JPWO2004046110A1 - メラニン凝集ホルモン受容体拮抗剤 - Google Patents
メラニン凝集ホルモン受容体拮抗剤 Download PDFInfo
- Publication number
- JPWO2004046110A1 JPWO2004046110A1 JP2004553173A JP2004553173A JPWO2004046110A1 JP WO2004046110 A1 JPWO2004046110 A1 JP WO2004046110A1 JP 2004553173 A JP2004553173 A JP 2004553173A JP 2004553173 A JP2004553173 A JP 2004553173A JP WO2004046110 A1 JPWO2004046110 A1 JP WO2004046110A1
- Authority
- JP
- Japan
- Prior art keywords
- lower alkyl
- piperidin
- optionally substituted
- phenyl
- fluorophenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 229940122023 Melanin concentrating hormone receptor antagonist Drugs 0.000 title claims abstract description 20
- 150000003839 salts Chemical class 0.000 claims abstract description 48
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 45
- 239000004480 active ingredient Substances 0.000 claims abstract description 14
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 196
- -1 N- [bis (4-fluorophenyl) methyl] -2- {1-[(2E) -3- (4-cyanophenyl) prop-2-en-1-yl] piperidin-4-yl} -N- Methylacetamide Chemical compound 0.000 claims description 153
- 125000000217 alkyl group Chemical group 0.000 claims description 82
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 49
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 42
- 125000003118 aryl group Chemical group 0.000 claims description 40
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 35
- 229910052736 halogen Inorganic materials 0.000 claims description 30
- 150000002367 halogens Chemical class 0.000 claims description 29
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 26
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 20
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 125000002947 alkylene group Chemical group 0.000 claims description 8
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 5
- 229940123502 Hormone receptor antagonist Drugs 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 125000005647 linker group Chemical group 0.000 claims description 5
- 125000003107 substituted aryl group Chemical group 0.000 claims description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 claims description 4
- 125000004450 alkenylene group Chemical group 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- GPTFURBXHJWNHR-UHFFFAOYSA-N protopine Chemical compound C1=C2C(=O)CC3=CC=C4OCOC4=C3CN(C)CCC2=CC2=C1OCO2 GPTFURBXHJWNHR-UHFFFAOYSA-N 0.000 claims description 3
- SKZKKFZAGNVIMN-UHFFFAOYSA-N Salicilamide Chemical compound NC(=O)C1=CC=CC=C1O SKZKKFZAGNVIMN-UHFFFAOYSA-N 0.000 claims description 2
- 230000004931 aggregating effect Effects 0.000 claims description 2
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 2
- 230000003579 anti-obesity Effects 0.000 claims description 2
- 125000002837 carbocyclic group Chemical group 0.000 claims description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
- 229940047583 cetamide Drugs 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 239000003689 hormone receptor blocking agent Substances 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 4
- 239000000883 anti-obesity agent Substances 0.000 abstract description 3
- 229940125710 antiobesity agent Drugs 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 143
- 239000000243 solution Substances 0.000 description 128
- 238000006243 chemical reaction Methods 0.000 description 121
- 239000002904 solvent Substances 0.000 description 114
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 106
- 230000002829 reductive effect Effects 0.000 description 105
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 94
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 82
- 239000000203 mixture Substances 0.000 description 81
- 235000019439 ethyl acetate Nutrition 0.000 description 71
- 238000004519 manufacturing process Methods 0.000 description 69
- 238000001816 cooling Methods 0.000 description 66
- 238000003756 stirring Methods 0.000 description 58
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 49
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 48
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 47
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 47
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 44
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- 238000010898 silica gel chromatography Methods 0.000 description 35
- 238000010438 heat treatment Methods 0.000 description 33
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 32
- 238000012360 testing method Methods 0.000 description 31
- 239000012044 organic layer Substances 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 229920006395 saturated elastomer Polymers 0.000 description 28
- 239000007787 solid Substances 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 239000000126 substance Substances 0.000 description 27
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 25
- 238000000034 method Methods 0.000 description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
- 239000012442 inert solvent Substances 0.000 description 23
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 23
- 235000017557 sodium bicarbonate Nutrition 0.000 description 23
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
- 150000001412 amines Chemical class 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 20
- 238000001914 filtration Methods 0.000 description 20
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 19
- 101800002739 Melanin-concentrating hormone Proteins 0.000 description 19
- 238000001704 evaporation Methods 0.000 description 19
- 239000007858 starting material Substances 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 102400001132 Melanin-concentrating hormone Human genes 0.000 description 18
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
- 101150106280 Mchr1 gene Proteins 0.000 description 17
- 108700036626 Melanin-concentrating hormone receptor 1 Proteins 0.000 description 17
- 102100027375 Melanin-concentrating hormone receptor 1 Human genes 0.000 description 17
- 230000000694 effects Effects 0.000 description 17
- 239000012280 lithium aluminium hydride Substances 0.000 description 17
- 239000011259 mixed solution Substances 0.000 description 16
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 15
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 14
- 239000013078 crystal Substances 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- 239000005089 Luciferase Substances 0.000 description 12
- 238000001035 drying Methods 0.000 description 12
- 230000005764 inhibitory process Effects 0.000 description 12
- 239000002994 raw material Substances 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- 239000002585 base Substances 0.000 description 11
- 239000003638 chemical reducing agent Substances 0.000 description 11
- 235000011167 hydrochloric acid Nutrition 0.000 description 11
- 239000002198 insoluble material Substances 0.000 description 11
- 229910000027 potassium carbonate Inorganic materials 0.000 description 11
- 125000006239 protecting group Chemical group 0.000 description 11
- 238000006722 reduction reaction Methods 0.000 description 11
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
- 102000029828 Melanin-concentrating hormone receptor Human genes 0.000 description 10
- 108010047068 Melanin-concentrating hormone receptor Proteins 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 238000009739 binding Methods 0.000 description 10
- 108090000623 proteins and genes Proteins 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 150000003335 secondary amines Chemical class 0.000 description 10
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 9
- 101000581404 Mus musculus Melanin-concentrating hormone receptor 1 Proteins 0.000 description 9
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 9
- 150000002513 isocyanates Chemical class 0.000 description 9
- 108060001084 Luciferase Proteins 0.000 description 8
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 8
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 8
- 235000011054 acetic acid Nutrition 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 7
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
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- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 6
- 235000015165 citric acid Nutrition 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
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- 150000002576 ketones Chemical class 0.000 description 6
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- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
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- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 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 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 5
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- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 5
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
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- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 4
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 4
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 4
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
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- SEQKRHFRPICQDD-UHFFFAOYSA-N N-tris(hydroxymethyl)methylglycine Chemical compound OCC(CO)(CO)[NH2+]CC([O-])=O SEQKRHFRPICQDD-UHFFFAOYSA-N 0.000 description 4
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- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
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Images
Classifications
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- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
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- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- Health & Medical Sciences (AREA)
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- Public Health (AREA)
- Medicinal Chemistry (AREA)
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- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2002332950 | 2002-11-15 | ||
JP2002332950 | 2002-11-15 | ||
PCT/JP2003/014534 WO2004046110A1 (fr) | 2002-11-15 | 2003-11-14 | Antagoniste du recepteur d'hormone de concentration de la melanine |
Publications (1)
Publication Number | Publication Date |
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JPWO2004046110A1 true JPWO2004046110A1 (ja) | 2006-03-16 |
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JP2004553173A Withdrawn JPWO2004046110A1 (ja) | 2002-11-15 | 2003-11-14 | メラニン凝集ホルモン受容体拮抗剤 |
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JP (1) | JPWO2004046110A1 (fr) |
AU (1) | AU2003284402A1 (fr) |
WO (1) | WO2004046110A1 (fr) |
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CA2517888C (fr) | 2003-03-14 | 2012-05-01 | Ono Pharmaceutical Co., Ltd. | Derives heterocycliques renfermant de l'azote et medicaments contenant ces derives comme principe actif |
WO2005012254A1 (fr) | 2003-07-22 | 2005-02-10 | Arena Pharmaceuticals, Inc. | Derives de diaryl et arylheteroaryl uree utilises en tant que modulateurs du recepteur de la serotonine 5-ht2a utiles pour la prophylaxie et le traitement de troubles associes a ce dernier |
JP2008511552A (ja) * | 2004-08-30 | 2008-04-17 | ニューロメッド ファーマシューティカルズ リミテッド | カルシウムチャネルブロッカーとしての尿素誘導体 |
TWI400232B (zh) | 2004-09-13 | 2013-07-01 | Ono Pharmaceutical Co | 含氮雜環衍生物及以該含氮雜環衍生物為有效成分之藥劑 |
CA2644368A1 (fr) | 2006-03-10 | 2007-09-20 | Ono Pharmaceutical Co., Ltd. | Derive heterocyclique azote et agent pharmaceutique comprenant le derive en tant que principe actif |
BRPI0712823A2 (pt) | 2006-06-23 | 2012-07-24 | Abbott Lab | derivados de ciclopropil amina como moduladores de receptor de histamina h3 |
US9108948B2 (en) | 2006-06-23 | 2015-08-18 | Abbvie Inc. | Cyclopropyl amine derivatives |
TWI415845B (zh) | 2006-10-03 | 2013-11-21 | Arena Pharm Inc | 用於治療與5-ht2a血清素受體相關聯病症之作為5-ht2a血清素受體之調節劑的吡唑衍生物 |
JPWO2008044632A1 (ja) * | 2006-10-06 | 2010-02-12 | 大正製薬株式会社 | 1−ナフチルアルキルピペリジン誘導体 |
EP2190844B3 (fr) | 2007-08-15 | 2013-07-17 | Arena Pharmaceuticals, Inc. | Dérivés d'imidazo[1,2-a]pyridine utilisés comme modulateurs du récepteur sérotoninergique 5-ht2a dans le traitement des troubles qui lui sont associés |
TW201446748A (zh) | 2007-08-22 | 2014-12-16 | Astrazeneca Ab | 環丙基醯胺衍生物 |
WO2009123714A2 (fr) | 2008-04-02 | 2009-10-08 | Arena Pharmaceuticals, Inc. | Procédés de préparation de dérivés de pyrazole utiles comme modulateurs du récepteur de la sérotonine 5-ht<sb>2a</sb> |
US8377968B2 (en) | 2008-06-02 | 2013-02-19 | Zalicus Pharmaceuticals, Ltd. | N-piperidinyl acetamide derivatives as calcium channel blockers |
SI2364142T1 (en) | 2008-10-28 | 2018-06-29 | Arena Pharmaceuticals, Inc. | The modulators of the serotonin 5-HT2A receptor are useful in the treatment of disorders associated with it |
US9126946B2 (en) | 2008-10-28 | 2015-09-08 | Arena Pharmaceuticals, Inc. | Processes useful for the preparation of 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)urea and crystalline forms related thereto |
EP2375899B1 (fr) | 2009-01-12 | 2015-02-25 | Array Biopharma Inc. | Composés contenant de la pipéridine et leur utilisation dans le traitement du diabète |
TW201039825A (en) | 2009-02-20 | 2010-11-16 | Astrazeneca Ab | Cyclopropyl amide derivatives 983 |
US9186353B2 (en) | 2009-04-27 | 2015-11-17 | Abbvie Inc. | Treatment of osteoarthritis pain |
US8673920B2 (en) | 2009-05-06 | 2014-03-18 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
BR112012020629A2 (pt) | 2010-02-18 | 2018-06-19 | Astrazeneca Ab | forma cristalina, e, método para a terapia de um distúrbio |
WO2012037258A1 (fr) | 2010-09-16 | 2012-03-22 | Abbott Laboratories | Procédés de préparation de dérivés cyclopropyliques substitués en 1,2 |
WO2012058116A1 (fr) | 2010-10-27 | 2012-05-03 | Merck Sharp & Dohme Corp. | Inhibiteurs du canal potassique de la médullaire externe rénale |
WO2012058134A1 (fr) | 2010-10-29 | 2012-05-03 | Merck Sharp & Dohme Corp. | Inhibiteurs du canal à potassium de la medulla externe du rein |
WO2012113103A1 (fr) | 2011-02-25 | 2012-08-30 | Helsinn Healthcare S.A. | Urées asymétriques et leurs utilisations médicales |
CN103717224A (zh) * | 2011-06-07 | 2014-04-09 | 独立行政法人科学技术振兴机构 | 一氧化碳(co)对脂肪酸和胆固醇摄取的抑制 |
US9062070B2 (en) | 2011-08-19 | 2015-06-23 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
US9527830B2 (en) | 2011-09-16 | 2016-12-27 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
WO2013062892A1 (fr) | 2011-10-25 | 2013-05-02 | Merck Sharp & Dohme Corp. | Inhibiteurs du canal potassique médullaire extérieur rénal |
US8999991B2 (en) | 2011-10-25 | 2015-04-07 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
WO2013066717A1 (fr) | 2011-10-31 | 2013-05-10 | Merck Sharp & Dohme Corp. | Inhibiteurs du canal potassique médullaire externe rénal |
US9493474B2 (en) | 2011-10-31 | 2016-11-15 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
EP2773199B1 (fr) | 2011-10-31 | 2019-04-10 | Merck Sharp & Dohme Corp. | Inhibiteurs du canal potassique médullaire externe rénal |
WO2013090271A1 (fr) | 2011-12-16 | 2013-06-20 | Merck Sharp & Dohme Corp. | Inhibiteurs du canal à potassium de la medulla externe du rein |
AR092031A1 (es) | 2012-07-26 | 2015-03-18 | Merck Sharp & Dohme | Inhibidores del canal de potasio medular externo renal |
US9777002B2 (en) | 2012-11-29 | 2017-10-03 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
EP2934533B1 (fr) | 2012-12-19 | 2017-11-15 | Merck Sharp & Dohme Corp. | Inhibiteurs du canal potassique médullaire externe rénal |
WO2014126944A2 (fr) | 2013-02-18 | 2014-08-21 | Merck Sharp & Dohme Corp. | Inhibiteurs du canal potassique médullaire extérieur rénal |
US10208023B2 (en) | 2013-03-01 | 2019-02-19 | Mark G. DeGiacomo | Heterocyclic inhibitors of the sodium channel |
US9765074B2 (en) | 2013-03-15 | 2017-09-19 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
EP3027625B1 (fr) | 2013-07-31 | 2018-05-30 | Merck Sharp & Dohme Corp. | Derives spiro-fusionnes de piperidine utiles dans le traitement, entre autres, de l'hypertension et de l' insuffisance cardiaque aiguë ou chronique |
WO2016127358A1 (fr) | 2015-02-12 | 2016-08-18 | Merck Sharp & Dohme Corp. | Inhibiteurs du canal potassique médullaire externe rénal |
MX2017016413A (es) | 2015-06-12 | 2018-08-01 | Axovant Sciences Gmbh | Derivados de diaril y arilheteroaril urea como moduladores del receptor 5ht2a de serotonina útiles para la profilaxis y el tratamineto de un trastorno conductual del sueño rem. |
MX2018000465A (es) | 2015-07-15 | 2018-09-17 | Axovant Sciences Gmbh | Derivados de diaril y arilheteroaril urea como moduladores del receptor de serotonina 5-ht2a útiles para la profilaxis y el tratamiento de alucinaciones asociadas con una enfermedad neurodegenerativa. |
FI3390355T3 (fi) | 2016-03-22 | 2023-04-04 | Helsinn Healthcare Sa | Asymmetrisiä bentseenisulfonyyliureoita ja niiden lääketieteellisiä käyttöjä |
US9650338B1 (en) | 2016-07-29 | 2017-05-16 | VDM Biochemicals, Inc. | Opioid antagonist compounds and methods of making and using |
BR112022000429A2 (pt) | 2019-07-11 | 2022-03-29 | Praxis Prec Medicines Inc | Formulações de moduladores do canal de cálcio tipo t e métodos de uso dos mesmos |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
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GB1473262A (en) * | 1974-11-20 | 1977-05-11 | Delalande Sa | Derivatives of n-3,4,5-trimethoxy cinnamoyl-piperazine their process of preparation and their therapeutic application |
GB1575310A (en) * | 1976-11-16 | 1980-09-17 | Anphar Sa | Piperidine derivatives |
FR2522325B1 (fr) * | 1982-02-26 | 1985-08-09 | Delalande Sa | Nouveaux derives aryliques de la piperazine, de l'homopiperazine et de n,n'-dialkyl diamino-1,2 ethane, leur procede de preparation et leur application en therapeutique |
EP1219294A4 (fr) * | 1999-09-20 | 2005-01-26 | Antagonistes de l'hormone de concentration de la melanine | |
CA2386474A1 (fr) * | 1999-09-20 | 2001-03-29 | Takeda Chemical Industries, Ltd. | Antagoniste de l'hormone de concentration de la melanine |
JP2001172257A (ja) * | 1999-10-05 | 2001-06-26 | Fujisawa Pharmaceut Co Ltd | 有機スルホンアミド化合物 |
FR2804429B1 (fr) * | 2000-01-31 | 2003-05-09 | Adir | Nouveaux derives de 4-sulfonamides piperidine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
EP1448526B1 (fr) * | 2001-11-26 | 2009-10-21 | Schering Corporation | Antagonistes de la mch base de pip ridine pour le traitement de l'ob sit et des troubles li s au syst me nerveux central (cns) |
-
2003
- 2003-11-14 AU AU2003284402A patent/AU2003284402A1/en not_active Abandoned
- 2003-11-14 JP JP2004553173A patent/JPWO2004046110A1/ja not_active Withdrawn
- 2003-11-14 WO PCT/JP2003/014534 patent/WO2004046110A1/fr active Application Filing
Also Published As
Publication number | Publication date |
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WO2004046110A1 (fr) | 2004-06-03 |
AU2003284402A1 (en) | 2004-06-15 |
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