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 |
|---|---|---|---|
| US12652908P | 2008-05-05 | 2008-05-05 | |
| US126529P | 2008-05-05 | ||
| US18830308P | 2008-08-07 | 2008-08-07 | |
| US188303P | 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
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| 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 |
|---|---|
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| EP (1) | EP2274295B1 (enExample) |
| JP (3) | JP4790871B2 (enExample) |
| KR (2) | KR20130029116A (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 |
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| CN102099036B (zh) | 2008-06-03 | 2015-05-27 | 英特芒尼公司 | 用于治疗炎性疾患和纤维化疾患的化合物和方法 |
| JP2012511514A (ja) * | 2008-12-10 | 2012-05-24 | メルク・カナダ・インコーポレイテツド | レニン阻害剤としての３，４−置換ピペリジン誘導体 |
| TWI562977B (en) * | 2010-11-05 | 2016-12-21 | Bayer Ip Gmbh | Process for the preparation of substituted n-(benzyl)cyclopropanamines by imine hydrogenation |
| 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 |
| JP6525437B2 (ja) | 2014-04-02 | 2019-06-05 | インターミューン， インコーポレイテッド | 抗線維性ピリジノン |
| 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 |
| WO2021219513A1 (en) | 2020-04-28 | 2021-11-04 | Basf Se | Pesticidal compounds |
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| EP0941086A4 (en) | 1996-11-01 | 2000-07-12 | Nitromed Inc | NITROSIZED AND NITROSYLATED PHOSPHODIESTERASE INHIBITING COMPOUNDS, COMPOSITIONS AND THEIR USE |
| 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 |
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| MXPA05011497A (es) | 2003-04-30 | 2005-12-15 | Actelion Pharmaceuticals Ltd | Derivados de tropano y su uso como inhibidores de la enzima de conversion de angiotensina (ace). |
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| MXPA05011496A (es) | 2003-04-30 | 2005-12-15 | Actelion Pharmaceuticals Ltd | Derivados de azabiciclononeno. |
| BRPI0409882A (pt) | 2003-05-02 | 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 |
| TW200513461A (en) | 2003-10-01 | 2005-04-16 | Speedel Experimenta Ag | Organische verbindungen |
| AU2004283814A1 (en) | 2003-10-09 | 2005-05-06 | Actelion Pharmaceuticals Ltd. | Tetrahydropyridine derivatives |
| EP1678176A1 (en) | 2003-10-13 | 2006-07-12 | Actelion Pharmaceuticals Ltd. | Diazabicyclononene derivatives and their use as renin inhibitors |
| CA2540817A1 (en) | 2003-10-23 | 2005-05-06 | Olivier Bezencon | Diazabicyclononene and tetrahydropyridine derivatives as renin inhibitors |
| CN1890239A (zh) | 2003-12-05 | 2007-01-03 | 埃科特莱茵药品有限公司 | 二氮杂二环壬烯及带有新的侧链的四氢吡啶衍生物 |
| CA2547547A1 (en) | 2003-12-05 | 2005-06-16 | Actelion Pharmaceuticals Ltd | Diazabicyclononene derivatives and their use as renin inhibitors |
| TW200613274A (en) * | 2004-07-09 | 2006-05-01 | Speedel Experimenta Ag | Organic compounds |
| 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 |
| WO2006021399A2 (en) | 2004-08-25 | 2006-03-02 | Actelion Pharmaceuticals Ltd | Azabicyclononene derivatives as renin inhibitors |
| 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 |
| US7915259B2 (en) | 2005-01-28 | 2011-03-29 | Actelion Pharmaceuticals Ltd. | Diazabicyclononene derivatives and use thereof |
| 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 |
| TW200716622A (en) | 2005-03-31 | 2007-05-01 | Speedel Experimenta Ag | Substituted piperidines |
| EP1863763A1 (en) | 2005-03-31 | 2007-12-12 | Speedel Experimenta AG | 3,4,5-substituted piperidines as renin inhibitors |
| GB0510810D0 (en) | 2005-05-26 | 2005-06-29 | Novartis Ag | Organic compounds |
| MX2007014722A (es) * | 2005-05-27 | 2008-02-15 | Actelion Pharmaceuticals Ltd | Nuevos derivados de amida de acido piperidin carboxilico. |
| 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 |
| JP2009502751A (ja) | 2005-07-22 | 2009-01-29 | メルク フロスト カナダ リミテツド | レニン阻害薬 |
| 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 |
| PE20071177A1 (es) | 2005-12-30 | 2008-01-18 | Novartis Ag | Derivados de 3,5-piridina como inhibidores de renina |
| EP1816122A3 (en) * | 2006-01-19 | 2007-09-19 | Speedel Experimenta AG | 3,4,5-substituted piperidines as therapeutic compounds |
| BRPI0707349A2 (pt) | 2006-02-02 | 2011-05-03 | Actelion Pharmaceuticals Ltd | composto, composição farmacêutica, e, uso de um composto |
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| US20110207783A1 (en) | 2007-08-07 | 2011-08-25 | Daniel Dube | Renin inhibitors |
| AU2008331456A1 (en) * | 2007-12-04 | 2009-06-11 | Merck Frosst Canada Ltd | Renin inhibitors |
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| EP2467385A4 (en) | 2009-08-18 | 2013-01-16 | Merck Canada Inc | Renin Inhibitors |
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- 2009-05-04 MY MYPI20105036 patent/MY152042A/en unknown
- 2009-05-04 CN CN200980116219.5A patent/CN102015682B/zh not_active Expired - Fee Related
- 2009-05-04 US US12/990,927 patent/US8889714B2/en not_active Expired - Fee Related
- 2009-05-04 SG SG2013055702A patent/SG192543A1/en unknown
- 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
- 2009-05-04 CA CA2722734A patent/CA2722734C/en not_active Expired - Fee Related
- 2009-05-04 BR BRPI0912388A patent/BRPI0912388A2/pt not_active Application Discontinuation
- 2009-05-04 WO PCT/CA2009/000611 patent/WO2009135299A1/en not_active Ceased
- 2009-05-04 JP JP2011507765A patent/JP4790871B2/ja not_active Expired - Fee Related
- 2009-05-04 NZ NZ589019A patent/NZ589019A/xx not_active IP Right Cessation
- 2009-05-04 ES ES09741617.6T patent/ES2548134T3/es active Active
- 2009-05-04 MX MX2010012067A patent/MX2010012067A/es active IP Right Grant
- 2009-05-04 KR KR1020107024856A patent/KR101403311B1/ko not_active Expired - Fee Related
- 2009-05-04 PL PL09741617T patent/PL2274295T3/pl unknown
- 2009-05-04 AU AU2009243875A patent/AU2009243875B2/en not_active Ceased
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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 MA MA33335A patent/MA32296B1/fr unknown
- 2010-11-11 CO CO10141827A patent/CO6311081A2/es not_active Application Discontinuation
- 2010-11-24 CR CR11809A patent/CR11809A/es not_active Application Discontinuation
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2011
- 2011-06-01 JP JP2011123054A patent/JP5587246B2/ja not_active Expired - Fee Related
- 2011-06-01 JP JP2011123057A patent/JP5653842B2/ja not_active Expired - Fee Related
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