MX2007008558A - Tetrahidropiridinas 3,4,(5)-sustituidas. - Google Patents
Tetrahidropiridinas 3,4,(5)-sustituidas.Info
- Publication number
- MX2007008558A MX2007008558A MX2007008558A MX2007008558A MX2007008558A MX 2007008558 A MX2007008558 A MX 2007008558A MX 2007008558 A MX2007008558 A MX 2007008558A MX 2007008558 A MX2007008558 A MX 2007008558A MX 2007008558 A MX2007008558 A MX 2007008558A
- Authority
- MX
- Mexico
- Prior art keywords
- alkyl
- substituted
- unsubstituted
- intermediary
- alkoxy
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 claims abstract description 304
- 150000001875 compounds Chemical class 0.000 claims abstract description 228
- -1 tetrahydropyridine compound Chemical class 0.000 claims abstract description 214
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 61
- 108090000783 Renin Proteins 0.000 claims abstract description 50
- 102100028255 Renin Human genes 0.000 claims abstract description 49
- 230000000694 effects Effects 0.000 claims abstract description 48
- 238000000034 method Methods 0.000 claims abstract description 46
- 125000001424 substituent group Chemical group 0.000 claims abstract description 43
- 201000010099 disease Diseases 0.000 claims abstract description 40
- 238000011282 treatment Methods 0.000 claims abstract description 36
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 25
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 19
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 16
- 241001465754 Metazoa Species 0.000 claims abstract description 10
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 claims abstract description 7
- 239000000463 material Substances 0.000 claims description 210
- 125000003545 alkoxy group Chemical group 0.000 claims description 147
- 125000000217 alkyl group Chemical group 0.000 claims description 137
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 101
- 239000000203 mixture Substances 0.000 claims description 98
- 229910052757 nitrogen Inorganic materials 0.000 claims description 82
- 229910052739 hydrogen Inorganic materials 0.000 claims description 76
- 150000003839 salts Chemical class 0.000 claims description 68
- 125000001624 naphthyl group Chemical group 0.000 claims description 63
- 239000001257 hydrogen Substances 0.000 claims description 55
- 125000005843 halogen group Chemical group 0.000 claims description 54
- 125000000623 heterocyclic group Chemical group 0.000 claims description 47
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 44
- 229910052799 carbon Inorganic materials 0.000 claims description 44
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 36
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 31
- 125000006239 protecting group Chemical group 0.000 claims description 30
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 30
- 125000003118 aryl group Chemical group 0.000 claims description 29
- 125000004076 pyridyl group Chemical group 0.000 claims description 28
- 125000002252 acyl group Chemical group 0.000 claims description 27
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
- 125000003107 substituted aryl group Chemical group 0.000 claims description 25
- 125000000304 alkynyl group Chemical group 0.000 claims description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
- 125000003342 alkenyl group Chemical group 0.000 claims description 22
- 239000007858 starting material Substances 0.000 claims description 22
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 20
- 150000002431 hydrogen Chemical group 0.000 claims description 20
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 19
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 18
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 17
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 16
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 16
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- 125000001041 indolyl group Chemical group 0.000 claims description 15
- 230000008569 process Effects 0.000 claims description 15
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 14
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 13
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 13
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 13
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 125000003386 piperidinyl group Chemical group 0.000 claims description 13
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 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
- 125000002947 alkylene group Chemical group 0.000 claims description 11
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 11
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
- 125000002950 monocyclic group Chemical group 0.000 claims description 10
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 10
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 10
- 125000002873 tetrahydrofuranonyl group Chemical group 0.000 claims description 10
- 125000001544 thienyl group Chemical group 0.000 claims description 10
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 10
- 241000282414 Homo sapiens Species 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- PDQRQJVPEFGVRK-UHFFFAOYSA-N 2,1,3-benzothiadiazole Chemical compound C1=CC=CC2=NSN=C21 PDQRQJVPEFGVRK-UHFFFAOYSA-N 0.000 claims description 8
- 125000004423 acyloxy 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
- 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
- 125000005956 isoquinolyl group Chemical group 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
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 8
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 8
- 125000005493 quinolyl group Chemical group 0.000 claims description 8
- 229920006395 saturated elastomer Polymers 0.000 claims description 8
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 8
- 125000001425 triazolyl group Chemical group 0.000 claims description 8
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 125000006413 ring segment Chemical group 0.000 claims description 7
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 6
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 6
- 125000005059 halophenyl group Chemical group 0.000 claims description 6
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 6
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 6
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 6
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 5
- 125000002431 aminoalkoxy group Chemical group 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 5
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 5
- 229910052740 iodine Inorganic materials 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
- 125000004450 alkenylene group Chemical group 0.000 claims description 4
- 125000004419 alkynylene 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
- 125000004181 carboxyalkyl group Chemical group 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
- 125000001188 haloalkyl group Chemical group 0.000 claims description 4
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- 125000005186 naphthyloxy group Chemical group C1(=CC=CC2=CC=CC=C12)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
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 4
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 claims description 4
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000002768 hydroxyalkyl 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
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([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
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 3
- 125000003367 polycyclic group Chemical group 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 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
- 125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [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
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 2
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 2
- 125000003368 amide 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
- 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 group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000002619 bicyclic group Chemical group 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 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
- 125000004993 haloalkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 claims description 2
- 125000004995 haloalkylthio group Chemical group 0.000 claims description 2
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 2
- 125000005182 hydroxyalkylcarbonyl group Chemical group 0.000 claims description 2
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001326 naphthylalkyl group Chemical group 0.000 claims description 2
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 claims description 2
- 239000001301 oxygen Chemical group 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 2
- 239000011593 sulfur Chemical group 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 22
- 125000001589 carboacyl group Chemical group 0.000 claims 7
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims 2
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims 2
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims 1
- 210000003692 ilium Anatomy 0.000 claims 1
- 125000005146 naphthylsulfonyl group Chemical group C1(=CC=CC2=CC=CC=C12)S(=O)(=O)* 0.000 claims 1
- 125000005561 phenanthryl group Chemical group 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
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 102
- VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical class C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 abstract description 3
- 230000036961 partial effect Effects 0.000 abstract description 2
- 150000002894 organic compounds Chemical class 0.000 abstract 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 271
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 270
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 220
- 238000009833 condensation Methods 0.000 description 137
- 230000005494 condensation Effects 0.000 description 137
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 123
- 229910001868 water Inorganic materials 0.000 description 107
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 106
- 235000019439 ethyl acetate Nutrition 0.000 description 102
- 239000012230 colorless oil Substances 0.000 description 94
- 230000002829 reductive effect Effects 0.000 description 73
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 72
- 239000011541 reaction mixture Substances 0.000 description 72
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 68
- 238000006243 chemical reaction Methods 0.000 description 67
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 66
- 239000012267 brine Substances 0.000 description 59
- 238000003818 flash chromatography Methods 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 57
- 239000012074 organic phase Substances 0.000 description 57
- 239000000741 silica gel Substances 0.000 description 57
- 229910002027 silica gel Inorganic materials 0.000 description 57
- 230000029936 alkylation Effects 0.000 description 55
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 52
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 46
- 239000002904 solvent Substances 0.000 description 46
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 239000000243 solution Substances 0.000 description 42
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
- 238000005481 NMR spectroscopy Methods 0.000 description 38
- 238000003756 stirring Methods 0.000 description 36
- 239000002253 acid Substances 0.000 description 33
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 32
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 30
- 238000005859 coupling reaction Methods 0.000 description 26
- 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 26
- 230000008878 coupling Effects 0.000 description 25
- 238000010168 coupling process Methods 0.000 description 25
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 239000002585 base Substances 0.000 description 24
- 230000007062 hydrolysis Effects 0.000 description 23
- 238000006460 hydrolysis reaction Methods 0.000 description 23
- 239000007832 Na2SO4 Substances 0.000 description 21
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 21
- 208000035475 disorder Diseases 0.000 description 21
- 230000009467 reduction Effects 0.000 description 21
- 238000006722 reduction reaction Methods 0.000 description 21
- 229910052938 sodium sulfate Inorganic materials 0.000 description 21
- 235000011152 sodium sulphate Nutrition 0.000 description 21
- 238000005160 1H NMR spectroscopy Methods 0.000 description 20
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- 238000012360 testing method Methods 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- OLNJUISKUQQNIM-UHFFFAOYSA-N indole-3-carbaldehyde Chemical compound C1=CC=C2C(C=O)=CNC2=C1 OLNJUISKUQQNIM-UHFFFAOYSA-N 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- 239000003112 inhibitor Substances 0.000 description 16
- 239000003921 oil Substances 0.000 description 16
- 230000031709 bromination Effects 0.000 description 15
- 238000005893 bromination reaction Methods 0.000 description 15
- 238000006268 reductive amination reaction Methods 0.000 description 15
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 14
- 230000001419 dependent effect Effects 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
- 238000010511 deprotection reaction Methods 0.000 description 13
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 13
- 239000000843 powder Substances 0.000 description 13
- 238000010992 reflux Methods 0.000 description 13
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 12
- 208000011580 syndromic disease Diseases 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 11
- 208000010877 cognitive disease Diseases 0.000 description 11
- 239000012043 crude product Substances 0.000 description 11
- 239000004480 active ingredient Substances 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- 235000019341 magnesium sulphate Nutrition 0.000 description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- 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 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
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- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 1
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Classifications
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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
- C07D401/12—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
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- 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
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- 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
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- 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
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- 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
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- 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
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- 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
-
- 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 (1)
| Publication Number | Publication Date |
|---|---|
| MX2007008558A true MX2007008558A (es) | 2007-08-14 |
Family
ID=34224619
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2007008558A MX2007008558A (es) | 2005-01-14 | 2006-01-12 | Tetrahidropiridinas 3,4,(5)-sustituidas. |
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) |
Families Citing this family (12)
| 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 |
| WO2011054530A1 (en) * | 2009-11-05 | 2011-05-12 | Fibrostatin, S.L. | Gpbp inhibition using q2 peptidomimetics |
| 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 |
| JP6158193B2 (ja) * | 2012-09-14 | 2017-07-05 | 田辺三菱製薬株式会社 | 新規レニン阻害薬 |
| EP3246309B1 (en) | 2015-01-13 | 2020-01-01 | Nissan Chemical Corporation | Method for treating tin compound in reaction mixture |
| 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 |
Family Cites Families (7)
| 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 |
| MXPA04012136A (es) * | 2002-06-27 | 2005-04-19 | Actelion Pharmaceuticals Ltd | Nuevos derivados de tetrahidropiridina como inhibidores de renina. |
| EP1620403B1 (en) * | 2003-04-29 | 2007-11-28 | Actelion Pharmaceuticals Ltd. | Novel 3,4-disubstituted 1,2,3,6-tetrahydropyridine derivatives |
| AU2004283814A1 (en) * | 2003-10-09 | 2005-05-06 | Actelion Pharmaceuticals Ltd. | Tetrahydropyridine derivatives |
-
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
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 |
| JP2008526910A (ja) | 2008-07-24 |
| 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 |
| AU2006205877B2 (en) | 2010-01-07 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FA | Abandonment or withdrawal |