ES2390004T3 - Derivados sustituidos de piperidina espirocíclica como ligandos del receptor de la histamina 3(H3) - Google Patents
Derivados sustituidos de piperidina espirocíclica como ligandos del receptor de la histamina 3(H3) Download PDFInfo
- Publication number
- ES2390004T3 ES2390004T3 ES09707104T ES09707104T ES2390004T3 ES 2390004 T3 ES2390004 T3 ES 2390004T3 ES 09707104 T ES09707104 T ES 09707104T ES 09707104 T ES09707104 T ES 09707104T ES 2390004 T3 ES2390004 T3 ES 2390004T3
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- Spain
- Prior art keywords
- optionally substituted
- ring system
- occurrence
- independently
- alkyl
- Prior art date
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- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 title description 14
- 229960001340 histamine Drugs 0.000 title description 7
- 239000003446 ligand Substances 0.000 title description 7
- 150000003053 piperidines Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 255
- 239000000203 mixture Substances 0.000 claims abstract description 121
- -1 methylenedioxyl Chemical group 0.000 claims abstract description 109
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 105
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 104
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 104
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 65
- 150000003839 salts Chemical class 0.000 claims abstract description 56
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims abstract description 47
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 45
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 42
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 38
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 38
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 28
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims abstract description 26
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 25
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 22
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims abstract description 22
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims abstract description 22
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 20
- 101100294102 Caenorhabditis elegans nhr-2 gene Proteins 0.000 claims abstract description 15
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 15
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 14
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims abstract description 9
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 7
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims abstract description 7
- AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical class OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 claims abstract description 6
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims abstract description 5
- 108010081348 HRT1 protein Hairy Proteins 0.000 claims abstract description 4
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims abstract description 4
- 125000000815 N-oxide group Chemical group 0.000 claims abstract 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 76
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 60
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 45
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 42
- 229910052757 nitrogen Inorganic materials 0.000 claims description 42
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 39
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 31
- 208000035475 disorder Diseases 0.000 claims description 27
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 27
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 26
- 125000002757 morpholinyl group Chemical group 0.000 claims description 21
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 125000004193 piperazinyl group Chemical group 0.000 claims description 17
- 125000003386 piperidinyl group Chemical group 0.000 claims description 17
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 15
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 12
- 201000003631 narcolepsy Diseases 0.000 claims description 11
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 11
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 10
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 10
- 208000030814 Eating disease Diseases 0.000 claims description 10
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 10
- 206010062519 Poor quality sleep Diseases 0.000 claims description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 235000014632 disordered eating Nutrition 0.000 claims description 10
- 239000001301 oxygen Chemical group 0.000 claims description 10
- 239000011593 sulfur Chemical group 0.000 claims description 10
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 9
- 208000008589 Obesity Diseases 0.000 claims description 9
- 125000002393 azetidinyl group Chemical group 0.000 claims description 9
- 208000010877 cognitive disease Diseases 0.000 claims description 9
- 125000002541 furyl group Chemical group 0.000 claims description 9
- 235000020824 obesity Nutrition 0.000 claims description 9
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 9
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 9
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 9
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 9
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 9
- 125000000335 thiazolyl group Chemical group 0.000 claims description 9
- 208000024827 Alzheimer disease Diseases 0.000 claims description 8
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 6
- 206010061218 Inflammation Diseases 0.000 claims description 6
- 208000019695 Migraine disease Diseases 0.000 claims description 6
- 208000019022 Mood disease Diseases 0.000 claims description 6
- 208000002193 Pain Diseases 0.000 claims description 6
- 230000036626 alertness Effects 0.000 claims description 6
- 206010015037 epilepsy Diseases 0.000 claims description 6
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 6
- 230000001771 impaired effect Effects 0.000 claims description 6
- 230000004054 inflammatory process Effects 0.000 claims description 6
- 206010027599 migraine Diseases 0.000 claims description 6
- 201000003152 motion sickness Diseases 0.000 claims description 6
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
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- 208000023504 respiratory system disease Diseases 0.000 claims description 6
- 201000000980 schizophrenia Diseases 0.000 claims description 6
- 208000026139 Memory disease Diseases 0.000 claims description 5
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 5
- 125000005050 dihydrooxazolyl group Chemical group O1C(NC=C1)* 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 5
- 125000001041 indolyl group Chemical group 0.000 claims description 5
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 5
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
- 125000002971 oxazolyl group Chemical group 0.000 claims description 5
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 5
- 125000005988 1,1-dioxo-thiomorpholinyl group Chemical group 0.000 claims description 4
- 125000005955 1H-indazolyl group Chemical group 0.000 claims description 4
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 4
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 4
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000005872 benzooxazolyl group Chemical group 0.000 claims description 4
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000000160 oxazolidinyl group Chemical group 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 230000006735 deficit Effects 0.000 claims description 2
- 208000013403 hyperactivity Diseases 0.000 claims description 2
- 206010000117 Abnormal behaviour Diseases 0.000 claims 1
- 208000010643 digestive system disease Diseases 0.000 claims 1
- 230000020595 eating behavior Effects 0.000 claims 1
- 208000018685 gastrointestinal system disease Diseases 0.000 claims 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 298
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 216
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 150
- 239000000243 solution Substances 0.000 description 96
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 89
- 241000700159 Rattus Species 0.000 description 85
- 238000000034 method Methods 0.000 description 80
- 238000005160 1H NMR spectroscopy Methods 0.000 description 63
- 230000027455 binding Effects 0.000 description 50
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 47
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 44
- 238000006243 chemical reaction Methods 0.000 description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
- 235000019439 ethyl acetate Nutrition 0.000 description 38
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 37
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 32
- 239000012267 brine Substances 0.000 description 28
- 239000012044 organic layer Substances 0.000 description 28
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 25
- 238000000746 purification Methods 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
- 239000000047 product Substances 0.000 description 22
- 102000004384 Histamine H3 receptors Human genes 0.000 description 21
- 108090000981 Histamine H3 receptors Proteins 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 125000004432 carbon atom Chemical group C* 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- 239000012528 membrane Substances 0.000 description 19
- 239000011541 reaction mixture Substances 0.000 description 18
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 17
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 16
- 229910052681 coesite Inorganic materials 0.000 description 16
- 229910052906 cristobalite Inorganic materials 0.000 description 16
- 239000000377 silicon dioxide Substances 0.000 description 16
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- 238000004440 column chromatography Methods 0.000 description 15
- 235000017557 sodium bicarbonate Nutrition 0.000 description 15
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 14
- 230000000694 effects Effects 0.000 description 14
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- 150000001204 N-oxides Chemical class 0.000 description 12
- 239000011780 sodium chloride Substances 0.000 description 12
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- 102000005962 receptors Human genes 0.000 description 11
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- 239000007858 starting material Substances 0.000 description 11
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 11
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 10
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 10
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- 229910052739 hydrogen Inorganic materials 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
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- 239000000556 agonist Substances 0.000 description 8
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- 229910001629 magnesium chloride Inorganic materials 0.000 description 8
- 201000002859 sleep apnea Diseases 0.000 description 8
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 7
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- XNQIOISZPFVUFG-RXMQYKEDSA-N (R)-alpha-methylhistamine Chemical compound C[C@@H](N)CC1=CN=CN1 XNQIOISZPFVUFG-RXMQYKEDSA-N 0.000 description 6
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- YDCBXYAESLCOPJ-UHFFFAOYSA-N 1'-cyclobutylspiro[3,4-dihydrochromene-2,4'-piperidine]-6-ol Chemical compound C1CC2=CC(O)=CC=C2OC1(CC1)CCN1C1CCC1 YDCBXYAESLCOPJ-UHFFFAOYSA-N 0.000 description 4
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Classifications
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- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
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Landscapes
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- Pulmonology (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6290708P | 2008-01-30 | 2008-01-30 | |
| US62907 | 2008-01-30 | ||
| PCT/US2009/032709 WO2009097567A1 (en) | 2008-01-30 | 2009-01-30 | Substituted spirocyclic piperidine derivatives as histamine-3 (h3) receptor ligands |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2390004T3 true ES2390004T3 (es) | 2012-11-05 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES09707104T Active ES2390004T3 (es) | 2008-01-30 | 2009-01-30 | Derivados sustituidos de piperidina espirocíclica como ligandos del receptor de la histamina 3(H3) |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US8513232B2 (enExample) |
| EP (1) | EP2250176B1 (enExample) |
| JP (1) | JP5524083B2 (enExample) |
| CA (1) | CA2712897A1 (enExample) |
| ES (1) | ES2390004T3 (enExample) |
| MX (1) | MX2010008375A (enExample) |
| WO (1) | WO2009097567A1 (enExample) |
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| NZ574873A (en) * | 2006-07-25 | 2012-03-30 | Cephalon Inc | Pyridazinone derivatives as h3 inhibitors |
| CA2712897A1 (en) | 2008-01-30 | 2009-08-06 | Pharmacopeia, Inc. | Substituted spirocyclic piperidine derivatives as histamine-3 (h3) receptor ligands |
| ES2479440T3 (es) | 2008-01-30 | 2014-07-24 | Cephalon, Inc. | Derivados de piridazina sustituidos que tienen actividad antagonista de histamina H3 |
| WO2009142732A2 (en) * | 2008-05-20 | 2009-11-26 | Cephalon, Inc. | Substituted pyridazinone derivatives as histamine-3 (h3) receptor ligands |
| SG176105A1 (en) * | 2009-06-26 | 2011-12-29 | Novartis Ag | 1, 3-disubstituted imidazolidin-2-one derivatives as inhibitors of cyp 17 |
| WO2011020193A1 (en) * | 2009-08-18 | 2011-02-24 | Merck Frosst Canada Ltd. | Renin inhibitors |
| WO2011057382A1 (en) * | 2009-10-13 | 2011-05-19 | Merck Frosst Canada Ltd. | Spirocyclic piperidine derivatives useful as renin inhibitors |
| TW201206893A (en) | 2010-07-09 | 2012-02-16 | Abbott Healthcare Products Bv | Bisaryl (thio) morpholine derivatives as S1P modulators |
| TW201643169A (zh) | 2010-07-09 | 2016-12-16 | 艾伯維股份有限公司 | 作為s1p調節劑的螺-哌啶衍生物 |
| TWI522361B (zh) | 2010-07-09 | 2016-02-21 | 艾伯維公司 | 作為s1p調節劑的稠合雜環衍生物 |
| US9029399B2 (en) | 2011-04-28 | 2015-05-12 | Novartis Ag | 17α-hydroxylase/C17,20-lyase inhibitors |
| WO2013151982A1 (en) | 2012-04-03 | 2013-10-10 | Arena Pharmaceuticals, Inc. | Methods and compounds useful in treating pruritus, and methods for identifying such compounds |
| EA035727B1 (ru) | 2013-10-18 | 2020-07-31 | Селджен Квонтисел Рисёрч, Инк. | Ингибиторы бромодомена |
| AR104259A1 (es) | 2015-04-15 | 2017-07-05 | Celgene Quanticel Res Inc | Inhibidores de bromodominio |
| EP3445750A4 (en) | 2016-04-18 | 2019-11-27 | Celgene Quanticel Research, Inc. | THERAPEUTIC COMPOUNDS |
| US10150754B2 (en) | 2016-04-19 | 2018-12-11 | Celgene Quanticel Research, Inc. | Histone demethylase inhibitors |
| EP3535244A1 (en) * | 2016-11-02 | 2019-09-11 | Abbvie Deutschland GmbH & Co. KG | Spiro-compounds as s1p modulators |
| EP3554637A4 (en) * | 2016-12-14 | 2020-05-20 | 89Bio Ltd. | Spiropiperidine derivatives |
| PH12022551033A1 (en) | 2019-10-31 | 2023-06-14 | Escape Bio Inc | Solid forms of an s1p-receptor modulator |
| GB201917101D0 (en) * | 2019-11-25 | 2020-01-08 | Uea Enterprises Ltd | Method for digesting nucleic acid in a sample |
| WO2024251040A1 (zh) * | 2023-06-09 | 2024-12-12 | 广州市联瑞制药有限公司 | Irak4降解剂及其用途 |
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| US4166120A (en) * | 1978-04-14 | 1979-08-28 | American Hoechst Corporation | Analgesic and tranquilizing benzoylpropyl-spiro[dihydrobenzofuran]piperidines and pyrrolidines |
| PL360373A1 (en) | 2000-08-08 | 2004-09-06 | Ortho Mcneil Pharmaceutical, Inc. | Non-imidazole aryloxypiperidines as h3 receptor ligands |
| EP1481679B1 (en) * | 2002-03-01 | 2010-08-25 | Takeda Pharmaceutical Company Limited | Antidepressant |
| SE0202133D0 (sv) * | 2002-07-08 | 2002-07-08 | Astrazeneca Ab | Novel compounds |
| WO2005007644A1 (ja) | 2003-06-27 | 2005-01-27 | Banyu Pharmaceutical Co., Ltd | ヘテロアリールオキシ含窒素飽和へテロ環誘導体 |
| EP1646611A1 (en) | 2003-07-15 | 2006-04-19 | Merck & Co., Inc. | Hydroxypyridine cgrp receptor antagonists |
| US7338962B2 (en) * | 2003-10-01 | 2008-03-04 | Adolor Corporation | Spirocyclic heterocyclic derivatives and methods of their use |
| SE0403160D0 (sv) | 2004-12-23 | 2004-12-23 | Biovitrum Ab | New compounds |
| EP1866293A1 (en) | 2005-03-31 | 2007-12-19 | UCB Pharma, S.A. | Compounds comprising an oxazole or thiazole moiety, processes for making them, and their uses |
| EP1707203A1 (en) | 2005-04-01 | 2006-10-04 | Bioprojet | Treatment of parkinson's disease obstructive sleep apnea, dementia with lewy bodies, vascular dementia with non-imidazole alkylamines histamine H3- receptor ligands |
| EP1717235A3 (en) | 2005-04-29 | 2007-02-28 | Bioprojet | Phenoxypropylpiperidines and -pyrrolidines and their use as histamine H3-receptor ligands |
| WO2007063385A2 (en) * | 2005-12-01 | 2007-06-07 | Pfizer Products Inc. | Spirocyclic amine histamine-3 receptor antagonists |
| WO2007088462A1 (en) * | 2006-02-01 | 2007-08-09 | Pfizer Products Inc. | Spirochromane antagonists of the h-3 receptor |
| US20100317679A1 (en) * | 2007-09-21 | 2010-12-16 | Ligand Pharmaceuticals, Inc. | Substituted aryl-fused spirocyclic amines |
| CA2712897A1 (en) | 2008-01-30 | 2009-08-06 | Pharmacopeia, Inc. | Substituted spirocyclic piperidine derivatives as histamine-3 (h3) receptor ligands |
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- 2009-01-30 ES ES09707104T patent/ES2390004T3/es active Active
- 2009-01-30 EP EP09707104A patent/EP2250176B1/en not_active Not-in-force
- 2009-01-30 JP JP2010545227A patent/JP5524083B2/ja not_active Expired - Fee Related
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2010
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| CA2712897A1 (en) | 2009-08-06 |
| US20110071131A1 (en) | 2011-03-24 |
| EP2250176B1 (en) | 2012-08-01 |
| WO2009097567A1 (en) | 2009-08-06 |
| HK1149555A1 (en) | 2011-10-07 |
| MX2010008375A (es) | 2011-03-04 |
| US8513232B2 (en) | 2013-08-20 |
| EP2250176A1 (en) | 2010-11-17 |
| JP2011511001A (ja) | 2011-04-07 |
| JP5524083B2 (ja) | 2014-06-18 |
| WO2009097567A4 (en) | 2009-10-29 |
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