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US 8,557,824 B2Granted
Thiazole derivatives
AssigneeMerck Patent GmbH
InventorsKai Schiemann, Melanie Schultz, Andree Blaukat, Ingo Kober, Wolfgang Staehle
Life of this patent
Estimating the term…
Abstract
Compounds of the formula (I), in which R1, R2, R3, R4, K, G, E and W
Claims19
A compound of formula I
- in which
- R1 denotes a fused bicyclic unsaturated or aromatic heterocycle having 1 to 4 N, 0 and/or S atoms, which is unsubstituted or mono-, di- or trisubstituted by A, Ar, SR, NR2, Hal, NO2, CN, (CR2)n[X(CR2)n]p—Y, CONR2, OR5 and/or ═O (carbonyl oxygen),
- R2, R3 each, independently of one another, denote H, A, Ar, OR, SR, NR2, Hal, NO2, CN or (CR2)n[X(CR2)n]p—Y,
- R4 denotes H, Hal, A, OR, NR2 or (CR2)n[X(CR2)n]p—Y,
- X denotes O, NR or CR2,
- Y denotes OR or NR2,
- R5 denotes H or unbranched or branched alkyl having 1, 2, 3, 4, 5 or 6 C atoms, in which 1-7 H atoms may be replaced by F and/or Cl,
- K denotes C═O, CR2CO or CR2,
- E denotes COOCH2, CONHCH2 or COCH2O,
- R denotes H or unbranched or branched alkyl having 1, 2, 3, 4, 5 or 6 C atoms,
- W denotes Ar or Het,
- G denotes CH or N,
- Ar denotes phenyl, naphthyl or biphenyl, each of which is unsubstituted or mono-, di-, tri-, tetra- or pentasubstituted by Hal, A, (CR2)nOR, (CR2)NR2, SR, NO2, CN, COOR, CONR2, NRCOA, NRSO2A, SO2NR2, S(O)qA, CO-Het, (CR2)nHet, O(CR2)n-NR2, O(CR2)nHet, NHCOOA, NHCONR2, NHCOO(CR2)nNR2, NHCOO(CR2)nHet, NHCONH(CR2)nNR2, NHCONH(CR2)nHet, OCONH(CR2)nNR2, OCONH(CR2)nHet, CONR(CR2)nNR2, CONR(CR2)nHet and/or COA,
- Het denotes a mono-, bi- or tricyclic saturated, unsaturated or aromatic heterocycle having 1 to 4 N, O and/or S atoms, which is unsubstituted or mono-, di- or trisubstituted by Hal, A, (CR2)nOR, (CR2)nNR2, SR, NO2, CN, COOR, CONR2, NRCOA, NRSO2A, SO2NR2, S(O)qA, CO-Het1, (CR2)nHet1, O(CR2)nNR2, O(CR2)nHet1, NHCOOA, NHCONR2, NHCOO(CR2)nNR2, NHCOO(CR2)nHet1, NHCONH(CR2)nNR2, NHCONH(CR2)nHet1, OCONH(CR2)nNR2, OCONH(CR2)nHet1, CO-Het1, CHO, COA, ═S, ═NH, ═NA and/or ═O (carbonyl oxygen),
- Het1 denotes a monocyclic saturated heterocycle having 1 to 2 N and/or O atoms, which may be mono- or disubstituted by A, OA, OH, Hal and/or ═O (carbonyl oxygen),
- A denotes unbranched or branched alkyl having 1-10 C atoms, in which 1-7 H atoms may be replaced by OR, CN, NR2, F and/or Cl and/or in which one or two non-adjacent CH2 groups may be replaced by O, NH, S, SO, SO2 and/or by CH═CH groups, or cyclic alkyl having 3-7 C atoms,
- m denotes 1,
- n denotes 1,
- p denotes 1,
- q denotes 0, 1 or 2, and
- Hal denotes F, Cl, Br or I,
- or a pharmaceutically acceptable salt or tautomer thereof.
19 more elements
A compound of formula I
- in which
- R1 denotes a bicyclic unsaturated or aromatic heterocycle, which is one of the following groups
- which is unsubstituted or mono-, di- or trisubstituted by A, Ar, SR, NR2, Hal, NO2,
- CN, (CR2)n[X(CR2)n]p—Y, CONR2, OR5 and/or ═O (carbonyl oxygen),
- R2 denotes H or A,
- R3 denotes H,
- R4 denotes H,
- X denotes O, NR or CR2,
- Y denotes OR or NR2,
- R5 denotes H or unbranched or branched alkyl having 1, 2, 3 or 4 C atoms, in which 1-5 H atoms may be replaced by F,
- K denotes CO or CH2,
- E denotes COOCH2, COOCH2CH2, SO2CH2CH2, CONHCH2, COCH2O or COCH2CH2,
- R denotes H or methyl,
- W denotes Ar or Het,
- G denotes CH or N,
- Ar denotes phenyl, naphthyl or biphenyl, each of which is unsubstituted or mono-, di-, tri-, tetra- or pentasubstituted by Hal, A, (CR2)n Het, SA and/or OA,
- Het denotes piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyrimidinyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, pyridazinyl, pyrazinyl, benzimidazolyl, benzotriazolyl, indolyl, benzo-1,3-dioxolyl, indazolyl tetrahydro-pyridazine, imidazolidinyl benzoxazolyl or benzo-2,1,3-thiadiazolyl, each of which is unsubstituted or mono- or disubstituted by A, NH2, and/or ═O (carbonyl oxygen),
- A denotes unbranched or branched alkyl having 1-10 C atoms, in which 1-7 H atoms may be replaced by F and/or Cl,
- m denotes 1,
- n denotes 1,
- p denotes 1, and
- Hal denotes F, Cl, Br or I,
- or a pharmaceutically acceptable salt or tautomer thereof.
20 more elements
A compound which is one of the following compounds
- No.
- Name and/or structure
- “A1”
- 4-Chlorobenzyl 4-[4-(1H-benzotriazol-5-ylcarbamoyl)thiazol-
- 2-yl]piperazine-1-carboxylate
- “A2”
- 4-Chlorobenzyl 4-[4-(2-oxo-2,3-dihydrobenzoxazol-6-yl-
- carbamoyl)thiazol-2-yl]piperazine-1-carboxylate
- “A3”
- 4-Trifluoromethylsulfanylbenzyl 4-[4-(1H-benzotriazol-5-yl-
- carbamoyl)thiazol-2-yl]piperazine-1-carboxylate
- “A4”
- 4-Trifluoromethoxybenzyl 4-[4-(1H-benzotriazol-5-yl-
- carbamoyl)thiazol-2-yl]piperazine-1-carboxylate
- “A5”
- 4-Trifluoromethylbenzyl 4-[4-(1H-benzotriazol-5-
- ylcarbamoyl)thiazol-2-yl]piperazine-1-carboxylate
- “A6”
- 4-Fluorobenzyl 4-[4-(1H-benzotriazol-5-ylcarbamoyl)thiazol-
- 2-yl]piperazine-1-carboxylate
- “A7”
- 4-Methylbenzyl 4-[4-(1H-benzotriazol-5-ylcarbamoyl)thiazol-
- 2-yl]piperazine-1-carboxylate
- “A8”
- 4-Ethylbenzyl 4-[4-(1H-benzotriazol-5-ylcarbamoyl)thiazol-2-
- yl]piperazine-1-carboxylate
- “A9”
- 3,5-Dichlorobenzyl 4-[4-(1H-benzotriazol-5-ylcarbamoyl)-
- thiazol-2-yl]piperazine-1-carboxylate
- “A10”
- 4-Trifluoromethylsulfanylbenzyl 4-[4-(2-oxo-2,3-dihydro-
- benzoxazol-6-ylcarbamoyl)thiazol-2-yl]piperazine-1-
- carboxylate
- “A11”
- 4-Trifluoromethoxybenzyl 4-[4-(2-oxo-2,3-dihydro-
- benzoxazol-6-ylcarbamoyl)thiazol-2-yl]piperazine-1-
- carboxylate
- “A12”
- 4-Trifluoromethylbenzyl 4-[4-(2-oxo-2,3-dihydrobenzoxazol-
- 6-ylcarbamoyl)thiazol-2-yl]piperazine-1-carboxylate
- 13
- 3,5-Dichlorobenzyl 4-{5-[(1H-benzotriazol-5-ylamino)methyl]-
- 4-methylthiazol-2-yl}piperidine-1-carboxylate
- “A13”
- 4-Fluorobenzyl 4-[4-(2-oxo-2,3-dihydrobenzoxazol-6-
- ylcarbamoyl)thiazol-2-yl]piperazine-1-carboxylate
- “A14”
- 4-Methylbenzyl 4-[4-(2-oxo-2,3-dihydrobenzoxazol-6-
- ylcarbamoyl)thiazol-2-yl]piperazine-1-carboxylate
- “A15”
- 4-Ethylbenzyl 4-[4-(2-oxo-2,3-dihydrobenzoxazol-6-
- ylcarbamoyl)thiazol-2-yl]piperazine-1-carboxylate
- “A16”
- 3,5-Dichlorobenzyl 4-[4-(2-oxo-2,3-dihydrobenzoxazol-6-
- ylcarbamoyl)thiazol-2-yl]piperazine-1-carboxylate
- “A17”
- 4-tert-Butylbenzyl 4-[4-(1H-benzotriazol-5-ylcarbamoyl)-
- thiazol-2-yl]piperazine-1-carboxylate
- “A18”
- 4-tert-Butylbenzyl 4-[4-(2-oxo-2,3-dihydrobenzoxazol-6-
- ylcarbamoyl)thiazol-2-yl]piperazine-1-carboxylate
- “A19”
- 4-Phenylbenzyl 4-[4-(2-oxo-2,3-dihydrobenzoxazol-6-
- ylcarbamoyl)thiazol-2-yl]piperazine-1-carboxylate
- “A20”
- 4-Morpholin-4-ylmethylbenzyl 4-[4-(2-oxo-2,3-dihydro-
- benzoxazol-6-ylcarbamoyl)thiazol-2-yl]piperazine-1-
- carboxylate
- “A21”
- 4-Trifluoromethylsulfanylbenzyl 4-[4-(1H-indazol-5-yl-
- carbamoyl)thiazol-2-yl]piperazine-1-carboxylate
- “A22”
- 4-Trifluoromethylsulfanylbenzyl 4-[4-(1H-indo1-5-yl-
- carbamoyl)thiazol-2-yl]piperazine-1-carboxylate
- “A23”
- 4-Trifluoromethylsulfanylbenzyl 4-[4-(benzothiazol-6-yl-
- carbamoyl)thiazol-2-yl]piperazine-1-carboxylate
- “A24”
- 4-Trifluoromethylsulfanylbenzyl 4-[4-(benzo-1,2,5-thiadiazol-
- 5-ylcarbamoyl)thiazol-2-yl]piperazine-1-carboxylate
- “A25”
- 4-Trifluoromethylsulfanylbenzyl 4-[4-(2-trifluoromethyl-1H-
- benzimidazol-5-ylcarbamoyl)thiazol-2-yl]piperazine-1-
- carboxylate
- “A26”
- N-(1H-Benzotriazol-5-yl)-2-{4-[2-(4-chlorophenoxy)acetyl]-
- piperazin-1-yl}thiazole-4-carboxamide
- “A27”
- N-(1H-Benzotriazol-5-yl)-2-{4-[2-(4-chlorophenylamino)-
- acetyl]piperazin-1-yl}thiazole-4-carboxamide
- “A28”
- 4-Chlorobenzyl 4-[4-(2-oxo-2,3-dihydrobenzoxazol-6-yl-
- carbamoyl)thiazol-2-yl]piperidine-1-carboxylate
- “A29”
- 4-Chlorobenzyl 4-[4-(1H-benzotriazol-5-ylcarbamoyl)thiazol-
- 2-yl]piperidine-1-carboxylate
- “A30”
- 4-Isopropylbenzyl 4-[4-(2-oxo-2,3-dihydrobenzoxazol-6-yl-
- carbamoyl)thiazol-2-yl]piperidine-1-carboxylate
- “A31”
- 3,4-Dimethylbenzyl 4-[4-(2-oxo-2,3-dihydrobenzoxazol-6-yl-
- carbamoyl)thiazol-2-yl]piperidine-1-carboxylate
- “A32”
- 3,4-Dimethylbenzyl 4-[4-(1H-benzotriazol-5-ylcarbamoyl)-
- thiazol-2-yl]piperidine-1-carboxylate
- “A33”
- 2,4-Dichlorobenzyl 4-[4-(2-oxo-2,3-dihydrobenzoxazol-6-yl-
- carbamoyl)thiazol-2-yl]piperidine-1-carboxylate
- “A34”
- 2,4-Dichlorobenzyl 4-[4-(1H-benzotriazol-5-ylcarbamoyl)-
- thiazol-2-yl]piperidine-1-carboxylate
- “A35”
- 3,5-Dichlorobenzyl 4-[4-(2-oxo-2,3-dihydrobenzoxazol-6-yl-
- carbamoyl)thiazol-2-yl]piperidine-1-carboxylate
- “A36”
- 4-Trifluoromethylsulfanylbenzyl 4-[4-(2-oxo-2,3-dihydro-
- benzoxazol-6-ylcarbamoyl)thiazol-2-yl]piperidine-1-
- carboxylate
- “A37”
- 4-Trifluoromethylbenzyl 4-[4-(2-oxo-2,3-dihydrobenzoxazol-
- 6-ylcarbamoyl)thiazol-2-yl]piperidine-1-carboxylate
- “A38”
- 4-Chlorobenzyl 4-{4-[(1H-benzotriazol-5-ylamino)methyl]-
- thiazol-2-yl}piperidine-1-carboxylate
- “A39”
- 4-Chlorobenzyl 4-{5-[(1H-benzotriazol-5-ylamino)methyl]-4-
- methylthiazol-2-yl}piperidine-1-carboxylate
- “A40”
- N-(4-Trifluoromethoxybenzyl)-4-[4-(1H-benzotriazol-5-yl-
- carbamoyl)thiazol-2-yl]piperidine-1-carboxamide
- “A41”
- N-(1H-Benzotriazol-5-yl)-2-{1-[2-(4-chlorophenoxy)acetyl]-
- piperidin-4-yl}thiazole-4-carboxamide
- “A42”
- N-(1H-Benzotriazol-5-yl)-2-{1-[3-(4-trifluoromethylphenyl)-
- propionyl]piperidin-4-yl}thiazole-4-carboxamide
- “A43”
- N-(1H-Benzotriazol-5-yl)-2-[1-(2-phenylethylsulfonyl)-
- piperidin-4-yl]thiazole-4-carboxamide
- “A44”
- 4-Chlorobenzyl 4-[4-(2-trifluoromethyl-1H-benzimidazol-5-yl-
- carbamoyl)thiazol-2-yl]piperidine-1-carboxylate
- “A45”
- 4-Chlorobenzyl 4-[4-(1H-indazol-5-ylcarbamoyl)thiazol-2-yl]-
- piperidine-1-carboxylate
- “A46”
- N-(2-Trifluoromethyl-1H-benzimidazol-5-yl)-2-{1-[3-(4-
- trifluoromethylphenyl)propionyl]piperidin-4-yl}thiazole-4-
- carboxamide
- “A47”
- N-(2-Oxo-2,3-dihydrobenzoxazol-6-yl)-2-{1-[3-(4-
- trifluoromethylphenyl)propionyl]piperidin-4-yl}thiazole-4-
- carboxamide
- “A48”
- 1-{4-[4-[(1H-Benzotriazol-5-ylamino)methyl]thiazol-2-yl}-
- piperidin-1-yl)-3-(4-trifluoromethylphenyl)propan-1-one
- “A49”
- 3,5-Dichlorobenzyl 4-{4-[(1H-benzotriazol-5-ylamino)methyl]-
- thiazol-2-yl}piperidine-1-carboxylate
- “A50”
- 4-Trifluoromethylsulfanylbenzyl 4-{5-[(1H-benzotriazol-5-yl-
- amino)methyl]-4-methylthiazol-2-yl}piperidine-1-carboxylate
- “A51”
- 3,5-Dichlorobenzyl 4-[4-(benzothiazol-6-ylcarbamoyl)thiazol-
- 2-yl]piperidine-1-carboxylate
- “A52”
- N-(Benzothiazol-6-yl)-2-{1-[3-(4-trifluoromethylphenyl)-
- propionyl]piperidin-4-yl}thiazole-4-carboxamide
- “A53”
- N-(2-Oxo-2,3-dihydro-1H-benzimidazol-5-yl)-2-{1-[3-(4-
- trifluoromethylphenyl)propionyl]piperidin-4-yl}thiazole-4-
- carboxamide
- “A54”
- 4-Chlorobenzyl 4-[4-(2-oxo-2,3-dihydro-1H-benzimidazol-5-
- ylcarbamoyl)thiazol-2-yl]piperidine-1-carboxylate
- “A55”
- 3,5-Dichlorobenzyl 4-[4-(1H-benzimidazol-5-ylcarbamoyl)-
- thiazol-2-yl]piperidine-1-carboxylate
- “A56”
- 3,5-Dichlorobenzyl 4-[5-(1H-benzotriazol-5-ylcarbamoyl)-4-
- methylthiazol-2-yl]piperidine-1-carboxylate
- or a pharmaceutically acceptable salt or tautomer thereof.
179 more elements
A compound which is one of the following compounds
- “B1”
- 4-Chlorobenzyl 4-[4-(3-amino-1H-indazol-6-ylcarbamoyl)-
- thiazol-2-yl]piperidine-1-carboxylate
- “B2”
- 3,5-Dichlorobenzyl 4-[4-(3-amino-1H-indazol-6-yl-
- carbamoyl)thiazol-2-yl]piperidine-1-carboxylate
- “B3”
- 4-Chlorobenzyl 4-[4-(3-imidazol-1-ylpropylcarbamoyl)thiazol-
- 2-yl]piperidine-1-carboxylate
- “B4”
- 4-Chlorobenzyl 4-{4-[4-(4-methyl-6-oxo-1,4,5,6-tetrahydro-
- pyridazin-3-yl)phenylcarbamoyl]thiazol-2-yl}piperidine-1-
- carboxylate
- “B5”
- 4-Chlorobenzyl 4-{4-[3-(4-methyl-2,5-dioxoimidazolidin-4-yl)-
- propylcarbamoyl]thiazol-2-yl}piperidine-1-carboxylate
- “B6”
- 4-Chlorobenzyl 4-[4-(2-imidazol-1-ylethylcarbamoyl)thiazol-
- 2-yl]piperidine-1-carboxylate
- “B7”
- N-(3-Amino-1H-indazol-5-yl)-2-{1-[3-(4-trifluoromethyl-
- phenyl)propionyl]piperidin-4-yl}thiazole-4-carboxamide
- “B8”
- 4-Chlorobenzyl 4-{4-[2-(2-amino-1H-benzimidazol-5-yl)-
- ethylcarbamoyl]thiazol-2-yl}piperidine-1-carboxylate
- “B9”
- 4-Chlorobenzyl 4-[4-(3-amino-1H-indazol-5-ylcarbamoyl)-
- thiazol-2-yl]piperidine-1-carboxylate
- “B10”
- 3,5-Dichlorobenzyl 4-{4-[2-(1H-imidazol-4-yl)-
- ethylcarbamoyl]thiazol-2-yl}piperidine-1-carboxylate
- “B11”
- 4-Chlorobenzyl 4-{4-[3-(3-oxo-3H-pyrazol-4-yl)-
- propylcarbamoyl]thiazol-2-yl}piperidine-1-carboxylate
- “B12”
- 3,5-Dichlorobenzyl 4-[4-(2-imidazol-1-ylethylcarbamoyl)-
- thiazol-2-yl]piperidine-1-carboxylate
- “B13”
- 4-Chlorobenzyl 4-[4-(2-oxo-2,3-dihydrobenzoxazol-6-yl)-
- thiazol-2-yl]piperidine-1-carboxylate
- “B14”
- N-(4-Chlorophenyl)-4-[4-(1H-benzotriazol-5-ylcarbamoyl)-
- thiazol-2-yl]pipendine-1-carboxamide
- “B16”
- 3,5-Dichlorobenzyl 4-{4-[(1H-benzotriazol-5-ylcarbamoyl)-
- methyl]-5-methylthiazol-2-yl}pipendine-1-carboxylate
- or a pharmaceutically acceptable salt or tautomer thereof.
44 more elements
Dependencies are inferred from the claim text.