JP2008526910A - ３，４，（５）−置換テトラヒドロピリジン - Google Patents
３，４，（５）−置換テトラヒドロピリジン Download PDFInfo
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- JP2008526910A JP2008526910A JP2007550751A JP2007550751A JP2008526910A JP 2008526910 A JP2008526910 A JP 2008526910A JP 2007550751 A JP2007550751 A JP 2007550751A JP 2007550751 A JP2007550751 A JP 2007550751A JP 2008526910 A JP2008526910 A JP 2008526910A
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- Prior art keywords
- alkyl
- substituted
- unsubstituted
- alkoxy
- phenyl
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- 125000004853 tetrahydropyridinyl group Chemical class N1(CCCC=C1)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 224
- -1 tetrahydropyridine compound Chemical class 0.000 claims abstract description 204
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 54
- 108090000783 Renin Proteins 0.000 claims abstract description 50
- 102100028255 Renin Human genes 0.000 claims abstract description 48
- 125000001424 substituent group Chemical group 0.000 claims abstract description 48
- 230000000694 effects Effects 0.000 claims abstract description 45
- 238000000034 method Methods 0.000 claims abstract description 38
- 238000011282 treatment Methods 0.000 claims abstract description 37
- 201000010099 disease Diseases 0.000 claims abstract description 34
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 28
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 21
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 17
- 230000001419 dependent effect Effects 0.000 claims abstract description 14
- 238000004519 manufacturing process Methods 0.000 claims abstract description 14
- 230000008569 process Effects 0.000 claims abstract description 11
- 241001465754 Metazoa Species 0.000 claims abstract description 10
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims description 298
- 239000000463 material Substances 0.000 claims description 210
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 124
- 239000000203 mixture Substances 0.000 claims description 93
- 125000001624 naphthyl group Chemical group 0.000 claims description 83
- 229910052757 nitrogen Inorganic materials 0.000 claims description 77
- 150000003839 salts Chemical class 0.000 claims description 71
- 125000005843 halogen group Chemical group 0.000 claims description 63
- 229910052739 hydrogen Inorganic materials 0.000 claims description 63
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 53
- 239000001257 hydrogen Substances 0.000 claims description 50
- 125000000623 heterocyclic group Chemical group 0.000 claims description 47
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 38
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 36
- 125000004076 pyridyl group Chemical group 0.000 claims description 36
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 35
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 34
- 229910052799 carbon Inorganic materials 0.000 claims description 34
- 125000006239 protecting group Chemical group 0.000 claims description 34
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 32
- 125000003118 aryl group Chemical group 0.000 claims description 30
- 125000003107 substituted aryl group Chemical group 0.000 claims description 26
- 239000007858 starting material Substances 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 125000002252 acyl group Chemical group 0.000 claims description 21
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 20
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 20
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 125000003236 benzoyl group Chemical class [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 17
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 15
- 125000001041 indolyl group Chemical group 0.000 claims description 15
- 125000003386 piperidinyl group Chemical group 0.000 claims description 15
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 14
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 14
- 229920006395 saturated elastomer Polymers 0.000 claims description 13
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 12
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000000304 alkynyl group Chemical group 0.000 claims description 11
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 11
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- 125000002950 monocyclic group Chemical group 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- 125000001544 thienyl group Chemical group 0.000 claims description 10
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 9
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 9
- 125000002873 tetrahydrofuranonyl group Chemical group 0.000 claims description 9
- 125000005955 1H-indazolyl group Chemical group 0.000 claims description 8
- 125000005605 benzo group Chemical group 0.000 claims description 8
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 8
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 8
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 8
- 125000004193 piperazinyl group Chemical group 0.000 claims description 8
- 125000006413 ring segment Chemical group 0.000 claims description 8
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 8
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 8
- 125000001425 triazolyl group Chemical group 0.000 claims description 8
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 7
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 7
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 7
- 125000005493 quinolyl group Chemical group 0.000 claims description 7
- 125000005059 halophenyl group Chemical group 0.000 claims description 6
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
- 125000003367 polycyclic group Chemical group 0.000 claims description 6
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000000524 functional group Chemical group 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000001038 naphthoyl group Chemical class C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 claims description 5
- 125000005186 naphthyloxy group Chemical group C1(=CC=CC2=CC=CC=C12)O* 0.000 claims description 5
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 5
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 4
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000005170 cycloalkyloxycarbonyl group Chemical group 0.000 claims description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 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 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 125000005146 naphthylsulfonyl group Chemical group C1(=CC=CC2=CC=CC=C12)S(=O)(=O)* 0.000 claims description 4
- 125000005029 naphthylthio group Chemical group C1(=CC=CC2=CC=CC=C12)S* 0.000 claims description 4
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims description 4
- 125000004423 acyloxy group Chemical group 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000005185 naphthylcarbonyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 claims description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 125000004054 acenaphthylenyl group Chemical group C1(=CC2=CC=CC3=CC=CC1=C23)* 0.000 claims description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 2
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 2
- 125000005142 aryl oxy sulfonyl group Chemical group 0.000 claims description 2
- 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
- 125000005110 aryl thio group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000002619 bicyclic group Chemical group 0.000 claims description 2
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 2
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 2
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 2
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000005561 phenanthryl group Chemical group 0.000 claims description 2
- 125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 23
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 2
- TVEXGJYMHHTVKP-UHFFFAOYSA-N 6-oxabicyclo[3.2.1]oct-3-en-7-one Chemical compound C1C2C(=O)OC1C=CC2 TVEXGJYMHHTVKP-UHFFFAOYSA-N 0.000 claims 1
- 125000005236 alkanoylamino group Chemical group 0.000 claims 1
- 125000003368 amide group Chemical group 0.000 claims 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 9
- VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical class C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 abstract description 6
- 230000036961 partial effect Effects 0.000 abstract description 3
- 239000000543 intermediate Substances 0.000 description 1302
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 269
- 238000004128 high performance liquid chromatography Methods 0.000 description 269
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 222
- 238000009833 condensation Methods 0.000 description 131
- 230000005494 condensation Effects 0.000 description 131
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 117
- 235000019439 ethyl acetate Nutrition 0.000 description 103
- 239000012230 colorless oil Substances 0.000 description 95
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 72
- 239000011541 reaction mixture Substances 0.000 description 72
- 230000002829 reductive effect Effects 0.000 description 72
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 66
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 66
- 239000000741 silica gel Substances 0.000 description 59
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- 238000006243 chemical reaction Methods 0.000 description 58
- 238000003818 flash chromatography Methods 0.000 description 58
- 239000012074 organic phase Substances 0.000 description 58
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 58
- 238000005804 alkylation reaction Methods 0.000 description 49
- 239000011734 sodium Substances 0.000 description 48
- 230000029936 alkylation Effects 0.000 description 47
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 46
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 239000002904 solvent Substances 0.000 description 44
- 238000003756 stirring Methods 0.000 description 42
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 38
- 238000005481 NMR spectroscopy Methods 0.000 description 36
- 239000000243 solution Substances 0.000 description 32
- 238000005859 coupling reaction Methods 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 26
- 230000008878 coupling Effects 0.000 description 26
- 238000010168 coupling process Methods 0.000 description 26
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 24
- 239000002585 base Substances 0.000 description 23
- 230000007062 hydrolysis Effects 0.000 description 23
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- 239000002253 acid Substances 0.000 description 22
- 238000005160 1H NMR spectroscopy Methods 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
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- OLNJUISKUQQNIM-UHFFFAOYSA-N indole-3-carbaldehyde Chemical compound C1=CC=C2C(C=O)=CNC2=C1 OLNJUISKUQQNIM-UHFFFAOYSA-N 0.000 description 18
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- 239000003112 inhibitor Substances 0.000 description 15
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 14
- LQMZSVRCDYSUIJ-UHFFFAOYSA-N 1-o-tert-butyl 5-o-methyl 4-(trifluoromethylsulfonyloxy)-3,6-dihydro-2h-pyridine-1,5-dicarboxylate Chemical compound COC(=O)C1=C(OS(=O)(=O)C(F)(F)F)CCN(C(=O)OC(C)(C)C)C1 LQMZSVRCDYSUIJ-UHFFFAOYSA-N 0.000 description 13
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- 238000000746 purification Methods 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
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- 239000004480 active ingredient Substances 0.000 description 8
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
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- PVIGUZZDWGININ-UHFFFAOYSA-N 1-(bromomethyl)-2,3-dichlorobenzene Chemical compound ClC1=CC=CC(CBr)=C1Cl PVIGUZZDWGININ-UHFFFAOYSA-N 0.000 description 7
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- 229910052783 alkali metal Inorganic materials 0.000 description 7
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- 239000002243 precursor Substances 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
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- WFWQWTPAPNEOFE-UHFFFAOYSA-N (3-hydroxyphenyl)boronic acid Chemical compound OB(O)C1=CC=CC(O)=C1 WFWQWTPAPNEOFE-UHFFFAOYSA-N 0.000 description 6
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- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- 201000009395 primary hyperaldosteronism Diseases 0.000 description 6
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- 208000037803 restenosis Diseases 0.000 description 6
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 5
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 5
- 208000006888 Agnosia Diseases 0.000 description 5
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- VCZQFJFZMMALHB-UHFFFAOYSA-N tetraethylsilane Chemical compound CC[Si](CC)(CC)CC VCZQFJFZMMALHB-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 229960004605 timolol Drugs 0.000 description 1
- GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229960005461 torasemide Drugs 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 229960002051 trandolapril Drugs 0.000 description 1
- WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical group [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 description 1
- VIYXXANHGYSBLY-UHFFFAOYSA-N trimethylsilyl 2,2,2-trifluoroacetate Chemical compound C[Si](C)(C)OC(=O)C(F)(F)F VIYXXANHGYSBLY-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- 238000010518 undesired secondary reaction Methods 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 229910006384 μ-Br Inorganic materials 0.000 description 1
Classifications
-
- 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
- C07D401/12—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 linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/78—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- 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
- C07D401/10—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 linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Obesity (AREA)
- Neurology (AREA)
- Hematology (AREA)
- Hospice & Palliative Care (AREA)
- Ophthalmology & Optometry (AREA)
- Urology & Nephrology (AREA)
- Child & Adolescent Psychology (AREA)
- Vascular Medicine (AREA)
- Psychiatry (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0500784.4A GB0500784D0 (en) | 2005-01-14 | 2005-01-14 | Organic compounds |
| PCT/EP2006/000216 WO2006074924A1 (en) | 2005-01-14 | 2006-01-12 | 3,4,(5)-substituted tetrahvdropyridines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008526910A true JP2008526910A (ja) | 2008-07-24 |
| JP2008526910A5 JP2008526910A5 (enExample) | 2009-02-26 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007550751A Pending JP2008526910A (ja) | 2005-01-14 | 2006-01-12 | ３，４，（５）−置換テトラヒドロピリジン |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US20100029647A1 (enExample) |
| EP (1) | EP1841740A1 (enExample) |
| JP (1) | JP2008526910A (enExample) |
| KR (1) | KR20070094918A (enExample) |
| CN (1) | CN101103002A (enExample) |
| AU (1) | AU2006205877B2 (enExample) |
| BR (1) | BRPI0606321A2 (enExample) |
| CA (1) | CA2590898A1 (enExample) |
| GB (1) | GB0500784D0 (enExample) |
| MX (1) | MX2007008558A (enExample) |
| RU (1) | RU2007130791A (enExample) |
| WO (1) | WO2006074924A1 (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013510077A (ja) * | 2009-11-05 | 2013-03-21 | フィブロスタチン ソシエダ リミターダ | 擬似ｑ２ペプチドを用いるｇｐｂｐ抑制 |
| JPWO2014042263A1 (ja) * | 2012-09-14 | 2016-08-18 | 田辺三菱製薬株式会社 | 新規レニン阻害薬 |
| KR20170102483A (ko) | 2015-01-13 | 2017-09-11 | 닛산 가가쿠 고교 가부시키 가이샤 | 반응 혼합물 중의 주석 화합물의 처리 방법 |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0505969D0 (en) * | 2005-03-23 | 2005-04-27 | Novartis Ag | Organic compounds |
| GB0514203D0 (en) | 2005-07-11 | 2005-08-17 | Novartis Ag | Organic compounds |
| PE20071177A1 (es) | 2005-12-30 | 2008-01-18 | Novartis Ag | Derivados de 3,5-piridina como inhibidores de renina |
| EP1908471A1 (en) * | 2006-10-04 | 2008-04-09 | Speedel Experimenta AG | Tetrahydropyridines as renin inhibitors |
| US8129538B1 (en) | 2007-03-28 | 2012-03-06 | Takeda Pharmaceutical Company Limited | Renin inhibitors |
| CA2689109A1 (en) | 2007-06-25 | 2008-12-31 | Novartis Ag | N5-(2-ethoxyethyl)-n3-(2-pyridinyl) -3,5-piperidinedicarboxamide derivatives for use as renin inhibitors |
| MY152042A (en) | 2008-05-05 | 2014-08-15 | Actelion Pharmaceuticals Ltd | 3,4- substituted piperidine derivatives as renin inhibitors |
| KR101834362B1 (ko) | 2011-03-18 | 2018-03-05 | 바이엘 인텔렉쳐 프로퍼티 게엠베하 | N-(3-카바모일페닐)-1h-피라졸-5-카복사미드 유도체 및 동물 해충을 구제하기 위한 그의 용도 |
| CN110577974B (zh) * | 2019-09-10 | 2021-07-20 | 杭州澳赛诺生物科技有限公司 | 手性3-羟基-1,2,3,6-四氢吡啶的合成方法 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004002957A1 (en) * | 2002-06-27 | 2004-01-08 | Actelion Pharmaceuticals Ltd | Novel tetrahydropyridine derivatives as renin inhibitors |
| WO2004096769A1 (en) * | 2003-04-29 | 2004-11-11 | Actelion Pharmaceuticals Ltd | Novel 3,4-disubstituted 1,2,3,6-tetrahydropyridine derivatives |
| WO2005040120A1 (en) * | 2003-10-09 | 2005-05-06 | Actelion Pharmaceuticals Ltd | Tetrahydropyridine derivatives |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HUP9900926A3 (en) * | 1995-09-07 | 2002-12-28 | Hoffmann La Roche | New 4-(oxyalkoxyphenyl)-3-oxy-piperidines for treating heart and kidney insufficiency |
| US6376672B1 (en) * | 1999-04-27 | 2002-04-23 | Hoffmann-La Roche Inc. | Naphthalenylmethoxypiperidines as renin inhibitors |
| US6197959B1 (en) * | 1999-04-27 | 2001-03-06 | Hoffmann-La Roche Inc. | Piperidine derivatives |
| PL213029B1 (pl) * | 2002-05-20 | 2012-12-31 | Bristol Myers Squibb Co | Podstawiona pochodna cykloalkilowa, zawierajaca ja kompozycja oraz ich zastosowanie |
-
2005
- 2005-01-14 GB GBGB0500784.4A patent/GB0500784D0/en not_active Ceased
-
2006
- 2006-01-12 JP JP2007550751A patent/JP2008526910A/ja active Pending
- 2006-01-12 US US11/722,398 patent/US20100029647A1/en not_active Abandoned
- 2006-01-12 EP EP06700380A patent/EP1841740A1/en not_active Withdrawn
- 2006-01-12 RU RU2007130791/04A patent/RU2007130791A/ru not_active Application Discontinuation
- 2006-01-12 BR BRPI0606321-7A patent/BRPI0606321A2/pt not_active IP Right Cessation
- 2006-01-12 CN CNA2006800023806A patent/CN101103002A/zh active Pending
- 2006-01-12 MX MX2007008558A patent/MX2007008558A/es not_active Application Discontinuation
- 2006-01-12 AU AU2006205877A patent/AU2006205877B2/en not_active Expired - Fee Related
- 2006-01-12 KR KR1020077016005A patent/KR20070094918A/ko not_active Withdrawn
- 2006-01-12 CA CA002590898A patent/CA2590898A1/en not_active Abandoned
- 2006-01-12 WO PCT/EP2006/000216 patent/WO2006074924A1/en not_active Ceased
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004002957A1 (en) * | 2002-06-27 | 2004-01-08 | Actelion Pharmaceuticals Ltd | Novel tetrahydropyridine derivatives as renin inhibitors |
| WO2004096769A1 (en) * | 2003-04-29 | 2004-11-11 | Actelion Pharmaceuticals Ltd | Novel 3,4-disubstituted 1,2,3,6-tetrahydropyridine derivatives |
| WO2005040120A1 (en) * | 2003-10-09 | 2005-05-06 | Actelion Pharmaceuticals Ltd | Tetrahydropyridine derivatives |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013510077A (ja) * | 2009-11-05 | 2013-03-21 | フィブロスタチン ソシエダ リミターダ | 擬似ｑ２ペプチドを用いるｇｐｂｐ抑制 |
| US9199936B2 (en) | 2009-11-05 | 2015-12-01 | Fibrostatin Sociedad Limitada | GPBP inhibition using Q2 peptidomimetics |
| US10544083B2 (en) | 2009-11-05 | 2020-01-28 | Universitat De València | GPBP inhibition using Q2 peptidomimetics |
| JPWO2014042263A1 (ja) * | 2012-09-14 | 2016-08-18 | 田辺三菱製薬株式会社 | 新規レニン阻害薬 |
| KR20170102483A (ko) | 2015-01-13 | 2017-09-11 | 닛산 가가쿠 고교 가부시키 가이샤 | 반응 혼합물 중의 주석 화합물의 처리 방법 |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2006205877A1 (en) | 2006-07-20 |
| GB0500784D0 (en) | 2005-02-23 |
| CA2590898A1 (en) | 2006-07-20 |
| US20100029647A1 (en) | 2010-02-04 |
| RU2007130791A (ru) | 2009-02-20 |
| WO2006074924A1 (en) | 2006-07-20 |
| BRPI0606321A2 (pt) | 2009-06-16 |
| EP1841740A1 (en) | 2007-10-10 |
| CN101103002A (zh) | 2008-01-09 |
| KR20070094918A (ko) | 2007-09-27 |
| WO2006074924A8 (en) | 2007-04-19 |
| MX2007008558A (es) | 2007-08-14 |
| AU2006205877B2 (en) | 2010-01-07 |
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