CA2963951C - Tetrahydroisoquinoline derivatives - Google Patents
Tetrahydroisoquinoline derivatives Download PDFInfo
- Publication number
- CA2963951C CA2963951C CA2963951A CA2963951A CA2963951C CA 2963951 C CA2963951 C CA 2963951C CA 2963951 A CA2963951 A CA 2963951A CA 2963951 A CA2963951 A CA 2963951A CA 2963951 C CA2963951 C CA 2963951C
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- dihydroisoquinolin
- methy1
- ethanone
- alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
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- 125000003039 tetrahydroisoquinolinyl group Chemical class C1(NCCC2=CC=CC=C12)* 0.000 title abstract 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 19
- -1 Ci_6alkylsulfanyl Chemical group 0.000 claims description 521
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 295
- 125000000217 alkyl group Chemical group 0.000 claims description 167
- 150000001875 compounds Chemical class 0.000 claims description 165
- 229910052739 hydrogen Inorganic materials 0.000 claims description 123
- 239000001257 hydrogen Substances 0.000 claims description 123
- 229910052736 halogen Inorganic materials 0.000 claims description 119
- 150000002367 halogens Chemical group 0.000 claims description 118
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 104
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 86
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 78
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 63
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 51
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 51
- 150000003839 salts Chemical class 0.000 claims description 48
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 44
- 125000000623 heterocyclic group Chemical group 0.000 claims description 41
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 38
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 36
- 125000003545 alkoxy group Chemical group 0.000 claims description 34
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 31
- 125000003368 amide group Chemical group 0.000 claims description 30
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 25
- 125000003118 aryl group Chemical group 0.000 claims description 25
- 125000001424 substituent group Chemical group 0.000 claims description 25
- 125000004414 alkyl thio group Chemical group 0.000 claims description 24
- 208000010877 cognitive disease Diseases 0.000 claims description 22
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- 125000003277 amino group Chemical group 0.000 claims description 19
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 16
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 15
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 15
- 125000005257 alkyl acyl group Chemical group 0.000 claims description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 14
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 14
- 208000027061 mild cognitive impairment Diseases 0.000 claims description 14
- 125000002757 morpholinyl group Chemical group 0.000 claims description 14
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 13
- 125000004043 oxo group Chemical group O=* 0.000 claims description 13
- 208000018737 Parkinson disease Diseases 0.000 claims description 12
- 125000005281 alkyl ureido group Chemical group 0.000 claims description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims description 12
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 claims description 12
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 12
- 230000002265 prevention Effects 0.000 claims description 11
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 11
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 10
- 238000002560 therapeutic procedure Methods 0.000 claims description 10
- 125000001091 aminosulfinyl group Chemical group [H]N([H])S(*)=O 0.000 claims description 9
- 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 201000000980 schizophrenia Diseases 0.000 claims description 9
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 8
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 8
- 208000028698 Cognitive impairment Diseases 0.000 claims description 8
- 208000024827 Alzheimer disease Diseases 0.000 claims description 7
- 206010002942 Apathy Diseases 0.000 claims description 7
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 7
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 7
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 7
- 206010012289 Dementia Diseases 0.000 claims description 7
- 208000023105 Huntington disease Diseases 0.000 claims description 7
- 208000016285 Movement disease Diseases 0.000 claims description 7
- 230000007000 age related cognitive decline Effects 0.000 claims description 7
- 230000001149 cognitive effect Effects 0.000 claims description 7
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 206010013663 drug dependence Diseases 0.000 claims description 7
- 208000013403 hyperactivity Diseases 0.000 claims description 7
- 210000004558 lewy body Anatomy 0.000 claims description 7
- 239000003176 neuroleptic agent Substances 0.000 claims description 7
- 208000019116 sleep disease Diseases 0.000 claims description 7
- 208000011117 substance-related disease Diseases 0.000 claims description 7
- 208000024891 symptom Diseases 0.000 claims description 7
- 229940126027 positive allosteric modulator Drugs 0.000 claims description 6
- 125000005195 alkyl amino carbonyloxy group Chemical group 0.000 claims description 5
- CXHHBNMLPJOKQD-UHFFFAOYSA-M methyl carbonate Chemical compound COC([O-])=O CXHHBNMLPJOKQD-UHFFFAOYSA-M 0.000 claims description 5
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 5
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
- VSEAAEQOQBMPQF-UHFFFAOYSA-N morpholin-3-one Chemical compound O=C1COCCN1 VSEAAEQOQBMPQF-UHFFFAOYSA-N 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 3
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 2
- YMJLEPMVGQBLHL-UHFFFAOYSA-N 1h-pyrazole-5-carbonitrile Chemical compound N#CC1=CC=NN1 YMJLEPMVGQBLHL-UHFFFAOYSA-N 0.000 claims 1
- VLCPQJCYZTXACO-CYBMUJFWSA-N 2-(2-fluorophenyl)-1-[(1r)-1-methyl-3,4-dihydro-1h-isoquinolin-2-yl]ethanone Chemical compound N1([C@@H](C2=CC=CC=C2CC1)C)C(=O)CC1=CC=CC=C1F VLCPQJCYZTXACO-CYBMUJFWSA-N 0.000 claims 1
- 230000003281 allosteric effect Effects 0.000 abstract description 7
- 201000010099 disease Diseases 0.000 abstract description 5
- 230000008901 benefit Effects 0.000 abstract description 3
- 239000008177 pharmaceutical agent Substances 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 314
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 274
- 230000015572 biosynthetic process Effects 0.000 description 216
- 238000003786 synthesis reaction Methods 0.000 description 216
- 239000000203 mixture Substances 0.000 description 160
- 239000000243 solution Substances 0.000 description 157
- 239000011541 reaction mixture Substances 0.000 description 156
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 102
- 239000012044 organic layer Substances 0.000 description 102
- 239000007787 solid Substances 0.000 description 94
- 238000000034 method Methods 0.000 description 92
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 89
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 88
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 88
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 87
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 80
- 239000003480 eluent Substances 0.000 description 78
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 70
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 66
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 65
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 65
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 63
- 150000002431 hydrogen Chemical group 0.000 description 62
- 239000000543 intermediate Substances 0.000 description 59
- 238000000746 purification Methods 0.000 description 56
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 55
- 239000012047 saturated solution Substances 0.000 description 55
- 229910052938 sodium sulfate Inorganic materials 0.000 description 55
- 235000011152 sodium sulphate Nutrition 0.000 description 55
- 239000007832 Na2SO4 Substances 0.000 description 54
- 239000007864 aqueous solution Substances 0.000 description 52
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 51
- 235000019341 magnesium sulphate Nutrition 0.000 description 51
- 239000002253 acid Substances 0.000 description 46
- 150000001412 amines Chemical class 0.000 description 46
- 235000017557 sodium bicarbonate Nutrition 0.000 description 44
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 44
- 238000004440 column chromatography Methods 0.000 description 42
- 238000005160 1H NMR spectroscopy Methods 0.000 description 41
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 39
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- 238000006243 chemical reaction Methods 0.000 description 39
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 38
- 238000004458 analytical method Methods 0.000 description 35
- 239000003921 oil Substances 0.000 description 33
- 235000019198 oils Nutrition 0.000 description 33
- 239000002904 solvent Substances 0.000 description 31
- 230000002378 acidificating effect Effects 0.000 description 30
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 26
- 239000012267 brine Substances 0.000 description 24
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
- 239000007858 starting material Substances 0.000 description 19
- 238000010828 elution Methods 0.000 description 18
- 125000000369 oxido group Chemical group [*]=O 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- 125000001153 fluoro group Chemical group F* 0.000 description 17
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 17
- 102000005962 receptors Human genes 0.000 description 17
- 108020003175 receptors Proteins 0.000 description 17
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 16
- 239000000706 filtrate Substances 0.000 description 16
- 238000004128 high performance liquid chromatography Methods 0.000 description 16
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 16
- 238000000926 separation method Methods 0.000 description 16
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 16
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 15
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 15
- 239000002585 base Substances 0.000 description 15
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 15
- 238000004808 supercritical fluid chromatography Methods 0.000 description 15
- 125000001425 triazolyl group Chemical group 0.000 description 15
- 125000004076 pyridyl group Chemical group 0.000 description 14
- 150000003526 tetrahydroisoquinolines Chemical class 0.000 description 14
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 13
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 13
- 229910052794 bromium Inorganic materials 0.000 description 13
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 13
- 239000012071 phase Substances 0.000 description 13
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- 229910021529 ammonia Inorganic materials 0.000 description 11
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 11
- 125000000753 cycloalkyl group Chemical group 0.000 description 11
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 10
- SFAILOOQFZNOAU-UHFFFAOYSA-N 2-(2,6-dichlorophenyl)acetic acid Chemical compound OC(=O)CC1=C(Cl)C=CC=C1Cl SFAILOOQFZNOAU-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 238000005481 NMR spectroscopy Methods 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- 229910052786 argon Inorganic materials 0.000 description 10
- 230000008878 coupling Effects 0.000 description 10
- 238000010168 coupling process Methods 0.000 description 10
- 238000005859 coupling reaction Methods 0.000 description 10
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 10
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 239000012279 sodium borohydride Substances 0.000 description 10
- 229910000033 sodium borohydride Inorganic materials 0.000 description 10
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 235000011114 ammonium hydroxide Nutrition 0.000 description 9
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 9
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 9
- 239000002798 polar solvent Substances 0.000 description 9
- 239000003643 water by type Substances 0.000 description 9
- QPILYVQSKNWRDD-QMMMGPOBSA-N (1s)-1-methyl-1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2[C@H](C)NCCC2=C1 QPILYVQSKNWRDD-QMMMGPOBSA-N 0.000 description 8
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 8
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 125000005843 halogen group Chemical group 0.000 description 8
- PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 description 8
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 8
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 8
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 7
- 239000012230 colorless oil Substances 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 7
- 229940086542 triethylamine Drugs 0.000 description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Substances ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
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- QZDNARZGAULENZ-UHFFFAOYSA-N ethyl 2-(2-acetylphenyl)-2,2-difluoroacetate Chemical compound C(C)(=O)C1=C(C=CC=C1)C(C(=O)OCC)(F)F QZDNARZGAULENZ-UHFFFAOYSA-N 0.000 description 3
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- LZFZEGAXESFMBJ-UHFFFAOYSA-N methyl 2-(3-bromo-5-chloropyridin-4-yl)acetate Chemical compound BrC=1C=NC=C(C=1CC(=O)OC)Cl LZFZEGAXESFMBJ-UHFFFAOYSA-N 0.000 description 3
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- SLOMWHFIGBXKDG-UHFFFAOYSA-N tert-butyl 2-cyano-2-(3,5-dichloro-2-methoxypyridin-4-yl)acetate Chemical compound C(#N)C(C(=O)OC(C)(C)C)C1=C(C(=NC=C1Cl)OC)Cl SLOMWHFIGBXKDG-UHFFFAOYSA-N 0.000 description 3
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- UHSKFQJFRQCDBE-UHFFFAOYSA-N ropinirole Chemical compound CCCN(CCC)CCC1=CC=CC2=C1CC(=O)N2 UHSKFQJFRQCDBE-UHFFFAOYSA-N 0.000 description 1
- 229960001879 ropinirole Drugs 0.000 description 1
- KFQYTPMOWPVWEJ-INIZCTEOSA-N rotigotine Chemical compound CCCN([C@@H]1CC2=CC=CC(O)=C2CC1)CCC1=CC=CS1 KFQYTPMOWPVWEJ-INIZCTEOSA-N 0.000 description 1
- 229960003179 rotigotine Drugs 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- MEZLKOACVSPNER-GFCCVEGCSA-N selegiline Chemical compound C#CCN(C)[C@H](C)CC1=CC=CC=C1 MEZLKOACVSPNER-GFCCVEGCSA-N 0.000 description 1
- 229960003946 selegiline Drugs 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 229940001089 sinemet Drugs 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000004289 sodium hydrogen sulphite Substances 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000008259 solid foam Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 125000005555 sulfoximide group Chemical group 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000003956 synaptic plasticity Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940000238 tasmar Drugs 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- LQPZDJHBTUZFNB-XLLULAGJSA-N tert-butyl (1S)-1-methyl-5-(2,2,2-trifluoro-1-hydroxyethyl)-3,4-dihydro-1H-isoquinoline-2-carboxylate Chemical compound C[C@@H]1N(CCC2=C(C=CC=C12)C(C(F)(F)F)O)C(=O)OC(C)(C)C LQPZDJHBTUZFNB-XLLULAGJSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical class N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- MIQPIUSUKVNLNT-UHFFFAOYSA-N tolcapone Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC(O)=C(O)C([N+]([O-])=O)=C1 MIQPIUSUKVNLNT-UHFFFAOYSA-N 0.000 description 1
- 229960004603 tolcapone Drugs 0.000 description 1
- PHLBKPHSAVXXEF-UHFFFAOYSA-N trazodone Chemical compound ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 PHLBKPHSAVXXEF-UHFFFAOYSA-N 0.000 description 1
- 229960003991 trazodone Drugs 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- KIEXGUUJAYEUSM-UHFFFAOYSA-N trifluoromethylsilane Chemical compound FC(F)(F)[SiH3] KIEXGUUJAYEUSM-UHFFFAOYSA-N 0.000 description 1
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 1
- 125000004953 trihalomethyl group Chemical group 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 125000005500 uronium group Chemical group 0.000 description 1
- MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 description 1
- 229960000604 valproic acid Drugs 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 229960000607 ziprasidone Drugs 0.000 description 1
- MVWVFYHBGMAFLY-UHFFFAOYSA-N ziprasidone Chemical compound C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 MVWVFYHBGMAFLY-UHFFFAOYSA-N 0.000 description 1
- ZAFYATHCZYHLPB-UHFFFAOYSA-N zolpidem Chemical compound N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 ZAFYATHCZYHLPB-UHFFFAOYSA-N 0.000 description 1
- 229960001475 zolpidem Drugs 0.000 description 1
Classifications
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/06—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates
-
- 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
- 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
- C07D401/06—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 only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Epidemiology (AREA)
- Addiction (AREA)
- Hospice & Palliative Care (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14188174 | 2014-10-08 | ||
| EP14188174.8 | 2014-10-08 | ||
| PCT/EP2015/073053 WO2016055479A1 (en) | 2014-10-08 | 2015-10-06 | Tetrahydroisoquinoline derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2963951A1 CA2963951A1 (en) | 2016-04-14 |
| CA2963951C true CA2963951C (en) | 2023-02-28 |
Family
ID=51790569
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2963951A Active CA2963951C (en) | 2014-10-08 | 2015-10-06 | Tetrahydroisoquinoline derivatives |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US10105359B2 (enExample) |
| EP (1) | EP3204359B1 (enExample) |
| JP (1) | JP6622299B2 (enExample) |
| CN (1) | CN107001278B (enExample) |
| BR (1) | BR112017007123B1 (enExample) |
| CA (1) | CA2963951C (enExample) |
| CY (1) | CY1123417T1 (enExample) |
| DK (1) | DK3204359T3 (enExample) |
| EA (1) | EA035544B1 (enExample) |
| ES (1) | ES2821821T3 (enExample) |
| HR (1) | HRP20201469T1 (enExample) |
| HU (1) | HUE050664T2 (enExample) |
| LT (1) | LT3204359T (enExample) |
| PL (1) | PL3204359T3 (enExample) |
| PT (1) | PT3204359T (enExample) |
| RS (1) | RS60933B1 (enExample) |
| SI (1) | SI3204359T1 (enExample) |
| WO (1) | WO2016055479A1 (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA3012560A1 (en) * | 2016-02-25 | 2017-08-31 | Asceneuron S.A. | Glycosidase inhibitors |
| JP6908623B2 (ja) * | 2016-04-13 | 2021-07-28 | ユーシービー バイオファルマ エスアールエル | テトラヒドロイソキノリン誘導体 |
| CN107698433A (zh) * | 2017-09-12 | 2018-02-16 | 潍坊滨海石油化工有限公司 | 苯乙酸的制备方法 |
| EA202091323A1 (ru) | 2017-12-01 | 2020-10-09 | Юсб Байофарма Срл | Визуализирующие средства |
| TWI725408B (zh) * | 2018-04-20 | 2021-04-21 | 美商美國禮來大藥廠 | 多巴胺d1受體正向異位調節劑 |
| CN114008032B (zh) * | 2019-07-01 | 2023-11-10 | Ucb生物制药有限责任公司 | 作为d1正变构调节剂的取代的四氢异喹啉衍生物 |
| AU2020299953B2 (en) * | 2019-07-01 | 2025-06-05 | UCB Biopharma SRL | A substituted tetrahydroisoquinoline derivative as a D1 positive allosteric modulator |
| CN115916338A (zh) * | 2020-04-24 | 2023-04-04 | 加利福尼亚大学董事会 | Nurr1受体调节剂及其用途 |
| CN111943930B (zh) * | 2020-08-25 | 2022-11-01 | 南京三元阳普医药科技有限公司 | Lasmiditan的合成工艺 |
| DK4200280T3 (da) * | 2020-10-07 | 2024-03-04 | Lilly Co Eli | Phenyl-3,4-dihydroisoquinolin-2(1H)-yl-ethan-on-derivater som positive allosteriske modulatorer af dopamin-D1-receptorer |
| WO2022117678A1 (en) | 2020-12-03 | 2022-06-09 | UCB Biopharma SRL | Octahydroisoquinolinyl derivatives |
| US20240083875A1 (en) | 2020-12-18 | 2024-03-14 | UCB Biopharma SRL | Dihydroisoquinolinyl derivatives |
| CN116601161A (zh) * | 2020-12-18 | 2023-08-15 | Ucb生物制药有限责任公司 | 2-(3,5-二氯-1-甲基-吲唑-4-基)-1-[(1s,3r)-3-(羟基甲基)-5-(1-羟基-1-甲基-乙基)-1-甲基-3,4-二氢-1h-异喹啉-2-基]乙酮的前药 |
| US20240000769A1 (en) * | 2020-12-18 | 2024-01-04 | UCB Biopharma SRL | Amorphous solid dispersions |
| PL4263517T3 (pl) * | 2020-12-18 | 2025-03-31 | UCB Biopharma SRL | Podstawiona pochodna tetrahydroizochinoliny jako pozytywny modulator allosteryczny d1 |
| AU2022234744B2 (en) | 2021-03-08 | 2025-06-26 | Eli Lilly And Company | Use of mevidalen and other d1 positive allosteric modulators in the treatment of hallucinations and dementia-related psychosis |
| CN117337173A (zh) | 2021-03-09 | 2024-01-02 | 伊莱利利公司 | 美维达林和其他d1正向别构调节剂用于减缓帕金森氏病进展的用途 |
| CN114671810B (zh) * | 2022-03-21 | 2024-03-22 | 济南鸿湾生物技术有限公司 | 一种咪唑苯脲的制备方法 |
| CN115611768B (zh) * | 2022-11-14 | 2024-03-05 | 郑州大学 | 一种3,4-二氯苯腈的合成方法 |
| CN118724764B (zh) * | 2024-06-07 | 2025-11-18 | 绍兴文理学院 | 一种芳基伯磺酰胺类化合物的制备方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4766131A (en) * | 1980-10-17 | 1988-08-23 | Pennwalt Corporation | 2-amino (or hydroxy) phenethyl-1,2,3,4-tetrahydroisoquinolines as analgesics |
| MXPA04005988A (es) * | 2001-12-19 | 2004-09-27 | Lundbeck & Co As H | 3,4-dihidro-1h-isoquinolin-2-il-derivados. |
| JP4685861B2 (ja) * | 2004-04-29 | 2011-05-18 | アベンティス・ファーマスーティカルズ・インコーポレイテツド | ドーパミンアゴニストとしての３−ピペリジニルイソクロマン−５−オール |
| MX2009009415A (es) * | 2007-03-01 | 2009-09-11 | Janssen Pharmaceutica Nv | Compuestos de tetrahidroisoquinolina como moduladores del receptor h3 de la histamina. |
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2015
- 2015-10-06 LT LTEP15775688.3T patent/LT3204359T/lt unknown
- 2015-10-06 HU HUE15775688A patent/HUE050664T2/hu unknown
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- 2015-10-06 PL PL15775688.3T patent/PL3204359T3/pl unknown
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- 2015-10-06 DK DK15775688.3T patent/DK3204359T3/da active
- 2015-10-06 EA EA201790785A patent/EA035544B1/ru not_active IP Right Cessation
- 2015-10-06 RS RS20201139A patent/RS60933B1/sr unknown
- 2015-10-06 CN CN201580064005.3A patent/CN107001278B/zh not_active Expired - Fee Related
- 2015-10-06 US US15/517,795 patent/US10105359B2/en active Active
- 2015-10-06 PT PT157756883T patent/PT3204359T/pt unknown
- 2015-10-06 CA CA2963951A patent/CA2963951C/en active Active
- 2015-10-06 JP JP2017518989A patent/JP6622299B2/ja active Active
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- 2015-10-06 ES ES15775688T patent/ES2821821T3/es active Active
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2020
- 2020-09-30 CY CY20201100923T patent/CY1123417T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| RS60933B1 (sr) | 2020-11-30 |
| EA201790785A1 (ru) | 2017-10-31 |
| US10105359B2 (en) | 2018-10-23 |
| LT3204359T (lt) | 2020-10-12 |
| HRP20201469T1 (hr) | 2020-12-11 |
| BR112017007123B1 (pt) | 2023-01-31 |
| BR112017007123A2 (pt) | 2017-12-19 |
| WO2016055479A1 (en) | 2016-04-14 |
| DK3204359T3 (da) | 2020-09-14 |
| ES2821821T3 (es) | 2021-04-27 |
| PL3204359T3 (pl) | 2021-03-22 |
| EA035544B1 (ru) | 2020-07-03 |
| EP3204359A1 (en) | 2017-08-16 |
| HUE050664T2 (hu) | 2020-12-28 |
| CA2963951A1 (en) | 2016-04-14 |
| JP2017530185A (ja) | 2017-10-12 |
| PT3204359T (pt) | 2020-09-24 |
| CN107001278B (zh) | 2020-11-24 |
| CN107001278A (zh) | 2017-08-01 |
| CY1123417T1 (el) | 2021-12-31 |
| SI3204359T1 (sl) | 2020-10-30 |
| EP3204359B1 (en) | 2020-07-01 |
| US20170304292A1 (en) | 2017-10-26 |
| JP6622299B2 (ja) | 2019-12-18 |
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