ES2548134T3 - Derivados de piperidina 3,4-sustituida como inhibidores de renina - Google Patents
Derivados de piperidina 3,4-sustituida como inhibidores de renina Download PDFInfo
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- ES2548134T3 ES2548134T3 ES09741617.6T ES09741617T ES2548134T3 ES 2548134 T3 ES2548134 T3 ES 2548134T3 ES 09741617 T ES09741617 T ES 09741617T ES 2548134 T3 ES2548134 T3 ES 2548134T3
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- optionally substituted
- halogens
- alkylene
- equiv
- metil
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- 239000002461 renin inhibitor Substances 0.000 title description 12
- 229940086526 renin-inhibitors Drugs 0.000 title description 11
- 150000003053 piperidines Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 242
- 150000002367 halogens Chemical class 0.000 claims abstract description 166
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 161
- 150000003839 salts Chemical class 0.000 claims abstract description 49
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 48
- 239000001257 hydrogen Substances 0.000 claims abstract description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 44
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims abstract description 36
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 31
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 26
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 24
- 125000001424 substituent group Chemical group 0.000 claims abstract description 21
- 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 20
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 18
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 15
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 14
- 125000002837 carbocyclic group Chemical group 0.000 claims abstract description 14
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 14
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 13
- 125000003118 aryl group Chemical group 0.000 claims abstract description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 13
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 12
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 11
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims abstract description 10
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 8
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 8
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 8
- 125000006730 (C2-C5) alkynyl group Chemical group 0.000 claims abstract description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 7
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 3
- 125000006833 (C1-C5) alkylene group Chemical group 0.000 claims description 103
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 96
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
- 150000002431 hydrogen Chemical group 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 8
- 201000006370 kidney failure Diseases 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 206010020772 Hypertension Diseases 0.000 claims description 7
- 238000011321 prophylaxis Methods 0.000 claims description 7
- 206010019280 Heart failures Diseases 0.000 claims description 6
- 125000004450 alkenylene group Chemical group 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 4
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 206010007572 Cardiac hypertrophy Diseases 0.000 claims description 3
- 208000006029 Cardiomegaly Diseases 0.000 claims description 3
- 208000031229 Cardiomyopathies Diseases 0.000 claims description 3
- 208000010412 Glaucoma Diseases 0.000 claims description 3
- 206010063897 Renal ischaemia Diseases 0.000 claims description 3
- 230000009787 cardiac fibrosis Effects 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 208000017169 kidney disease Diseases 0.000 claims description 3
- 208000031225 myocardial ischemia Diseases 0.000 claims description 3
- 201000001119 neuropathy Diseases 0.000 claims description 3
- 230000007823 neuropathy Effects 0.000 claims description 3
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 3
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 3
- 201000002793 renal fibrosis Diseases 0.000 claims description 3
- 208000037803 restenosis Diseases 0.000 claims description 3
- 208000019901 Anxiety disease Diseases 0.000 claims description 2
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 2
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 2
- 206010020571 Hyperaldosteronism Diseases 0.000 claims description 2
- 206010038419 Renal colic Diseases 0.000 claims description 2
- 206010039710 Scleroderma Diseases 0.000 claims description 2
- 238000002399 angioplasty Methods 0.000 claims description 2
- 230000036506 anxiety Effects 0.000 claims description 2
- 208000010877 cognitive disease Diseases 0.000 claims description 2
- 230000004406 elevated intraocular pressure Effects 0.000 claims description 2
- 229940125721 immunosuppressive agent Drugs 0.000 claims description 2
- 239000003018 immunosuppressive agent Substances 0.000 claims description 2
- 201000001881 impotence Diseases 0.000 claims description 2
- 201000009395 primary hyperaldosteronism Diseases 0.000 claims description 2
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 230000002792 vascular Effects 0.000 claims description 2
- 238000007631 vascular surgery Methods 0.000 claims description 2
- 238000007675 cardiac surgery Methods 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract description 3
- 240000000543 Pentas lanceolata Species 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 470
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 258
- 150000001412 amines Chemical class 0.000 description 255
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 249
- 235000019439 ethyl acetate Nutrition 0.000 description 234
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 210
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 202
- 239000000243 solution Substances 0.000 description 171
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 158
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 151
- 239000000706 filtrate Substances 0.000 description 122
- 239000007832 Na2SO4 Substances 0.000 description 116
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 116
- 229910052681 coesite Inorganic materials 0.000 description 116
- 229910052906 cristobalite Inorganic materials 0.000 description 116
- 239000000377 silicon dioxide Substances 0.000 description 116
- 235000012239 silicon dioxide Nutrition 0.000 description 116
- 229910052938 sodium sulfate Inorganic materials 0.000 description 116
- 235000011152 sodium sulphate Nutrition 0.000 description 116
- 229910052682 stishovite Inorganic materials 0.000 description 116
- 229910052905 tridymite Inorganic materials 0.000 description 116
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 111
- 244000257039 Duranta repens Species 0.000 description 107
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 91
- 239000000284 extract Substances 0.000 description 87
- 239000012267 brine Substances 0.000 description 86
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 86
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 76
- 239000000725 suspension Substances 0.000 description 74
- 238000000034 method Methods 0.000 description 72
- 239000012043 crude product Substances 0.000 description 71
- 238000003818 flash chromatography Methods 0.000 description 69
- 238000000746 purification Methods 0.000 description 68
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 67
- -1 racemates Chemical class 0.000 description 67
- 239000003921 oil Substances 0.000 description 65
- 238000006243 chemical reaction Methods 0.000 description 64
- 235000019198 oils Nutrition 0.000 description 64
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 61
- 239000000203 mixture Substances 0.000 description 58
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 54
- 239000012230 colorless oil Substances 0.000 description 44
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 44
- 235000019341 magnesium sulphate Nutrition 0.000 description 44
- 239000011541 reaction mixture Substances 0.000 description 41
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 38
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical group CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 37
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 35
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 35
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 34
- 239000003153 chemical reaction reagent Substances 0.000 description 32
- 239000007787 solid Substances 0.000 description 31
- 239000008346 aqueous phase Substances 0.000 description 30
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
- 230000002152 alkylating effect Effects 0.000 description 26
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
- 229910052757 nitrogen Inorganic materials 0.000 description 24
- 239000000126 substance Substances 0.000 description 24
- 239000003039 volatile agent Substances 0.000 description 24
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 23
- 238000001914 filtration Methods 0.000 description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
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- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 19
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 19
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 18
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 18
- 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 18
- 235000019270 ammonium chloride Nutrition 0.000 description 17
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 17
- 235000017557 sodium bicarbonate Nutrition 0.000 description 17
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 17
- 239000012279 sodium borohydride Substances 0.000 description 16
- 229910000033 sodium borohydride Inorganic materials 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- 239000000463 material Substances 0.000 description 15
- 230000003287 optical effect Effects 0.000 description 15
- 125000004432 carbon atom Chemical group C* 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical class O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 12
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 11
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- 150000002466 imines Chemical class 0.000 description 11
- 229910000029 sodium carbonate Inorganic materials 0.000 description 11
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- 239000004912 1,5-cyclooctadiene Substances 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 10
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- 108090000783 Renin Proteins 0.000 description 9
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- 239000003814 drug Substances 0.000 description 9
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- 239000012312 sodium hydride Substances 0.000 description 9
- 229910000104 sodium hydride Inorganic materials 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 102100028255 Renin Human genes 0.000 description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 8
- 239000012298 atmosphere Substances 0.000 description 8
- 239000002131 composite material Substances 0.000 description 8
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 8
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
- 238000004809 thin layer chromatography Methods 0.000 description 8
- BCJVBDBJSMFBRW-UHFFFAOYSA-N 4-diphenylphosphanylbutyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 BCJVBDBJSMFBRW-UHFFFAOYSA-N 0.000 description 7
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- 230000029936 alkylation Effects 0.000 description 7
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- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 7
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
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- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
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- FBAOFKFCKHJXRU-VOTSOKGWSA-N 2-[(e)-3-methoxyprop-1-enyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound COC\C=C\B1OC(C)(C)C(C)(C)O1 FBAOFKFCKHJXRU-VOTSOKGWSA-N 0.000 description 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
- 206010016654 Fibrosis Diseases 0.000 description 5
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 5
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- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 5
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 5
- 125000005587 carbonate group Chemical group 0.000 description 5
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- JDWGHSSDIYJEFC-UHFFFAOYSA-N n-[[5-(3-methoxypropyl)-2-methylsulfanylphenyl]methyl]cyclopropanamine Chemical compound COCCCC1=CC=C(SC)C(CNC2CC2)=C1 JDWGHSSDIYJEFC-UHFFFAOYSA-N 0.000 description 1
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- OVZQVGZERAFSPI-UHFFFAOYSA-N quinoline-8-carbaldehyde Chemical compound C1=CN=C2C(C=O)=CC=CC2=C1 OVZQVGZERAFSPI-UHFFFAOYSA-N 0.000 description 1
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- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- 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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US188303P | 2000-03-10 | ||
| US12652908P | 2008-05-05 | 2008-05-05 | |
| US126529P | 2008-05-05 | ||
| US18830308P | 2008-08-07 | 2008-08-07 | |
| PCT/CA2009/000611 WO2009135299A1 (en) | 2008-05-05 | 2009-05-04 | 3, 4 - substituted piperidine derivatives as renin inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2548134T3 true ES2548134T3 (es) | 2015-10-14 |
Family
ID=41264366
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES09741617.6T Active ES2548134T3 (es) | 2008-05-05 | 2009-05-04 | Derivados de piperidina 3,4-sustituida como inhibidores de renina |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US8889714B2 (enExample) |
| EP (1) | EP2274295B1 (enExample) |
| JP (3) | JP4790871B2 (enExample) |
| KR (2) | KR101403311B1 (enExample) |
| CN (1) | CN102015682B (enExample) |
| AU (1) | AU2009243875B2 (enExample) |
| BR (1) | BRPI0912388A2 (enExample) |
| CA (1) | CA2722734C (enExample) |
| CO (1) | CO6311081A2 (enExample) |
| CR (1) | CR11809A (enExample) |
| DO (1) | DOP2010000329A (enExample) |
| EA (1) | EA020853B1 (enExample) |
| ES (1) | ES2548134T3 (enExample) |
| IL (1) | IL208467A (enExample) |
| MA (1) | MA32296B1 (enExample) |
| MX (1) | MX2010012067A (enExample) |
| MY (1) | MY152042A (enExample) |
| NI (1) | NI201000188A (enExample) |
| NZ (1) | NZ589019A (enExample) |
| PL (1) | PL2274295T3 (enExample) |
| SG (1) | SG192543A1 (enExample) |
| SV (1) | SV2010003723A (enExample) |
| WO (1) | WO2009135299A1 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2296653B1 (en) | 2008-06-03 | 2016-01-27 | Intermune, Inc. | Compounds and methods for treating inflammatory and fibrotic disorders |
| WO2010066028A1 (en) * | 2008-12-10 | 2010-06-17 | Merck Frosst Canada Ltd. | 3,4 - substituted piperidine derivatives as renin inhibitors |
| TWI622573B (zh) * | 2010-11-05 | 2018-05-01 | 拜耳知識產權公司 | 藉由亞胺氫化製備經取代ｎ－（苄基）環丙胺之方法 |
| UA112897C2 (uk) * | 2012-05-09 | 2016-11-10 | Байєр Фарма Акцієнгезелльшафт | Біциклічно заміщені урацили та їх застосування для лікування і/або профілактики захворювань |
| AR092742A1 (es) | 2012-10-02 | 2015-04-29 | Intermune Inc | Piridinonas antifibroticas |
| RU2692485C2 (ru) | 2014-04-02 | 2019-06-25 | Интермьюн, Инк. | Противофиброзные пиридиноны |
| CN107602381B (zh) * | 2017-09-11 | 2021-03-16 | 陕西莱特光电材料股份有限公司 | 一种萘甲酸酯类衍生物及其制备方法 |
| CN108033876A (zh) * | 2017-12-20 | 2018-05-15 | 江汉大学 | 一种5-溴-2-氯苯甲醛的制备方法 |
| EP3887357A1 (en) | 2018-11-28 | 2021-10-06 | Basf Se | Pesticidal compounds |
| BR112022021631A2 (pt) | 2020-04-28 | 2022-12-06 | Basf Se | Compostos, composição, métodos para combater ou controlar pragas invertebradas, para proteger plantas em crescimento e para tratar ou proteger um animal, semente e uso de um composto |
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| US5380758A (en) | 1991-03-29 | 1995-01-10 | Brigham And Women's Hospital | S-nitrosothiols as smooth muscle relaxants and therapeutic uses thereof |
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| KR100384979B1 (ko) | 1995-09-07 | 2003-10-17 | 에프. 호프만-라 로슈 아게 | 심부전증및신부전증치료용의신규한4-(옥시알콕시페닐)-3-옥시-피페리딘 |
| US5994294A (en) | 1996-02-02 | 1999-11-30 | Nitromed, Inc. | Nitrosated and nitrosylated α-adrenergic receptor antagonist compounds, compositions and their uses |
| JP2001504457A (ja) | 1996-11-01 | 2001-04-03 | ニトロメド インコーポレーテッド | ニトロソ化およびニトロシル化ホスホジエステラーゼ阻害剤化合物、組成物及びその使用法 |
| IT1295694B1 (it) | 1996-11-14 | 1999-05-27 | Nicox Sa | Nitrossi derivati per la preparazione di medicamenti ad attivita antitrombinica |
| IT1292426B1 (it) * | 1997-06-27 | 1999-02-08 | Nicox Sa | Sali nitrati di ace-inibitori |
| HU230302B1 (hu) | 2000-10-20 | 2015-12-28 | Eisai R&D Management Co., Ltd. | Nitrogéntartalmú aromás származékok és ezeket tartalmazó gyógyászati készítmények |
| AU2003233963B2 (en) | 2002-04-29 | 2008-09-11 | Actelion Pharmaceuticals Ltd | 7-aryl-3,9-diazabicyclo(3.3.1)non-6-ene derivatives and their use as renin inhibitors in the treatment of hypertension, cardiovascular or renal diseases |
| BR0312000A (pt) | 2002-06-27 | 2005-03-22 | Actelion Pharmaceuticals Ltd | Compostos, composições farmacêuticas, método para o tratamento ou profilaxia de doenças, e, uso dos compostos |
| US20040204455A1 (en) | 2003-04-10 | 2004-10-14 | Cody Wayne Livingston | Piperidine derivative rennin inhibitors |
| AU2004234040A1 (en) | 2003-04-28 | 2004-11-11 | Actelion Pharmaceuticals Ltd | Diazabicyclononene and tetrahydropyridine derivatives as renin inhibitors |
| BRPI0409881A (pt) | 2003-04-29 | 2006-05-23 | Actelion Pharmaceuticals Ltd | compostos, composições farmacêuticas, método para o tratamento ou profilaxia de doenças, e, usos de compostos e de um ou mais compostos em combinação com outros compostos farmacologicamente ativos |
| RU2005137174A (ru) | 2003-04-30 | 2006-03-27 | Актелион Фармасьютикалз Лтд. (Ch) | Азабициклононеновые производные |
| WO2004096799A1 (en) | 2003-04-30 | 2004-11-11 | Actelion Pharmaceuticals Ltd | Tropane derivatives and their use as ace inhibitors |
| EP1622685A1 (en) | 2003-04-30 | 2006-02-08 | Actelion Pharmaceuticals Ltd. | 9-azabicyclo[3.3.1]non-6-ene derivatives with a heteroatom at the 3-position as renin inhibitors |
| KR20060015573A (ko) | 2003-05-02 | 2006-02-17 | 액테리온 파마슈티칼 리미티드 | 신규한 디아자비시클로노넨 유도체 |
| TW200513461A (en) | 2003-10-01 | 2005-04-16 | Speedel Experimenta Ag | Organische verbindungen |
| WO2005040120A1 (en) | 2003-10-09 | 2005-05-06 | Actelion Pharmaceuticals Ltd | Tetrahydropyridine derivatives |
| JP2007508262A (ja) | 2003-10-13 | 2007-04-05 | アクテリオン ファマシューティカルズ リミテッド | 新規ジアザビシクロノネン誘導体およびその使用 |
| JP2007509099A (ja) | 2003-10-23 | 2007-04-12 | アクテリオン ファマシューティカルズ リミテッド | 新規ジアザビシクロノネンおよび新規極性側鎖を有するテトラヒドロピリジン誘導体 |
| AU2004295092A1 (en) | 2003-12-05 | 2005-06-16 | Actelion Pharmaceuticals Ltd. | Azabicyclooctene and other tetrahydropyridine derivatives with a new side-chain |
| WO2005054243A1 (en) | 2003-12-05 | 2005-06-16 | Actelion Pharmaceuticals Ltd | Diazabicyclononene derivatives and their use as renin inhibitors |
| AR053406A1 (es) * | 2004-07-09 | 2007-05-09 | Speedel Experimenta Ag | Derivados de piperidina como inhibidores de renina. composiciones farmaceuticas |
| WO2006021399A2 (en) | 2004-08-25 | 2006-03-02 | Actelion Pharmaceuticals Ltd | Azabicyclononene derivatives as renin inhibitors |
| ATE462703T1 (de) | 2004-08-25 | 2010-04-15 | Actelion Pharmaceuticals Ltd | Bicyclononen-derivate als renin-inhibitoren |
| WO2006021403A1 (en) | 2004-08-25 | 2006-03-02 | Actelion Pharmaceuticals Ltd | Bicyclononene derivatives |
| WO2006021401A2 (en) | 2004-08-25 | 2006-03-02 | Actelion Pharmaceuticals Ltd | Bicylononene derivatives |
| WO2006058546A1 (en) | 2004-12-01 | 2006-06-08 | Actelion Pharmaceuticals Ltd | Novel lactame derivatives as renin inhibitors |
| AR052263A1 (es) | 2004-12-08 | 2007-03-07 | Actelion Pharmaceuticals Ltd | Derivado de diazabiciclononeno |
| WO2006063610A1 (en) | 2004-12-17 | 2006-06-22 | Actelion Pharmaceuticals Ltd | Heteroaryl substituted diazabicyclononene derivatives |
| GB0428526D0 (en) | 2004-12-30 | 2005-02-09 | Novartis Ag | Organic compounds |
| GB0500784D0 (en) * | 2005-01-14 | 2005-02-23 | Novartis Ag | Organic compounds |
| ATE514697T1 (de) | 2005-01-28 | 2011-07-15 | Actelion Pharmaceuticals Ltd | 7-ä4-ä2-(2,6-dichloro-4- methylphenoxy)ethoxyüphenylü-3,9- diazabicycloä3.3.1ünon-6-ene-6-carbonsäure- cyclopropyl-(2,3-dimethylbenzyl)amid als renin- hemmer für die behandlung von bluthochdruck |
| WO2006092268A1 (en) | 2005-03-02 | 2006-09-08 | Actelion Pharmaceuticals Ltd | Bicyclic five-membered heteroaryl derivatives and their use as renin inhibitors |
| GB0504850D0 (en) * | 2005-03-09 | 2005-04-13 | Novartis Ag | Organic compounds |
| EP1863763A1 (en) | 2005-03-31 | 2007-12-12 | Speedel Experimenta AG | 3,4,5-substituted piperidines as renin inhibitors |
| TW200716622A (en) | 2005-03-31 | 2007-05-01 | Speedel Experimenta Ag | Substituted piperidines |
| GB0510810D0 (en) | 2005-05-26 | 2005-06-29 | Novartis Ag | Organic compounds |
| BRPI0609890A2 (pt) | 2005-05-27 | 2010-05-04 | Actelion Pharmaceuticals Ltd | composto, composição farmacêutica, e, uso de um composto |
| GB0511063D0 (en) | 2005-05-31 | 2005-07-06 | Novartis Ag | Organic compounds |
| WO2006131884A2 (en) | 2005-06-07 | 2006-12-14 | Actelion Pharmaceuticals Ltd | Thiazole substituted diazabicyclononane or-nonene derivatives as renin inhibitors |
| CA2615048A1 (en) | 2005-07-22 | 2007-01-25 | Merck Frosst Canada Ltd. | Renin inhibitors |
| WO2007034406A1 (en) | 2005-09-22 | 2007-03-29 | Actelion Pharmaceuticals Ltd | Pyrrolidine-3-carboxylic acid amide derivatives and their use as inhibitors of renin |
| WO2007034445A2 (en) | 2005-09-26 | 2007-03-29 | Actelion Pharmaceuticals Ltd | Novel piperazine derivatives as renin inhibitors for cardiovascular events and renal insufficiency |
| WO2007049224A1 (en) | 2005-10-25 | 2007-05-03 | Actelion Pharmaceuticals Ltd | Novel hexahydro- or octahydro-cyclopenta[c]pyrrole derivatives |
| PT2420491E (pt) | 2005-12-30 | 2013-10-14 | Novartis Ag | Compostos de piperidina 3,5-substituída como inibidores de renina |
| EP1816122A3 (en) * | 2006-01-19 | 2007-09-19 | Speedel Experimenta AG | 3,4,5-substituted piperidines as therapeutic compounds |
| RU2425032C2 (ru) | 2006-02-02 | 2011-07-27 | Актелион Фармасьютикалз Лтд | Вторичные амины в качестве ингибиторов ренина |
| BRPI0708487A2 (pt) | 2006-03-03 | 2011-05-31 | Actelion Pharmaceuticals Ltd | composto, composição farmacêutica que o compreende e seu uso |
| CL2007000595A1 (es) | 2006-03-08 | 2008-01-04 | Actelion Pharmaceuticals Ltd | Compuestos derivados de piperidina; composicion farmaceutica y uso para el tratamiento y/o profilaxis de enfermedades seleccionadas entre hipertension, insuficiencia cardiaca congestiva e insuficiencia renal entre otras. |
| EP2081927B1 (en) | 2006-09-18 | 2011-08-17 | Vitae Pharmaceuticals, Inc. | Piperidine derivatives as renin inhibitors |
| DE602007007664D1 (de) * | 2006-11-17 | 2010-08-19 | Merck Frosst Canada Inc | Renininhibitoren |
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| US20110207783A1 (en) | 2007-08-07 | 2011-08-25 | Daniel Dube | Renin inhibitors |
| CA2707565A1 (en) * | 2007-12-04 | 2009-06-11 | Merck Frosst Canada Ltd. | Renin inhibitors |
| JP2011520924A (ja) | 2008-05-22 | 2011-07-21 | メルク フロスト カナダ リミテツド | レニン阻害剤としての３，４−置換ピペリジン誘導体 |
| WO2011020193A1 (en) | 2009-08-18 | 2011-02-24 | Merck Frosst Canada Ltd. | Renin inhibitors |
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2009
- 2009-05-04 CA CA2722734A patent/CA2722734C/en not_active Expired - Fee Related
- 2009-05-04 CN CN200980116219.5A patent/CN102015682B/zh not_active Expired - Fee Related
- 2009-05-04 MY MYPI20105036 patent/MY152042A/en unknown
- 2009-05-04 KR KR1020107024856A patent/KR101403311B1/ko not_active Expired - Fee Related
- 2009-05-04 WO PCT/CA2009/000611 patent/WO2009135299A1/en not_active Ceased
- 2009-05-04 ES ES09741617.6T patent/ES2548134T3/es active Active
- 2009-05-04 JP JP2011507765A patent/JP4790871B2/ja not_active Expired - Fee Related
- 2009-05-04 MX MX2010012067A patent/MX2010012067A/es active IP Right Grant
- 2009-05-04 AU AU2009243875A patent/AU2009243875B2/en not_active Ceased
- 2009-05-04 SG SG2013055702A patent/SG192543A1/en unknown
- 2009-05-04 US US12/990,927 patent/US8889714B2/en not_active Expired - Fee Related
- 2009-05-04 NZ NZ589019A patent/NZ589019A/xx not_active IP Right Cessation
- 2009-05-04 PL PL09741617T patent/PL2274295T3/pl unknown
- 2009-05-04 BR BRPI0912388A patent/BRPI0912388A2/pt not_active Application Discontinuation
- 2009-05-04 EP EP09741617.6A patent/EP2274295B1/en active Active
- 2009-05-04 EA EA201071269A patent/EA020853B1/ru not_active IP Right Cessation
- 2009-05-04 KR KR1020137003332A patent/KR20130029116A/ko not_active Withdrawn
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2010
- 2010-10-04 IL IL208467A patent/IL208467A/en not_active IP Right Cessation
- 2010-11-03 DO DO2010000329A patent/DOP2010000329A/es unknown
- 2010-11-04 SV SV2010003723A patent/SV2010003723A/es not_active Application Discontinuation
- 2010-11-05 NI NI201000188A patent/NI201000188A/es unknown
- 2010-11-11 CO CO10141827A patent/CO6311081A2/es not_active Application Discontinuation
- 2010-11-11 MA MA33335A patent/MA32296B1/fr unknown
- 2010-11-24 CR CR11809A patent/CR11809A/es not_active Application Discontinuation
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2011
- 2011-06-01 JP JP2011123057A patent/JP5653842B2/ja not_active Expired - Fee Related
- 2011-06-01 JP JP2011123054A patent/JP5587246B2/ja not_active Expired - Fee Related
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