Pentafluorosulphanyl-Substituted Compound And Its Use For Producing Medicaments
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Abstract
The present invention relates to pentafluorosulphanyl-substituted compounds, methods for their production, medicaments containing such compounds and the use of such compounds for producing medicaments.
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Citations
43 Claims
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1-21. -21. (canceled)
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22. A pentafluorosulphanyl-substituted compound corresponding to formula I
wherein n is 0, 1, 2, 3 or 4; -
R1 represents one or more mutually independent groups selected from the group consisting of;
H, F, Cl, Br, I, —
CN, —
NC, —
NO2, —
SO3H, —
S(═
O2)NH2, —
NH2, —
OH, —
SH, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, sec-pentyl, n-hexyl, —
O—
CH3, —
O—
C2H5, —
O—
CH(CH3)2, —
O—
C(CH3)3, —
S—
CH3, —
S—
C2H5, —
S—
CH(CH3)2, —
S—
C(CH3)3, —
N(CH3)2, —
N(C2H5)2, —
NH—
CH3, —
NH—
C2H5, —
NH—
C(═
O)—
CH3, —
NH—
C(═
O)—
C2H5, —
C(═
O)—
NH2, —
C(═
O)—
CH3, —
C(═
O)—
C2H5, —
C(═
O)—
OH, —
C(═
O)—
OCH3 and —
C(═
O)—
OC2H5;R2 represents a group -A-B-D, -E-F or —
N(H)-G, which can be bound to position 2, 3, 4, 5 or 6 of the phenyl group of formula I;
ora group -Q-B-D;
wherein Q represents a group selected from the group consisting of;
oxazolyl, thiazolyl, isoxazolyl, isothiazolyl and imidazolyl, which is condensed with the phenyl group of formula I and thereby forms a optionally substituted group selected from the group consisting of;
benzoxazolyl, benzothiazolyl, benzisothiazolyl and benzimidazolyl;A represents a group selected from the group consisting of; —
N(R3)—
C(═
O)—
N(R4)—
, —
N(R3)—
C(═
S)—
N(R4)—
, —
N(R5)—
C(═
O)—
, —
N(R5)—
C(═
S)—
,B represents a group selected from the group consisting of; which may optionally be substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of;
methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, sec-pentyl and n-hexyl;
ora phenylene group, which may be substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of;
F, Cl, Br, —
CF3, —
OH, —
O—
CH3, —
O—
C2H5, —
O—
CF3, —
O—
CHF2, —
O—
CF2H, —
S—
CF3, —
S—
CHF2, —
S—
CF2H, —
NO2, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl and tert-butyl;D represents a group selected from the group consisting of;
phenyl, [1,3,5]-triazinyl, pyridinyl, pyridazinyl, pyrimidinyl, quinolinyl, isoquinolinyl and pyrazinyl, which may optionally be substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of;
F, Cl, Br, —
CF3, —
OH, —
O—
CH3, —
O—
C2H5, —
O—
CF3, —
O—
CHF2, —
O—
CF2H, —
S—
CF3, —
S—
CHF2, —
S—
CF2H, —
NO2, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, sec-pentyl, n-hexyl, —
NH—
S(═
O)2—
CH3 and —
NH—
S(═
O)2—
C2H5;E represents a group selected from the group consisting of;
—
(CH2)—
(CH2)—
N(R7)—
C(═
O)—
N(R8)—
, —
(CH2)—
(CH2)—
N(R7)—
C(═
S)—
N(R8)—
, —
(CH2)—
N(R9)—
C(═
O)—
N(R10)—
, —
(CH2)—
N(R9)—
C(═
S)—
N(R10)—
, —
CH═
CH—
C(═
O)—
N(R11)—
, —
CH═
CH—
C(═
S)—
N(R11)—
, —
(CH2)—
(CH2)—
N(R12)—
C(═
O)—
N(R13)—
(CH2)—
(CH2)—
, —
(CH2)—
(CH2)—
N(R12)—
C(═
S)—
N(R13)—
(CH2)—
(CH2)—
, —
(CH2)—
N(R14)—
C(═
O)—
N(R15)—
(CH2)—
, —
(CH2)—
N(R14)—
C(═
S)—
N(R15)—
(CH2)—
, —
N(R16)—
C(═
O)—
N(R17)—
, —
N(R16)—
C(═
S)—
N(R17)—
, —
(CH2)—
N(R18)—
C(═
O)—
CH(CH3)—
, —
(CH2)—
N(R18)—
C(═
S)—
CH(CH3)—
, —
C(═
O)—
N(R19)—
(CH2)—
, —
C(═
S)—
N(R19)—
(CH2)—
, —
N(R20)—
(CH2)—
C(═
O)—
N(R21)—
, —
N(R20)—
(CH2)—
C(═
S)—
N(R21)—
, —
(CH2)—
(CH2)—
N(R22)—
C(═
O)—
, —
(CH2)—
(CH2)—
N(R22)—
C(═
S)—
, —
CH(CH3)—
N(R23)—
C(═
O)—
, —
CH(CH3)—
N(R23)—
C(═
S)—
, —
(CH2)—
N(R24)—
C(═
O)—
N(R25)—
CH(CH3)— and
—
(CH2)—
N(R24)—
C(═
S)—
N(R25)—
CH(CH3)—
;F represents a group selected from the group consisting of;
quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, (1,4)-benzodioxanyl, (1,3)-benzdioxolyl, (1,2,3,4)-tetrahydronaphthyl, (1,2,3,4)-tetrahydroquinolinyl, (1,2,3,4)-tetrahydroisoquinolinyl, benzoxazolyl, benzothiazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazolyl, 2-oxo-2,3-dihydro-1H-benzimidazolyl, 2-benzoxazolinonyl and 2-benzothiazolinonyl, which may optionally be substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of;
F, Cl, Br, —
CF3, —
OH, —
O—
CH3, —
O—
C2H5, —
O—
CF3, —
O—
CHF2, —
O—
CF2H, —
S—
CF3, —
S—
CHF2, —
S—
CF2H, —
NO2, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, sec-pentyl, n-hexyl, —
NH—
S(═
O)2—
CH3 and —
NH—
S(═
O)2—
C2H5;
ora naphthyl group, which is substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of;
F, Cl, Br, —
CF3, —
OH, —
O—
CH3, —
O—
C2H5, —
O—
CF3, —
O—
CHF2, —
O—
CF2H, —
S—
CF3, —
S—
CHF2, —
S—
CF2H, —
NO2, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, sec-pentyl, n-hexyl, —
NH—
S(═
O)2—
CH3 or —
NH—
S(═
O)2—
C2H5;
ora phenyl group, which is substituted with 2, 3, 4 or 5 substituents, independently selected from the group consisting of;
F, Cl, Br, —
CF3, —
OH, —
O—
CH3, —
O—
C2H5, —
O—
CF3, —
O—
CHF2, —
O—
CF2H, —
S—
CF3, —
S—
CHF2, —
S—
CF2H, —
NO2, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, sec-pentyl, n-hexyl, —
NH—
S(═
O)2—
CH3 or —
NH—
S(═
O)2—
C2H5;G represents a group selected from the group consisting of; J represents a group selected from the group consisting of;
phenyl, [1,3,5]-triazinyl, pyridinyl, pyrimidinyl, pyridazinyl, quinolinyl, isoquinolinyl and pyrazinyl, which may optionally be substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of;
F, Cl, Br, —
CF3, —
OH, —
O—
CH3, —
O—
C2H5, —
O—
CF3, —
O—
CHF2, —
O—
CF2H, —
S—
CF3, —
S—
CHF2, —
S—
CF2H, —
NO2, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, sec-pentyl, n-hexyl, —
NH—
S(═
O)2—
CH3 and —
NH—
S(═
O)2—
C2H5;K represents a group selected from the group consisting of;
piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, thiomorpholinyl, (1,2,3,6)-tetrahydropyridinyl, cyclohexyl, cyclopentyl, cycloheptyl, azepanyl and diazepanyl, which may be substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of;
methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, sec-pentyl, n-hexyl, —
NH—
CH3, —
NH—
C2H5, —
N(CH3)2 and —
N(C2H5);
or a —
NR26R27-group;M represents a phenyl group, which may be substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of;
—
SF5, F, Cl, Br, —
CF3, —
OH, —
O—
CH3, —
O—
C2H5, —
O—
CF3, —
O—
CHF2, —
O—
CF2H, —
S—
CF3, —
S—
CHF2, —
S—
CF2H, —
NO2, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl and tert-butyl and/or can be bound via a —
O—
CH2—
, —
S—
CH2—
, —
CH2—
CH2—
, —
CH═
CH—
or —
CH2-group;R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24 and R25 each independently represent hydrogen or a group selected from the group consisting of;
hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, sec-pentyl and n-hexyl; andR26 and R27 each independently represent a group selected from the group consisting of;
hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, sec-pentyl and n-hexyl;or a salt or solvate thereof. - View Dependent Claims (23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43)
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29. A compound according to claim 22, wherein D represents a group selected from the group consisting of:
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30. A compound according to claim 22, wherein F represents a group selected from the group consisting of:
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31. A compound according to claim 22, wherein J represents a group selected from the group consisting of:
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32. A compound according to claim 22, wherein K represents a group selected from the group consisting of:
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33. A compound according claim 22, wherein M represents a group selected from the group consisting of:
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34. A compound according to claim 22, wherein
n is 0, R2 represents a group -A-B-D, -E-F or — - N(H)-G, which can be bound to position 4 of the phenyl group of formula I;
ora group -Q-B-D;
wherein Q represents a group selected from the group consisting of;
oxazolyl, thiazolyl, isoxazolyl, isothiazolyl and imidazolyl, which is condensed with the phenyl group of formula I in positions 4 and 5 and thereby forms an optionally substituted group selected from the group consisting of;
benzoxazolyl, benzothiazolyl, benzisothiazolyl and benzimidazolyl;A represents a group selected from the group consisting of; —
N(R3)—
C(═
O)—
N(R4)—
, —
N(R3)—
C(═
S)—
N(R4)—
, —
N(R5)—
C(═
O)—
, —
N(R5)—
C(═
S)—
,B represents a group selected from the group consisting of; D represents a group selected from the group consisting of; E represents a group selected from the group consisting of;
—
(CH2)—
(CH2)—
N(R7)—
C(═
O)—
N(R8), —
(CH2)—
(CH2)—
N(R7)—
C(═
S)—
N(R8)—
, —
(CH2)—
N(R9)—
C(═
O)—
N(R10)—
, —
(CH2)—
N(R9)—
C(═
S)—
N(R10)—
, —
CH═
CH—
C(═
O)—
N(R11)—
, —
CH═
CH—
C(═
S)—
N(R11)—
, —
(CH2)—
(CH2)—
N(R12)—
C(═
O)—
N(R13)—
(CH2)—
(CH2)—
, —
(CH2)—
(CH2)—
N(R12)—
C(═
S)—
N(R13)—
(CH2)—
(CH2)—
, —
(CH2)—
N(R14)—
C(═
O)—
N(R15)—
(CH2)—
, —
(CH2)—
N(R14)—
C(═
S)—
N(R15)—
(CH2)—
, —
N(R16)—
C(═
O)—
N(R17)—
, —
N(R16)—
C(═
S)—
N(R17)—
, —
(CH2)—
N(R18)—
C(═
O)—
CH(CH3)—
, —
(CH2)—
N(R18)—
C(═
S)—
CH(CH3)—
, —
C(═
O)—
N(R19)—
(CH2)—
, —
C(═
S)—
N(R19)—
(CH2)—
, —
N(R20)—
(CH2)—
C(═
O)—
N(R21)—
, —
N(R20)—
(CH2)—
C(═
S)—
N(R21)—
, —
(CH2)—
(CH2)—
N(R22)—
C(═
O)—
, —
(CH2)—
(CH2)—
N(R22)—
C(═
S)—
, —
CH(CH3)—
N(R23)—
C(═
O)—
, —
CH(CH3)—
N(R23)—
C(═
S)—
, —
(CH2)—
N(R24)—
C(═
O)—
N(R25)—
CH(CH3)—
, and —
(CH2)—
N(R24)—
C(═
S)—
N(R25)—
CH(CH3)—
;F represents a group selected from the group consisting of; G represents a group selected from the group consisting of; J represents a group selected from the group consisting of; K represents a group selected from the group consisting of; M represents a group selected from the group consisting of; and R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24 and R25 each represent hydrogen.
- N(H)-G, which can be bound to position 4 of the phenyl group of formula I;
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35. A compound according to claim 22, selected from the group consisting of:
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[1] N-{4-[3-(4-pentafluorosulphanyl-benzyl)-thioureidomethyl]-2-fluoro-phenyl}-methane sulphonamide; [2] 4-(3-chloropyridin-2-yl)-piperazine-1-carboxy-(4-pentafluorosulphanyl-phenyl)-amide; [3] 4-(3-chloro-pyridin-2-yl)-piperazine-1-thiocarboxy-(4-pentafluorosulphanyl-phenyl)-amide; [4] 3-(4-pentafluorosulphanyl-phenyl)-N-(2,3-dihydro-benzo[1,4] dioxin-6-yl)-acrylamide; [5] N-(4-pentafluorosulphanyl-benzyl)-2-(3-fluoro-4-methanesulphonylamino-phenyl)-propionamide; [6] (2R)—
N-(4-pentafluorosulphanyl-benzyl)-2-(3-fluoro-4-methansulphonylamino-phenyl)-propionamide;[7] (2S)—
N-(4-pentafluorosulphanyl-benzyl)-2-(3-fluoro-4-methanesulphonylamino-phenyl)-propionamide;[8] N-(4-pentafluorosulphanyl-phenyl)-4-pyridin-2-yl-benzamide [9] 1-(4-pentafluorosulphanyl-benzyl)-3-(7-hydroxy-naphthalen-1-yl)-urea; [10] 4-(3-chloro-pyrazin-2-yl)-3,6-dihydro-2H-pyridine-1-carboxy-(4-pentafluorosulphanyl-phenyl)-amide; [11] (4-pentafluorosulphanyl-phenyl)-[4-(4-methyl-piperazin-1-yl)-6-(2-trifluoromethyl-benzyloxy)-[1,3,5]triazin-2-yl]-amine; [12] (4-pentafluorosulphanyll-phenyl)-[6-(4-chloro-phenyl)-pyrimidin-4-yl]-amine; [13] 4-pentafluorosulphanyl-N-(2-oxo-2,3-dihydro-1H-benzoimidazol-5-ylmethyl)-benzamide; [14] (4-pentafluorosulphanyl-phenyl)-{6-[4-(3-chloro-pyridin-2-yl)-2-(R)-methyl-piperazin-1-yl]-pyrimidin-4-yl}-amine; [15] 3′
-chloro-3,6-dihydro-2H-[1,2′
]bipyridinyl-4-carboxy-(4-pentafluorosulphanyl-phenyl)-amide;[16] 2-(4-pentafluorosulphanyl-phenylamino)-N-(7-hydroxy-naphthalen-1-yl)-acetamide; [17] (4-pentafluorosulphanyl-phenyl)-[7-(3-trifluoromethyl-pyridin-2-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]-amine;
[18] 1-(4-pentafluorosulphanyl-benzyl)-3-isoquinolin-5-yl-urea;[19] 1-[2-(4-pentafluorosulphanyl-phenyl)-ethyl]-3-isoquinolin-5-yl-urea; [20] 1-(4-pentafluorosulphanyl-phenyl)-3-(7-hydroxy-5,6,7,8-tetrahydro-naphthalen-1-yl)-urea; [21] 1-[2-(4-pentafluorosulphanyl-phenyl)-ethyl]-3-quinolin-5-yl-urea; [22] 1-(4-pentafluorosulphanyl-phenyl)-3-(1-isoquinolin-5-yl-pyrrolidin-3-yl)-urea; [23] 5-pentafluorosulphanyl-2-[4-(3-chloro-pyridin-2-yl)-piperazin-1-yl]-benzooxazole; and [24] N-{4-[3-(4-pentafluorosulphanyl-benzyl)-ureidomethyl]-2-fluoro-phenyl}-methanesulphonamide.
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36. A process for producing a compounds of formula I according to claim 22, said process comprising reacting a compound of formula II
wherein R1 and n have the meanings given in claim 22, and X represents — - N═
C═
O, —
N═
C═
S, —
(CH2)—
N═
C═
O, —
(CH2)—
N═
C═
S, —
(CH2)—
N═
C═
S, —
(CH2)—
(CH2)—
N═
C═
O, —
(CH2)—
(CH2)—
N═
C═
S, —
CH(CH3)—
N═
C═
O or —
CH(CH3)—
N═
C═
S,in a reaction medium in the presence of a base, with a compound of formula H—
B-D;
wherein the group H—
B has at least one —
N(H)-group, H2N—
B-D, H2N—
F, H2N—
(CH2)—
F, H2N—
(CH2)—
(CH2)—
F or H2N—
CH(CH3)—
F;
wherein B, D and F have the meanings given in claim 22;
orreacting a compound of formula II, wherein R1 and n have the meanings given in claim 22, and X represents —
NH2, —
(CH2)—
NH2, —
CH(CH3)—
NH2 or —
(CH2)—
(CH2)—
NH2,in a reaction medium in the presence of a base, with a compound of formula F—
N═
C═
O, F—
N═
C═
S, F—
(CH2)—
N═
C═
O, F—
(CH2)—
N═
C═
S, F—
(CH)2—
(CH2)—
N═
C═
O, F—
(CH2)—
(CH2)—
N═
C═
S, F—
CH(CH3)—
N═
C═
O or F—
CH(CH3)—
N═
C═
S;
wherein F has the meaning given above; andto obtain a compound of formula I;
whereinR1 and n have the meanings given above, and R2 represents -A-B-D or -E-F, wherein A represents —
N(R3)—
C(═
O)—
N(R4)—
or —
N(R3)—
C(═
S)—
N(R4)—
;E represents a group selected from the group consisting of;
—
(CH2)—
(CH2)—
N(R7)—
C(═
O)—
N(R8)—
, —
(CH2)—
(CH2)—
N(R7)—
C(═
S)—
N(R8)—
, —
(CH2)—
N(R9)—
C(═
O)—
N(R10)—
, —
(CH2)—
N(R9)—
C(═
S)—
N(R10)—
, —
(CH2)—
(CH2)—
N(R12)—
C(═
O)—
N(R13)—
(CH2)—
(CH2)—
, —
(CH2)—
(CH2)—
N(R12)—
C(═
S)—
N(R13)—
(CH2)—
(CH2)—
, —
(CH2)—
N(R14)—
C(═
O)—
N(R15)—
(CH2)—
, —
(CH2)—
N(R14)—
C(═
S)—
N(R15)—
(CH2)—
, —
N(R16)—
C(═
O)—
N(R17)—
, —
N(R16)—
C(═
S)—
N(R17)—
, —
(CH2)—
N(R24)—
C(═
O)—
N(R25)—
CH(CH3)— and
—
(CH2)—
N(R24)—
C(═
S)—
N(R25)—
CH(CH3);
wherein R3, R4, R7, R8, R9, R10, R12, R13, R14, R15, R16, R17, R24 and R25 each represent hydrogen; andB, D and F have the meanings given above; and optionally reacting a compound of formula I;
whereinR1 and n have the meanings given above; and R2 represents -A-B-D or -E-F, wherein A represents —
N(R3)—
C(═
O)—
N(R4)—
or —
N(R3)—
C(═
S)—
N(R4)—
;E represents a group selected from the group consisting of;
—
(CH2)—
(CH2)—
N(R7)—
C(═
O)—
N(R8)—
, —
(CH2)—
(CH2)—
N(R7)—
C(═
S)—
N(R8)—
, —
(CH2)—
N(R9)—
C(═
O)—
N(R10)—
, —
(CH2)—
N(R9)—
C(═
S)—
N(R10)—
, —
(CH2)—
(CH2)—
N(R12)—
C(═
O)—
N(R13)—
(CH2)—
(CH2)—
, —
(CH2)—
(CH2)—
N(R12)—
C(═
S)—
N(R13)—
(CH2)—
(CH2)—
, —
(CH2)—
N(R14)—
C(═
O)—
N(R15)—
(CH2)—
, —
(CH2)—
N(R14)—
C(═
S)—
N(R15)—
(CH2)—
, —
N(R16)—
C(═
O)—
N(R17)—
, —
N(R16)—
C(═
S)—
N(R17)—
, —
(CH2)—
N(R24)—
C(═
O)—
N(R25)—
CH(CH3)— and
—
(CH2)—
N(R24)—
C(═
S)—
N(R25)—
CH(CH3)—
;
wherein R3, R4, R7, R8, R9, R10, R12, R13, R14, R15, R16, R17, R24 and R25 each represent hydrogen; andB, D and F have the meanings given in claim 22; in a reaction medium, in the presence of a base, with a compound of the formula LG-R3, LG-R4, LG-R7, LG-R8, LG-R9, LG-R10, LG-R12, LG-R13, LG-R14, LG-R15, LG-R16, LG-R17, LG-R24 or LG-R25;
wherein R3, R4, R7, R8, R9, R10, R12, R13, R14, R15, R16, R17, R24 and R25 have the meanings given in claim 22, with the exception of hydrogen and LG denotes a leaving group;to obtain a compound of formula I, wherein R1 and n have the meanings given above; and R2 represents -A-B-D or -E-F, wherein A represents —
N(R3)—
C(═
O)—
N(R4)—
or —
N(R3)—
C(═
S)—
N(R4)—
;E represents a group selected from the group consisting of;
—
(CH2)—
(CH2)—
N(R7)—
C(═
O)—
N(R8)—
, —
(CH2)—
(CH2)—
N(R7)—
C(═
S)—
N(R8)—
, —
(CH2)—
N(R9)—
C(═
O)—
N(R10)—
, —
(CH2)—
N(R9)—
C(═
S)—
N(R10)—
, —
(CH2)—
(CH2)—
N(R12)—
C(═
O)—
N(R13)—
(CH2)—
(CH2)—
, —
(CH2)—
(CH2)—
N(R12)—
C(═
S)—
N(R13)—
(CH2)—
(CH2)—
, —
(CH2)—
N(R14)—
C(═
O)—
N(R15)—
(CH2)—
, —
(CH2)—
N(R14)—
C(═
S)—
N(R15)—
(CH2)—
, —
N(R16)—
C(═
O)—
N(R17)—
, —
N(R16)—
C(═
S)—
N(R17)—
, —
(CH2)—
N(R24)—
C(═
O)—
N(R25)—
CH(CH3)— and
—
(CH2)—
N(R24)—
C(═
S)—
N(R25)—
CH(CH3)—
;
wherein R3, R4, R7, R8, R9, R10, R12, R13, R14, R15, R16, R17, R24 and R25 have the meanings given in claim 22 with the exception of hydrogen; andB, D and F have the meanings given in claim 22; and optionally isolating or purifying any of the obtained compounds.
- N═
-
37. A process for producing a compound of formula I according to claim 22, said process comprising:
-
reacting a compound of formula II wherein R1 and n have the meanings given in claim 22, and X represents —
NH2,in a reaction medium with a compound of the formula LG-G, wherein G has the meaning given in claim 22, and LG denotes a leaving group and to obtain a compound of formula I, wherein R1 and n have the meanings given above, and R2 represents —
N(H)-G, wherein G has the meaning given above;and optionally isolating or purifying the obtained compound.
-
-
38. A process for producing a compound of formula I according to claim 22, said process comprising:
-
reacting a compound of formula III wherein R1, n and Q have the meanings given in claim 22, and LG denotes a leaving group, in a reaction medium, with a compound of formula H—
B-D;
wherein the group H—
B has at least one —
N(H)—
group and B and D have the meanings given in claim 22,to obtain a compound of formula I, wherein R1 and n have the meanings given above, and R2 represents -Q-B-D, wherein Q, B and D have the meanings given above; and optionally isolating or purifying the obtained compound.
-
-
39. A process for producing a compound of formula I according to claim 22, said process comprising:
-
reacting a compound of formula II wherein R1 and n have the meanings given in claim 22, and X represents —
C(═
O)-LG, —
(CH2)—
C(═
O)-LG, —
(CH2)—
(CH2)—
C(═
O)-LG, —
CH(CH3)—
C(═
O)-LG, —
CH═
CH—
C(═
O)-LG or —
N(R20)—
CH2—
C(═
O)-LG, wherein LG denotes a leaving group, preferably a halogen atom, particularly preferably a chlorine atom and R20 has the meaning given in claim 22,in a reaction medium in the presence of a base, with at least one compound of formula H—
B-D;
wherein the group H—
B has at least one —
N(H)—
group, H2N—
B-D, H2N—
F, H2N—
(CH2)—
F, H2N—
(CH2)—
(CH2)—
F or H2N—
CH(CH3)—
F;
wherein B, D and F have the meanings given in claim 22;
orreacting a compound of formula II, wherein R1 and n have the meanings given in claim 22, and X represents —
NH2, —
(CH2)—
NH2, —
CH(CH3)—
NH2, —
(CH2)—
(CH2)—
NH2 or —
CH═
CH—
NH2,in a reaction medium, in the presence of a base, with a compound of formula F—
C(═
O)-LG, F—
(CH2)—
C(═
O)-LG, F—
(CH2)—
(CH2)—
C(═
O)-LG, F—
CH(CH3)—
C(═
O)-LG, F—
CH═
CH—
C(═
O)-LG or F—
N(R20)—
CH2—
C(═
O)-LG;
wherein F, R20 and LG have the meanings given above;to obtain a compound of formula I, wherein R1 and n have the meanings given above, and R2 represents -A-B-D or -E-F, wherein A represents —
N(R5)—
C(═
O)—
;E represents a group selected from the group consisting of;
—
CH═
CH—
C(═
O)—
N(R11), —
(CH2)—
N(R18)—
C(═
O)—
CH(CH3)—
, —
C(═
O)—
N(R19)—
(CH2)—
, —
N(R20)—
(CH2)—
C(═
O)—
N(R21)—
, —
(CH2)—
(CH2)—
N(R22)—
C(═
O)— and
—
CH(CH3)—
N(R23)—
C(═
O)—
;
wherein R5, R11, R18, R19, R20, R21, R22 and R23 each represent a hydrogen group; andB, D and F have the meanings given in claim 22; and optionally reacting a compound of formula I, wherein R1 and n have the meanings given above, and R2 represents -A-B-D or -E-F, wherein A represents —
N(R5)—
C(═
O)—
;E represents a group selected from the group consisting of;
—
CH═
CH—
C(═
O)—
N(R11), —
(CH2)—
N(R18)—
C(═
O)—
CH(CH3)—
, —
C(═
O)—
N(R19)—
(CH2)—
, —
N(R20)—
(CH2)—
C(═
O)—
N(R21)—
, —
(CH2)—
(CH2)—
N(R22)—
C(═
O)— and
—
CH(CH3)—
N(R23)—
C(═
O)—
;
wherein R5, R11, R18, R19, R20, R21, R22 and R23 each represent a hydrogen group; andB, D and F have the meanings given in claim 22; in a reaction medium in the presence of a base, with a compound of formula LG-R5, LG-R11, LG-R18, LG-R89, LG-R20, LG-R21, LG-R22 or LG-R23, wherein R5, R11, R18, R19, R20, R21, R22 and R23 have the meanings given in claim 22 with the exception of hydrogen, to obtain a compound of formula I, wherein R1 and n have the meanings given above, and R2 represents -A-B-D or -E-F, wherein A represents —
N(R5)—
C(═
O)—
;E represents a group selected from the group consisting of;
—
CH═
CH—
C(═
O)—
N(R11), —
(CH2)—
N(R18)—
C(═
O)—
CH(CH3)—
, —
C(═
O)—
N(R19)—
(CH2)—
, —
N(R20)—
(CH2)—
C(═
O)—
N(R21)—
, —
(CH2)—
(CH2)—
N(R22)—
C(═
O)— and
—
CH(CH3)—
N(R23)—
C(═
O)—
;
wherein R5, R11, R18, R19, R20, R21, R22 and R23 have the meanings given in claim 22; andB, D and F have the meanings given in claim 22; and optionally reacting a compound of formula I, wherein R1 and n have the meanings given above, and R2 represents -A-B-D or -E-F, wherein A represents —
N(R5)—
C(═
O)—
;E represents a group selected from the group consisting of;
—
CH═
CH—
C(═
O)—
N(R11), —
(CH2)—
N(R18)—
C(═
O)—
CH(CH3)—
, —
C(═
O)—
N(R19)—
(CH2)—
, —
N(R20)—
(CH2)—
C(═
O)—
N(R21)—
, —
(CH2)—
(CH2)—
N(R22)—
C(═
O)— and
—
CH(CH3)—
N(R23)—
C(═
O)—
;
wherein R5, R11, R18, R19, R20, R21, R22 and R23 have the meanings given in claim 22; andB, D and F have the meanings given in claim 22, in a reaction medium, with a compound of formula IV wherein the phenyl groups optionally may be substituted with 1 or 2 substituents independently selected from the group consisting of;
methoxy, phenoxy, Cl, methyl and Br, or with phosphorus pentasulphide,to obtain a compound of formula I, wherein R1 and n have the meanings given above, and R2 represents -A-B-D or -E-F, wherein A represents —
N(R5)—
C(═
S)—
;E represents a group selected from the group consisting of;
—
CH═
CH—
C(═
S)—
N(R11), —
(CH2)—
N(R18)—
C(═
S)—
CH(CH3)—
, —
C(═
S)—
N(R19)—
(CH2)—
, —
N(R20)—
(CH2)—
C(═
S)—
N(R21)—
, —
(CH2)—
(CH2)—
N(R22)—
C(═
S)— and
—
CH(CH3)—
N(R23)—
C(═
S)—
;
wherein R5, R11, R18, R19, R20, R21, R22 and R23 d have the meanings given in claim 22; andB, D and F have the meanings given in claim 22; and optionally isolating or purifying any of the obtained compounds.
-
-
40. A process for producing a compound of formula I according to claim 22;
- said process comprising;
reacting a compound of formula II wherein R1 and n have the meanings given in claim 22, and X represents —
NH2 or —
NHR6;
wherein R6 has the meaning given in claim 22, in a reaction medium,with a compound of formula A-B-D, wherein B and D have the meanings given in claim 22, and A represents a group selected from the group consisting of; wherein LG denotes a leaving group, in a reaction medium, to obtain a compound of formula I, wherein R1, R6 and n have the meanings given above, and R2 represents -A-B-D, wherein B and D have the meanings given above, and A has the meaning given in claim 22 with the exception of —
N(R3)—
C(═
O)—
N(R4)—
, —
N(R3)—
C(═
S)—
N(R4)—
, —
N(R5)—
C(═
O)— and
—
N(R5)—
C(═
S)—
;and optionally isolating or purifying the obtained compound.
- said process comprising;
-
41. A pharmaceutical composition comprising a compound according to claim 22 and at least one physiologically compatible excipient.
-
42. A method of treating or inhibiting a disorder or disease state selected from the group consisting of pain;
- migraine;
depression;
urinary incontinence;
stress incontinence;
overactive bladder;
coughing;
osteoporosis;
neurodegenerative diseases;
eating disorders;
anxiety;
cognitive dysfunctions;
cognitive inadequacies;
epilepsy;
diarrhea;
pruritus;
medicament, drug or alcohol abuse;
medicament, drug or alcohol dependency or addiction;
withdrawal symptoms of medicament, drug or alcohol dependency;
development of tolerance to medicaments;
or for regulating nutrient uptake;
modulating motor activity;
regulating the cardiovascular system;
local anaesthesia;
increasing alertness;
increasing libido;
diuresis or antinatriuresis, in a subject in need thereof, said method comprising administering to said subject a pharmacologically effective amount of a compound according to claim 22.
- migraine;
-
43. A method according to claim 22, wherein said disorder or disease state is pain selected from the group consisting of acute pain, chronic pain, neuropathic pain and visceral pain;
- a neurodegenerative disease selected from the group consisting of Parkinson'"'"'s disease, Huntingdon'"'"'s chorea, Alzheimer'"'"'s disease and multiple sclerosis; and
eating disorder selected from the group consisting of bulimia, anorexia, obesity and cachexia;
a memory deficiency;
attention deficit syndrome;
or development of tolerance to opioids.
- a neurodegenerative disease selected from the group consisting of Parkinson'"'"'s disease, Huntingdon'"'"'s chorea, Alzheimer'"'"'s disease and multiple sclerosis; and
Specification