NO315609B1 - Substituerte 1,2,3,4-tetrahydronaftalenderivater, farmasöytisk formuleringinneholdende slike, fremgangsmåte for deres fremstilling, oganvendelse derav - Google Patents

Substituerte 1,2,3,4-tetrahydronaftalenderivater, farmasöytisk formuleringinneholdende slike, fremgangsmåte for deres fremstilling, oganvendelse derav Download PDF

Info

Publication number: NO315609B1
Authority: NO; Norway
Prior art keywords: compound; formula; tetrahydro; methylpiperazin; mmol
Prior art date: 1997-07-25

Application number

NO20000356A

Other languages

English (en)

Norwegian (no)

Other versions

NO20000356L (no

NO20000356D0 (no

Inventor

Stefan Berg

Mats Torbjoern Linderberg

Svante Bertil Ross

Seth-Olov Thorberg

Bengt Ulff

Original Assignee

Astra Ab

Priority date (The priority date 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 date listed.)

1997-07-25

Filing date

2000-01-24

Publication date

2003-09-29

2000-01-24 Application filed by Astra Ab filed Critical Astra Ab

2000-01-24 Publication of NO20000356D0 publication Critical patent/NO20000356D0/no

2000-03-27 Publication of NO20000356L publication Critical patent/NO20000356L/no

2003-09-29 Publication of NO315609B1 publication Critical patent/NO315609B1/no

Links

238000000034 method Methods 0.000 title claims description 45
239000008194 pharmaceutical composition Chemical class 0.000 title claims description 9
230000008569 process Effects 0.000 title claims description 4
238000002360 preparation method Methods 0.000 title description 13
CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical class C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 title description 5
150000001875 compounds Chemical class 0.000 claims description 284
238000006243 chemical reaction Methods 0.000 claims description 165
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 68
-1 (R)-N-[5-ethyl-8-(4-methylpiperidin-1-yl)-1,2,3,4-tetrahydro-2-naphthyl]-(4-morpholino- carbonyl)benzamide Chemical compound 0.000 claims description 66
229910052757 nitrogen Inorganic materials 0.000 claims description 48
229910052739 hydrogen Inorganic materials 0.000 claims description 43
229910052727 yttrium Inorganic materials 0.000 claims description 35
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 33
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 32
239000001257 hydrogen Substances 0.000 claims description 30
150000003839 salts Chemical class 0.000 claims description 28
239000003795 chemical substances by application Substances 0.000 claims description 25
229910052736 halogen Inorganic materials 0.000 claims description 23
150000002367 halogens Chemical class 0.000 claims description 18
125000000520 N-substituted aminocarbonyl group Chemical group [*]NC(=O)* 0.000 claims description 17
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
125000003118 aryl group Chemical group 0.000 claims description 15
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
208000035475 disorder Diseases 0.000 claims description 15
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 14
125000006239 protecting group Chemical group 0.000 claims description 14
239000005557 antagonist Substances 0.000 claims description 13
150000002431 hydrogen Chemical class 0.000 claims description 12
239000003153 chemical reaction reagent Substances 0.000 claims description 11
125000002757 morpholinyl group Chemical group 0.000 claims description 10
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
239000012458 free base Substances 0.000 claims description 9
230000002140 halogenating effect Effects 0.000 claims description 9
230000003213 activating effect Effects 0.000 claims description 8
KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 8
125000001424 substituent group Chemical group 0.000 claims description 8
208000019901 Anxiety disease Diseases 0.000 claims description 7
230000010933 acylation Effects 0.000 claims description 7
238000005917 acylation reaction Methods 0.000 claims description 7
229910052799 carbon Inorganic materials 0.000 claims description 7
238000004519 manufacturing process Methods 0.000 claims description 7
239000012453 solvate Substances 0.000 claims description 7
230000033228 biological regulation Effects 0.000 claims description 6
239000003814 drug Substances 0.000 claims description 6
230000001404 mediated effect Effects 0.000 claims description 5
208000007848 Alcoholism Diseases 0.000 claims description 4
206010003805 Autism Diseases 0.000 claims description 4
208000020706 Autistic disease Diseases 0.000 claims description 4
208000032841 Bulimia Diseases 0.000 claims description 4
206010006550 Bulimia nervosa Diseases 0.000 claims description 4
208000012661 Dyskinesia Diseases 0.000 claims description 4
208000017701 Endocrine disease Diseases 0.000 claims description 4
206010020772 Hypertension Diseases 0.000 claims description 4
208000026139 Memory disease Diseases 0.000 claims description 4
208000019695 Migraine disease Diseases 0.000 claims description 4
208000019022 Mood disease Diseases 0.000 claims description 4
208000002193 Pain Diseases 0.000 claims description 4
208000018737 Parkinson disease Diseases 0.000 claims description 4
206010036618 Premenstrual syndrome Diseases 0.000 claims description 4
208000006011 Stroke Diseases 0.000 claims description 4
206010043903 Tobacco abuse Diseases 0.000 claims description 4
206010046543 Urinary incontinence Diseases 0.000 claims description 4
206010047163 Vasospasm Diseases 0.000 claims description 4
239000004480 active ingredient Substances 0.000 claims description 4
230000016571 aggressive behavior Effects 0.000 claims description 4
201000007930 alcohol dependence Diseases 0.000 claims description 4
208000022531 anorexia Diseases 0.000 claims description 4
229910002091 carbon monoxide Inorganic materials 0.000 claims description 4
206010061428 decreased appetite Diseases 0.000 claims description 4
208000013403 hyperactivity Diseases 0.000 claims description 4
206010027599 migraine Diseases 0.000 claims description 4
208000001022 morbid obesity Diseases 0.000 claims description 4
230000001575 pathological effect Effects 0.000 claims description 4
208000022821 personality disease Diseases 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
201000000980 schizophrenia Diseases 0.000 claims description 4
208000012201 sexual and gender identity disease Diseases 0.000 claims description 4
208000015891 sexual disease Diseases 0.000 claims description 4
239000002168 alkylating agent Substances 0.000 claims description 3
229940100198 alkylating agent Drugs 0.000 claims description 3
210000003169 central nervous system Anatomy 0.000 claims description 3
238000002560 therapeutic procedure Methods 0.000 claims description 3
206010028980 Neoplasm Diseases 0.000 claims description 2
239000000969 carrier Substances 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
229940079593 drug Drugs 0.000 claims description 2
230000012010 growth Effects 0.000 claims description 2
OXZHFWAHGKDGDI-LJQANCHMSA-N n-[(2r)-5-bromo-8-piperazin-1-yl-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound C([C@H](CC=12)NC(=O)C=3C=CC(=CC=3)N3CCOCC3)CC=1C(Br)=CC=C2N1CCNCC1 OXZHFWAHGKDGDI-LJQANCHMSA-N 0.000 claims description 2
XCSBGPAPGUIEFO-OAQYLSRUSA-N n-[(2r)-5-methoxy-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound C([C@H](CC=12)NC(=O)C=3C=CC(=CC=3)N3CCOCC3)CC=1C(OC)=CC=C2N1CCN(C)CC1 XCSBGPAPGUIEFO-OAQYLSRUSA-N 0.000 claims description 2
VIOXDKIMIOUIHG-OAQYLSRUSA-N n-[(2r)-5-methyl-8-piperazin-1-yl-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound C([C@H](CC=12)NC(=O)C=3C=CC(=CC=3)N3CCOCC3)CC=1C(C)=CC=C2N1CCNCC1 VIOXDKIMIOUIHG-OAQYLSRUSA-N 0.000 claims description 2
230000004614 tumor growth Effects 0.000 claims 2
DDSZVHSDJFPOLH-HXUWFJFHSA-N 4-butoxy-n-[(2r)-5-hydroxy-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1=CC(OCCCC)=CC=C1C(=O)N[C@H]1CC2=C(N3CCN(C)CC3)C=CC(O)=C2CC1 DDSZVHSDJFPOLH-HXUWFJFHSA-N 0.000 claims 1
208000015114 central nervous system disease Diseases 0.000 claims 1
GKDNUPUMUMETCH-HSZRJFAPSA-N n-[(2r)-5-(methoxymethyl)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical group C([C@H](CC=12)NC(=O)C=3C=CC(=CC=3)N3CCOCC3)CC=1C(COC)=CC=C2N1CCN(C)CC1 GKDNUPUMUMETCH-HSZRJFAPSA-N 0.000 claims 1
BEEWOAIWRLZBGZ-HSZRJFAPSA-N n-[(2r)-5-ethyl-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound C([C@H](CC=12)NC(=O)C=3C=CC(=CC=3)N3CCOCC3)CC=1C(CC)=CC=C2N1CCN(C)CC1 BEEWOAIWRLZBGZ-HSZRJFAPSA-N 0.000 claims 1
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 188
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 180
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 169
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 156
239000002904 solvent Substances 0.000 description 154
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 150
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 131
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 126
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 116
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 99
239000000243 solution Substances 0.000 description 97
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 84
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 81
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 75
238000002451 electron ionisation mass spectrometry Methods 0.000 description 69
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 61
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 58
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
239000003480 eluent Substances 0.000 description 56
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 54
229910001868 water Inorganic materials 0.000 description 54
239000002585 base Substances 0.000 description 52
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 48
239000011541 reaction mixture Substances 0.000 description 48
239000000203 mixture Substances 0.000 description 46
239000000741 silica gel Substances 0.000 description 44
229910002027 silica gel Inorganic materials 0.000 description 44
235000011054 acetic acid Nutrition 0.000 description 43
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
239000003921 oil Substances 0.000 description 41
235000019198 oils Nutrition 0.000 description 41
239000012074 organic phase Substances 0.000 description 39
239000003054 catalyst Substances 0.000 description 36
229910052763 palladium Inorganic materials 0.000 description 35
239000011734 sodium Substances 0.000 description 35
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 34
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 34
235000011121 sodium hydroxide Nutrition 0.000 description 33
239000007787 solid Substances 0.000 description 33
239000013078 crystal Substances 0.000 description 30
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 30
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 29
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 28
238000010992 reflux Methods 0.000 description 28
QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical group C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 27
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 27
238000000746 purification Methods 0.000 description 27
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 25
239000012043 crude product Substances 0.000 description 25
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 24
239000000908 ammonium hydroxide Substances 0.000 description 24
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 23
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 21
239000000460 chlorine Substances 0.000 description 21
239000012071 phase Substances 0.000 description 20
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 20
102000005962 receptors Human genes 0.000 description 19
108020003175 receptors Proteins 0.000 description 19
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 18
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 17
229910052759 nickel Inorganic materials 0.000 description 17
229910052697 platinum Inorganic materials 0.000 description 17
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 16
238000005984 hydrogenation reaction Methods 0.000 description 16
229910000027 potassium carbonate Inorganic materials 0.000 description 16
229910052703 rhodium Inorganic materials 0.000 description 16
239000010948 rhodium Substances 0.000 description 16
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 16
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 15
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 15
229910052794 bromium Inorganic materials 0.000 description 15
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 14
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
239000012267 brine Substances 0.000 description 14
230000009467 reduction Effects 0.000 description 14
238000006722 reduction reaction Methods 0.000 description 14
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 14
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
239000002253 acid Substances 0.000 description 13
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 12
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 12
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 12
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 12
239000007864 aqueous solution Substances 0.000 description 12
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 12
229910052801 chlorine Inorganic materials 0.000 description 12
239000012044 organic layer Substances 0.000 description 12
235000015320 potassium carbonate Nutrition 0.000 description 12
229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
229920006395 saturated elastomer Polymers 0.000 description 11
125000005270 trialkylamine group Chemical group 0.000 description 11
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 10
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
238000004458 analytical method Methods 0.000 description 10
239000008346 aqueous phase Substances 0.000 description 10
238000003776 cleavage reaction Methods 0.000 description 10
230000000694 effects Effects 0.000 description 10
239000012039 electrophile Substances 0.000 description 10
239000003446 ligand Substances 0.000 description 10
IHDRUIHIJWCTIY-JOCHJYFZSA-N n-[(2r)-5-methyl-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound C1CN(C)CCN1C1=CC=C(C)C2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)N1CCOCC1)CC2 IHDRUIHIJWCTIY-JOCHJYFZSA-N 0.000 description 10
239000002244 precipitate Substances 0.000 description 10
230000007017 scission Effects 0.000 description 10
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 10
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 9
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 9
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 9
230000000638 stimulation Effects 0.000 description 9
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 8
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 8
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
239000000010 aprotic solvent Substances 0.000 description 8
238000004440 column chromatography Methods 0.000 description 8
238000001816 cooling Methods 0.000 description 8
238000010438 heat treatment Methods 0.000 description 8
229910000069 nitrogen hydride Inorganic materials 0.000 description 8
235000011118 potassium hydroxide Nutrition 0.000 description 8
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 8
229910052708 sodium Inorganic materials 0.000 description 8
235000017557 sodium bicarbonate Nutrition 0.000 description 8
238000003756 stirring Methods 0.000 description 8
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
BPLUKJNHPBNVQL-UHFFFAOYSA-N triphenylarsine Chemical compound C1=CC=CC=C1[As](C=1C=CC=CC=1)C1=CC=CC=C1 BPLUKJNHPBNVQL-UHFFFAOYSA-N 0.000 description 8
DLQYXUGCCKQSRJ-UHFFFAOYSA-N tris(furan-2-yl)phosphane Chemical compound C1=COC(P(C=2OC=CC=2)C=2OC=CC=2)=C1 DLQYXUGCCKQSRJ-UHFFFAOYSA-N 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
229910052786 argon Inorganic materials 0.000 description 7
235000019445 benzyl alcohol Nutrition 0.000 description 7
239000000872 buffer Substances 0.000 description 7
239000003638 chemical reducing agent Substances 0.000 description 7
239000012230 colorless oil Substances 0.000 description 7
125000005843 halogen group Chemical group 0.000 description 7
239000010410 layer Substances 0.000 description 7
XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 7
239000000377 silicon dioxide Substances 0.000 description 7
COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 7
XVAJKPNTGSKZSQ-UHFFFAOYSA-N 4-morpholinobenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1N1CCOCC1 XVAJKPNTGSKZSQ-UHFFFAOYSA-N 0.000 description 6
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
230000002378 acidificating effect Effects 0.000 description 6
239000013543 active substance Substances 0.000 description 6
150000001298 alcohols Chemical class 0.000 description 6
KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 6
229940073608 benzyl chloride Drugs 0.000 description 6
ZDKRMIJRCHPKLW-UHFFFAOYSA-N benzyl methanesulfonate Chemical compound CS(=O)(=O)OCC1=CC=CC=C1 ZDKRMIJRCHPKLW-UHFFFAOYSA-N 0.000 description 6
238000005574 benzylation reaction Methods 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
238000007336 electrophilic substitution reaction Methods 0.000 description 6
230000026030 halogenation Effects 0.000 description 6
238000005658 halogenation reaction Methods 0.000 description 6
229910052744 lithium Inorganic materials 0.000 description 6
239000012280 lithium aluminium hydride Substances 0.000 description 6
210000001640 nerve ending Anatomy 0.000 description 6
229940076279 serotonin Drugs 0.000 description 6
235000009518 sodium iodide Nutrition 0.000 description 6
239000000725 suspension Substances 0.000 description 6
WBVYTRBDTHQZAL-GFCCVEGCSA-N (2r)-5-methoxy-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C([C@@H](N)CC=12)CC=1C(OC)=CC=C2N1CCN(C)CC1 WBVYTRBDTHQZAL-GFCCVEGCSA-N 0.000 description 5
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 5
108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 5
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 5
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 5
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
239000000556 agonist Substances 0.000 description 5
229910052783 alkali metal Inorganic materials 0.000 description 5
125000000217 alkyl group Chemical group 0.000 description 5
239000003610 charcoal Substances 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
239000000499 gel Substances 0.000 description 5
230000007062 hydrolysis Effects 0.000 description 5
238000006460 hydrolysis reaction Methods 0.000 description 5
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
239000011777 magnesium Substances 0.000 description 5
229910052749 magnesium Inorganic materials 0.000 description 5
229910052751 metal Inorganic materials 0.000 description 5
239000002184 metal Substances 0.000 description 5
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 5
229910017604 nitric acid Inorganic materials 0.000 description 5
238000012746 preparative thin layer chromatography Methods 0.000 description 5
239000000047 product Substances 0.000 description 5
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 4
BWZVCCNYKMEVEX-UHFFFAOYSA-N 2,4,6-Trimethylpyridine Chemical compound CC1=CC(C)=NC(C)=C1 BWZVCCNYKMEVEX-UHFFFAOYSA-N 0.000 description 4
102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 4
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
102000007527 Autoreceptors Human genes 0.000 description 4
108010071131 Autoreceptors Proteins 0.000 description 4
108010010803 Gelatin Proteins 0.000 description 4
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
239000007832 Na2SO4 Substances 0.000 description 4
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
239000012445 acidic reagent Substances 0.000 description 4
150000001335 aliphatic alkanes Chemical class 0.000 description 4
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
OVHDZBAFUMEXCX-UHFFFAOYSA-N benzyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1=CC=CC=C1 OVHDZBAFUMEXCX-UHFFFAOYSA-N 0.000 description 4
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 4
239000008273 gelatin Substances 0.000 description 4
229920000159 gelatin Polymers 0.000 description 4
235000019322 gelatine Nutrition 0.000 description 4
235000011852 gelatine desserts Nutrition 0.000 description 4
239000007788 liquid Substances 0.000 description 4
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 4
150000004702 methyl esters Chemical class 0.000 description 4
239000012434 nucleophilic reagent Substances 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 4
229910000104 sodium hydride Inorganic materials 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
230000005062 synaptic transmission Effects 0.000 description 4
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 4
238000010626 work up procedure Methods 0.000 description 4
WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 description 3
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 3
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
HNXCGAFMTICJHZ-UHFFFAOYSA-N 5-methoxy-8-nitro-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid Chemical compound C1C(C(O)=O)CCC2=C1C([N+]([O-])=O)=CC=C2OC HNXCGAFMTICJHZ-UHFFFAOYSA-N 0.000 description 3
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 3
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
229910006024 SO2Cl2 Inorganic materials 0.000 description 3
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 3
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
150000001350 alkyl halides Chemical class 0.000 description 3
150000001408 amides Chemical class 0.000 description 3
229910021529 ammonia Inorganic materials 0.000 description 3
230000036506 anxiety Effects 0.000 description 3
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 3
229960001653 citalopram Drugs 0.000 description 3
230000017858 demethylation Effects 0.000 description 3
238000010520 demethylation reaction Methods 0.000 description 3
238000003818 flash chromatography Methods 0.000 description 3
235000019253 formic acid Nutrition 0.000 description 3
239000007903 gelatin capsule Substances 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 3
PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 3
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
125000004193 piperazinyl group Chemical group 0.000 description 3
235000011181 potassium carbonates Nutrition 0.000 description 3
230000001681 protective effect Effects 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
230000001105 regulatory effect Effects 0.000 description 3
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 3
235000011149 sulphuric acid Nutrition 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 3
AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 2
SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
ZNCCPHHCNRVDCO-LLVKDONJSA-N (2r)-5-(difluoromethoxy)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1CN(C)CCN1C1=CC=C(OC(F)F)C2=C1C[C@H](N)CC2 ZNCCPHHCNRVDCO-LLVKDONJSA-N 0.000 description 2
YCOFIZUAZAFJBR-CQSZACIVSA-N (2r)-5-(methoxymethyl)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C([C@@H](N)CC=12)CC=1C(COC)=CC=C2N1CCN(C)CC1 YCOFIZUAZAFJBR-CQSZACIVSA-N 0.000 description 2
MWGQZBJICSMDDI-LLVKDONJSA-N (2r)-5-bromo-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1CN(C)CCN1C1=CC=C(Br)C2=C1C[C@H](N)CC2 MWGQZBJICSMDDI-LLVKDONJSA-N 0.000 description 2
MFZYGHMKYJLMCS-SNVBAGLBSA-N (2r)-5-bromo-8-piperazin-1-yl-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C([C@H](CC1=2)N)CC1=C(Br)C=CC=2N1CCNCC1 MFZYGHMKYJLMCS-SNVBAGLBSA-N 0.000 description 2
KAVYEHCWLZTVAS-CQSZACIVSA-N (2r)-5-ethyl-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C([C@@H](N)CC=12)CC=1C(CC)=CC=C2N1CCN(C)CC1 KAVYEHCWLZTVAS-CQSZACIVSA-N 0.000 description 2
IIZNVHAEKCAWCC-CYBMUJFWSA-N (2r)-5-methyl-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1CN(C)CCN1C1=CC=C(C)C2=C1C[C@H](N)CC2 IIZNVHAEKCAWCC-CYBMUJFWSA-N 0.000 description 2
XREGDYSHTRIPFG-GFCCVEGCSA-N (2r)-5-methyl-8-piperazin-1-yl-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C([C@@H](N)CC=12)CC=1C(C)=CC=C2N1CCNCC1 XREGDYSHTRIPFG-GFCCVEGCSA-N 0.000 description 2
JKOKSUARGAQGCX-CYBMUJFWSA-N (2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](N)CC2 JKOKSUARGAQGCX-CYBMUJFWSA-N 0.000 description 2
XGHZJQXPMFEDAT-GFCCVEGCSA-N (2r)-8-piperazin-1-yl-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C([C@H](CC1=2)N)CC1=CC=CC=2N1CCNCC1 XGHZJQXPMFEDAT-GFCCVEGCSA-N 0.000 description 2
AUHZEENZYGFFBQ-UHFFFAOYSA-N 1,3,5-Me3C6H3 Natural products CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 2
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
QBPISWMTLKTKMK-UHFFFAOYSA-N 1-[(4-aminophenyl)methyl]pyridin-2-one Chemical compound C1=CC(N)=CC=C1CN1C(=O)C=CC=C1 QBPISWMTLKTKMK-UHFFFAOYSA-N 0.000 description 2
HUUPVABNAQUEJW-UHFFFAOYSA-N 1-methylpiperidin-4-one Chemical compound CN1CCC(=O)CC1 HUUPVABNAQUEJW-UHFFFAOYSA-N 0.000 description 2
YQUVCSBJEUQKSH-UHFFFAOYSA-N 3,4-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 description 2
UYEMGAFJOZZIFP-UHFFFAOYSA-N 3,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC(O)=C1 UYEMGAFJOZZIFP-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
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 2
HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
GLCNLSFPYIMZJK-UHFFFAOYSA-N 5-methoxy-8-(4-methylpiperazin-1-yl)-n-(4-morpholin-4-ylphenyl)-1,2,3,4-tetrahydronaphthalene-2-carboxamide Chemical compound C1=2CC(C(=O)NC=3C=CC(=CC=3)N3CCOCC3)CCC=2C(OC)=CC=C1N1CCN(C)CC1 GLCNLSFPYIMZJK-UHFFFAOYSA-N 0.000 description 2
JMQUFKWBATWTAM-UHFFFAOYSA-N 5-methoxy-8-(4-methylpiperazin-1-yl)-n-[2-(morpholine-4-carbonyl)phenyl]-1,2,3,4-tetrahydronaphthalene-2-carboxamide Chemical compound C1=2CC(C(=O)NC=3C(=CC=CC=3)C(=O)N3CCOCC3)CCC=2C(OC)=CC=C1N1CCN(C)CC1 JMQUFKWBATWTAM-UHFFFAOYSA-N 0.000 description 2
UATNZJWCVYMKPH-UHFFFAOYSA-N 5-methoxy-n-(4-morpholin-4-ylphenyl)-8-nitro-1,2,3,4-tetrahydronaphthalene-2-carboxamide Chemical compound C1CC=2C(OC)=CC=C([N+]([O-])=O)C=2CC1C(=O)NC(C=C1)=CC=C1N1CCOCC1 UATNZJWCVYMKPH-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
WZHYFINFDVOADE-UHFFFAOYSA-N 8-amino-5-methoxy-n-[2-(morpholine-4-carbonyl)phenyl]-1,2,3,4-tetrahydronaphthalene-2-carboxamide Chemical compound C1CC=2C(OC)=CC=C(N)C=2CC1C(=O)NC1=CC=CC=C1C(=O)N1CCOCC1 WZHYFINFDVOADE-UHFFFAOYSA-N 0.000 description 2
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
229920000945 Amylopectin Polymers 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-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
DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
241000700198 Cavia Species 0.000 description 2
241000700199 Cavia porcellus Species 0.000 description 2
VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
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 2
229930195725 Mannitol Natural products 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 2
RMUCZJUITONUFY-UHFFFAOYSA-N Phenelzine Chemical compound NNCCC1=CC=CC=C1 RMUCZJUITONUFY-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
QPQGTZMAQRXCJW-UHFFFAOYSA-N [chloro(phenyl)phosphoryl]benzene Chemical compound C=1C=CC=CC=1P(=O)(Cl)C1=CC=CC=C1 QPQGTZMAQRXCJW-UHFFFAOYSA-N 0.000 description 2
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
TVJORGWKNPGCDW-UHFFFAOYSA-N aminoboron Chemical compound N[B] TVJORGWKNPGCDW-UHFFFAOYSA-N 0.000 description 2
STFSECMHVCFKFX-UHFFFAOYSA-N aminotin Chemical compound [Sn]N STFSECMHVCFKFX-UHFFFAOYSA-N 0.000 description 2
239000000538 analytical sample Substances 0.000 description 2
RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
239000012300 argon atmosphere Substances 0.000 description 2
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
229940092714 benzenesulfonic acid Drugs 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 2
230000005540 biological transmission Effects 0.000 description 2
230000037396 body weight Effects 0.000 description 2
JAMFGQBENKSWOF-UHFFFAOYSA-N bromo(methoxy)methane Chemical compound COCBr JAMFGQBENKSWOF-UHFFFAOYSA-N 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
XGRJZXREYAXTGV-UHFFFAOYSA-N chlorodiphenylphosphine Chemical compound C=1C=CC=CC=1P(Cl)C1=CC=CC=C1 XGRJZXREYAXTGV-UHFFFAOYSA-N 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
235000015165 citric acid Nutrition 0.000 description 2
239000008120 corn starch Substances 0.000 description 2
239000013058 crude material Substances 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
VRLDVERQJMEPIF-UHFFFAOYSA-N dbdmh Chemical compound CC1(C)N(Br)C(=O)N(Br)C1=O VRLDVERQJMEPIF-UHFFFAOYSA-N 0.000 description 2
238000000354 decomposition reaction Methods 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
230000005684 electric field Effects 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000006260 foam Substances 0.000 description 2
230000006870 function Effects 0.000 description 2
239000011521 glass Substances 0.000 description 2
235000012208 gluconic acid Nutrition 0.000 description 2
229950006191 gluconic acid Drugs 0.000 description 2
229940088597 hormone Drugs 0.000 description 2
239000005556 hormone Substances 0.000 description 2
JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
230000006872 improvement Effects 0.000 description 2
238000011534 incubation Methods 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
239000013067 intermediate product Substances 0.000 description 2
239000011630 iodine Substances 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
239000008101 lactose Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 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
239000011976 maleic acid Substances 0.000 description 2
239000000594 mannitol Substances 0.000 description 2
235000010355 mannitol Nutrition 0.000 description 2
239000000463 material Substances 0.000 description 2
229940098779 methanesulfonic acid Drugs 0.000 description 2
YHXISWVBGDMDLQ-UHFFFAOYSA-N moclobemide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCCN1CCOCC1 YHXISWVBGDMDLQ-UHFFFAOYSA-N 0.000 description 2
229960004644 moclobemide Drugs 0.000 description 2
BYJYPZAHTUBRNT-HXUWFJFHSA-N n-[(2r)-5-bromo-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound C1CN(C)CCN1C1=CC=C(Br)C2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)N1CCOCC1)CC2 BYJYPZAHTUBRNT-HXUWFJFHSA-N 0.000 description 2
SOLWORTYZPSMAK-UHFFFAOYSA-N n-[bis(dimethylamino)boranyl]-n-methylmethanamine Chemical compound CN(C)B(N(C)C)N(C)C SOLWORTYZPSMAK-UHFFFAOYSA-N 0.000 description 2
MVWZZXSPDHCPMY-UHFFFAOYSA-N n-ethyl-n-tributylstannylethanamine Chemical compound CCCC[Sn](CCCC)(CCCC)N(CC)CC MVWZZXSPDHCPMY-UHFFFAOYSA-N 0.000 description 2
239000002858 neurotransmitter agent Substances 0.000 description 2
230000000802 nitrating effect Effects 0.000 description 2
238000006396 nitration reaction Methods 0.000 description 2
239000012299 nitrogen atmosphere Substances 0.000 description 2
125000004433 nitrogen atom Chemical group N* 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
229960002748 norepinephrine Drugs 0.000 description 2
SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
229960002296 paroxetine Drugs 0.000 description 2
239000004031 partial agonist Substances 0.000 description 2
229960000964 phenelzine Drugs 0.000 description 2
125000005936 piperidyl group Chemical class 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
229920001592 potato starch Polymers 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
230000028327 secretion Effects 0.000 description 2
230000000862 serotonergic effect Effects 0.000 description 2
239000001632 sodium acetate Substances 0.000 description 2
235000017281 sodium acetate Nutrition 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
235000010356 sorbitol Nutrition 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 2
230000000946 synaptic effect Effects 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
238000001665 trituration Methods 0.000 description 2
230000007306 turnover Effects 0.000 description 2
235000015112 vegetable and seed oil Nutrition 0.000 description 2
239000008158 vegetable oil Substances 0.000 description 2
UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [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 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 description 1
BRQAPHCTBAPJLO-CYBMUJFWSA-N (2r)-5-methoxy-8-(1-methylpiperidin-4-yl)-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C([C@@H](N)CC=12)CC=1C(OC)=CC=C2C1CCN(C)CC1 BRQAPHCTBAPJLO-CYBMUJFWSA-N 0.000 description 1
HOEBGGFZFXKOQD-DDWIOCJRSA-N (2r)-8-bromo-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.C1=CC(Br)=C2C[C@H](N)CCC2=C1 HOEBGGFZFXKOQD-DDWIOCJRSA-N 0.000 description 1
GDFOHXLSNDZEHH-SBSPUUFOSA-N (2r)-8-methoxy-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.C1C[C@@H](N)CC2=C1C=CC=C2OC GDFOHXLSNDZEHH-SBSPUUFOSA-N 0.000 description 1
DNISEZBAYYIQFB-PHDIDXHHSA-N (2r,3r)-2,3-diacetyloxybutanedioic acid Chemical compound CC(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(C)=O DNISEZBAYYIQFB-PHDIDXHHSA-N 0.000 description 1
WBVYTRBDTHQZAL-LBPRGKRZSA-N (2s)-5-methoxy-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C([C@H](N)CC=12)CC=1C(OC)=CC=C2N1CCN(C)CC1 WBVYTRBDTHQZAL-LBPRGKRZSA-N 0.000 description 1
WEHVQIQNGXWTME-UHFFFAOYSA-N (4-aminophenyl)-morpholin-4-ylmethanone Chemical compound C1=CC(N)=CC=C1C(=O)N1CCOCC1 WEHVQIQNGXWTME-UHFFFAOYSA-N 0.000 description 1
DSXOOSUFCGJRKZ-LLVKDONJSA-N (6r)-6-amino-4-(4-methylpiperazin-1-yl)-5,6,7,8-tetrahydronaphthalen-1-ol Chemical compound C1CN(C)CCN1C1=CC=C(O)C2=C1C[C@H](N)CC2 DSXOOSUFCGJRKZ-LLVKDONJSA-N 0.000 description 1
RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
PQDSEDWZZSJLMC-ZREVKMQJSA-N (z)-but-2-enedioic acid;n-[(2r)-5-methyl-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound OC(=O)\C=C/C(O)=O.C1CN(C)CCN1C1=CC=C(C)C2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)N1CCOCC1)CC2 PQDSEDWZZSJLMC-ZREVKMQJSA-N 0.000 description 1
AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 description 1
IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical compound C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 description 1
WLXGQMVCYPUOLM-UHFFFAOYSA-N 1-hydroxyethanesulfonic acid Chemical compound CC(O)S(O)(=O)=O WLXGQMVCYPUOLM-UHFFFAOYSA-N 0.000 description 1
XWSGEVNYFYKXCP-UHFFFAOYSA-N 2-[carboxymethyl(methyl)amino]acetic acid Chemical compound OC(=O)CN(C)CC(O)=O XWSGEVNYFYKXCP-UHFFFAOYSA-N 0.000 description 1
KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
WTRIMJTZOOLIFZ-UHFFFAOYSA-N 2-bromo-2-methylpropanamide Chemical compound CC(C)(Br)C(N)=O WTRIMJTZOOLIFZ-UHFFFAOYSA-N 0.000 description 1
YMDZDFSUDFLGMX-UHFFFAOYSA-N 2-chloro-n-(2-chloroethyl)ethanamine;hydron;chloride Chemical compound [Cl-].ClCC[NH2+]CCCl YMDZDFSUDFLGMX-UHFFFAOYSA-N 0.000 description 1
WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
ALKYHXVLJMQRLQ-UHFFFAOYSA-N 3-Hydroxy-2-naphthoate Chemical compound C1=CC=C2C=C(O)C(C(=O)O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-N 0.000 description 1
BFTPXPCTGHARJF-UHFFFAOYSA-N 4-(morpholine-4-carbonyl)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C(=O)N1CCOCC1 BFTPXPCTGHARJF-UHFFFAOYSA-N 0.000 description 1
OXZYBOLWRXENKT-UHFFFAOYSA-N 4-(trifluoromethyl)benzoyl chloride Chemical compound FC(F)(F)C1=CC=C(C(Cl)=O)C=C1 OXZYBOLWRXENKT-UHFFFAOYSA-N 0.000 description 1
ALYNCZNDIQEVRV-PZFLKRBQSA-N 4-amino-3,5-ditritiobenzoic acid Chemical compound [3H]c1cc(cc([3H])c1N)C(O)=O ALYNCZNDIQEVRV-PZFLKRBQSA-N 0.000 description 1
WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
KMGCTFHTBKBITO-UHFFFAOYSA-N 4-butoxybenzoyl chloride Chemical compound CCCCOC1=CC=C(C(Cl)=O)C=C1 KMGCTFHTBKBITO-UHFFFAOYSA-N 0.000 description 1
PEKBTVBHUWRNPL-LJQANCHMSA-N 4-chloro-n-[(2r)-5-methyl-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1CN(C)CCN1C1=CC=C(C)C2=C1C[C@H](NC(=O)C=1C=CC(Cl)=CC=1)CC2 PEKBTVBHUWRNPL-LJQANCHMSA-N 0.000 description 1
RKIDDEGICSMIJA-UHFFFAOYSA-N 4-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C=C1 RKIDDEGICSMIJA-UHFFFAOYSA-N 0.000 description 1
ALDPGHZOCSRDNU-GOSISDBHSA-N 4-cyano-n-[(2r)-5-hydroxy-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1CN(C)CCN1C1=CC=C(O)C2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)C#N)CC2 ALDPGHZOCSRDNU-GOSISDBHSA-N 0.000 description 1
229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
PHNDZBFLOPIMSM-UHFFFAOYSA-N 4-morpholin-4-ylaniline Chemical compound C1=CC(N)=CC=C1N1CCOCC1 PHNDZBFLOPIMSM-UHFFFAOYSA-N 0.000 description 1
210000002348 5-ht neuron Anatomy 0.000 description 1
CZGSIXQMWGCMSF-UHFFFAOYSA-N 8-amino-5-methoxy-n-(4-morpholin-4-ylphenyl)-1,2,3,4-tetrahydronaphthalene-2-carboxamide Chemical compound C1CC=2C(OC)=CC=C(N)C=2CC1C(=O)NC(C=C1)=CC=C1N1CCOCC1 CZGSIXQMWGCMSF-UHFFFAOYSA-N 0.000 description 1
208000008811 Agoraphobia Diseases 0.000 description 1
208000024827 Alzheimer disease Diseases 0.000 description 1
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
239000005695 Ammonium acetate Substances 0.000 description 1
229910015845 BBr3 Inorganic materials 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
208000020925 Bipolar disease Diseases 0.000 description 1
101150041968 CDC13 gene Proteins 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
BPIAZYVKTAESAL-KLQYNRQASA-N Cl.N[C@H]1CC2=CC=CC(=C2CC1)OC.Cl Chemical compound Cl.N[C@H]1CC2=CC=CC(=C2CC1)OC.Cl BPIAZYVKTAESAL-KLQYNRQASA-N 0.000 description 1
GDLIGKIOYRNHDA-UHFFFAOYSA-N Clomipramine Chemical compound C1CC2=CC=C(Cl)C=C2N(CCCN(C)C)C2=CC=CC=C21 GDLIGKIOYRNHDA-UHFFFAOYSA-N 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
206010012374 Depressed mood Diseases 0.000 description 1
208000020401 Depressive disease Diseases 0.000 description 1
208000026331 Disruptive, Impulse Control, and Conduct disease Diseases 0.000 description 1
208000030814 Eating disease Diseases 0.000 description 1
244000165918 Eucalyptus papuana Species 0.000 description 1
208000019454 Feeding and Eating disease Diseases 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
102000014630 G protein-coupled serotonin receptor activity proteins Human genes 0.000 description 1
230000005526 G1 to G0 transition Effects 0.000 description 1
208000018522 Gastrointestinal disease Diseases 0.000 description 1
208000011688 Generalised anxiety disease Diseases 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
208000030990 Impulse-control disease Diseases 0.000 description 1
239000001358 L(+)-tartaric acid Substances 0.000 description 1
235000011002 L(+)-tartaric acid Nutrition 0.000 description 1
FEWJPZIEWOKRBE-LWMBPPNESA-N L-(+)-Tartaric acid Natural products OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
229940123685 Monoamine oxidase inhibitor Drugs 0.000 description 1
SNIXRMIHFOIVBB-UHFFFAOYSA-N N-Hydroxyl-tryptamine Chemical compound C1=CC=C2C(CCNO)=CNC2=C1 SNIXRMIHFOIVBB-UHFFFAOYSA-N 0.000 description 1
208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
239000005662 Paraffin oil Substances 0.000 description 1
DPWPWRLQFGFJFI-UHFFFAOYSA-N Pargyline Chemical compound C#CCN(C)CC1=CC=CC=C1 DPWPWRLQFGFJFI-UHFFFAOYSA-N 0.000 description 1
206010034912 Phobia Diseases 0.000 description 1
102000003946 Prolactin Human genes 0.000 description 1
108010057464 Prolactin Proteins 0.000 description 1
241000283984 Rodentia Species 0.000 description 1
206010041250 Social phobia Diseases 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 description 1
102000002852 Vasopressins Human genes 0.000 description 1
108010004977 Vasopressins Proteins 0.000 description 1
HHRFWSALGNYPHA-UHFFFAOYSA-N [N].C1CNCCN1 Chemical compound [N].C1CNCCN1 HHRFWSALGNYPHA-UHFFFAOYSA-N 0.000 description 1
239000000205 acacia gum Substances 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
230000004913 activation Effects 0.000 description 1
229910001508 alkali metal halide Inorganic materials 0.000 description 1
150000008045 alkali metal halides Chemical class 0.000 description 1
125000003545 alkoxy group Chemical group 0.000 description 1
125000005907 alkyl ester group Chemical group 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
229960004909 aminosalicylic acid Drugs 0.000 description 1
235000019257 ammonium acetate Nutrition 0.000 description 1
229940043376 ammonium acetate Drugs 0.000 description 1
230000003042 antagnostic effect Effects 0.000 description 1
230000001430 anti-depressive effect Effects 0.000 description 1
KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
238000010533 azeotropic distillation Methods 0.000 description 1
125000005605 benzo group Chemical group 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
LURYMYITPCOQAU-UHFFFAOYSA-N benzoyl isocyanate Chemical compound O=C=NC(=O)C1=CC=CC=C1 LURYMYITPCOQAU-UHFFFAOYSA-N 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N beta-hydroxyethanesulfonic acid Natural products OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
239000006172 buffering agent Substances 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
239000011575 calcium Substances 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
CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
239000008116 calcium stearate Substances 0.000 description 1
235000013539 calcium stearate Nutrition 0.000 description 1
239000002775 capsule Substances 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
239000008112 carboxymethyl-cellulose Substances 0.000 description 1
210000005056 cell body Anatomy 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
229960004606 clomipramine Drugs 0.000 description 1
238000000576 coating method Methods 0.000 description 1
239000003086 colorant Substances 0.000 description 1
230000001276 controlling effect Effects 0.000 description 1
230000001054 cortical effect Effects 0.000 description 1
239000006184 cosolvent Substances 0.000 description 1
239000007822 coupling agent Substances 0.000 description 1
239000010779 crude oil Substances 0.000 description 1
238000005520 cutting process Methods 0.000 description 1
HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
230000020335 dealkylation Effects 0.000 description 1
238000006900 dealkylation reaction Methods 0.000 description 1
230000006735 deficit Effects 0.000 description 1
230000003001 depressive effect Effects 0.000 description 1
230000000994 depressogenic effect Effects 0.000 description 1
238000001514 detection method Methods 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
238000000113 differential scanning calorimetry Methods 0.000 description 1
125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
ZGTMUACCHSMWAC-UHFFFAOYSA-N disodium;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid Chemical compound [Na+].[Na+].OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O ZGTMUACCHSMWAC-UHFFFAOYSA-N 0.000 description 1
235000014632 disordered eating Nutrition 0.000 description 1
GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 1
229940052760 dopamine agonists Drugs 0.000 description 1
239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
230000000857 drug effect Effects 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000000975 dye Substances 0.000 description 1
208000024732 dysthymic disease Diseases 0.000 description 1
230000002526 effect on cardiovascular system Effects 0.000 description 1
238000010828 elution Methods 0.000 description 1
150000002081 enamines Chemical class 0.000 description 1
230000002708 enhancing effect Effects 0.000 description 1
DSGUSEBCDAKBCM-UHFFFAOYSA-N ethane-1,2-disulfonic acid;dihydrate Chemical compound O.O.OS(=O)(=O)CCS(O)(=O)=O DSGUSEBCDAKBCM-UHFFFAOYSA-N 0.000 description 1
AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 description 1
229960002464 fluoxetine Drugs 0.000 description 1
229960004038 fluvoxamine Drugs 0.000 description 1
CJOFXWAVKWHTFT-XSFVSMFZSA-N fluvoxamine Chemical compound COCCCC\C(=N/OCCN)C1=CC=C(C(F)(F)F)C=C1 CJOFXWAVKWHTFT-XSFVSMFZSA-N 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
208000029364 generalized anxiety disease Diseases 0.000 description 1
239000011491 glass wool Substances 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
239000000174 gluconic acid Substances 0.000 description 1
229960004275 glycolic acid Drugs 0.000 description 1
239000008187 granular material Substances 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
230000036571 hydration Effects 0.000 description 1
238000006703 hydration reaction Methods 0.000 description 1
235000011167 hydrochloric acid Nutrition 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
229960000890 hydrocortisone Drugs 0.000 description 1
239000005457 ice water Substances 0.000 description 1
AUONNNVJUCSETH-UHFFFAOYSA-N icosanoyl icosanoate Chemical compound CCCCCCCCCCCCCCCCCCCC(=O)OC(=O)CCCCCCCCCCCCCCCCCCC AUONNNVJUCSETH-UHFFFAOYSA-N 0.000 description 1
150000003949 imides Chemical class 0.000 description 1
150000002466 imines Chemical class 0.000 description 1
230000036540 impulse transmission Effects 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
238000006138 lithiation reaction Methods 0.000 description 1
230000004807 localization Effects 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
201000005296 lung carcinoma Diseases 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
208000024714 major depressive disease Diseases 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
229940099690 malic acid Drugs 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
AGJSNMGHAVDLRQ-HUUJSLGLSA-N methyl (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-HUUJSLGLSA-N 0.000 description 1
TXHUEPIEVTWFCS-UHFFFAOYSA-N methyl 5-methoxy-8-nitro-1,2,3,4-tetrahydronaphthalene-2-carboxylate Chemical compound C1=CC([N+]([O-])=O)=C2CC(C(=O)OC)CCC2=C1OC TXHUEPIEVTWFCS-UHFFFAOYSA-N 0.000 description 1
DYGVMAIASODCIW-UHFFFAOYSA-N methyl 5-methoxy-8-nitro-1,2,3,4-tetrahydronaphthalene-2-carboxylate;methyl 5-methoxy-1,2,3,4-tetrahydronaphthalene-2-carboxylate Chemical compound C1=CC=C(OC)C2=C1CC(C(=O)OC)CC2.C1=CC([N+]([O-])=O)=C2CC(C(=O)OC)CCC2=C1OC DYGVMAIASODCIW-UHFFFAOYSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
239000002899 monoamine oxidase inhibitor Substances 0.000 description 1
235000019799 monosodium phosphate Nutrition 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
ZBSPAQLDWFWLKA-HXUWFJFHSA-N n-[(2r)-5-(difluoromethoxy)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound C1CN(C)CCN1C1=CC=C(OC(F)F)C2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)N1CCOCC1)CC2 ZBSPAQLDWFWLKA-HXUWFJFHSA-N 0.000 description 1
GTFLUNMXBZEEFW-OAQYLSRUSA-N n-[(2r)-5-bromo-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-(morpholine-4-carbonyl)benzamide Chemical compound C1CN(C)CCN1C1=CC=C(Br)C2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)C(=O)N1CCOCC1)CC2 GTFLUNMXBZEEFW-OAQYLSRUSA-N 0.000 description 1
WZMSJJIAEOODBC-JOCHJYFZSA-N n-[(2r)-5-methoxy-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-(morpholine-4-carbonyl)benzamide Chemical compound C([C@H](CC=12)NC(=O)C=3C=CC(=CC=3)C(=O)N3CCOCC3)CC=1C(OC)=CC=C2N1CCN(C)CC1 WZMSJJIAEOODBC-JOCHJYFZSA-N 0.000 description 1
MZCIWKHRVTWHAL-VZYDHVRKSA-N n-[(2r)-5-methyl-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide;sulfuric acid Chemical compound OS(O)(=O)=O.C1CN(C)CCN1C1=CC=C(C)C2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)N1CCOCC1)CC2 MZCIWKHRVTWHAL-VZYDHVRKSA-N 0.000 description 1
CCUKQFHHPNQNAU-LJQANCHMSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-(trifluoromethyl)benzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)C(F)(F)F)CC2 CCUKQFHHPNQNAU-LJQANCHMSA-N 0.000 description 1
125000006606 n-butoxy group Chemical group 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
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
210000005036 nerve Anatomy 0.000 description 1
230000007383 nerve stimulation Effects 0.000 description 1
230000001537 neural effect Effects 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
239000011664 nicotinic acid Substances 0.000 description 1
229960003512 nicotinic acid Drugs 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
208000019906 panic disease Diseases 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
235000011007 phosphoric acid Nutrition 0.000 description 1
RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
208000028173 post-traumatic stress disease Diseases 0.000 description 1
230000001242 postsynaptic effect Effects 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
229940097325 prolactin Drugs 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
229940095574 propionic acid Drugs 0.000 description 1
208000020016 psychiatric disease Diseases 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
210000001609 raphe nuclei Anatomy 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
239000000018 receptor agonist Substances 0.000 description 1
229940044601 receptor agonist Drugs 0.000 description 1
239000002464 receptor antagonist Substances 0.000 description 1
229940044551 receptor antagonist Drugs 0.000 description 1
238000005932 reductive alkylation reaction Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
MQTUXRKNJYPMCG-CYBMUJFWSA-N robalzotan Chemical compound C1CCC1N([C@H]1COC=2C(F)=CC=C(C=2C1)C(=O)N)C1CCC1 MQTUXRKNJYPMCG-CYBMUJFWSA-N 0.000 description 1
229910052701 rubidium Inorganic materials 0.000 description 1
235000019204 saccharin Nutrition 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
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
238000012216 screening Methods 0.000 description 1
208000012672 seasonal affective disease Diseases 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
229960002073 sertraline Drugs 0.000 description 1
VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 1
230000009329 sexual behaviour Effects 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
239000012439 solid excipient Substances 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
201000001716 specific phobia Diseases 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-M succinate(1-) Chemical compound OC(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-M 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
229960005137 succinic acid Drugs 0.000 description 1
IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
229950000244 sulfanilic acid Drugs 0.000 description 1
239000000829 suppository Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
229940095064 tartrate Drugs 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
DEEFVBOHUQYLLZ-XMMPIXPASA-N tert-butyl 4-[(7R)-4-methyl-7-[(4-morpholin-4-ylbenzoyl)amino]-5,6,7,8-tetrahydronaphthalen-1-yl]piperazine-1-carboxylate Chemical compound CC1=C2CC[C@H](CC2=C(C=C1)N1CCN(CC1)C(=O)OC(C)(C)C)NC(C1=CC=C(C=C1)N1CCOCC1)=O DEEFVBOHUQYLLZ-XMMPIXPASA-N 0.000 description 1
GGGBHGKCSXURHO-JOCHJYFZSA-N tert-butyl 4-[(7r)-4-bromo-7-[(4-morpholin-4-ylbenzoyl)amino]-5,6,7,8-tetrahydronaphthalen-1-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C(Br)C2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)N1CCOCC1)CC2 GGGBHGKCSXURHO-JOCHJYFZSA-N 0.000 description 1
DSNAAEGYBPDGNZ-CYBMUJFWSA-N tert-butyl 4-[(7r)-7-amino-4-bromo-5,6,7,8-tetrahydronaphthalen-1-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C(Br)C2=C1C[C@H](N)CC2 DSNAAEGYBPDGNZ-CYBMUJFWSA-N 0.000 description 1
KNODWTCYFYFCEU-OAHLLOKOSA-N tert-butyl 4-[(7r)-7-amino-4-methyl-5,6,7,8-tetrahydronaphthalen-1-yl]piperazine-1-carboxylate Chemical compound C([C@@H](N)CC=12)CC=1C(C)=CC=C2N1CCN(C(=O)OC(C)(C)C)CC1 KNODWTCYFYFCEU-OAHLLOKOSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
235000010215 titanium dioxide Nutrition 0.000 description 1
PNQBEPDZQUOCNY-UHFFFAOYSA-N trifluoroacetyl chloride Chemical compound FC(F)(F)C(Cl)=O PNQBEPDZQUOCNY-UHFFFAOYSA-N 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
229960003726 vasopressin Drugs 0.000 description 1
239000011345 viscous material Substances 0.000 description 1
239000001993 wax Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
- 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
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
- 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
- A61P25/06—Antimigraine agents
- 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
- A61P25/22—Anxiolytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/24—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/205—Radicals derived from carbonic acid
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline

NO20000356A 1997-07-25 2000-01-24 Substituerte 1,2,3,4-tetrahydronaftalenderivater, farmasöytisk formuleringinneholdende slike, fremgangsmåte for deres fremstilling, oganvendelse derav NO315609B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
SE9702799A SE9702799D0 (sv)	1997-07-25	1997-07-25	New compounds
PCT/SE1998/001390 WO1999005134A1 (en)	1997-07-25	1998-07-15	Substituted 1,2,3,4-tetrahydronaphthalene derivatives

Publications (3)

Publication Number	Publication Date
NO20000356D0 NO20000356D0 (no)	2000-01-24
NO20000356L NO20000356L (no)	2000-03-27
NO315609B1 true NO315609B1 (no)	2003-09-29

Family

ID=20407828

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO20000356A NO315609B1 (no)	1997-07-25	2000-01-24	Substituerte 1,2,3,4-tetrahydronaftalenderivater, farmasöytisk formuleringinneholdende slike, fremgangsmåte for deres fremstilling, oganvendelse derav

Country Status (37)

Country	Link
US (3)	US6313118B1 (sv)
EP (1)	EP1000048B1 (sv)
JP (1)	JP3895923B2 (sv)
KR (1)	KR20010022171A (sv)
CN (1)	CN1270585A (sv)
AR (2)	AR013370A1 (sv)
AT (1)	ATE228510T1 (sv)
AU (1)	AU739569B2 (sv)
BR (1)	BR9811042A (sv)
CA (1)	CA2296518A1 (sv)
DE (1)	DE69809755T2 (sv)
DK (1)	DK1000048T3 (sv)
DZ (1)	DZ2569A1 (sv)
EE (1)	EE04238B1 (sv)
ES (1)	ES2187983T3 (sv)
HK (1)	HK1025963A1 (sv)
HR (1)	HRP980404B1 (sv)
HU (1)	HUP0004334A3 (sv)
ID (1)	ID24583A (sv)
IL (1)	IL134108A0 (sv)
IS (1)	IS5358A (sv)
MA (1)	MA26521A1 (sv)
NO (1)	NO315609B1 (sv)
NZ (1)	NZ502384A (sv)
PL (1)	PL338563A1 (sv)
PT (1)	PT1000048E (sv)
RU (1)	RU2194696C2 (sv)
SE (1)	SE9702799D0 (sv)
SI (1)	SI1000048T1 (sv)
SK (1)	SK283918B6 (sv)
TN (1)	TNSN98141A1 (sv)
TR (1)	TR200000229T2 (sv)
TW (1)	TW438781B (sv)
UA (1)	UA69389C2 (sv)
WO (1)	WO1999005134A1 (sv)
YU (1)	YU2300A (sv)
ZA (1)	ZA986588B (sv)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SE9601110D0 (sv)	1996-03-22	1996-03-22	Astra Ab	Substituted 1,2,3,4-tetrahydronaphthalene derivatives
SE9900190D0 (sv) *	1999-01-22	1999-01-22	Astra Ab	New compounds
SE9904724D0 (sv) *	1999-12-22	1999-12-22	Carlsson A Research Ab	New modulators of dopamine neurotransmission I
SE0002729D0 (sv) *	2000-07-20	2000-07-20	Astrazeneca Ab	Novel compound form
AR034206A1 (es)	2001-02-16	2004-02-04	Solvay Pharm Bv	Un procedimiento para la preparacion de mesilatos de derivados de piperazina y dichos mesilatos
SE0102856D0 (sv) *	2001-08-27	2001-08-27	Astrazeneca Ab	A new method
SE0103644D0 (sv) *	2001-11-01	2001-11-01	Astrazeneca Ab	Therapeutic isoquinoline compounds
US7101881B2 (en) *	2003-06-11	2006-09-05	Pfizer Inc	Tetrahydroquinolines
SE0301798D0 (sv) *	2003-06-19	2003-06-19	Astrazeneca Ab	New use IV
SE0301794D0 (sv) *	2003-06-19	2003-06-19	Astrazeneca Ab	New use III
JP2008500383A (ja) *	2004-05-21	2008-01-10	ファイザー・プロダクツ・インク	５−ｈｔ１ｂアンタゴニスト、インバースアゴニストおよび部分アゴニストとしてのテトラヒドロナフチルピペラジン類
US20080033050A1 (en) *	2006-08-04	2008-02-07	Richards Patricia Allison Tewe	Method of treating thermoregulatory disfunction with paroxetine
WO2008130319A2 (en) *	2007-04-23	2008-10-30	Astrazeneca Ab	Novel n-tetrahydronaphtalene or n-chromane carboxamide derivatives for the treatment of pain
WO2008130323A1 (en) *	2007-04-23	2008-10-30	Astrazeneca Ab	Novel 8-piperazine-tetrahydronaphtalene derivatives for the treatment of pain
WO2008130322A1 (en) *	2007-04-23	2008-10-30	Astrazeneca Ab	Novel 5-heterocyclyl-chromane derivatives for the treatment of pain
SA08290245B1 (ar) *	2007-04-23	2012-02-12	استرازينيكا ايه بي	مشتقات كربو كساميد جديدة من -n (8-اريل رباعي هيدرو نفثالين غير متجانس- 2- يل) أو -n (5-اريل كرومان غير متجانس -3-يل) لعلاج الألم
WO2008130321A2 (en) *	2007-04-23	2008-10-30	Astrazeneca Ab	Novel n-tetrahydronaphtalene or 5-heterocyclyl-chromane or 8-heterocyclyl-tetrahydronaphtalene derivatives for the treatment of pain
EP2098511A1 (en)	2008-03-07	2009-09-09	Solvias AG	Process for preparing compounds containing a hydronaphtalene structure with an unsymmetrically substituted benzene ring
AU2009260905B2 (en)	2008-06-20	2012-08-23	Astrazeneca Ab	Dibenzothiazepine derivatives and use thereof
GB201002563D0 (en)	2010-02-15	2010-03-31	Cambridge Entpr Ltd	Compounds
GB201111704D0 (en)	2011-07-07	2011-08-24	Takeda Pharmaceutical	Novel compounds
GB201111705D0 (en)	2011-07-07	2011-08-24	Takeda Pharmaceutical	Compounds and their use
JO3115B1 (ar)	2011-08-22	2017-09-20	Takeda Pharmaceuticals Co	مركبات بيريدازينون واستخدامها كمثبطات daao
GB201209587D0 (en)	2012-05-30	2012-07-11	Takeda Pharmaceutical	Therapeutic compounds
CN105324372B (zh)	2013-06-21	2018-03-06	武田药品工业株式会社	作为前动力蛋白受体调节剂的1‑磺酰基哌啶衍生物
GB201314286D0 (en)	2013-08-08	2013-09-25	Takeda Pharmaceutical	Therapeutic Compounds
GB201318222D0 (en)	2013-10-15	2013-11-27	Takeda Pharmaceutical	Novel compounds
GB201320905D0 (en)	2013-11-27	2014-01-08	Takeda Pharmaceutical	Therapeutic compounds
TW201613864A (en)	2014-02-20	2016-04-16	Takeda Pharmaceutical	Novel compounds
GB201616839D0 (en)	2016-10-04	2016-11-16	Takeda Pharmaceutical Company Limited	Therapeutic compounds
GB201619514D0 (en)	2016-11-18	2017-01-04	Takeda Pharmaceuticals Co	Novel compounds
JP2021138648A (ja)	2020-03-04	2021-09-16	武田薬品工業株式会社	経口固形製剤

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3919624A1 (de)	1989-06-15	1990-12-20	Boehringer Ingelheim Kg	Neue 2,5-diaminotetraline, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel
GB9119920D0 (en)	1991-09-18	1991-10-30	Glaxo Group Ltd	Chemical compounds
GB9119932D0 (en)	1991-09-18	1991-10-30	Glaxo Group Ltd	Chemical compounds
EP0533268B1 (en)	1991-09-18	2001-08-16	Glaxo Group Limited	Benzanilide derivatives as 5-HT1D antagonists
DK148392D0 (da)	1992-12-09	1992-12-09	Lundbeck & Co As H	Heterocykliske forbindelser
GB2273930A (en)	1992-12-30	1994-07-06	Glaxo Group Ltd	Benzanilide derivatives
EP0689536B1 (en) *	1993-03-16	2001-05-23	Pfizer Inc.	Naphthalene derivatives
EP0724580A1 (en)	1993-10-19	1996-08-07	Smithkline Beecham Plc	Benzanilide derivatives as 5ht-1d receptor antagonists
SE9601110D0 (sv) *	1996-03-22	1996-03-22	Astra Ab	Substituted 1,2,3,4-tetrahydronaphthalene derivatives

1997
- 1997-07-25 SE SE9702799A patent/SE9702799D0/sv unknown
1998
- 1998-07-13 TW TW087111330A patent/TW438781B/zh not_active IP Right Cessation
- 1998-07-15 DK DK98934104T patent/DK1000048T3/da active
- 1998-07-15 KR KR1020007000743A patent/KR20010022171A/ko not_active Application Discontinuation
- 1998-07-15 SI SI9830343T patent/SI1000048T1/xx unknown
- 1998-07-15 AT AT98934104T patent/ATE228510T1/de not_active IP Right Cessation
- 1998-07-15 BR BR9811042-0A patent/BR9811042A/pt not_active IP Right Cessation
- 1998-07-15 US US09/171,577 patent/US6313118B1/en not_active Expired - Fee Related
- 1998-07-15 UA UA2000021064A patent/UA69389C2/uk unknown
- 1998-07-15 NZ NZ502384A patent/NZ502384A/en unknown
- 1998-07-15 TR TR2000/00229T patent/TR200000229T2/xx unknown
- 1998-07-15 AU AU83703/98A patent/AU739569B2/en not_active Ceased
- 1998-07-15 HU HU0004334A patent/HUP0004334A3/hu unknown
- 1998-07-15 WO PCT/SE1998/001390 patent/WO1999005134A1/en not_active Application Discontinuation
- 1998-07-15 DE DE69809755T patent/DE69809755T2/de not_active Expired - Fee Related
- 1998-07-15 RU RU2000104802/04A patent/RU2194696C2/ru not_active IP Right Cessation
- 1998-07-15 PT PT98934104T patent/PT1000048E/pt unknown
- 1998-07-15 SK SK1883-99A patent/SK283918B6/sk unknown
- 1998-07-15 JP JP2000504131A patent/JP3895923B2/ja not_active Expired - Fee Related
- 1998-07-15 ES ES98934104T patent/ES2187983T3/es not_active Expired - Lifetime
- 1998-07-15 CN CN98809246A patent/CN1270585A/zh active Pending
- 1998-07-15 MA MA25169A patent/MA26521A1/fr unknown
- 1998-07-15 EE EEP200000041A patent/EE04238B1/xx not_active IP Right Cessation
- 1998-07-15 PL PL98338563A patent/PL338563A1/xx unknown
- 1998-07-15 IL IL13410898A patent/IL134108A0/xx unknown
- 1998-07-15 CA CA002296518A patent/CA2296518A1/en not_active Abandoned
- 1998-07-15 EP EP98934104A patent/EP1000048B1/en not_active Expired - Lifetime
- 1998-07-15 YU YU2300A patent/YU2300A/sh unknown
- 1998-07-15 ID IDW20000122A patent/ID24583A/id unknown
- 1998-07-22 DZ DZ980179A patent/DZ2569A1/xx active
- 1998-07-23 HR HR980404A patent/HRP980404B1/xx not_active IP Right Cessation
- 1998-07-23 TN TNTNSN98141A patent/TNSN98141A1/fr unknown
- 1998-07-23 ZA ZA986588A patent/ZA986588B/xx unknown
- 1998-07-24 AR ARP980103667A patent/AR013370A1/es unknown
2000
- 2000-01-24 NO NO20000356A patent/NO315609B1/no not_active IP Right Cessation
- 2000-01-24 IS IS5358A patent/IS5358A/is unknown
- 2000-08-17 HK HK00105178A patent/HK1025963A1/xx not_active IP Right Cessation
2001
- 2001-07-10 US US09/902,123 patent/US6534652B2/en not_active Expired - Fee Related
- 2001-07-10 US US09/902,000 patent/US6410532B2/en not_active Expired - Fee Related
2004
- 2004-10-25 AR ARP040103875A patent/AR046193A2/es unknown

Also Published As

Publication number	Publication date
MA26521A1 (fr)	2004-12-20
ATE228510T1 (de)	2002-12-15
AU8370398A (en)	1999-02-16
HRP980404A2 (en)	1999-04-30
US20010051626A1 (en)	2001-12-13
US6410532B2 (en)	2002-06-25
PT1000048E (pt)	2003-03-31
ES2187983T3 (es)	2003-06-16
IS5358A (is)	2000-01-24
CA2296518A1 (en)	1999-02-04
DK1000048T3 (da)	2003-03-03
SI1000048T1 (en)	2003-04-30
HUP0004334A3 (en)	2002-10-28
AR013370A1 (es)	2000-12-27
TR200000229T2 (tr)	2000-06-21
RU2194696C2 (ru)	2002-12-20
SK283918B6 (sk)	2004-05-04
US6313118B1 (en)	2001-11-06
NO20000356L (no)	2000-03-27
EE04238B1 (et)	2004-02-16
US20010051623A1 (en)	2001-12-13
NZ502384A (en)	2001-05-25
DE69809755D1 (de)	2003-01-09
DE69809755T2 (de)	2003-07-17
CN1270585A (zh)	2000-10-18
BR9811042A (pt)	2000-08-15
DZ2569A1 (fr)	2003-02-15
HK1025963A1 (en)	2000-12-01
AR046193A2 (es)	2005-11-30
HUP0004334A2 (en)	2001-03-28
PL338563A1 (en)	2000-11-06
NO20000356D0 (no)	2000-01-24
UA69389C2 (uk)	2004-09-15
AU739569B2 (en)	2001-10-18
IL134108A0 (en)	2001-04-30
TNSN98141A1 (fr)	2005-03-15
TW438781B (en)	2001-06-07
EP1000048B1 (en)	2002-11-27
SK188399A3 (en)	2000-07-11
HRP980404B1 (en)	2002-10-31
EE200000041A (et)	2000-10-16
ZA986588B (en)	1999-01-25
YU2300A (sh)	2002-10-18
KR20010022171A (ko)	2001-03-15
US6534652B2 (en)	2003-03-18
JP2001510837A (ja)	2001-08-07
EP1000048A1 (en)	2000-05-17
WO1999005134A1 (en)	1999-02-04
SE9702799D0 (sv)	1997-07-25
JP3895923B2 (ja)	2007-03-22
ID24583A (id)	2000-07-27

Legal Events

Date	Code	Title	Description
2006-02-27	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
NO315609B1 (no)	2003-09-29	Substituerte 1,2,3,4-tetrahydronaftalenderivater, farmasöytisk formuleringinneholdende slike, fremgangsmåte for deres fremstilling, oganvendelse derav
AU709856B2 (en)	1999-09-09	Substituted 1,2,3,4-tetrahydronaphthalene derivatives
US6670359B2 (en)	2003-12-30	Substituted chroman derivatives
US6159971A (en)	2000-12-12	Combination of a 5-HT reuptake inhibitor and a h5-HT1B anatagonist or partial agonist
EP1025096B1 (en)	2003-11-26	Substituted chroman derivatives
EP1025094B1 (en)	2004-08-25	Substituted indan derivatives
NZ530137A (en)	2005-09-30	4-phenyl-1-piperazinyl, -piperidinyl and -tetrahydropyridyl derivatives
AU778674B2 (en)	2004-12-16	New morpholinobenzamide salts
MXPA00000676A (en)	2001-05-07	Substituted 1,2,3,4-tetrahydronaphthalene derivatives
NZ503174A (en)	2002-03-01	A synergistic combination of a benzopyran selective 5-HT 1A antagonist and a selective h5-HT 1B antagonist or partial agonist
CZ2000275A3 (cs)	2000-09-13	Substituované 1,2,2,4-tetrahydronaftalenové deriváty
MXPA01007403A (en)	2002-03-05	New morpholinobenzamide salts