IL104170A

IL104170A - History of Tetra-hydroisoquinoline Process for their preparation and pharmaceutical preparations containing them

History of Tetra-hydroisoquinoline Process for their preparation and pharmaceutical preparations containing them

Info

Publication number: IL104170A
Authority: IL; Israel
Prior art keywords: mixture; carbon atoms; methyl; ether; formula
Prior art date: 1991-12-23

Application number

IL10417092A

Other languages

English (en)

Hebrew (he)

Other versions

IL104170A0 (en

Original Assignee

Boots Co Plc

Priority date

1991-12-23

Filing date

1992-12-18

Publication date

1999-04-11

1992-12-18 Application filed by Boots Co Plc filed Critical Boots Co Plc

1993-05-13 Publication of IL104170A0 publication Critical patent/IL104170A0/xx

1999-04-11 Publication of IL104170A publication Critical patent/IL104170A/en

Links

238000000034 method Methods 0.000 title claims description 29
238000002360 preparation method Methods 0.000 title claims description 11
239000008194 pharmaceutical composition Substances 0.000 title claims description 9
230000008569 process Effects 0.000 title claims description 5
125000003039 tetrahydroisoquinolinyl group Chemical class C1(NCCC2=CC=CC=C12)* 0.000 title abstract 2
150000003839 salts Chemical class 0.000 claims abstract description 43
208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims abstract description 6
208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims abstract description 6
208000028698 Cognitive impairment Diseases 0.000 claims abstract description 6
206010043118 Tardive Dyskinesia Diseases 0.000 claims abstract description 6
208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims abstract description 6
208000010877 cognitive disease Diseases 0.000 claims abstract description 6
206010013663 drug dependence Diseases 0.000 claims abstract description 6
208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims abstract description 6
208000011117 substance-related disease Diseases 0.000 claims abstract description 6
208000011580 syndromic disease Diseases 0.000 claims abstract description 6
239000000203 mixture Substances 0.000 claims description 407
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 261
150000001875 compounds Chemical class 0.000 claims description 199
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 126
125000004432 carbon atom Chemical group C* 0.000 claims description 72
-1 chloro, bromo, methyl Chemical group 0.000 claims description 62
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 55
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 43
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 42
125000001309 chloro group Chemical group Cl* 0.000 claims description 30
125000000217 alkyl group Chemical group 0.000 claims description 24
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
125000005843 halogen group Chemical group 0.000 claims description 19
125000003545 alkoxy group Chemical group 0.000 claims description 18
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 claims description 16
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 14
125000000068 chlorophenyl group Chemical group 0.000 claims description 11
125000004093 cyano group Chemical group *C#N 0.000 claims description 11
125000001153 fluoro group Chemical group F* 0.000 claims description 10
125000001424 substituent group Chemical group 0.000 claims description 10
125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 9
125000001246 bromo group Chemical group Br* 0.000 claims description 9
125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 7
125000004414 alkyl thio group Chemical group 0.000 claims description 7
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 7
125000001624 naphthyl group Chemical group 0.000 claims description 7
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
238000003776 cleavage reaction Methods 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
230000007017 scission Effects 0.000 claims description 6
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 5
125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 5
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 5
208000018737 Parkinson disease Diseases 0.000 claims description 5
230000029936 alkylation Effects 0.000 claims description 5
238000005804 alkylation reaction Methods 0.000 claims description 5
125000006684 polyhaloalkyl group Polymers 0.000 claims description 5
201000000980 schizophrenia Diseases 0.000 claims description 4
150000003526 tetrahydroisoquinolines Chemical class 0.000 claims description 4
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 3
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
125000001931 aliphatic group Chemical group 0.000 claims description 3
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
125000002947 alkylene group Chemical group 0.000 claims description 3
125000000623 heterocyclic group Chemical group 0.000 claims description 3
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 2
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
125000002252 acyl group Chemical group 0.000 claims description 2
125000003342 alkenyl group Chemical group 0.000 claims description 2
229910052799 carbon Inorganic materials 0.000 claims description 2
125000003074 decanoyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
125000000268 heptanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000000400 lauroyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([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
125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([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
125000003696 stearoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([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
125000000547 substituted alkyl group Chemical group 0.000 claims description 2
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
AXNBRAABOINRNO-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclopropyl]-6-fluoro-2-methyl-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound CN1CCC2=CC(F)=C(O)C=C2C1C1(C=2C(=CC=CC=2)Cl)CC1 AXNBRAABOINRNO-UHFFFAOYSA-N 0.000 claims 1
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 1
FXCIEQJPMSJEII-UHFFFAOYSA-N 6-methoxy-2-methyl-3,4-dihydro-1h-isoquinoline Chemical compound C1N(C)CCC2=CC(OC)=CC=C21 FXCIEQJPMSJEII-UHFFFAOYSA-N 0.000 claims 1
AFHJQYHRLPMKHU-XXWVOBANSA-N Aloin Natural products O=C1c2c(O)cc(CO)cc2[C@H]([C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O2)c2c1c(O)ccc2 AFHJQYHRLPMKHU-XXWVOBANSA-N 0.000 claims 1
AFHJQYHRLPMKHU-CGISPIQUSA-N aloin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1C2=CC(CO)=CC(O)=C2C(=O)C2=C(O)C=CC=C21 AFHJQYHRLPMKHU-CGISPIQUSA-N 0.000 claims 1
150000002148 esters Chemical class 0.000 abstract description 13
208000028017 Psychotic disease Diseases 0.000 abstract description 5
229940035676 analgesics Drugs 0.000 abstract 1
239000000730 antalgic agent Substances 0.000 abstract 1
201000010099 disease Diseases 0.000 abstract 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 640
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 368
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 264
239000000243 solution Substances 0.000 description 224
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 203
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 193
239000002904 solvent Substances 0.000 description 183
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 153
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 137
239000000047 product Substances 0.000 description 137
229940093499 ethyl acetate Drugs 0.000 description 123
235000019439 ethyl acetate Nutrition 0.000 description 123
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 116
239000007787 solid Substances 0.000 description 115
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 113
239000000284 extract Substances 0.000 description 110
239000011541 reaction mixture Substances 0.000 description 105
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 101
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 90
238000001704 evaporation Methods 0.000 description 80
238000002844 melting Methods 0.000 description 80
230000008018 melting Effects 0.000 description 80
238000010992 reflux Methods 0.000 description 80
230000008020 evaporation Effects 0.000 description 79
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 76
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 72
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 72
235000011114 ammonium hydroxide Nutrition 0.000 description 72
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 70
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 68
239000012044 organic layer Substances 0.000 description 68
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 63
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 62
239000003921 oil Substances 0.000 description 61
235000019198 oils Nutrition 0.000 description 61
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 60
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 56
239000003208 petroleum Substances 0.000 description 56
238000001914 filtration Methods 0.000 description 54
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 52
238000010533 azeotropic distillation Methods 0.000 description 50
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 48
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 47
239000007858 starting material Substances 0.000 description 47
229960000583 acetic acid Drugs 0.000 description 44
238000000746 purification Methods 0.000 description 44
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 43
239000010410 layer Substances 0.000 description 43
238000006243 chemical reaction Methods 0.000 description 40
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
239000003610 charcoal Substances 0.000 description 39
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 38
239000012362 glacial acetic acid Substances 0.000 description 31
229910052757 nitrogen Inorganic materials 0.000 description 31
239000000706 filtrate Substances 0.000 description 30
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
239000012267 brine Substances 0.000 description 29
239000008098 formaldehyde solution Substances 0.000 description 29
235000017557 sodium bicarbonate Nutrition 0.000 description 29
229910000030 sodium bicarbonate Inorganic materials 0.000 description 29
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 29
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 28
229910052943 magnesium sulfate Inorganic materials 0.000 description 26
235000019341 magnesium sulphate Nutrition 0.000 description 26
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 26
229910000027 potassium carbonate Inorganic materials 0.000 description 24
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 22
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
235000006408 oxalic acid Nutrition 0.000 description 22
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 22
238000003818 flash chromatography Methods 0.000 description 20
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 20
239000012279 sodium borohydride Substances 0.000 description 20
229910000033 sodium borohydride Inorganic materials 0.000 description 20
BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 19
229920006395 saturated elastomer Polymers 0.000 description 18
235000015096 spirit Nutrition 0.000 description 17
238000003756 stirring Methods 0.000 description 17
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
239000012259 ether extract Substances 0.000 description 16
150000003891 oxalate salts Chemical class 0.000 description 16
230000003287 optical effect Effects 0.000 description 15
239000000725 suspension Substances 0.000 description 15
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
229960001760 dimethyl sulfoxide Drugs 0.000 description 14
239000012458 free base Substances 0.000 description 14
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 14
239000012258 stirred mixture Substances 0.000 description 14
238000006722 reduction reaction Methods 0.000 description 13
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 12
239000012074 organic phase Substances 0.000 description 12
230000009467 reduction Effects 0.000 description 12
238000009835 boiling Methods 0.000 description 11
238000001816 cooling Methods 0.000 description 11
239000003826 tablet Substances 0.000 description 11
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 10
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
239000002253 acid Substances 0.000 description 10
238000004821 distillation Methods 0.000 description 10
235000019253 formic acid Nutrition 0.000 description 10
239000003446 ligand Substances 0.000 description 10
ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 10
229920000388 Polyphosphate Polymers 0.000 description 9
229940117803 phenethylamine Drugs 0.000 description 9
239000001205 polyphosphate Substances 0.000 description 9
235000011176 polyphosphates Nutrition 0.000 description 9
239000002244 precipitate Substances 0.000 description 9
230000002829 reductive effect Effects 0.000 description 9
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
238000010438 heat treatment Methods 0.000 description 8
238000000159 protein binding assay Methods 0.000 description 8
229910052938 sodium sulfate Inorganic materials 0.000 description 8
235000011152 sodium sulphate Nutrition 0.000 description 8
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 7
230000027455 binding Effects 0.000 description 7
239000002775 capsule Substances 0.000 description 7
239000000463 material Substances 0.000 description 7
239000012299 nitrogen atmosphere Substances 0.000 description 7
ANOUKFYBOAKOIR-UHFFFAOYSA-N 3,4-dimethoxyphenylethylamine Chemical compound COC1=CC=C(CCN)C=C1OC ANOUKFYBOAKOIR-UHFFFAOYSA-N 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
239000008346 aqueous phase Substances 0.000 description 6
HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 6
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
229910000041 hydrogen chloride Inorganic materials 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
NCPXQVVMIXIKTN-UHFFFAOYSA-N trisodium;phosphite Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])[O-] NCPXQVVMIXIKTN-UHFFFAOYSA-N 0.000 description 6
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 5
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 5
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical class ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
239000000872 buffer Substances 0.000 description 5
239000008187 granular material Substances 0.000 description 5
238000004128 high performance liquid chromatography Methods 0.000 description 5
239000007788 liquid Substances 0.000 description 5
239000000546 pharmaceutical excipient Substances 0.000 description 5
239000011734 sodium Substances 0.000 description 5
229910052708 sodium Inorganic materials 0.000 description 5
229910000029 sodium carbonate Inorganic materials 0.000 description 5
PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 4
JFAASIIJRHQHSF-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclopropyl]-6-methoxy-2-methyl-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound C1=2C=C(O)C(OC)=CC=2CCN(C)C1C1(C=2C(=CC=CC=2)Cl)CC1 JFAASIIJRHQHSF-UHFFFAOYSA-N 0.000 description 4
IBYHHJPAARCAIE-UHFFFAOYSA-N 1-bromo-2-chloroethane Chemical compound ClCCBr IBYHHJPAARCAIE-UHFFFAOYSA-N 0.000 description 4
SVSUIHVKXBTVBI-UHFFFAOYSA-N 1-phenylcyclobutane-1-carbonyl chloride Chemical compound C=1C=CC=CC=1C1(C(=O)Cl)CCC1 SVSUIHVKXBTVBI-UHFFFAOYSA-N 0.000 description 4
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 4
DIVQKHQLANKJQO-UHFFFAOYSA-N 3-methoxytyramine Chemical compound COC1=CC(CCN)=CC=C1O DIVQKHQLANKJQO-UHFFFAOYSA-N 0.000 description 4
LTPVSOCPYWDIFU-UHFFFAOYSA-N 4-methoxyphenylethylamine Chemical compound COC1=CC=C(CCN)C=C1 LTPVSOCPYWDIFU-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
241001091551 Clio Species 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
230000036592 analgesia Effects 0.000 description 4
229910052786 argon Inorganic materials 0.000 description 4
239000002585 base Substances 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 4
239000003638 chemical reducing agent Substances 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
IPIVAXLHTVNRBS-UHFFFAOYSA-N decanoyl chloride Chemical compound CCCCCCCCCC(Cl)=O IPIVAXLHTVNRBS-UHFFFAOYSA-N 0.000 description 4
ZRRLFMPOAYZELW-UHFFFAOYSA-N disodium;hydrogen phosphite Chemical compound [Na+].[Na+].OP([O-])[O-] ZRRLFMPOAYZELW-UHFFFAOYSA-N 0.000 description 4
239000011521 glass Substances 0.000 description 4
SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 4
239000001117 sulphuric acid Substances 0.000 description 4
235000011149 sulphuric acid Nutrition 0.000 description 4
239000006228 supernatant Substances 0.000 description 4
239000000829 suppository Substances 0.000 description 4
YONLFQNRGZXBBF-ZIAGYGMSSA-N (2r,3r)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@@H](C(=O)O)[C@@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-ZIAGYGMSSA-N 0.000 description 3
VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 3
DZXGBZNKQQMGSE-UHFFFAOYSA-N 1-(4-chlorophenyl)cyclobutane-1-carbonyl chloride Chemical compound C=1C=C(Cl)C=CC=1C1(C(=O)Cl)CCC1 DZXGBZNKQQMGSE-UHFFFAOYSA-N 0.000 description 3
XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 3
OCQAXYHNMWVLRH-UHFFFAOYSA-N 2,3-dibenzoyl-2,3-dihydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(O)(C(O)=O)C(O)(C(=O)O)C(=O)C1=CC=CC=C1 OCQAXYHNMWVLRH-UHFFFAOYSA-N 0.000 description 3
RRYLJVQKSZWVQA-UHFFFAOYSA-N 2-(3-chloro-4-methoxyphenyl)ethanamine Chemical compound COC1=CC=C(CCN)C=C1Cl RRYLJVQKSZWVQA-UHFFFAOYSA-N 0.000 description 3
OPGMJXDCEQHKQD-UHFFFAOYSA-N 2-(3-methoxy-4-phenylmethoxyphenyl)ethanamine;hydrochloride Chemical compound Cl.COC1=CC(CCN)=CC=C1OCC1=CC=CC=C1 OPGMJXDCEQHKQD-UHFFFAOYSA-N 0.000 description 3
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
101710114762 50S ribosomal protein L11, chloroplastic Proteins 0.000 description 3
101100325793 Arabidopsis thaliana BCA2 gene Proteins 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
239000005708 Sodium hypochlorite Substances 0.000 description 3
239000007983 Tris buffer Substances 0.000 description 3
HBVDEXCJALUQMJ-UHFFFAOYSA-N [1-[1-(2-chlorophenyl)cyclopropyl]-6-fluoro-2-methyl-3,4-dihydro-1h-isoquinolin-7-yl] decanoate Chemical compound CN1CCC=2C=C(F)C(OC(=O)CCCCCCCCC)=CC=2C1C1(C=2C(=CC=CC=2)Cl)CC1 HBVDEXCJALUQMJ-UHFFFAOYSA-N 0.000 description 3
239000007900 aqueous suspension Substances 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
150000001735 carboxylic acids Chemical class 0.000 description 3
238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
238000010908 decantation Methods 0.000 description 3
MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
239000002702 enteric coating Substances 0.000 description 3
238000009505 enteric coating Methods 0.000 description 3
125000001033 ether group Chemical group 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
239000008101 lactose Substances 0.000 description 3
238000004811 liquid chromatography Methods 0.000 description 3
229910052744 lithium Inorganic materials 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
230000011987 methylation Effects 0.000 description 3
238000007069 methylation reaction Methods 0.000 description 3
239000008188 pellet Substances 0.000 description 3
239000001267 polyvinylpyrrolidone Substances 0.000 description 3
229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
238000001556 precipitation Methods 0.000 description 3
238000002953 preparative HPLC Methods 0.000 description 3
SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 3
239000006188 syrup Substances 0.000 description 3
235000020357 syrup Nutrition 0.000 description 3
UWYZHKAOTLEWKK-UHFFFAOYSA-N tetrahydro-isoquinoline Natural products C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 3
125000003944 tolyl group Chemical group 0.000 description 3
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
GDVIDBDQSYVBSD-UHFFFAOYSA-N 1,3-diiodo-2,2-dimethylpropane Chemical compound ICC(C)(C)CI GDVIDBDQSYVBSD-UHFFFAOYSA-N 0.000 description 2
RCLWNOHFLKPNEE-UHFFFAOYSA-N 1-(2-methoxyphenyl)-n-[2-(3-methoxy-4-phenylmethoxyphenyl)ethyl]cyclopropane-1-carboxamide Chemical compound C=1C=C(OCC=2C=CC=CC=2)C(OC)=CC=1CCNC(=O)C1(C=2C(=CC=CC=2)OC)CC1 RCLWNOHFLKPNEE-UHFFFAOYSA-N 0.000 description 2
VUEKQWHCWVLVDY-UHFFFAOYSA-N 1-(2-methoxyphenyl)cyclopropane-1-carbonitrile Chemical compound COC1=CC=CC=C1C1(C#N)CC1 VUEKQWHCWVLVDY-UHFFFAOYSA-N 0.000 description 2
OFNKZXXMJFWXBK-UHFFFAOYSA-N 1-(2-methoxyphenyl)cyclopropane-1-carbonyl chloride Chemical compound COC1=CC=CC=C1C1(C(Cl)=O)CC1 OFNKZXXMJFWXBK-UHFFFAOYSA-N 0.000 description 2
CZPYUTXQDVNAFL-UHFFFAOYSA-N 1-(2-methoxyphenyl)cyclopropane-1-carboxylic acid Chemical compound COC1=CC=CC=C1C1(C(O)=O)CC1 CZPYUTXQDVNAFL-UHFFFAOYSA-N 0.000 description 2
AZCOFCSZMYBQSA-UHFFFAOYSA-N 1-[1-(2,4-dichlorophenyl)cyclopropyl]-6-fluoro-7-methoxy-2-methyl-3,4-dihydro-1h-isoquinoline Chemical compound CN1CCC=2C=C(F)C(OC)=CC=2C1C1(C=2C(=CC(Cl)=CC=2)Cl)CC1 AZCOFCSZMYBQSA-UHFFFAOYSA-N 0.000 description 2
NBOTTXDUXPXYPD-UHFFFAOYSA-N 1-[1-(2-bromophenyl)cyclobutyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-1h-isoquinoline Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(C)C1C1(C=2C(=CC=CC=2)Br)CCC1 NBOTTXDUXPXYPD-UHFFFAOYSA-N 0.000 description 2
RGPKMRFPELCRDF-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)-3,3-dimethylcyclobutyl]-6-methoxy-1,2,3,4-tetrahydroisoquinolin-7-ol Chemical compound C1=2C=C(O)C(OC)=CC=2CCNC1C1(C=2C(=CC=CC=2)Cl)CC(C)(C)C1 RGPKMRFPELCRDF-UHFFFAOYSA-N 0.000 description 2
QICYWVYJKOUWST-UHFFFAOYSA-M 1-[1-(2-chlorophenyl)cyclopentyl]-6-methoxy-2-methyl-7-phenylmethoxy-3,4-dihydroisoquinolin-2-ium;iodide Chemical compound [I-].COC1=CC=2CC[N+](C)=C(C3(CCCC3)C=3C(=CC=CC=3)Cl)C=2C=C1OCC1=CC=CC=C1 QICYWVYJKOUWST-UHFFFAOYSA-M 0.000 description 2
YDWXMBNXHTXUAX-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclopropyl]-2,6-dimethyl-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound CN1CCC2=CC(C)=C(O)C=C2C1C1(C=2C(=CC=CC=2)Cl)CC1 YDWXMBNXHTXUAX-UHFFFAOYSA-N 0.000 description 2
ZKQBFKLUIWKISD-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclopropyl]-6-fluoro-2-methyl-3,4-dihydro-1h-isoquinolin-7-ol;hydrobromide Chemical compound Br.CN1CCC2=CC(F)=C(O)C=C2C1C1(C=2C(=CC=CC=2)Cl)CC1 ZKQBFKLUIWKISD-UHFFFAOYSA-N 0.000 description 2
OTVXCOMXQONLIR-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclopropyl]-6-fluoro-7-methoxy-3,4-dihydroisoquinoline Chemical compound N=1CCC=2C=C(F)C(OC)=CC=2C=1C1(C=2C(=CC=CC=2)Cl)CC1 OTVXCOMXQONLIR-UHFFFAOYSA-N 0.000 description 2
DTTYIQOJWOVAGD-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclopropyl]-6-methoxy-2-(2-methoxyethyl)-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound COCCN1CCC2=CC(OC)=C(O)C=C2C1C1(C=2C(=CC=CC=2)Cl)CC1 DTTYIQOJWOVAGD-UHFFFAOYSA-N 0.000 description 2
PVDQOHXYHSIAFZ-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclopropyl]-6-methoxy-2-methyl-3,4-dihydro-1h-isoquinolin-7-ol;hydrobromide Chemical compound Br.C1=2C=C(O)C(OC)=CC=2CCN(C)C1C1(C=2C(=CC=CC=2)Cl)CC1 PVDQOHXYHSIAFZ-UHFFFAOYSA-N 0.000 description 2
YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 2
KZFLDUJYFFFLRT-UHFFFAOYSA-N 1-naphthalen-1-ylcyclopropane-1-carbonitrile Chemical compound C=1C=CC2=CC=CC=C2C=1C1(C#N)CC1 KZFLDUJYFFFLRT-UHFFFAOYSA-N 0.000 description 2
KLQLFEXYCVHSTO-UHFFFAOYSA-N 1-naphthalen-1-ylcyclopropane-1-carbonyl chloride Chemical compound C=1C=CC2=CC=CC=C2C=1C1(C(=O)Cl)CC1 KLQLFEXYCVHSTO-UHFFFAOYSA-N 0.000 description 2
OUJODVKEBCXFEI-UHFFFAOYSA-N 1-naphthalen-1-ylcyclopropane-1-carboxylic acid Chemical compound C=1C=CC2=CC=CC=C2C=1C1(C(=O)O)CC1 OUJODVKEBCXFEI-UHFFFAOYSA-N 0.000 description 2
MRDUURPIPLIGQX-UHFFFAOYSA-N 2-(2-chlorophenyl)acetonitrile Chemical compound ClC1=CC=CC=C1CC#N MRDUURPIPLIGQX-UHFFFAOYSA-N 0.000 description 2
GLMWLELOJCRYRI-UHFFFAOYSA-N 2-(3-methoxy-4-phenylmethoxyphenyl)ethanamine Chemical compound COC1=CC(CCN)=CC=C1OCC1=CC=CC=C1 GLMWLELOJCRYRI-UHFFFAOYSA-N 0.000 description 2
KRFPNQWLMKNFHY-UHFFFAOYSA-M 2-[1-(6,7-dimethoxy-2-methyl-3,4-dihydroisoquinolin-2-ium-1-yl)cyclobutyl]benzonitrile;iodide Chemical compound [I-].C1=2C=C(OC)C(OC)=CC=2CC[N+](C)=C1C1(C=2C(=CC=CC=2)C#N)CCC1 KRFPNQWLMKNFHY-UHFFFAOYSA-M 0.000 description 2
125000004746 2-methylpropyloxycarbonyl group Chemical group CC(COC(=O)*)C 0.000 description 2
CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 2
101710142585 50S ribosomal protein 6, chloroplastic Proteins 0.000 description 2
101710082414 50S ribosomal protein L12, chloroplastic Proteins 0.000 description 2
101710164994 50S ribosomal protein L13, chloroplastic Proteins 0.000 description 2
101710177347 50S ribosomal protein L15, chloroplastic Proteins 0.000 description 2
101710125690 50S ribosomal protein L17, chloroplastic Proteins 0.000 description 2
101710149636 50S ribosomal protein L18, chloroplastic Proteins 0.000 description 2
101710087140 50S ribosomal protein L22, chloroplastic Proteins 0.000 description 2
101710139119 50S ribosomal protein L27, chloroplastic Proteins 0.000 description 2
101710166678 50S ribosomal protein L28, chloroplastic Proteins 0.000 description 2
101710121741 50S ribosomal protein L29, chloroplastic Proteins 0.000 description 2
101710115003 50S ribosomal protein L31, chloroplastic Proteins 0.000 description 2
DLOVJKVPOHJCHW-UHFFFAOYSA-N 6-chloro-1-[1-(4-chlorophenyl)cyclobutyl]-2-methyl-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound CN1CCC2=CC(Cl)=C(O)C=C2C1C1(C=2C=CC(Cl)=CC=2)CCC1 DLOVJKVPOHJCHW-UHFFFAOYSA-N 0.000 description 2
FBDWPNJMNWWSBY-UHFFFAOYSA-N 6-methoxy-1-[1-(2-methoxyphenyl)cyclopropyl]-7-phenylmethoxy-3,4-dihydroisoquinoline Chemical compound COC1=CC=2CCN=C(C3(CC3)C=3C(=CC=CC=3)OC)C=2C=C1OCC1=CC=CC=C1 FBDWPNJMNWWSBY-UHFFFAOYSA-N 0.000 description 2
MBLGDJPFOMNQTN-UHFFFAOYSA-N 6-methoxy-2-methyl-1-(1-phenylcyclobutyl)-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound C1=2C=C(O)C(OC)=CC=2CCN(C)C1C1(C=2C=CC=CC=2)CCC1 MBLGDJPFOMNQTN-UHFFFAOYSA-N 0.000 description 2
IAAVLAMKIFPECU-UHFFFAOYSA-N 6-methoxy-2-methyl-1-[1-(2-methylsulfanylphenyl)cyclobutyl]-7-phenylmethoxy-3,4-dihydro-1h-isoquinoline Chemical compound COC1=CC=2CCN(C)C(C3(CCC3)C=3C(=CC=CC=3)SC)C=2C=C1OCC1=CC=CC=C1 IAAVLAMKIFPECU-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
102100033040 Carbonic anhydrase 12 Human genes 0.000 description 2
102100033041 Carbonic anhydrase 13 Human genes 0.000 description 2
102100033007 Carbonic anhydrase 14 Human genes 0.000 description 2
102100032566 Carbonic anhydrase-related protein 10 Human genes 0.000 description 2
102100033029 Carbonic anhydrase-related protein 11 Human genes 0.000 description 2
229920000623 Cellulose acetate phthalate Polymers 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
101150049660 DRD2 gene Proteins 0.000 description 2
102100034323 Disintegrin and metalloproteinase domain-containing protein 2 Human genes 0.000 description 2
108050004812 Dopamine receptor Proteins 0.000 description 2
102000015554 Dopamine receptor Human genes 0.000 description 2
101000867855 Homo sapiens Carbonic anhydrase 12 Proteins 0.000 description 2
101000867860 Homo sapiens Carbonic anhydrase 13 Proteins 0.000 description 2
101000867862 Homo sapiens Carbonic anhydrase 14 Proteins 0.000 description 2
101000867836 Homo sapiens Carbonic anhydrase-related protein 10 Proteins 0.000 description 2
101000867841 Homo sapiens Carbonic anhydrase-related protein 11 Proteins 0.000 description 2
101000780288 Homo sapiens Disintegrin and metalloproteinase domain-containing protein 2 Proteins 0.000 description 2
101001075218 Homo sapiens Gastrokine-1 Proteins 0.000 description 2
101001057156 Homo sapiens Melanoma-associated antigen C2 Proteins 0.000 description 2
101000874141 Homo sapiens Probable ATP-dependent RNA helicase DDX43 Proteins 0.000 description 2
101000821981 Homo sapiens Sarcoma antigen 1 Proteins 0.000 description 2
LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
235000019759 Maize starch Nutrition 0.000 description 2
102100027252 Melanoma-associated antigen C2 Human genes 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
102100035724 Probable ATP-dependent RNA helicase DDX43 Human genes 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
102100021466 Sarcoma antigen 1 Human genes 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
101001075055 Spinacia oleracea 50S ribosomal protein L19, chloroplastic Proteins 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
BQAQHVQZFVHTNZ-UHFFFAOYSA-N [1-[1-(2-chlorophenyl)cyclobutyl]-6-fluoro-2-methyl-3,4-dihydro-1h-isoquinolin-7-yl] decanoate Chemical compound CN1CCC=2C=C(F)C(OC(=O)CCCCCCCCC)=CC=2C1C1(C=2C(=CC=CC=2)Cl)CCC1 BQAQHVQZFVHTNZ-UHFFFAOYSA-N 0.000 description 2
VBKOIMOYANNPFE-UHFFFAOYSA-N [1-[1-(2-chlorophenyl)cyclopropyl]-6-methoxy-2-methyl-3,4-dihydro-1h-isoquinolin-7-yl] hexadecanoate Chemical compound CN1CCC=2C=C(OC)C(OC(=O)CCCCCCCCCCCCCCC)=CC=2C1C1(C=2C(=CC=CC=2)Cl)CC1 VBKOIMOYANNPFE-UHFFFAOYSA-N 0.000 description 2
ZVXVWCGNWQEEMF-UHFFFAOYSA-N [1-[1-(2-chlorophenyl)cyclopropyl]-6-methoxy-2-methyl-3,4-dihydro-1h-isoquinolin-7-yl] octadecanoate Chemical compound CN1CCC=2C=C(OC)C(OC(=O)CCCCCCCCCCCCCCCCC)=CC=2C1C1(C=2C(=CC=CC=2)Cl)CC1 ZVXVWCGNWQEEMF-UHFFFAOYSA-N 0.000 description 2
HFEHLDPGIKPNKL-UHFFFAOYSA-N allyl iodide Chemical compound ICC=C HFEHLDPGIKPNKL-UHFFFAOYSA-N 0.000 description 2
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
229910000085 borane Inorganic materials 0.000 description 2
MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 2
229940081734 cellulose acetate phthalate Drugs 0.000 description 2
150000001805 chlorine compounds Chemical class 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
239000013256 coordination polymer Substances 0.000 description 2
239000013078 crystal Substances 0.000 description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
239000011928 denatured alcohol Substances 0.000 description 2
FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical class CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
238000000921 elemental analysis Methods 0.000 description 2
239000012530 fluid Substances 0.000 description 2
238000009472 formulation Methods 0.000 description 2
238000001030 gas--liquid chromatography Methods 0.000 description 2
239000007903 gelatin capsule Substances 0.000 description 2
238000011534 incubation Methods 0.000 description 2
238000001802 infusion Methods 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
230000014759 maintenance of location Effects 0.000 description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
239000000155 melt Substances 0.000 description 2
229910017604 nitric acid Inorganic materials 0.000 description 2
125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
239000002245 particle Substances 0.000 description 2
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
239000012265 solid product Substances 0.000 description 2
239000011877 solvent mixture Substances 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
238000013268 sustained release Methods 0.000 description 2
239000012730 sustained-release form Substances 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
238000011200 topical administration Methods 0.000 description 2
239000012049 topical pharmaceutical composition Substances 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 2
238000005406 washing Methods 0.000 description 2
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
PDJQCHVMABBNQW-MIXQCLKLSA-L (1z,5z)-cycloocta-1,5-diene;rhodium;dichloride Chemical compound [Cl-].[Cl-].[Rh].[Rh].C\1C\C=C/CC\C=C/1.C\1C\C=C/CC\C=C/1 PDJQCHVMABBNQW-MIXQCLKLSA-L 0.000 description 1
CYHMKGIVLYBEFY-UHFFFAOYSA-N (2-methylsulfanylphenyl)methanol Chemical compound CSC1=CC=CC=C1CO CYHMKGIVLYBEFY-UHFFFAOYSA-N 0.000 description 1
OCQAXYHNMWVLRH-ROUUACIJSA-N (2s,3s)-2,3-dibenzoyl-2,3-dihydroxybutanedioic acid Chemical class O=C([C@](O)(C(=O)O)[C@@](O)(C(O)=O)C(=O)C=1C=CC=CC=1)C1=CC=CC=C1 OCQAXYHNMWVLRH-ROUUACIJSA-N 0.000 description 1
GOTMKOSCLKVOGG-OAHLLOKOSA-N (5R)-8-chloro-3-methyl-5-phenyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol Chemical compound C1([C@@H]2C3=CC(O)=C(Cl)C=C3CCN(C2)C)=CC=CC=C1 GOTMKOSCLKVOGG-OAHLLOKOSA-N 0.000 description 1
BGRJTUBHPOOWDU-NSHDSACASA-N (S)-(-)-sulpiride Chemical compound CCN1CCC[C@H]1CNC(=O)C1=CC(S(N)(=O)=O)=CC=C1OC BGRJTUBHPOOWDU-NSHDSACASA-N 0.000 description 1
IOEPOEDBBPRAEI-UHFFFAOYSA-N 1,2-dihydroisoquinoline Chemical compound C1=CC=C2CNC=CC2=C1 IOEPOEDBBPRAEI-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 1
CXMPUDXYQDLRPF-UHFFFAOYSA-N 1-(2,3-dihydro-1-benzofuran-7-yl)cyclopropane-1-carbonitrile Chemical compound C=1C=CC=2CCOC=2C=1C1(C#N)CC1 CXMPUDXYQDLRPF-UHFFFAOYSA-N 0.000 description 1
DLKDGBXWTWCJTA-UHFFFAOYSA-N 1-(2,3-dihydro-1-benzofuran-7-yl)cyclopropane-1-carboxylic acid Chemical compound C=1C=CC=2CCOC=2C=1C1(C(=O)O)CC1 DLKDGBXWTWCJTA-UHFFFAOYSA-N 0.000 description 1
FYUGFGAZAXNWND-UHFFFAOYSA-N 1-(2,4-dichlorophenyl)-n-[2-(3-fluoro-4-methoxyphenyl)ethyl]cyclopropane-1-carboxamide Chemical compound C1=C(F)C(OC)=CC=C1CCNC(=O)C1(C=2C(=CC(Cl)=CC=2)Cl)CC1 FYUGFGAZAXNWND-UHFFFAOYSA-N 0.000 description 1
MJKYYHUTSFNMGZ-UHFFFAOYSA-N 1-(2-chlorophenyl)-2,2-dimethylcyclobutane-1-carbonitrile Chemical compound CC1(C)CCC1(C#N)C1=CC=CC=C1Cl MJKYYHUTSFNMGZ-UHFFFAOYSA-N 0.000 description 1
RPXXLTHKTZKNRY-UHFFFAOYSA-N 1-(2-chlorophenyl)-n-[2-(4-methoxy-3-methylphenyl)ethyl]cyclopropane-1-carboxamide Chemical compound C1=C(C)C(OC)=CC=C1CCNC(=O)C1(C=2C(=CC=CC=2)Cl)CC1 RPXXLTHKTZKNRY-UHFFFAOYSA-N 0.000 description 1
CUAMRXCKUHKQDK-UHFFFAOYSA-N 1-(2-chlorophenyl)-n-[2-(4-methoxy-3-phenylphenyl)ethyl]cyclobutane-1-carboxamide Chemical compound C1=C(C=2C=CC=CC=2)C(OC)=CC=C1CCNC(=O)C1(C=2C(=CC=CC=2)Cl)CCC1 CUAMRXCKUHKQDK-UHFFFAOYSA-N 0.000 description 1
LLPLRZGMYMYZMF-UHFFFAOYSA-N 1-(2-chlorophenyl)-n-[2-(4-methoxyphenyl)ethyl]cyclopropane-1-carboxamide Chemical compound C1=CC(OC)=CC=C1CCNC(=O)C1(C=2C(=CC=CC=2)Cl)CC1 LLPLRZGMYMYZMF-UHFFFAOYSA-N 0.000 description 1
MVIWGPPSRRVDIU-UHFFFAOYSA-N 1-(2-chlorophenyl)cyclopropane-1-carbonyl chloride Chemical compound C=1C=CC=C(Cl)C=1C1(C(=O)Cl)CC1 MVIWGPPSRRVDIU-UHFFFAOYSA-N 0.000 description 1
GAOPRYSAZAKGGF-UHFFFAOYSA-N 1-(2-methylsulfanylphenyl)cyclobutane-1-carboxylic acid Chemical compound CSC1=CC=CC=C1C1(C(O)=O)CCC1 GAOPRYSAZAKGGF-UHFFFAOYSA-N 0.000 description 1
XYSRHOKREWGGFE-UHFFFAOYSA-N 1-(4-chlorophenyl)cyclobutane-1-carboxylic acid Chemical compound C=1C=C(Cl)C=CC=1C1(C(=O)O)CCC1 XYSRHOKREWGGFE-UHFFFAOYSA-N 0.000 description 1
KKMVJOZLYNVVSK-UHFFFAOYSA-N 1-(4-methoxyphenyl)cyclobutane-1-carbonitrile Chemical compound C1=CC(OC)=CC=C1C1(C#N)CCC1 KKMVJOZLYNVVSK-UHFFFAOYSA-N 0.000 description 1
MGGREZZPMDSBIA-UHFFFAOYSA-N 1-(4-methoxyphenyl)cyclobutane-1-carbonyl chloride Chemical compound C1=CC(OC)=CC=C1C1(C(Cl)=O)CCC1 MGGREZZPMDSBIA-UHFFFAOYSA-N 0.000 description 1
FKPWMQWXYOZELT-UHFFFAOYSA-N 1-(4-methoxyphenyl)cyclobutane-1-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C1(C(O)=O)CCC1 FKPWMQWXYOZELT-UHFFFAOYSA-N 0.000 description 1
INHNXVKDZSOCRH-UHFFFAOYSA-N 1-[1-(2,3-dihydro-1-benzofuran-7-yl)cyclopropyl]-6-methoxy-7-phenylmethoxy-3,4-dihydroisoquinoline Chemical compound COC1=CC=2CCN=C(C3(CC3)C=3C=4OCCC=4C=CC=3)C=2C=C1OCC1=CC=CC=C1 INHNXVKDZSOCRH-UHFFFAOYSA-N 0.000 description 1
WBOPWXISNRSBCS-UHFFFAOYSA-N 1-[1-(2,4-dichlorophenyl)cyclobutyl]-2-methyl-3,4-dihydro-1h-isoquinoline-6,7-diol Chemical compound CN1CCC2=CC(O)=C(O)C=C2C1C1(C=2C(=CC(Cl)=CC=2)Cl)CCC1 WBOPWXISNRSBCS-UHFFFAOYSA-N 0.000 description 1
VOAPDEGPMKKTOZ-UHFFFAOYSA-N 1-[1-(2,4-dichlorophenyl)cyclobutyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline Chemical compound C1=2C=C(OC)C(OC)=CC=2CCNC1C1(C=2C(=CC(Cl)=CC=2)Cl)CCC1 VOAPDEGPMKKTOZ-UHFFFAOYSA-N 0.000 description 1
NTBMIRATQMQCGL-UHFFFAOYSA-N 1-[1-(2,4-dichlorophenyl)cyclobutyl]-6-methoxy-2-methyl-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound C1=2C=C(O)C(OC)=CC=2CCN(C)C1C1(C=2C(=CC(Cl)=CC=2)Cl)CCC1 NTBMIRATQMQCGL-UHFFFAOYSA-N 0.000 description 1
CFIPGNVCJHAVLT-UHFFFAOYSA-N 1-[1-(2,4-dichlorophenyl)cyclopropyl]-6-fluoro-7-methoxy-3,4-dihydroisoquinoline Chemical compound N=1CCC=2C=C(F)C(OC)=CC=2C=1C1(C=2C(=CC(Cl)=CC=2)Cl)CC1 CFIPGNVCJHAVLT-UHFFFAOYSA-N 0.000 description 1
QRVPXDZQJLZKSL-UHFFFAOYSA-N 1-[1-(2-bromo-4,5-dimethoxyphenyl)cyclobutyl]-6-methoxy-2-methyl-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound C1=2C=C(O)C(OC)=CC=2CCN(C)C1C1(C=2C(=CC(OC)=C(OC)C=2)Br)CCC1 QRVPXDZQJLZKSL-UHFFFAOYSA-N 0.000 description 1
JEVUCIUAEIQQCK-UHFFFAOYSA-N 1-[1-(2-bromophenyl)cyclobutyl]-2-methyl-3,4-dihydro-1h-isoquinoline-6,7-diol Chemical compound CN1CCC2=CC(O)=C(O)C=C2C1C1(C=2C(=CC=CC=2)Br)CCC1 JEVUCIUAEIQQCK-UHFFFAOYSA-N 0.000 description 1
XQLPLVYQZXJYEW-UHFFFAOYSA-N 1-[1-(2-bromophenyl)cyclobutyl]-6,7-dimethoxy-3,4-dihydro-2h-quinoline Chemical compound C1=2C=C(OC)C(OC)=CC=2CCCN1C1(C=2C(=CC=CC=2)Br)CCC1 XQLPLVYQZXJYEW-UHFFFAOYSA-N 0.000 description 1
BUDGHUOHDMVBCJ-UHFFFAOYSA-N 1-[1-(2-bromophenyl)cyclobutyl]-6-chloro-7-methoxy-3,4-dihydroisoquinoline Chemical compound N=1CCC=2C=C(Cl)C(OC)=CC=2C=1C1(C=2C(=CC=CC=2)Br)CCC1 BUDGHUOHDMVBCJ-UHFFFAOYSA-N 0.000 description 1
SLJPRXUSDKLFBF-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)-3,3-dimethylcyclobutyl]-6-methoxy-2-methyl-3,4-dihydro-1h-isoquinolin-7-ol;hydrobromide Chemical compound Br.C1=2C=C(O)C(OC)=CC=2CCN(C)C1C1(C=2C(=CC=CC=2)Cl)CC(C)(C)C1 SLJPRXUSDKLFBF-UHFFFAOYSA-N 0.000 description 1
QXBVLBFFLNWPOJ-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclobutyl]-2,6-dimethyl-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound CN1CCC2=CC(C)=C(O)C=C2C1C1(C=2C(=CC=CC=2)Cl)CCC1 QXBVLBFFLNWPOJ-UHFFFAOYSA-N 0.000 description 1
BUCITZKLVIJZGE-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclobutyl]-2-methyl-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound CN1CCC2=CC=C(O)C=C2C1C1(C=2C(=CC=CC=2)Cl)CCC1 BUCITZKLVIJZGE-UHFFFAOYSA-N 0.000 description 1
RTRXVWHVNZGEFI-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclobutyl]-2-methyl-3,4-dihydro-1h-isoquinoline-6,7-diol Chemical compound CN1CCC2=CC(O)=C(O)C=C2C1C1(C=2C(=CC=CC=2)Cl)CCC1 RTRXVWHVNZGEFI-UHFFFAOYSA-N 0.000 description 1
IOTSVMBIDHHGAO-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclobutyl]-6-fluoro-2-methyl-3,4-dihydro-1h-isoquinolin-7-ol;hydrobromide Chemical compound Br.CN1CCC2=CC(F)=C(O)C=C2C1C1(C=2C(=CC=CC=2)Cl)CCC1 IOTSVMBIDHHGAO-UHFFFAOYSA-N 0.000 description 1
HRLLEHQHEFYEOO-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclobutyl]-6-methoxy-2-methyl-3,4-dihydro-1h-isoquinolin-7-ol;hydrobromide Chemical compound Br.C1=2C=C(O)C(OC)=CC=2CCN(C)C1C1(C=2C(=CC=CC=2)Cl)CCC1 HRLLEHQHEFYEOO-UHFFFAOYSA-N 0.000 description 1
TYCQRGVDRPELES-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclobutyl]-7-methoxy-2,6-dimethyl-3,4-dihydro-1h-isoquinoline Chemical compound CN1CCC=2C=C(C)C(OC)=CC=2C1C1(C=2C(=CC=CC=2)Cl)CCC1 TYCQRGVDRPELES-UHFFFAOYSA-N 0.000 description 1
UAFZMWOEELHHJW-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclopentyl]-6-methoxy-2-methyl-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound C1=2C=C(O)C(OC)=CC=2CCN(C)C1C1(C=2C(=CC=CC=2)Cl)CCCC1 UAFZMWOEELHHJW-UHFFFAOYSA-N 0.000 description 1
CHHCISQLILYTHB-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclopentyl]-6-methoxy-7-phenylmethoxy-3,4-dihydroisoquinoline Chemical compound COC1=CC=2CCN=C(C3(CCCC3)C=3C(=CC=CC=3)Cl)C=2C=C1OCC1=CC=CC=C1 CHHCISQLILYTHB-UHFFFAOYSA-N 0.000 description 1
SJCNROKNZQINIY-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclopropyl]-2,6-dimethyl-3,4-dihydro-1h-isoquinolin-7-ol;hydrochloride Chemical compound Cl.CN1CCC2=CC(C)=C(O)C=C2C1C1(C=2C(=CC=CC=2)Cl)CC1 SJCNROKNZQINIY-UHFFFAOYSA-N 0.000 description 1
DPEUTFNJTFKRHQ-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclopropyl]-2-(2-hydroxyethyl)-6-methoxy-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound C1=2C=C(O)C(OC)=CC=2CCN(CCO)C1C1(C=2C(=CC=CC=2)Cl)CC1 DPEUTFNJTFKRHQ-UHFFFAOYSA-N 0.000 description 1
GANDKDRMCAVQMT-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclopropyl]-6-methoxy-2-(2-methoxyethyl)-7-phenylmethoxy-3,4-dihydro-1h-isoquinoline Chemical compound C1=C2C(C3(CC3)C=3C(=CC=CC=3)Cl)N(CCOC)CCC2=CC(OC)=C1OCC1=CC=CC=C1 GANDKDRMCAVQMT-UHFFFAOYSA-N 0.000 description 1
AJEUWOIWAAFZDI-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclopropyl]-6-methoxy-7-phenylmethoxy-1,2,3,4-tetrahydroisoquinoline Chemical compound COC1=CC=2CCNC(C3(CC3)C=3C(=CC=CC=3)Cl)C=2C=C1OCC1=CC=CC=C1 AJEUWOIWAAFZDI-UHFFFAOYSA-N 0.000 description 1
PKFMOMNEMGOSJQ-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclopropyl]-6-methoxy-7-phenylmethoxy-3,4-dihydroisoquinoline Chemical compound COC1=CC=2CCN=C(C3(CC3)C=3C(=CC=CC=3)Cl)C=2C=C1OCC1=CC=CC=C1 PKFMOMNEMGOSJQ-UHFFFAOYSA-N 0.000 description 1
QGWYWIIRGUNZRQ-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclopropyl]-7-methoxy-1,2,3,4-tetrahydroisoquinoline Chemical compound C12=CC(OC)=CC=C2CCNC1C1(C=2C(=CC=CC=2)Cl)CC1 QGWYWIIRGUNZRQ-UHFFFAOYSA-N 0.000 description 1
HBJQVCNOQMUUKD-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclopropyl]-7-methoxy-2-methyl-3,4-dihydro-1h-isoquinoline Chemical compound C12=CC(OC)=CC=C2CCN(C)C1C1(C=2C(=CC=CC=2)Cl)CC1 HBJQVCNOQMUUKD-UHFFFAOYSA-N 0.000 description 1
LWMCMTIWZWZFEN-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclopropyl]-7-methoxy-6-methyl-1,2,3,4-tetrahydroisoquinoline Chemical compound N1CCC=2C=C(C)C(OC)=CC=2C1C1(C=2C(=CC=CC=2)Cl)CC1 LWMCMTIWZWZFEN-UHFFFAOYSA-N 0.000 description 1
VEWASVARELZPKJ-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)cyclopropyl]-7-methoxy-6-methyl-3,4-dihydroisoquinoline Chemical compound N=1CCC=2C=C(C)C(OC)=CC=2C=1C1(C=2C(=CC=CC=2)Cl)CC1 VEWASVARELZPKJ-UHFFFAOYSA-N 0.000 description 1
IUJVJBVPYOUXQC-UHFFFAOYSA-N 1-[1-(2-fluorophenyl)cyclobutyl]-2-methyl-3,4-dihydro-1h-isoquinoline-6,7-diol Chemical compound CN1CCC2=CC(O)=C(O)C=C2C1C1(C=2C(=CC=CC=2)F)CCC1 IUJVJBVPYOUXQC-UHFFFAOYSA-N 0.000 description 1
VWJOZOYYYWSXPE-UHFFFAOYSA-N 1-[1-(3,4-dichlorophenyl)cyclobutyl]-2-methyl-3,4-dihydro-1h-isoquinoline-6,7-diol Chemical compound CN1CCC2=CC(O)=C(O)C=C2C1C1(C=2C=C(Cl)C(Cl)=CC=2)CCC1 VWJOZOYYYWSXPE-UHFFFAOYSA-N 0.000 description 1
HOWKOUFBOPBVLB-UHFFFAOYSA-N 1-[1-(3-chlorophenyl)cyclobutyl]-2-methyl-3,4-dihydro-1h-isoquinoline-6,7-diol Chemical compound CN1CCC2=CC(O)=C(O)C=C2C1C1(C=2C=C(Cl)C=CC=2)CCC1 HOWKOUFBOPBVLB-UHFFFAOYSA-N 0.000 description 1
ARKGTLXENIGTCE-UHFFFAOYSA-N 1-[1-(4-bromophenyl)cyclobutyl]-2-methyl-3,4-dihydro-1h-isoquinoline-6,7-diol Chemical compound CN1CCC2=CC(O)=C(O)C=C2C1C1(C=2C=CC(Br)=CC=2)CCC1 ARKGTLXENIGTCE-UHFFFAOYSA-N 0.000 description 1
NPFNIUAFERIART-UHFFFAOYSA-N 1-[1-(4-chlorophenyl)cyclobutyl]-2-ethyl-3,4-dihydro-1h-isoquinoline-6,7-diol Chemical compound CCN1CCC2=CC(O)=C(O)C=C2C1C1(C=2C=CC(Cl)=CC=2)CCC1 NPFNIUAFERIART-UHFFFAOYSA-N 0.000 description 1
BMQBQXFYNMNBPT-UHFFFAOYSA-N 1-[1-(4-chlorophenyl)cyclobutyl]-2-methyl-3,4-dihydro-1h-isoquinolin-5-ol Chemical compound CN1CCC2=C(O)C=CC=C2C1C1(C=2C=CC(Cl)=CC=2)CCC1 BMQBQXFYNMNBPT-UHFFFAOYSA-N 0.000 description 1
QNMBHTKXANGKPO-UHFFFAOYSA-N 1-[1-(4-chlorophenyl)cyclobutyl]-2-methyl-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound CN1CCC2=CC=C(O)C=C2C1C1(C=2C=CC(Cl)=CC=2)CCC1 QNMBHTKXANGKPO-UHFFFAOYSA-N 0.000 description 1
SEVXVBKEABUDLR-UHFFFAOYSA-N 1-[1-(4-chlorophenyl)cyclobutyl]-2-methyl-3,4-dihydro-1h-isoquinoline-6,7-diol Chemical compound CN1CCC2=CC(O)=C(O)C=C2C1C1(C=2C=CC(Cl)=CC=2)CCC1 SEVXVBKEABUDLR-UHFFFAOYSA-N 0.000 description 1
GWONLSDGDBUCDN-UHFFFAOYSA-N 1-[1-(4-chlorophenyl)cyclopropyl]-2-methyl-3,4-dihydro-1h-isoquinoline-6,7-diol Chemical compound CN1CCC2=CC(O)=C(O)C=C2C1C1(C=2C=CC(Cl)=CC=2)CC1 GWONLSDGDBUCDN-UHFFFAOYSA-N 0.000 description 1
KEDWGQBVOOBYMV-UHFFFAOYSA-N 1-[1-(4-fluorophenyl)cyclobutyl]-2-methyl-3,4-dihydro-1h-isoquinoline-6,7-diol Chemical compound CN1CCC2=CC(O)=C(O)C=C2C1C1(C=2C=CC(F)=CC=2)CCC1 KEDWGQBVOOBYMV-UHFFFAOYSA-N 0.000 description 1
CJBMESUMDHAYMR-UHFFFAOYSA-N 1-[1-(4-hydroxyphenyl)cyclopentyl]-2-methyl-3,4-dihydro-1h-isoquinoline-6,7-diol Chemical compound CN1CCC2=CC(O)=C(O)C=C2C1C1(C=2C=CC(O)=CC=2)CCCC1 CJBMESUMDHAYMR-UHFFFAOYSA-N 0.000 description 1
OEIXASDDYLPZFJ-UHFFFAOYSA-N 1-[3-(trifluoromethyl)phenyl]cyclobutane-1-carboxylic acid Chemical compound C=1C=CC(C(F)(F)F)=CC=1C1(C(=O)O)CCC1 OEIXASDDYLPZFJ-UHFFFAOYSA-N 0.000 description 1
QNTNAULRPWEWSU-UHFFFAOYSA-N 1-[4-(trifluoromethoxy)phenyl]cyclobutane-1-carbonitrile Chemical compound C1=CC(OC(F)(F)F)=CC=C1C1(C#N)CCC1 QNTNAULRPWEWSU-UHFFFAOYSA-N 0.000 description 1
RHPCYZLXNNRRMB-UHFFFAOYSA-N 1-phenylcyclopentane-1-carboxylic acid Chemical compound C=1C=CC=CC=1C1(C(=O)O)CCCC1 RHPCYZLXNNRRMB-UHFFFAOYSA-N 0.000 description 1
FKZTYZAEVWLXOS-UHFFFAOYSA-N 2,2-dimethyl-1-phenylcyclobutane-1-carbonitrile Chemical compound CC1(C)CCC1(C#N)C1=CC=CC=C1 FKZTYZAEVWLXOS-UHFFFAOYSA-N 0.000 description 1
WUXXIPOWZJYRNE-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-7-ylmethanol Chemical compound OCC1=CC=CC2=C1OCC2 WUXXIPOWZJYRNE-UHFFFAOYSA-N 0.000 description 1
ONTHGZCBSRNOMX-UHFFFAOYSA-N 2-(2,3-dihydro-1-benzofuran-7-yl)acetonitrile Chemical compound N#CCC1=CC=CC2=C1OCC2 ONTHGZCBSRNOMX-UHFFFAOYSA-N 0.000 description 1
KBQRQQFFSGMVHL-UHFFFAOYSA-N 2-(2-chloro-5-methoxyphenyl)acetonitrile Chemical compound COC1=CC=C(Cl)C(CC#N)=C1 KBQRQQFFSGMVHL-UHFFFAOYSA-N 0.000 description 1
CIJBYFPAVIDZBV-UHFFFAOYSA-N 2-(2-chloro-5-methoxyphenyl)ethanamine Chemical compound COC1=CC=C(Cl)C(CCN)=C1 CIJBYFPAVIDZBV-UHFFFAOYSA-N 0.000 description 1
DWJKILXTMUGXOU-UHFFFAOYSA-N 2-(2-methoxyphenyl)acetonitrile Chemical compound COC1=CC=CC=C1CC#N DWJKILXTMUGXOU-UHFFFAOYSA-N 0.000 description 1
CJJOYLKIRJBKNO-UHFFFAOYSA-N 2-(2-methylsulfanylphenyl)acetonitrile Chemical compound CSC1=CC=CC=C1CC#N CJJOYLKIRJBKNO-UHFFFAOYSA-N 0.000 description 1
NRQRIUDYDALEDD-UHFFFAOYSA-N 2-(3-bromo-4-methoxyphenyl)ethanamine;hydrobromide Chemical compound Br.COC1=CC=C(CCN)C=C1Br NRQRIUDYDALEDD-UHFFFAOYSA-N 0.000 description 1
NBFFCNUWKJZAKU-UHFFFAOYSA-N 2-(4-methoxy-3-methylphenyl)ethanamine Chemical compound COC1=CC=C(CCN)C=C1C NBFFCNUWKJZAKU-UHFFFAOYSA-N 0.000 description 1
WQRWSBWIAYYZAD-UHFFFAOYSA-N 2-(4-methoxy-3-phenylphenyl)ethanamine Chemical compound COC1=CC=C(CCN)C=C1C1=CC=CC=C1 WQRWSBWIAYYZAD-UHFFFAOYSA-N 0.000 description 1
GHKLXXBWQJOXKB-UHFFFAOYSA-N 2-(bromomethyl)-1-chloro-4-methoxybenzene Chemical compound COC1=CC=C(Cl)C(CBr)=C1 GHKLXXBWQJOXKB-UHFFFAOYSA-N 0.000 description 1
OQYOKXCHCNOMGN-UHFFFAOYSA-N 2-[1-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)cyclobutyl]benzonitrile Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN=C1C1(C=2C(=CC=CC=2)C#N)CCC1 OQYOKXCHCNOMGN-UHFFFAOYSA-N 0.000 description 1
JZEOPFIZWCNSMY-UHFFFAOYSA-N 2-[1-[1-(2-chlorophenyl)cyclopropyl]-7-methoxy-7-phenylmethoxy-1,3,4,6-tetrahydroisoquinolin-2-yl]ethanol Chemical compound C12=CC(OC)(OCC=3C=CC=CC=3)CC=C2CCN(CCO)C1C1(C=2C(=CC=CC=2)Cl)CC1 JZEOPFIZWCNSMY-UHFFFAOYSA-N 0.000 description 1
KXIZXPRLNNDQKS-UHFFFAOYSA-N 2-[3,4-bis(phenylmethoxy)phenyl]ethanamine;hydron;chloride Chemical compound Cl.C=1C=CC=CC=1COC1=CC(CCN)=CC=C1OCC1=CC=CC=C1 KXIZXPRLNNDQKS-UHFFFAOYSA-N 0.000 description 1
LYFCAROXYJTUQF-UHFFFAOYSA-N 2-[4-(trifluoromethoxy)phenyl]acetonitrile Chemical compound FC(F)(F)OC1=CC=C(CC#N)C=C1 LYFCAROXYJTUQF-UHFFFAOYSA-N 0.000 description 1
LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 1
CRZJPEIBPQWDGJ-UHFFFAOYSA-N 2-chloro-1,1-dimethoxyethane Chemical compound COC(CCl)OC CRZJPEIBPQWDGJ-UHFFFAOYSA-N 0.000 description 1
GDHXJNRAJRCGMX-UHFFFAOYSA-N 2-fluorobenzonitrile Chemical compound FC1=CC=CC=C1C#N GDHXJNRAJRCGMX-UHFFFAOYSA-N 0.000 description 1
DQVUPNADYWHSMY-UHFFFAOYSA-N 2-methyl-1-(1-naphthalen-2-ylcyclobutyl)-3,4-dihydro-1h-isoquinoline-6,7-diol Chemical compound CN1CCC2=CC(O)=C(O)C=C2C1C1(C=2C=C3C=CC=CC3=CC=2)CCC1 DQVUPNADYWHSMY-UHFFFAOYSA-N 0.000 description 1
CRHAHMOYLGYNME-UHFFFAOYSA-N 2-methyl-1-(1-phenylcyclobutyl)-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound CN1CCC2=CC=C(O)C=C2C1C1(C=2C=CC=CC=2)CCC1 CRHAHMOYLGYNME-UHFFFAOYSA-N 0.000 description 1
FUWLNDHWBCXLRC-UHFFFAOYSA-N 2-methyl-1-(1-phenylcyclobutyl)-3,4-dihydro-1h-isoquinoline-6,7-diol Chemical compound CN1CCC2=CC(O)=C(O)C=C2C1C1(C=2C=CC=CC=2)CCC1 FUWLNDHWBCXLRC-UHFFFAOYSA-N 0.000 description 1
SSCOIOMHMRSKGS-UHFFFAOYSA-N 2-methyl-1-(1-phenylcyclohexyl)-3,4-dihydro-1h-isoquinoline-6,7-diol Chemical compound CN1CCC2=CC(O)=C(O)C=C2C1C1(C=2C=CC=CC=2)CCCCC1 SSCOIOMHMRSKGS-UHFFFAOYSA-N 0.000 description 1
GVQFVHDRYSPAFD-UHFFFAOYSA-N 2-methyl-1-(1-phenylcyclopentyl)-3,4-dihydro-1h-isoquinoline-6,7-diol Chemical compound CN1CCC2=CC(O)=C(O)C=C2C1C1(C=2C=CC=CC=2)CCCC1 GVQFVHDRYSPAFD-UHFFFAOYSA-N 0.000 description 1
MOFBNVOUYBSXQY-UHFFFAOYSA-N 2-methyl-1-[1-(2-methylsulfanylphenyl)cyclobutyl]-3,4-dihydro-1h-isoquinoline-6,7-diol;hydrobromide Chemical compound Br.CSC1=CC=CC=C1C1(C2C3=CC(O)=C(O)C=C3CCN2C)CCC1 MOFBNVOUYBSXQY-UHFFFAOYSA-N 0.000 description 1
AXMRKQBRSSDZKG-UHFFFAOYSA-N 2-methyl-1-[1-(4-phenylphenyl)cyclobutyl]-3,4-dihydro-1h-isoquinoline-6,7-diol;hydrochloride Chemical compound Cl.CN1CCC2=CC(O)=C(O)C=C2C1C1(C=2C=CC(=CC=2)C=2C=CC=CC=2)CCC1 AXMRKQBRSSDZKG-UHFFFAOYSA-N 0.000 description 1
OQAPROJVVSPYCC-UHFFFAOYSA-N 2-methyl-1-[1-[3-(trifluoromethyl)phenyl]cyclobutyl]-3,4-dihydro-1h-isoquinoline-6,7-diol Chemical compound CN1CCC2=CC(O)=C(O)C=C2C1C1(C=2C=C(C=CC=2)C(F)(F)F)CCC1 OQAPROJVVSPYCC-UHFFFAOYSA-N 0.000 description 1
WJTYZENYZKZIQD-UHFFFAOYSA-N 2-methyl-6-nitro-1-(1-phenylcyclobutyl)-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound CN1CCC2=CC([N+]([O-])=O)=C(O)C=C2C1C1(C=2C=CC=CC=2)CCC1 WJTYZENYZKZIQD-UHFFFAOYSA-N 0.000 description 1
OQRMWUNUKVUHQO-UHFFFAOYSA-N 2-naphthalen-1-ylacetonitrile Chemical compound C1=CC=C2C(CC#N)=CC=CC2=C1 OQRMWUNUKVUHQO-UHFFFAOYSA-N 0.000 description 1
125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
BPPVUXSMLBXYGG-UHFFFAOYSA-N 4-[3-(4,5-dihydro-1,2-oxazol-3-yl)-2-methyl-4-methylsulfonylbenzoyl]-2-methyl-1h-pyrazol-3-one Chemical compound CC1=C(C(=O)C=2C(N(C)NC=2)=O)C=CC(S(C)(=O)=O)=C1C1=NOCC1 BPPVUXSMLBXYGG-UHFFFAOYSA-N 0.000 description 1
GTZBYPUABINJKB-UHFFFAOYSA-N 5-chloro-2-methyl-1-(1-phenylcyclobutyl)-3,4-dihydro-1h-isoquinolin-8-ol Chemical compound CN1CCC2=C(Cl)C=CC(O)=C2C1C1(C=2C=CC=CC=2)CCC1 GTZBYPUABINJKB-UHFFFAOYSA-N 0.000 description 1
YBTHFOIUPSEEFD-UHFFFAOYSA-N 5-chloro-2-methyl-1-(1-phenylcyclobutyl)-3,4-dihydro-1h-isoquinolin-8-ol;hydrobromide Chemical compound Br.CN1CCC2=C(Cl)C=CC(O)=C2C1C1(C=2C=CC=CC=2)CCC1 YBTHFOIUPSEEFD-UHFFFAOYSA-N 0.000 description 1
VWHHGZVKUVMTRJ-UHFFFAOYSA-N 5-chloro-2-methyl-1-(1-phenylcyclobutyl)-3,4-dihydro-1h-isoquinoline-6,7-diol Chemical compound CN1CCC2=C(Cl)C(O)=C(O)C=C2C1C1(C=2C=CC=CC=2)CCC1 VWHHGZVKUVMTRJ-UHFFFAOYSA-N 0.000 description 1
BSJFHBZEIVJOEG-UHFFFAOYSA-N 5-chloro-8-methoxy-2-methyl-1-(1-phenylcyclobutyl)-3,4-dihydro-1h-isoquinoline Chemical compound C1=2C(OC)=CC=C(Cl)C=2CCN(C)C1C1(C=2C=CC=CC=2)CCC1 BSJFHBZEIVJOEG-UHFFFAOYSA-N 0.000 description 1
101710156159 50S ribosomal protein L21, chloroplastic Proteins 0.000 description 1
101710118399 50S ribosomal protein L24, chloroplastic Proteins 0.000 description 1
XTXBWOYKFKSIDH-UHFFFAOYSA-N 6,7-dimethoxy-1-(1-naphthalen-2-ylcyclobutyl)-1,2,3,4-tetrahydroisoquinoline Chemical compound C1=2C=C(OC)C(OC)=CC=2CCNC1C1(C=2C=C3C=CC=CC3=CC=2)CCC1 XTXBWOYKFKSIDH-UHFFFAOYSA-N 0.000 description 1
ODMXAAQUDYMMIL-UHFFFAOYSA-N 6,7-dimethoxy-1-[1-(4-phenylphenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinoline;hydrochloride Chemical compound Cl.C1=2C=C(OC)C(OC)=CC=2CCNC1C1(C=2C=CC(=CC=2)C=2C=CC=CC=2)CCC1 ODMXAAQUDYMMIL-UHFFFAOYSA-N 0.000 description 1
WGHGQZPDGMUAPO-UHFFFAOYSA-N 6,7-dimethoxy-2-methyl-1-(1-phenylcyclobutyl)-3,4-dihydro-1h-isoquinoline;hydrochloride Chemical compound Cl.C1=2C=C(OC)C(OC)=CC=2CCN(C)C1C1(C=2C=CC=CC=2)CCC1 WGHGQZPDGMUAPO-UHFFFAOYSA-N 0.000 description 1
LBNOIYRLLHONLK-UHFFFAOYSA-N 6,8-dichloro-2-methyl-1-(1-phenylcyclobutyl)-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound CN1CCC2=CC(Cl)=C(O)C(Cl)=C2C1C1(C=2C=CC=CC=2)CCC1 LBNOIYRLLHONLK-UHFFFAOYSA-N 0.000 description 1
MWKIHXUMUYIJEN-UHFFFAOYSA-N 6-bromo-2-methyl-1-(1-phenylcyclobutyl)-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound CN1CCC2=CC(Br)=C(O)C=C2C1C1(C=2C=CC=CC=2)CCC1 MWKIHXUMUYIJEN-UHFFFAOYSA-N 0.000 description 1
SHNNOXASHCOCFC-UHFFFAOYSA-N 6-chloro-1-(3,3-dimethyl-1-phenylcyclobutyl)-2-methyl-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound CN1CCC2=CC(Cl)=C(O)C=C2C1C1(C=2C=CC=CC=2)CC(C)(C)C1 SHNNOXASHCOCFC-UHFFFAOYSA-N 0.000 description 1
ZNVGHRJAAOUILT-UHFFFAOYSA-N 6-chloro-7-methoxy-1-(1-phenylcyclobutyl)-1,2,3,4-tetrahydroisoquinoline Chemical compound N1CCC=2C=C(Cl)C(OC)=CC=2C1C1(C=2C=CC=CC=2)CCC1 ZNVGHRJAAOUILT-UHFFFAOYSA-N 0.000 description 1
OGXLDRRPGVUCNT-UHFFFAOYSA-N 6-methoxy-1-(1-naphthalen-1-ylcyclopropyl)-7-phenylmethoxy-1,2,3,4-tetrahydroisoquinoline Chemical compound COC1=CC=2CCNC(C3(CC3)C=3C4=CC=CC=C4C=CC=3)C=2C=C1OCC1=CC=CC=C1 OGXLDRRPGVUCNT-UHFFFAOYSA-N 0.000 description 1
DYAFZEZAIULNAC-UHFFFAOYSA-N 6-methoxy-1-[1-(2-methoxyphenyl)cyclobutyl]-2-methyl-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound C1=2C=C(O)C(OC)=CC=2CCN(C)C1C1(C=2C(=CC=CC=2)OC)CCC1 DYAFZEZAIULNAC-UHFFFAOYSA-N 0.000 description 1
LGXAUFQEWJRTPT-UHFFFAOYSA-N 6-methoxy-1-[1-(2-methoxyphenyl)cyclopropyl]-2-methyl-3,4-dihydro-1h-isoquinolin-7-ol;hydrochloride Chemical compound Cl.C1=2C=C(O)C(OC)=CC=2CCN(C)C1C1(C=2C(=CC=CC=2)OC)CC1 LGXAUFQEWJRTPT-UHFFFAOYSA-N 0.000 description 1
JOIBQNLRLHAAJH-UHFFFAOYSA-N 6-methoxy-1-[1-(2-methylsulfanylphenyl)cyclobutyl]-7-phenylmethoxy-1,2,3,4-tetrahydroisoquinoline Chemical compound COC1=CC=2CCNC(C3(CCC3)C=3C(=CC=CC=3)SC)C=2C=C1OCC1=CC=CC=C1 JOIBQNLRLHAAJH-UHFFFAOYSA-N 0.000 description 1
QYYUPFIFSJOBNB-UHFFFAOYSA-N 6-methoxy-1-[1-(2-methylsulfanylphenyl)cyclobutyl]-7-phenylmethoxy-3,4-dihydroisoquinoline Chemical compound COC1=CC=2CCN=C(C3(CCC3)C=3C(=CC=CC=3)SC)C=2C=C1OCC1=CC=CC=C1 QYYUPFIFSJOBNB-UHFFFAOYSA-N 0.000 description 1
KORIVOSSEFDHOB-UHFFFAOYSA-N 6-methoxy-1-[1-(2-methylthiophen-3-yl)cyclobutyl]-7-phenylmethoxy-1,2-dihydroisoquinoline Chemical compound COC1=CC=2C=CNC(C3(CCC3)C3=C(SC=C3)C)C=2C=C1OCC1=CC=CC=C1 KORIVOSSEFDHOB-UHFFFAOYSA-N 0.000 description 1
FIJDOQWMWKNVIQ-UHFFFAOYSA-N 6-methoxy-1-[1-(3-methoxyphenyl)cyclobutyl]-2-methyl-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound COC1=CC=CC(C2(CCC2)C2C3=CC(O)=C(OC)C=C3CCN2C)=C1 FIJDOQWMWKNVIQ-UHFFFAOYSA-N 0.000 description 1
ZYUXPDGUDMTCLU-UHFFFAOYSA-N 6-methoxy-2-methyl-1-(1-naphthalen-1-ylcyclopropyl)-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound C1=2C=C(O)C(OC)=CC=2CCN(C)C1C1(C=2C3=CC=CC=C3C=CC=2)CC1 ZYUXPDGUDMTCLU-UHFFFAOYSA-N 0.000 description 1
OBTGNKYLHOGCIT-UHFFFAOYSA-N 6-methoxy-2-methyl-1-(1-naphthalen-1-ylcyclopropyl)-3,4-dihydro-1h-isoquinolin-7-ol;hydrochloride Chemical compound Cl.C1=2C=C(O)C(OC)=CC=2CCN(C)C1C1(C=2C3=CC=CC=C3C=CC=2)CC1 OBTGNKYLHOGCIT-UHFFFAOYSA-N 0.000 description 1
AFXUYWNMNJKIKF-UHFFFAOYSA-N 6-methoxy-2-methyl-1-(1-naphthalen-1-ylcyclopropyl)-7-phenylmethoxy-3,4-dihydro-1h-isoquinoline Chemical compound COC1=CC=2CCN(C)C(C3(CC3)C=3C4=CC=CC=C4C=CC=3)C=2C=C1OCC1=CC=CC=C1 AFXUYWNMNJKIKF-UHFFFAOYSA-N 0.000 description 1
GKSRXSJCEGUZQA-UHFFFAOYSA-N 6-methoxy-2-methyl-1-(1-phenylcyclohexyl)-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound C1=2C=C(O)C(OC)=CC=2CCN(C)C1C1(C=2C=CC=CC=2)CCCCC1 GKSRXSJCEGUZQA-UHFFFAOYSA-N 0.000 description 1
YTCYCQJCAZWLLR-UHFFFAOYSA-N 6-methoxy-2-methyl-1-(1-phenylcyclopentyl)-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound C1=2C=C(O)C(OC)=CC=2CCN(C)C1C1(C=2C=CC=CC=2)CCCC1 YTCYCQJCAZWLLR-UHFFFAOYSA-N 0.000 description 1
FJOUDQRBJOJPFL-UHFFFAOYSA-N 6-methoxy-2-methyl-1-[1-[4-(trifluoromethoxy)phenyl]cyclobutyl]-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound C1=2C=C(O)C(OC)=CC=2CCN(C)C1C1(C=2C=CC(OC(F)(F)F)=CC=2)CCC1 FJOUDQRBJOJPFL-UHFFFAOYSA-N 0.000 description 1
VPBOSVULSWRTKR-UHFFFAOYSA-N 6-methoxy-2-methyl-1-[1-[4-(trifluoromethoxy)phenyl]cyclobutyl]-3,4-dihydro-1h-isoquinolin-7-ol;oxalic acid Chemical compound OC(=O)C(O)=O.C1=2C=C(O)C(OC)=CC=2CCN(C)C1C1(C=2C=CC(OC(F)(F)F)=CC=2)CCC1 VPBOSVULSWRTKR-UHFFFAOYSA-N 0.000 description 1
OCQNJMBADLPSIE-UHFFFAOYSA-N 6-methoxy-2-methyl-7-phenylmethoxy-1-[1-[4-(trifluoromethoxy)phenyl]cyclobutyl]-3,4-dihydro-1h-isoquinoline Chemical compound COC1=CC=2CCN(C)C(C3(CCC3)C=3C=CC(OC(F)(F)F)=CC=3)C=2C=C1OCC1=CC=CC=C1 OCQNJMBADLPSIE-UHFFFAOYSA-N 0.000 description 1
RTNBBODDQHYNHK-UHFFFAOYSA-N 6-methoxy-2-methyl-7-phenylmethoxy-1-[1-[4-(trifluoromethoxy)phenyl]cyclobutyl]-3,4-dihydro-1h-isoquinoline;hydrochloride Chemical compound Cl.COC1=CC=2CCN(C)C(C3(CCC3)C=3C=CC(OC(F)(F)F)=CC=3)C=2C=C1OCC1=CC=CC=C1 RTNBBODDQHYNHK-UHFFFAOYSA-N 0.000 description 1
KNYDTJASPJUZKY-UHFFFAOYSA-N 7-(chloromethyl)-2,3-dihydro-1-benzofuran Chemical compound ClCC1=CC=CC2=C1OCC2 KNYDTJASPJUZKY-UHFFFAOYSA-N 0.000 description 1
XLOAYWOSYABPNH-UHFFFAOYSA-N 7-chloro-2-methyl-1-(1-phenylcyclobutyl)-3,4-dihydro-1h-isoquinolin-6-ol Chemical compound CN1CCC2=CC(O)=C(Cl)C=C2C1C1(C=2C=CC=CC=2)CCC1 XLOAYWOSYABPNH-UHFFFAOYSA-N 0.000 description 1
RYZBDDFQEKBECB-UHFFFAOYSA-N 7-methoxy-1-(1-phenylcyclobutyl)-3,4-dihydroisoquinoline Chemical compound C12=CC(OC)=CC=C2CCN=C1C1(C=2C=CC=CC=2)CCC1 RYZBDDFQEKBECB-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
235000003911 Arachis Nutrition 0.000 description 1
244000105624 Arachis hypogaea Species 0.000 description 1
239000004342 Benzoyl peroxide Substances 0.000 description 1
OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
101100178983 Caenorhabditis elegans hyl-1 gene Proteins 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
238000004566 IR spectroscopy Methods 0.000 description 1
RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 1
YYTAYINRPUJPNH-UHFFFAOYSA-N Longimammatine Natural products C1NCCC2=CC(OC)=CC=C21 YYTAYINRPUJPNH-UHFFFAOYSA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
IAYQLUSHBJDQEM-UHFFFAOYSA-N N-(2-bromo-4,5-dimethoxyphenyl)cyclobutanecarboxamide Chemical compound C1(CCC1)C(=O)NC1=C(C=C(C(=C1)OC)OC)Br IAYQLUSHBJDQEM-UHFFFAOYSA-N 0.000 description 1
PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
241000700159 Rattus Species 0.000 description 1
241000978829 Senegalia modesta Species 0.000 description 1
239000004280 Sodium formate Substances 0.000 description 1
SQJXLDNECLCVAG-UHFFFAOYSA-N [1-[1-(2-chlorophenyl)cyclopropyl]-1,2,3,4-tetrahydroisoquinolin-7-yl] heptanoate Chemical compound C12=CC(OC(=O)CCCCCC)=CC=C2CCNC1C1(C=2C(=CC=CC=2)Cl)CC1 SQJXLDNECLCVAG-UHFFFAOYSA-N 0.000 description 1
IJPFZJNVMDGPBJ-UHFFFAOYSA-N [1-[1-(2-chlorophenyl)cyclopropyl]-6-methoxy-2-methyl-3,4-dihydro-1h-isoquinolin-7-yl] decanoate Chemical compound CN1CCC=2C=C(OC)C(OC(=O)CCCCCCCCC)=CC=2C1C1(C=2C(=CC=CC=2)Cl)CC1 IJPFZJNVMDGPBJ-UHFFFAOYSA-N 0.000 description 1
QTAXVZNXBCZOJF-UHFFFAOYSA-N [1-[1-(2-chlorophenyl)cyclopropyl]-6-methoxy-2-methyl-3,4-dihydro-1h-isoquinolin-7-yl] dodecanoate Chemical compound CN1CCC=2C=C(OC)C(OC(=O)CCCCCCCCCCC)=CC=2C1C1(C=2C(=CC=CC=2)Cl)CC1 QTAXVZNXBCZOJF-UHFFFAOYSA-N 0.000 description 1
JVDFTPJJIDEXRQ-UHFFFAOYSA-N [1-[1-(2-chlorophenyl)cyclopropyl]-6-methoxy-2-methyl-3,4-dihydro-1h-isoquinolin-7-yl] heptanoate Chemical compound CN1CCC=2C=C(OC)C(OC(=O)CCCCCC)=CC=2C1C1(C=2C(=CC=CC=2)Cl)CC1 JVDFTPJJIDEXRQ-UHFFFAOYSA-N 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000009471 action Effects 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
239000012042 active reagent Substances 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
229910000091 aluminium hydride Inorganic materials 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
235000001014 amino acid Nutrition 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
238000011914 asymmetric synthesis Methods 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
239000003637 basic solution Substances 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
150000001558 benzoic acid derivatives Chemical class 0.000 description 1
235000019400 benzoyl peroxide Nutrition 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
239000001273 butane Substances 0.000 description 1
JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
235000011148 calcium chloride Nutrition 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
235000011089 carbon dioxide Nutrition 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
JYYOBHFYCIDXHH-UHFFFAOYSA-N carbonic acid;hydrate Chemical compound O.OC(O)=O JYYOBHFYCIDXHH-UHFFFAOYSA-N 0.000 description 1
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
150000005829 chemical entities Chemical class 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
238000005660 chlorination reaction Methods 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 1
150000001860 citric acid derivatives Chemical class 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
239000006071 cream Substances 0.000 description 1
239000010779 crude oil Substances 0.000 description 1
GFBLFDSCAKHHGX-UHFFFAOYSA-N cyclobutanecarbonitrile Chemical compound N#CC1CCC1 GFBLFDSCAKHHGX-UHFFFAOYSA-N 0.000 description 1
JFWMYCVMQSLLOO-UHFFFAOYSA-N cyclobutanecarbonyl chloride Chemical compound ClC(=O)C1CCC1 JFWMYCVMQSLLOO-UHFFFAOYSA-N 0.000 description 1
SVPZJHKVRMRREG-UHFFFAOYSA-N cyclopentanecarbonitrile Chemical compound N#CC1CCCC1 SVPZJHKVRMRREG-UHFFFAOYSA-N 0.000 description 1
238000006264 debenzylation reaction Methods 0.000 description 1
230000017858 demethylation Effects 0.000 description 1
238000010520 demethylation reaction Methods 0.000 description 1
WVPKAWVFTPWPDB-UHFFFAOYSA-N dichlorophosphinic acid Chemical class OP(Cl)(Cl)=O WVPKAWVFTPWPDB-UHFFFAOYSA-N 0.000 description 1
229940043279 diisopropylamine Drugs 0.000 description 1
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
230000005593 dissociations Effects 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
UJNFXBCDXIUUHX-UHFFFAOYSA-N ditert-butylalumane Chemical compound CC(C)(C)[AlH]C(C)(C)C UJNFXBCDXIUUHX-UHFFFAOYSA-N 0.000 description 1
NQGIJDNPUZEBRU-UHFFFAOYSA-N dodecanoyl chloride Chemical compound CCCCCCCCCCCC(Cl)=O NQGIJDNPUZEBRU-UHFFFAOYSA-N 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000003814 drug Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000002662 enteric coated tablet Substances 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
XWBDWHCCBGMXKG-UHFFFAOYSA-N ethanamine;hydron;chloride Chemical compound Cl.CCN XWBDWHCCBGMXKG-UHFFFAOYSA-N 0.000 description 1
230000007717 exclusion Effects 0.000 description 1
239000000945 filler Substances 0.000 description 1
239000012467 final product Substances 0.000 description 1
230000037406 food intake Effects 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
230000004927 fusion Effects 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000000499 gel Substances 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
229940116364 hard fat Drugs 0.000 description 1
UCVODTZQZHMTPN-UHFFFAOYSA-N heptanoyl chloride Chemical compound CCCCCCC(Cl)=O UCVODTZQZHMTPN-UHFFFAOYSA-N 0.000 description 1
ARBOVOVUTSQWSS-UHFFFAOYSA-N hexadecanoyl chloride Chemical compound CCCCCCCCCCCCCCCC(Cl)=O ARBOVOVUTSQWSS-UHFFFAOYSA-N 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
239000005457 ice water Substances 0.000 description 1
239000007943 implant Substances 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
238000002955 isolation Methods 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
150000002688 maleic acid derivatives Chemical class 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
239000002609 medium Substances 0.000 description 1
JZMJDSHXVKJFKW-UHFFFAOYSA-N methyl sulfate Chemical class COS(O)(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-N 0.000 description 1
JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
238000003801 milling Methods 0.000 description 1
MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
GBECJBZMDVOGBS-UHFFFAOYSA-N n-[2-(3,4-dimethoxyphenyl)ethyl]cyclobutanecarboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CCNC(=O)C1CCC1 GBECJBZMDVOGBS-UHFFFAOYSA-N 0.000 description 1
LQHNGCWTSRCHJY-UHFFFAOYSA-N n-[2-(3-methoxy-4-phenylmethoxyphenyl)ethyl]-1-naphthalen-1-ylcyclopropane-1-carboxamide Chemical compound C=1C=C(OCC=2C=CC=CC=2)C(OC)=CC=1CCNC(=O)C1(C=2C3=CC=CC=C3C=CC=2)CC1 LQHNGCWTSRCHJY-UHFFFAOYSA-N 0.000 description 1
UVPUVUHWRJRFRD-UHFFFAOYSA-N n-[2-(4-methoxyphenyl)ethyl]-1-phenylcyclobutane-1-carboxamide Chemical compound C1=CC(OC)=CC=C1CCNC(=O)C1(C=2C=CC=CC=2)CCC1 UVPUVUHWRJRFRD-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
150000002823 nitrates Chemical class 0.000 description 1
238000006396 nitration reaction Methods 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
WTBAHSZERDXKKZ-UHFFFAOYSA-N octadecanoyl chloride Chemical compound CCCCCCCCCCCCCCCCCC(Cl)=O WTBAHSZERDXKKZ-UHFFFAOYSA-N 0.000 description 1
239000012053 oil suspension Substances 0.000 description 1
239000003883 ointment base Substances 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
BDOLXPFAFMNDOK-UHFFFAOYSA-N oxazaborolidine Chemical class B1CCON1 BDOLXPFAFMNDOK-UHFFFAOYSA-N 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
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 1
239000002831 pharmacologic agent Substances 0.000 description 1
HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 1
229910000073 phosphorus hydride Inorganic materials 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920000137 polyphosphoric acid Polymers 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
238000005932 reductive alkylation reaction Methods 0.000 description 1
238000009738 saturating Methods 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
239000011780 sodium chloride Substances 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
HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 1
235000019254 sodium formate Nutrition 0.000 description 1
239000004296 sodium metabisulphite Substances 0.000 description 1
235000010262 sodium metabisulphite Nutrition 0.000 description 1
RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
KIMPPGSMONZDMN-UHFFFAOYSA-N sodium;dihydrogen phosphite Chemical compound [Na+].OP(O)[O-] KIMPPGSMONZDMN-UHFFFAOYSA-N 0.000 description 1
239000012453 solvate Substances 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
238000002798 spectrophotometry method Methods 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
DKGZKTPJOSAWFA-UHFFFAOYSA-N spiperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCC2(C(NCN2C=2C=CC=CC=2)=O)CC1 DKGZKTPJOSAWFA-UHFFFAOYSA-N 0.000 description 1
229950001675 spiperone Drugs 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000000758 substrate Substances 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000002511 suppository base Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
229920003002 synthetic resin Polymers 0.000 description 1
239000000057 synthetic resin Substances 0.000 description 1
FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
230000009466 transformation Effects 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
150000003624 transition metals Chemical class 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 1
229910052721 tungsten Inorganic materials 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
238000010792 warming Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000008096 xylene Substances 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1