)
(309)
(310)
(311)
(312)
(313)
(314)
(315)
(316)
(317)
(318)
(319)
(320)
(321)
(322)
(323)
(324)
(325)
(326)
(327)
(328)
(329)
(330)
(331)
(332)
(333)
(334)
(335)
(336)
(337)
(338)
(339)
(340)
(341)
(342)
(343)
(344)
(345)
(346)
(347)
(348)
(349)
(350)
(351)
(352)
(353)
(354)
(355)
(356)
(357)
(358)
(359)
(360)
(361)
(362)
(363)
(364)
(365)
(366)
(367)
(368)
(369)
(370)
(371)
(372)
(373)
(374)
(375)
(376)
(377)
(378)
(379)
(380)
(381)
(382)
(383)
(384)
(385)
(386)
(387)
(388)
(389)
(390)
(391)
(392)
(393)
(394)
(395)
(396)
or a salt thereof.
29 . A physiologically acceptable salt of a compound according to any one of claims 1 to 28 .
30 . A pharmaceutical composition comprising a compound according to any one of claims 1 to 28 or a physiologically acceptable salt thereof, together with an inert carrier and/or diluent.
31 . A method for treatment of acute pain, visceral pain, neuropathic pain, inflammatory/pain receptor-mediated pain, tumour pain and headache which comprises administration to a host in need of such treatment a therapeutically effective amount of a compound according to any one of claims 1 to 28 or a physiologically acceptable salt thereof.
32 . A method for treatment of osteoarthritis which comprises administration to a host in need of such treatment a therapeutically effective amount of a compound according to any one of claims 1 to 28 or a physiologically acceptable salt thereof.Join the waitlist — get patent alerts
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