BRPI0709678A2 - compostos orgánicos - Google Patents
compostos orgánicos Download PDFInfo
- Publication number
- BRPI0709678A2 BRPI0709678A2 BRPI0709678-0A BRPI0709678A BRPI0709678A2 BR PI0709678 A2 BRPI0709678 A2 BR PI0709678A2 BR PI0709678 A BRPI0709678 A BR PI0709678A BR PI0709678 A2 BRPI0709678 A2 BR PI0709678A2
- Authority
- BR
- Brazil
- Prior art keywords
- alkyl
- hydrogen
- alkylamino
- aryl
- halogen
- Prior art date
Links
- 150000002894 organic compounds Chemical class 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 159
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 71
- 208000035475 disorder Diseases 0.000 claims abstract description 37
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 35
- 201000010099 disease Diseases 0.000 claims abstract description 34
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 claims abstract description 27
- 238000011282 treatment Methods 0.000 claims abstract description 27
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 claims abstract description 24
- 229960002478 aldosterone Drugs 0.000 claims abstract description 24
- 206010020772 Hypertension Diseases 0.000 claims abstract description 12
- 230000001404 mediated effect Effects 0.000 claims abstract description 11
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 9
- 206010019280 Heart failures Diseases 0.000 claims abstract description 8
- 208000001647 Renal Insufficiency Diseases 0.000 claims abstract description 7
- 201000006370 kidney failure Diseases 0.000 claims abstract description 7
- 208000011580 syndromic disease Diseases 0.000 claims abstract description 7
- 206010007559 Cardiac failure congestive Diseases 0.000 claims abstract description 6
- 238000007634 remodeling Methods 0.000 claims abstract description 6
- 102000008186 Collagen Human genes 0.000 claims abstract description 5
- 108010035532 Collagen Proteins 0.000 claims abstract description 5
- 206010048554 Endothelial dysfunction Diseases 0.000 claims abstract description 5
- 208000019025 Hypokalemia Diseases 0.000 claims abstract description 5
- 208000008589 Obesity Diseases 0.000 claims abstract description 5
- 229920001436 collagen Polymers 0.000 claims abstract description 5
- 208000029078 coronary artery disease Diseases 0.000 claims abstract description 5
- 230000008694 endothelial dysfunction Effects 0.000 claims abstract description 5
- 208000017169 kidney disease Diseases 0.000 claims abstract description 5
- 208000010125 myocardial infarction Diseases 0.000 claims abstract description 5
- 235000020824 obesity Nutrition 0.000 claims abstract description 5
- 208000024896 potassium deficiency disease Diseases 0.000 claims abstract description 5
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 4
- 230000009787 cardiac fibrosis Effects 0.000 claims abstract description 4
- 208000037803 restenosis Diseases 0.000 claims abstract description 4
- -1 cyano, carboxy Chemical group 0.000 claims description 260
- 229910052739 hydrogen Inorganic materials 0.000 claims description 214
- 239000001257 hydrogen Substances 0.000 claims description 213
- 125000003282 alkyl amino group Chemical group 0.000 claims description 212
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 185
- 125000003118 aryl group Chemical group 0.000 claims description 158
- 229910052736 halogen Chemical group 0.000 claims description 156
- 150000002367 halogens Chemical group 0.000 claims description 154
- 239000000203 mixture Substances 0.000 claims description 149
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 133
- 125000001072 heteroaryl group Chemical group 0.000 claims description 122
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 86
- 125000000217 alkyl group Chemical group 0.000 claims description 84
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 83
- 125000000623 heterocyclic group Chemical group 0.000 claims description 79
- 125000001424 substituent group Chemical group 0.000 claims description 79
- 125000003545 alkoxy group Chemical group 0.000 claims description 76
- 150000003573 thiols Chemical group 0.000 claims description 72
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 71
- 125000003342 alkenyl group Chemical group 0.000 claims description 69
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 67
- 150000003839 salts Chemical class 0.000 claims description 55
- 125000000304 alkynyl group Chemical group 0.000 claims description 50
- 125000004442 acylamino group Chemical group 0.000 claims description 49
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 48
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 45
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 35
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 33
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 33
- 230000003287 optical effect Effects 0.000 claims description 33
- 238000000034 method Methods 0.000 claims description 32
- 108010009911 Cytochrome P-450 CYP11B2 Proteins 0.000 claims description 31
- 102100024329 Cytochrome P450 11B2, mitochondrial Human genes 0.000 claims description 31
- 230000000694 effects Effects 0.000 claims description 31
- 230000002159 abnormal effect Effects 0.000 claims description 27
- 229910052760 oxygen Inorganic materials 0.000 claims description 27
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 25
- 229910052799 carbon Inorganic materials 0.000 claims description 25
- 239000001301 oxygen Substances 0.000 claims description 25
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 22
- 150000001721 carbon Chemical group 0.000 claims description 21
- 239000003814 drug Substances 0.000 claims description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims description 18
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 17
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 14
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 14
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 10
- 125000002252 acyl group Chemical group 0.000 claims description 9
- KCNKJCHARANTIP-SNAWJCMRSA-N allyl-{4-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-but-2-enyl}-methyl-amine Chemical group C=1OC2=CC(OC/C=C/CN(CC=C)C)=CC=C2C=1C1=CC=C(Br)C=C1 KCNKJCHARANTIP-SNAWJCMRSA-N 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- SYGWYBOJXOGMRU-UHFFFAOYSA-N chembl233051 Chemical compound C1=CC=C2C3=CC(C(N(CCN(C)C)C4=O)=O)=C5C4=CC=CC5=C3SC2=C1 SYGWYBOJXOGMRU-UHFFFAOYSA-N 0.000 claims description 8
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 8
- 125000001769 aryl amino group Chemical group 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 125000004986 diarylamino group Chemical group 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 239000004041 inotropic agent Substances 0.000 claims description 4
- 239000000883 anti-obesity agent Substances 0.000 claims description 3
- 229940030600 antihypertensive agent Drugs 0.000 claims description 3
- 239000002220 antihypertensive agent Substances 0.000 claims description 3
- 239000003524 antilipemic agent Substances 0.000 claims description 3
- 229940125710 antiobesity agent Drugs 0.000 claims description 3
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 3
- 230000006378 damage Effects 0.000 claims description 2
- 102200078752 rs201827340 Human genes 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 50
- 239000013543 active substance Substances 0.000 claims 2
- 125000006714 (C3-C10) heterocyclyl group Chemical group 0.000 claims 1
- 208000019622 heart disease Diseases 0.000 claims 1
- 229940123338 Aldosterone synthase inhibitor Drugs 0.000 abstract description 5
- 208000020832 chronic kidney disease Diseases 0.000 abstract description 5
- 208000022831 chronic renal failure syndrome Diseases 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 160
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 134
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 118
- 239000000243 solution Substances 0.000 description 76
- 238000005160 1H NMR spectroscopy Methods 0.000 description 73
- 238000006243 chemical reaction Methods 0.000 description 66
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 59
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 58
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
- 229910001868 water Inorganic materials 0.000 description 52
- 239000012071 phase Substances 0.000 description 47
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 46
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 45
- 238000004296 chiral HPLC Methods 0.000 description 44
- 229920006395 saturated elastomer Polymers 0.000 description 44
- 239000012074 organic phase Substances 0.000 description 42
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 41
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 40
- 239000011541 reaction mixture Substances 0.000 description 39
- 239000007787 solid Substances 0.000 description 38
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 37
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 34
- 239000002253 acid Substances 0.000 description 34
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 31
- 239000011734 sodium Substances 0.000 description 30
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 29
- 238000010898 silica gel chromatography Methods 0.000 description 28
- 239000010410 layer Substances 0.000 description 27
- 239000000741 silica gel Substances 0.000 description 24
- 229910002027 silica gel Inorganic materials 0.000 description 24
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 23
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 23
- 235000019341 magnesium sulphate Nutrition 0.000 description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
- 235000017557 sodium bicarbonate Nutrition 0.000 description 22
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 108010049356 Steroid 11-beta-Hydroxylase Proteins 0.000 description 20
- 229940002612 prodrug Drugs 0.000 description 20
- 239000000651 prodrug Substances 0.000 description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 19
- 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
- 102100024332 Cytochrome P450 11B1, mitochondrial Human genes 0.000 description 17
- 239000002585 base Substances 0.000 description 17
- 239000003795 chemical substances by application Substances 0.000 description 17
- 239000003921 oil Substances 0.000 description 17
- 235000019198 oils Nutrition 0.000 description 17
- 238000012360 testing method Methods 0.000 description 17
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 16
- 239000003153 chemical reaction reagent Substances 0.000 description 16
- 229910052757 nitrogen Inorganic materials 0.000 description 16
- 239000012044 organic layer Substances 0.000 description 16
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000003818 flash chromatography Methods 0.000 description 15
- CLUPOLFGIGLMIQ-UHFFFAOYSA-N heptane;propan-2-ol Chemical compound CC(C)O.CCCCCCC CLUPOLFGIGLMIQ-UHFFFAOYSA-N 0.000 description 15
- 238000000746 purification Methods 0.000 description 15
- 229960000583 acetic acid Drugs 0.000 description 14
- 239000012267 brine Substances 0.000 description 14
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 14
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 13
- 229920000742 Cotton Polymers 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 13
- UMYZHWLYICNGRQ-UHFFFAOYSA-N ethanol;heptane Chemical compound CCO.CCCCCCC UMYZHWLYICNGRQ-UHFFFAOYSA-N 0.000 description 13
- 239000003112 inhibitor Substances 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 125000000041 C6-C10 aryl group Chemical group 0.000 description 12
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 12
- 239000000460 chlorine Chemical group 0.000 description 12
- 229940079593 drug Drugs 0.000 description 12
- 230000005764 inhibitory process Effects 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
- 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 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 10
- 238000010828 elution Methods 0.000 description 10
- 125000005843 halogen group Chemical group 0.000 description 10
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 10
- 239000008346 aqueous phase Substances 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- 230000000875 corresponding effect Effects 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 238000004007 reversed phase HPLC Methods 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- PMAMZJXPHVPEGM-UHFFFAOYSA-N 4-[5-(hydroxymethyl)imidazol-1-yl]-3,3-dimethyl-4h-isochromen-1-one Chemical compound CC1(C)OC(=O)C2=CC=CC=C2C1N1C=NC=C1CO PMAMZJXPHVPEGM-UHFFFAOYSA-N 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 150000001408 amides Chemical class 0.000 description 7
- 229910052794 bromium Inorganic materials 0.000 description 7
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 150000003840 hydrochlorides Chemical class 0.000 description 7
- 229960000890 hydrocortisone Drugs 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
- 230000003647 oxidation Effects 0.000 description 7
- 238000007254 oxidation reaction Methods 0.000 description 7
- 238000006722 reduction reaction Methods 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- AHHRSTVKSSIXSD-UHFFFAOYSA-N 3-(3,3-dimethyl-1-oxo-4h-isochromen-4-yl)imidazole-4-carbaldehyde Chemical compound CC1(C)OC(=O)C2=CC=CC=C2C1N1C=NC=C1C=O AHHRSTVKSSIXSD-UHFFFAOYSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical class OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000001450 anions Chemical class 0.000 description 6
- 125000002619 bicyclic group Chemical group 0.000 description 6
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 150000002466 imines Chemical class 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
- 150000004702 methyl esters Chemical class 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 239000003755 preservative agent Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 230000000979 retarding effect Effects 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 6
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- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 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
- C07D401/04—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
-
- 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
- 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
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
-
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US78710406P | 2006-03-29 | 2006-03-29 | |
| US60/787,104 | 2006-03-29 | ||
| PCT/US2007/064974 WO2007117982A2 (en) | 2006-03-29 | 2007-03-27 | Organic compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BRPI0709678A2 true BRPI0709678A2 (pt) | 2011-07-19 |
Family
ID=38477291
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0709678-0A BRPI0709678A2 (pt) | 2006-03-29 | 2007-03-27 | compostos orgánicos |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US8153674B2 (enExample) |
| EP (2) | EP2001866A2 (enExample) |
| JP (1) | JP5197569B2 (enExample) |
| KR (1) | KR20080114769A (enExample) |
| CN (1) | CN101410389A (enExample) |
| AU (1) | AU2007234968A1 (enExample) |
| BR (1) | BRPI0709678A2 (enExample) |
| CA (1) | CA2644391A1 (enExample) |
| ES (1) | ES2442347T3 (enExample) |
| MX (1) | MX2008012402A (enExample) |
| RU (1) | RU2008142600A (enExample) |
| WO (1) | WO2007117982A2 (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103880827B (zh) | 2004-07-15 | 2017-01-04 | 阿尔巴尼分子研究公司 | 芳基和杂芳基取代的四氢异喹啉及其阻断去甲肾上腺素、多巴胺和血清素的重摄取的应用 |
| KR20090090395A (ko) * | 2006-12-18 | 2009-08-25 | 노파르티스 아게 | 4-이미다졸릴-1,2,3,4-테트라히드로퀴놀린 유도체 및 알도스테론/11-베타-히드록실라제 억제제로서의 그의 용도 |
| US8436035B2 (en) * | 2006-12-18 | 2013-05-07 | Novartis Ag | Organic compounds |
| EP2095819A1 (en) * | 2008-02-28 | 2009-09-02 | Maastricht University | N-benzyl imidazole derivatives and their use as aldosterone synthase inhibitors |
| US9156812B2 (en) | 2008-06-04 | 2015-10-13 | Bristol-Myers Squibb Company | Crystalline form of 6-[(4S)-2-methyl-4-(2-naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyridazin-3-amine |
| US8815894B2 (en) | 2009-05-12 | 2014-08-26 | Bristol-Myers Squibb Company | Crystalline forms of (S)-7-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydroisoquinoline and use thereof |
| EP2429295B1 (en) | 2009-05-12 | 2013-12-25 | Albany Molecular Research, Inc. | Aryl, heteroaryl, and heterocycle substituted tetrahydroisoquinolines and use thereof |
| KR101830447B1 (ko) | 2009-05-12 | 2018-02-20 | 알바니 몰레큘라 리써치, 인크. | 7-(［1,2,4］트리아졸로［1,5-α］피리딘-6-일)-4-(3,4-디클로로페닐)-1,2,3,4-테트라하이드로이소퀴놀린 및 이의 용도 |
| CN103958478B (zh) * | 2011-11-30 | 2017-08-01 | 霍夫曼-拉罗奇有限公司 | 双环二氢异喹啉‑1‑酮衍生物 |
| MY178867A (en) * | 2011-11-30 | 2020-10-21 | Hoffmann La Roche | New bicyclic dihydroisoquinoline-1-one derivatives |
| EP2639212B1 (en) | 2012-03-13 | 2016-03-09 | The Provost, Fellows, Foundation Scholars, & the other members of Board, of the College of the Holy & Undiv. Trinity of Queen Elizabeth near Dublin | Enantioselective organic anhydride reactions |
| MX368093B (es) * | 2014-07-24 | 2019-09-19 | Boehringer Ingelheim Int | Inhibidores de aldosterona sintasa. |
| WO2016123275A1 (en) * | 2015-01-30 | 2016-08-04 | Boehringer Ingelheim International Gmbh | Aldosterone synthase inhibitors |
| BR112019018700A2 (pt) | 2017-03-10 | 2020-04-07 | Embera Neurotherapeutics Inc | composições farmacêuticas e seus usos |
| CN109232607A (zh) * | 2018-09-20 | 2019-01-18 | 沈阳药科大学 | 劳拉替尼的合成方法 |
| WO2020223267A1 (en) | 2019-05-01 | 2020-11-05 | Boehringer Ingelheim International Gmbh | (r)-(2-methyloxiran-2-yl)methyl 4-bromobenzenesulfonate |
| KR20240122521A (ko) | 2021-12-14 | 2024-08-12 | 베링거 인겔하임 인터내셔날 게엠베하 | 만성 신장 질환 치료용 알도스테론 신타아제 억제제 |
| JP2025540715A (ja) * | 2022-11-23 | 2025-12-16 | 上▲海▼翰森生物医▲薬▼科技有限公司 | ピリジン多環系化合物阻害剤、及びその製造方法と使用 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4904300A (en) * | 1987-08-26 | 1990-02-27 | Ciba-Geigy Corp. | Imidazole derivatives |
| DE102004035322A1 (de) * | 2004-07-21 | 2006-02-16 | Universität des Saarlandes | Selektive Hemmstoffe humaner Corticoidsynthasen |
-
2007
- 2007-03-27 MX MX2008012402A patent/MX2008012402A/es not_active Application Discontinuation
- 2007-03-27 EP EP07759422A patent/EP2001866A2/en not_active Withdrawn
- 2007-03-27 ES ES10179603.5T patent/ES2442347T3/es active Active
- 2007-03-27 AU AU2007234968A patent/AU2007234968A1/en not_active Abandoned
- 2007-03-27 EP EP10179603.5A patent/EP2301931B1/en not_active Not-in-force
- 2007-03-27 CA CA002644391A patent/CA2644391A1/en not_active Abandoned
- 2007-03-27 US US12/295,155 patent/US8153674B2/en not_active Expired - Fee Related
- 2007-03-27 KR KR1020087023643A patent/KR20080114769A/ko not_active Withdrawn
- 2007-03-27 JP JP2009503206A patent/JP5197569B2/ja not_active Expired - Fee Related
- 2007-03-27 BR BRPI0709678-0A patent/BRPI0709678A2/pt not_active Application Discontinuation
- 2007-03-27 WO PCT/US2007/064974 patent/WO2007117982A2/en not_active Ceased
- 2007-03-27 CN CNA2007800110014A patent/CN101410389A/zh active Pending
- 2007-03-27 RU RU2008142600/04A patent/RU2008142600A/ru not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| ES2442347T3 (es) | 2014-02-11 |
| JP2009531457A (ja) | 2009-09-03 |
| EP2001866A2 (en) | 2008-12-17 |
| WO2007117982A2 (en) | 2007-10-18 |
| AU2007234968A1 (en) | 2007-10-18 |
| MX2008012402A (es) | 2008-10-09 |
| KR20080114769A (ko) | 2008-12-31 |
| EP2301931A1 (en) | 2011-03-30 |
| RU2008142600A (ru) | 2010-05-10 |
| JP5197569B2 (ja) | 2013-05-15 |
| CA2644391A1 (en) | 2007-10-18 |
| CN101410389A (zh) | 2009-04-15 |
| EP2301931B1 (en) | 2013-10-16 |
| WO2007117982A3 (en) | 2007-12-13 |
| US8153674B2 (en) | 2012-04-10 |
| US20090182007A1 (en) | 2009-07-16 |
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