NO330740B1 - Opioidreseptorantagonister - Google Patents
Opioidreseptorantagonister Download PDFInfo
- Publication number
- NO330740B1 NO330740B1 NO20051871A NO20051871A NO330740B1 NO 330740 B1 NO330740 B1 NO 330740B1 NO 20051871 A NO20051871 A NO 20051871A NO 20051871 A NO20051871 A NO 20051871A NO 330740 B1 NO330740 B1 NO 330740B1
- Authority
- NO
- Norway
- Prior art keywords
- methyl
- phenoxy
- mmol
- nicotinamide
- carboxamide
- Prior art date
Links
- 229940123257 Opioid receptor antagonist Drugs 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 250
- 208000008589 Obesity Diseases 0.000 claims abstract description 31
- 235000020824 obesity Nutrition 0.000 claims abstract description 31
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 238000011282 treatment Methods 0.000 claims abstract description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 26
- 201000010099 disease Diseases 0.000 claims abstract description 20
- 230000002265 prevention Effects 0.000 claims abstract description 10
- 239000012453 solvate Substances 0.000 claims abstract description 10
- -1 5 -(2-Fluoro-4- {[2-(tetrahydro-pyran -4-yl)-ethylamino]-methyl}-phenoxy)-pyrazine-2-carboxamide 6- {2-Methyl-4-[(3-methyl-butylamino)-methyl]-phenoxy}-nicotinamide Chemical compound 0.000 claims description 40
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 28
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 16
- 229960003966 nicotinamide Drugs 0.000 claims description 12
- 239000011570 nicotinamide Substances 0.000 claims description 12
- 125000004897 3-methylbutylamino group Chemical group CC(CCN*)C 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 208000024891 symptom Diseases 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 6
- 206010012601 diabetes mellitus Diseases 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- ORJMHMIAJUKSME-UHFFFAOYSA-N 5-[4-[[2-(4-fluorophenyl)ethylamino]methyl]-2-methoxyphenoxy]pyrazine-2-carboxamide Chemical compound C=1C=C(OC=2N=CC(=NC=2)C(N)=O)C(OC)=CC=1CNCCC1=CC=C(F)C=C1 ORJMHMIAJUKSME-UHFFFAOYSA-N 0.000 claims description 4
- DZZIJHPOQGYOHW-UHFFFAOYSA-N 6-[2,6-difluoro-4-[(3-methylbutylamino)methyl]phenoxy]pyridine-3-carboxamide Chemical compound FC1=CC(CNCCC(C)C)=CC(F)=C1OC1=CC=C(C(N)=O)C=N1 DZZIJHPOQGYOHW-UHFFFAOYSA-N 0.000 claims description 4
- QWNDOCKIKKQJNN-UHFFFAOYSA-N 6-[2-fluoro-4-[[2-(oxan-4-yl)ethylamino]methyl]phenoxy]pyridine-3-carboxamide Chemical compound N1=CC(C(=O)N)=CC=C1OC(C(=C1)F)=CC=C1CNCCC1CCOCC1 QWNDOCKIKKQJNN-UHFFFAOYSA-N 0.000 claims description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 claims description 4
- 230000004580 weight loss Effects 0.000 claims description 4
- KXIFIKGCMNZIRR-UHFFFAOYSA-N 5-[2-methoxy-4-[(pentylamino)methyl]phenoxy]pyrazine-2-carboxamide Chemical compound COC1=CC(CNCCCCC)=CC=C1OC1=CN=C(C(N)=O)C=N1 KXIFIKGCMNZIRR-UHFFFAOYSA-N 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- ZGCYVRNZWGUXNQ-UHFFFAOYSA-N Bevenopran Chemical compound C=1C=C(OC=2N=CC(=NC=2)C(N)=O)C(OC)=CC=1CNCCC1CCOCC1 ZGCYVRNZWGUXNQ-UHFFFAOYSA-N 0.000 claims description 3
- 208000002249 Diabetes Complications Diseases 0.000 claims description 3
- 206010012655 Diabetic complications Diseases 0.000 claims description 3
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 3
- 201000001421 hyperglycemia Diseases 0.000 claims description 3
- SRTJWEAYPLHPFJ-UHFFFAOYSA-N 5-[4-[(4,4-dimethylpentylamino)methyl]-2-methoxyphenoxy]pyrazine-2-carboxamide Chemical compound COC1=CC(CNCCCC(C)(C)C)=CC=C1OC1=CN=C(C(N)=O)C=N1 SRTJWEAYPLHPFJ-UHFFFAOYSA-N 0.000 claims description 2
- COOCONHDRCJRDK-UHFFFAOYSA-N 6-[2,3-difluoro-4-[(pentylamino)methyl]phenoxy]pyridine-3-carboxamide Chemical compound FC1=C(F)C(CNCCCCC)=CC=C1OC1=CC=C(C(N)=O)C=N1 COOCONHDRCJRDK-UHFFFAOYSA-N 0.000 claims description 2
- 208000020346 hyperlipoproteinemia Diseases 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- ADXBHKREPBWTDP-UHFFFAOYSA-N 6-[4-[(3-methylbutylamino)methyl]phenoxy]pyridine-3-carboxamide Chemical group C1=CC(CNCCC(C)C)=CC=C1OC1=CC=C(C(N)=O)C=N1 ADXBHKREPBWTDP-UHFFFAOYSA-N 0.000 claims 2
- 208000016261 weight loss Diseases 0.000 claims 2
- 125000004911 3,3-dimethylbutylamino group Chemical group CC(CCN*)(C)C 0.000 claims 1
- IBNFHMRDGWKDCH-UHFFFAOYSA-N 3-fluoro-4-[4-[(3-methylbutylamino)methyl]phenoxy]benzamide Chemical compound C1=CC(CNCCC(C)C)=CC=C1OC1=CC=C(C(N)=O)C=C1F IBNFHMRDGWKDCH-UHFFFAOYSA-N 0.000 claims 1
- 150000003892 tartrate salts Chemical class 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 60
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 255
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 251
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 143
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 135
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 121
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 115
- 229910001868 water Inorganic materials 0.000 description 108
- 235000019439 ethyl acetate Nutrition 0.000 description 95
- 238000003756 stirring Methods 0.000 description 88
- 239000000243 solution Substances 0.000 description 73
- 238000005481 NMR spectroscopy Methods 0.000 description 72
- 239000012141 concentrate Substances 0.000 description 69
- 239000011541 reaction mixture Substances 0.000 description 69
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 68
- 235000008504 concentrate Nutrition 0.000 description 68
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 63
- 238000006243 chemical reaction Methods 0.000 description 59
- 238000004128 high performance liquid chromatography Methods 0.000 description 59
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 51
- 239000007787 solid Substances 0.000 description 49
- 238000000034 method Methods 0.000 description 47
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 45
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 44
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 41
- 239000000284 extract Substances 0.000 description 41
- 239000012044 organic layer Substances 0.000 description 41
- 239000000047 product Substances 0.000 description 37
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 34
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- 239000012267 brine Substances 0.000 description 30
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 30
- 238000003818 flash chromatography Methods 0.000 description 27
- 239000012279 sodium borohydride Substances 0.000 description 27
- 229910000033 sodium borohydride Inorganic materials 0.000 description 27
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 26
- BMFVGAAISNGQNM-UHFFFAOYSA-N isopentylamine Chemical compound CC(C)CCN BMFVGAAISNGQNM-UHFFFAOYSA-N 0.000 description 26
- 238000003786 synthesis reaction Methods 0.000 description 26
- 230000015572 biosynthetic process Effects 0.000 description 25
- 239000002904 solvent Substances 0.000 description 25
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 24
- 238000005160 1H NMR spectroscopy Methods 0.000 description 23
- 239000002808 molecular sieve Substances 0.000 description 23
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical class OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 22
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
- 229910000027 potassium carbonate Inorganic materials 0.000 description 22
- 229910052938 sodium sulfate Inorganic materials 0.000 description 21
- 235000011152 sodium sulphate Nutrition 0.000 description 21
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 20
- 239000010410 layer Substances 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 150000002500 ions Chemical class 0.000 description 18
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 18
- 102000005962 receptors Human genes 0.000 description 18
- 108020003175 receptors Proteins 0.000 description 18
- 239000011734 sodium Substances 0.000 description 18
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 16
- 235000011181 potassium carbonates Nutrition 0.000 description 16
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 15
- 239000000543 intermediate Substances 0.000 description 15
- 238000006268 reductive amination reaction Methods 0.000 description 15
- 108090000137 Opioid Receptors Proteins 0.000 description 14
- 102000003840 Opioid Receptors Human genes 0.000 description 14
- 150000001299 aldehydes Chemical class 0.000 description 14
- 239000000460 chlorine Substances 0.000 description 14
- 239000007789 gas Substances 0.000 description 13
- ORIQLMBUPMABDV-UHFFFAOYSA-N 6-chloropyridine-3-carbonitrile Chemical compound ClC1=CC=C(C#N)C=N1 ORIQLMBUPMABDV-UHFFFAOYSA-N 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 125000001424 substituent group Chemical group 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 11
- 230000027455 binding Effects 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
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- 239000007921 spray Substances 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 241000700159 Rattus Species 0.000 description 10
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- 238000001819 mass spectrum Methods 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
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- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
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- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 8
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- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
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- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 7
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- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 7
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- LVVHEFJXPXAUDD-BULFRSBZSA-N 3-[(3r,4r)-1-[(3s)-3-cyclohexyl-3-hydroxypropyl]-3,4-dimethylpiperidin-4-yl]phenol Chemical compound C1([C@@H](O)CCN2C[C@@H]([C@](CC2)(C)C=2C=C(O)C=CC=2)C)CCCCC1 LVVHEFJXPXAUDD-BULFRSBZSA-N 0.000 description 6
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- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 4
- DXUBYPWSDCGLDJ-UHFFFAOYSA-N 5-(2-fluoro-4-formylphenoxy)pyrazine-2-carboxamide Chemical compound C1=NC(C(=O)N)=CN=C1OC1=CC=C(C=O)C=C1F DXUBYPWSDCGLDJ-UHFFFAOYSA-N 0.000 description 4
- DBGVQIBFUOKCRM-UHFFFAOYSA-N 6-(2,6-difluoro-4-formylphenoxy)pyridine-3-carboxamide Chemical compound N1=CC(C(=O)N)=CC=C1OC1=C(F)C=C(C=O)C=C1F DBGVQIBFUOKCRM-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 241000910494 Heth Species 0.000 description 4
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- OSWVFEQUZBKEKL-UHFFFAOYSA-N tert-butyl n-[2-[4-(5-cyanopyridin-2-yl)oxy-3,5-difluorophenyl]ethyl]carbamate Chemical compound FC1=CC(CCNC(=O)OC(C)(C)C)=CC(F)=C1OC1=CC=C(C#N)C=N1 OSWVFEQUZBKEKL-UHFFFAOYSA-N 0.000 description 1
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
- C07D213/643—2-Phenoxypyridines; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Application Number | Priority Date | Filing Date | Title |
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US41215802P | 2002-09-19 | 2002-09-19 | |
PCT/US2003/026300 WO2004026305A1 (en) | 2002-09-19 | 2003-09-17 | Diaryl ethers as opioid receptor antagonist |
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Families Citing this family (69)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6374762B1 (en) * | 1997-10-27 | 2002-04-23 | Correct Craft, Inc. | Water sport towing apparatus |
US20030170917A1 (en) * | 2002-03-01 | 2003-09-11 | Roche Diagnostics Corporation | Compounds, antibodies, reagent kits, methods of producing antibodies, and methods of detecting analytes |
DE60321207D1 (en) * | 2002-09-19 | 2008-07-03 | Lilly Co Eli | Diaryläther als opioid-rezeptor antagonisten |
GB0224557D0 (en) | 2002-10-22 | 2002-11-27 | Glaxo Group Ltd | Novel compounds |
CA2509413C (en) | 2002-12-20 | 2012-05-01 | Glaxo Group Limited | Benzazepine derivatives for the treatment of neurological disorders |
WO2004080968A1 (en) * | 2003-03-07 | 2004-09-23 | Eli Lilly And Company | 6-substituted nicotinamide derivatives as opioid receptor antagonists |
MXPA06002310A (es) | 2003-08-29 | 2006-05-25 | Ono Pharmaceutical Co | Compuesto capaz de enlazarse al receptor s1p y uso farmaceutico del mismo. |
CN101407471A (zh) | 2003-08-29 | 2009-04-15 | 小野药品工业株式会社 | 能够结合s1p受体的化合物及其药物用途 |
US7196100B2 (en) | 2003-12-12 | 2007-03-27 | Eli Lilly And Company | Opioid receptor antagonists |
CN1894240A (zh) * | 2003-12-22 | 2007-01-10 | 伊莱利利公司 | 阿片受体拮抗剂 |
KR101154830B1 (ko) | 2003-12-24 | 2012-06-18 | 프로시디온 리미티드 | Gpcr 수용체 효능제로서의 헤테로사이클릭 유도체 |
WO2005090286A1 (en) * | 2004-03-12 | 2005-09-29 | Eli Lilly And Company | Opioid receptor antagonists |
US7288543B2 (en) | 2004-03-12 | 2007-10-30 | Eli Lilly And Company | Opioid receptor antagonists |
ES2318472T3 (es) | 2004-03-15 | 2009-05-01 | Eli Lilly And Company | Derivados de 5-(5-(aminoetil)-indol-1-ilmetil)-benzamida y compuestos relacionados como antagonistas del receptor opioide para el tratamiento de la obesidad. |
WO2005092836A1 (en) | 2004-03-15 | 2005-10-06 | Eli Lilly And Company | Opioid receptor antagonists |
GB0408083D0 (en) * | 2004-04-08 | 2004-05-12 | Glaxo Group Ltd | Novel compounds |
PE20060115A1 (es) | 2004-07-23 | 2006-03-23 | Basf Ag | 2-(piridin-2-il)-pirimidinas como agentes fungicidas |
RU2007109794A (ru) * | 2004-08-19 | 2008-09-27 | Вертекс Фармасьютикалз, Инкорпорейтед (Us) | Модуляторы мускариновых рецепторов |
US7786141B2 (en) * | 2004-08-19 | 2010-08-31 | Vertex Pharmaceuticals Incorporated | Dihydrospiroindene modulators of muscarinic receptors |
AU2005309365B2 (en) * | 2004-11-29 | 2011-10-06 | Vertex Pharmaceuticals Incorporated | Modulators of muscarinic receptors |
EP2371811B1 (en) | 2004-12-13 | 2014-10-08 | Ono Pharmaceutical Co., Ltd. | Azetidinecarboxylic acid derivative and medicinal use thereof |
EP2527337A1 (en) * | 2005-04-14 | 2012-11-28 | Bristol-Myers Squibb Company | Inhibitors of 11-beta hydroxysteroid dehydrogenase type I |
WO2007047397A2 (en) | 2005-10-13 | 2007-04-26 | Smithkline Beecham Corporation | Phenol ethers as modulators of the opioid receptors |
CN101365682A (zh) | 2005-12-08 | 2009-02-11 | 千禧药品公司 | 具有激酶抑制活性的双环化合物 |
BRPI0620066A2 (pt) * | 2005-12-20 | 2011-11-01 | Novartis Ag | derivados de ácido nicotìnico como moduladores do receptor de glutamato metabotrópico, processo para preparação dos mesmos, composição farmacêutica e uso dos referidos derivados |
AU2006330866A1 (en) * | 2005-12-22 | 2007-07-05 | Vertex Pharmaceuticals Incorporated | Modulators of muscarinic receptors |
ATE517106T1 (de) * | 2006-02-22 | 2011-08-15 | Vertex Pharma | Kondensierte spiropiperidine als modulatoren muskarinartiger rezeptoren |
EP1988892A2 (en) | 2006-02-22 | 2008-11-12 | Vertex Pharmaceuticals Incorporated | Modulators of muscarinic receptors |
US9108948B2 (en) | 2006-06-23 | 2015-08-18 | Abbvie Inc. | Cyclopropyl amine derivatives |
EP2049472B1 (en) | 2006-06-23 | 2015-01-21 | AbbVie Bahamas Ltd. | Cyclopropyl amine derivatives as histamin h3 receptor modulators |
CN101500565A (zh) * | 2006-06-29 | 2009-08-05 | 弗特克斯药品有限公司 | 毒蕈碱性受体的调节剂 |
US8633175B2 (en) * | 2006-08-09 | 2014-01-21 | Glaxosmithkline Llc | Compounds as antagonists or inverse agonists at opioid receptors |
CN101553231A (zh) * | 2006-08-15 | 2009-10-07 | 弗特克斯药品有限公司 | 毒蕈碱受体调节剂 |
JP2010501561A (ja) | 2006-08-18 | 2010-01-21 | バーテックス ファーマシューティカルズ インコーポレイテッド | ムスカリン受容体の調節剤 |
EP2064199A1 (en) | 2006-09-08 | 2009-06-03 | Pfizer Products Inc. | Diaryl ether derivatives and uses thereof |
WO2008059335A1 (en) * | 2006-11-13 | 2008-05-22 | Pfizer Products Inc. | Diaryl, dipyridinyl and aryl-pyridinyl derivatives and uses thereof |
US8093246B2 (en) * | 2006-12-14 | 2012-01-10 | Lexicon Pharmaceuticals, Inc. | O-linked pyrimidin-4-amine-based compounds, compositions comprising them, and methods of their use to treat cancer |
IL180134A0 (en) * | 2006-12-17 | 2007-07-04 | David Ovadia | Process for the preparation of substituted cyanophenoxy-pyrimidinyloxy -phenyl acrylate derivatives |
US20080186971A1 (en) * | 2007-02-02 | 2008-08-07 | Tarari, Inc. | Systems and methods for processing access control lists (acls) in network switches using regular expression matching logic |
EP2152671A1 (en) * | 2007-05-22 | 2010-02-17 | Prosidion Limited | Bicyclic aryl and heteroaryl compounds for the treatment of metabolic disorders |
US8063247B2 (en) * | 2007-09-07 | 2011-11-22 | Prosidion Limited | Bicyclic aryl and heteroaryl receptor modulators |
MX2010002760A (es) * | 2007-09-12 | 2010-04-01 | Wyeth Llc | Derivados de isoquinolinilo e isoindolinilo como antagonistas de la histamina-3. |
CA2700724A1 (en) * | 2007-10-03 | 2009-04-09 | Vertex Pharmaceuticals Incorporated | Modulators of muscarinic receptors |
EP2252581B1 (en) * | 2008-01-22 | 2012-06-20 | Eli Lilly And Company | Kappa selective opioid receptor antagonist |
WO2010067233A1 (en) | 2008-12-08 | 2010-06-17 | Pfizer Inc. | 1,2,4 triazolo [4, 3 -a] [1,5] benzodiazepin-5 (6h) -ones as agonists of the cholecystokinin-1 receptor (cck-ir) |
US9186353B2 (en) | 2009-04-27 | 2015-11-17 | Abbvie Inc. | Treatment of osteoarthritis pain |
CN104958298A (zh) * | 2009-09-18 | 2015-10-07 | 阿得罗公司 | 阿片样受体拮抗剂用于胃肠道疾病的用途 |
WO2012064396A2 (en) | 2010-08-21 | 2012-05-18 | Georgetown University | Novel ezrin inhibitors and methods of making and using |
US8853390B2 (en) | 2010-09-16 | 2014-10-07 | Abbvie Inc. | Processes for preparing 1,2-substituted cyclopropyl derivatives |
WO2012075232A1 (en) * | 2010-12-04 | 2012-06-07 | Trevena, Inc. | Opioid receptor ligands and methods of using and making the same |
SI2688403T1 (sl) | 2011-03-23 | 2017-08-31 | Trevena, Inc. | Ligandi opioidnih receptorjev in metode uporabe in izdelave istega |
GB201118876D0 (en) * | 2011-11-01 | 2011-12-14 | Astex Therapeutics Ltd | Pharmaceutical compounds |
CA2858752C (en) | 2011-12-09 | 2019-12-31 | Research Triangle Institute | 1-substituted 4-arylpiperazines as kappa opioid receptor antagonists |
WO2013113788A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
WO2013113720A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
IN2014DN07220A (xx) | 2012-02-03 | 2015-04-24 | Basf Se | |
WO2013113778A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
KR20150131211A (ko) * | 2013-03-14 | 2015-11-24 | 켈탁시스, 인코퍼레이티드 | 류코트라이엔 a4 가수분해효소의 저해제 |
WO2017106306A1 (en) | 2015-12-14 | 2017-06-22 | Trevena, Inc. | Methods of treating hyperalgesia |
CN106117190B (zh) * | 2016-06-21 | 2019-03-29 | 山东川成医药股份有限公司 | 一种倍福普兰的合成方法 |
US10316021B2 (en) | 2016-11-28 | 2019-06-11 | Pfizer Inc. | Heteroarylphenoxy benzamide kappa opioid ligands |
CN108299411B (zh) * | 2017-01-13 | 2021-02-05 | 中国人民解放军军事医学科学院毒物药物研究所 | 4,4-二苯基哌啶类化合物或其可药用盐、药物组合物及用途 |
BR112019016775A2 (pt) | 2017-02-17 | 2020-03-31 | Trevena, Inc. | Compostos moduladores de receptor delta-opioide contendo aza-heterocíclico com 7 membros, métodos de uso e produção dos mesmos |
AU2018221148B2 (en) | 2017-02-17 | 2022-05-05 | Trevena, Inc. | 5-membered aza-heterocyclic containing delta-opioid receptor modulating compounds, methods of using and making the same |
EP3652165B1 (en) * | 2017-07-12 | 2021-08-25 | Bristol-Myers Squibb Company | Five membered-aminoheterocyclic and 5,6-or 6,6-membered bicyclic aminoheterocyclic inhibitors of rock for the treatment of heart failure |
CN118290322A (zh) * | 2018-08-24 | 2024-07-05 | 赛尼欧普罗有限责任公司 | 用于治疗病态状况的芳香型分子 |
US20220370409A1 (en) | 2021-05-04 | 2022-11-24 | Janssen Pharmaceuticals, Inc. | Compositions And Methods For The Treatment Of Depression |
TW202345796A (zh) | 2022-03-07 | 2023-12-01 | 美商健生醫藥公司 | 阿替卡普蘭(aticaprant)之形式 |
WO2023179542A1 (en) * | 2022-03-21 | 2023-09-28 | Gasherbrum Bio , Inc. | 5,8-dihydro-1,7-naphthyridine derivatives as glp-1 agonists for the treatment of diabetes |
Family Cites Families (36)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4191771A (en) * | 1974-09-06 | 1980-03-04 | Eli Lilly And Company | Analgesic method using 1,3,4-trisubstituted-4-arylpiperidines |
SE417011B (sv) * | 1979-03-05 | 1981-02-16 | Saab Scania Ab | Malanordning |
US4346091A (en) * | 1980-05-27 | 1982-08-24 | Shell Oil Company | Insecticidal combinations |
US4422646A (en) * | 1981-09-18 | 1983-12-27 | Tvi Energy Corporation | Infrared target for military applications and its use |
US4546983A (en) * | 1981-09-18 | 1985-10-15 | Tvi Energy Corporation | Multi-spectral target |
US4659089A (en) * | 1981-09-18 | 1987-04-21 | Tvi Energy Corporation | Multi-spectral target |
US4891379A (en) * | 1987-04-16 | 1990-01-02 | Kabushiki Kaisha Kobe Seikosho | Piperidine opioid antagonists |
NZ224236A (en) * | 1987-04-16 | 1990-08-28 | Lilly Co Eli | Trans 3,4 pyridine derivatives and pharmaceutical compositions |
US4792142A (en) * | 1987-11-13 | 1988-12-20 | Davies Robert M | Thermal target device |
US5065032A (en) * | 1990-09-10 | 1991-11-12 | Custom Training Aids | Thermal integrated target |
US5319213A (en) * | 1992-04-06 | 1994-06-07 | The United States Of America As Represented By The Secretary Of The Army | Thermal target test board |
ZA967892B (en) * | 1995-09-21 | 1998-03-18 | Lilly Co Eli | Selective β3 adrenergic agonists. |
ES2171839T3 (es) * | 1996-09-05 | 2002-09-16 | Lilly Co Eli | Analogos de carbazol como agonistas adrenergicos selectivos de beta3. |
US5969369A (en) * | 1997-08-29 | 1999-10-19 | Fogarty; Charles M. | Infrared emissive module |
CO5011072A1 (es) * | 1997-12-05 | 2001-02-28 | Lilly Co Eli | Etanolaminas pirazinil substituidas como agfonistas de los receptores |
SE9802209D0 (sv) | 1998-06-22 | 1998-06-22 | Astra Pharma Inc | Novel compounds |
AUPP796798A0 (en) | 1998-12-30 | 1999-01-28 | Fujisawa Pharmaceutical Co., Ltd. | New compound |
US6436959B1 (en) * | 1998-12-23 | 2002-08-20 | Ortho-Mcneil Pharmaceutical, Inc. | 4-[aryl(piperidin-4-yl)]aminobenzamides |
GB9828442D0 (en) * | 1998-12-24 | 1999-02-17 | Karobio Ab | Novel thyroid receptor ligands and method II |
GB9912411D0 (en) | 1999-05-28 | 1999-07-28 | Pfizer Ltd | Compounds useful in therapy |
US6337475B1 (en) * | 2000-02-24 | 2002-01-08 | The United States Of America As Represented By The Secretary Of The Army | Thermal silhouette target and zeroing technique |
SK632003A3 (en) * | 2000-07-13 | 2003-06-03 | Lilly Co Eli | Beta3 adrenergic agonists |
EP1341759B1 (en) | 2000-11-10 | 2006-06-14 | Eli Lilly And Company | 3-substituted oxindole beta 3 agonists |
US7507767B2 (en) * | 2001-02-08 | 2009-03-24 | Schering Corporation | Cannabinoid receptor ligands |
ES2566056T3 (es) | 2001-03-29 | 2016-04-08 | Eli Lilly And Company | N-(2-ariletil)bencilaminas como antagonistas del receptor 5-HT6 |
GB0109103D0 (en) * | 2001-04-11 | 2001-05-30 | Pfizer Ltd | Novel compounds |
DE60321207D1 (en) * | 2002-09-19 | 2008-07-03 | Lilly Co Eli | Diaryläther als opioid-rezeptor antagonisten |
WO2004080968A1 (en) * | 2003-03-07 | 2004-09-23 | Eli Lilly And Company | 6-substituted nicotinamide derivatives as opioid receptor antagonists |
ATE406360T1 (de) * | 2003-03-07 | 2008-09-15 | Lilly Co Eli | Antagonisten der opioidrezeptoren |
US6767015B1 (en) * | 2003-06-05 | 2004-07-27 | The United States Of America As Represented By The Secretary Of The Navy | Thermal target |
US7196100B2 (en) * | 2003-12-12 | 2007-03-27 | Eli Lilly And Company | Opioid receptor antagonists |
CN1894240A (zh) * | 2003-12-22 | 2007-01-10 | 伊莱利利公司 | 阿片受体拮抗剂 |
WO2005090286A1 (en) * | 2004-03-12 | 2005-09-29 | Eli Lilly And Company | Opioid receptor antagonists |
US7288543B2 (en) * | 2004-03-12 | 2007-10-30 | Eli Lilly And Company | Opioid receptor antagonists |
ES2318472T3 (es) * | 2004-03-15 | 2009-05-01 | Eli Lilly And Company | Derivados de 5-(5-(aminoetil)-indol-1-ilmetil)-benzamida y compuestos relacionados como antagonistas del receptor opioide para el tratamiento de la obesidad. |
WO2005092836A1 (en) * | 2004-03-15 | 2005-10-06 | Eli Lilly And Company | Opioid receptor antagonists |
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