NO311803B1 - Substituerte 1,2,3,4-tetrahydronaftalenderivater, farmasöytisk preparat inneholdende slike derivater, deresanvendelse, fremgangsmåte for deres fremstilling, og mellomprodukt - Google Patents
Substituerte 1,2,3,4-tetrahydronaftalenderivater, farmasöytisk preparat inneholdende slike derivater, deresanvendelse, fremgangsmåte for deres fremstilling, og mellomprodukt Download PDFInfo
- Publication number
- NO311803B1 NO311803B1 NO19984385A NO984385A NO311803B1 NO 311803 B1 NO311803 B1 NO 311803B1 NO 19984385 A NO19984385 A NO 19984385A NO 984385 A NO984385 A NO 984385A NO 311803 B1 NO311803 B1 NO 311803B1
- Authority
- NO
- Norway
- Prior art keywords
- compound
- methylpiperazin
- mmol
- tetrahydro
- naphthyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 61
- 230000008569 process Effects 0.000 title claims description 11
- 238000002360 preparation method Methods 0.000 title claims description 10
- 239000000825 pharmaceutical preparation Chemical class 0.000 title claims description 5
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical class C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 359
- 238000006243 chemical reaction Methods 0.000 claims description 135
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 81
- -1 NReR? Chemical group 0.000 claims description 77
- 229910052739 hydrogen Inorganic materials 0.000 claims description 43
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 43
- 125000004169 (C1-C6) alkyl group Chemical class 0.000 claims description 41
- 239000001257 hydrogen Substances 0.000 claims description 37
- 229910052736 halogen Inorganic materials 0.000 claims description 26
- 150000002367 halogens Chemical class 0.000 claims description 24
- 125000003386 piperidinyl group Chemical group 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 21
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 20
- 239000000460 chlorine Substances 0.000 claims description 20
- 125000006239 protecting group Chemical group 0.000 claims description 20
- 125000002757 morpholinyl group Chemical group 0.000 claims description 19
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 18
- 229910052801 chlorine Inorganic materials 0.000 claims description 18
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 17
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 17
- 229910052794 bromium Inorganic materials 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 208000035475 disorder Diseases 0.000 claims description 16
- 150000002431 hydrogen Chemical group 0.000 claims description 16
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 14
- 125000000520 N-substituted aminocarbonyl group Chemical group [*]NC(=O)* 0.000 claims description 13
- 239000005557 antagonist Substances 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 230000001404 mediated effect Effects 0.000 claims description 10
- 125000005913 (C3-C6) cycloalkyl group Chemical class 0.000 claims description 9
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 9
- 230000003213 activating effect Effects 0.000 claims description 9
- 239000012458 free base Substances 0.000 claims description 9
- 230000029936 alkylation Effects 0.000 claims description 8
- 238000005804 alkylation reaction Methods 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 125000004193 piperazinyl group Chemical group 0.000 claims description 8
- 208000019901 Anxiety disease Diseases 0.000 claims description 7
- 230000010933 acylation Effects 0.000 claims description 6
- 238000005917 acylation reaction Methods 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 230000009467 reduction Effects 0.000 claims description 5
- 208000007848 Alcoholism Diseases 0.000 claims description 4
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 4
- 208000036864 Attention deficit/hyperactivity disease 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
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- 208000019695 Migraine disease Diseases 0.000 claims description 4
- 208000019022 Mood disease Diseases 0.000 claims description 4
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- 208000002193 Pain Diseases 0.000 claims description 4
- 208000018737 Parkinson disease 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
- 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
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 4
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 4
- 210000003169 central nervous system Anatomy 0.000 claims description 4
- 206010061428 decreased appetite Diseases 0.000 claims description 4
- 206010027599 migraine Diseases 0.000 claims description 4
- QXHVKAKZJIOEQA-HSZRJFAPSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-(morpholine-4-carbonyl)benzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)C(=O)N1CCOCC1)CC2 QXHVKAKZJIOEQA-HSZRJFAPSA-N 0.000 claims description 4
- 235000020824 obesity Nutrition 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
- 230000001331 thermoregulatory effect Effects 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- NUNZZQXJJSVYFX-HHHXNRCGSA-N 4-(4-ethylphenyl)-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1=CC(CC)=CC=C1C1=CC=C(C(=O)N[C@H]2CC3=C(N4CCN(C)CC4)C=CC=C3CC2)C=C1 NUNZZQXJJSVYFX-HHHXNRCGSA-N 0.000 claims description 3
- RZGVRNVEYZRHRR-JOCHJYFZSA-N 4-butoxy-n-[(2r)-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=C2CC1 RZGVRNVEYZRHRR-JOCHJYFZSA-N 0.000 claims description 3
- OOEQHHKVTDYZTD-OAQYLSRUSA-N 4-morpholin-4-yl-n-[(2r)-8-piperazin-1-yl-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C([C@H](CC1=2)NC(=O)C=3C=CC(=CC=3)N3CCOCC3)CC1=CC=CC=2N1CCNCC1 OOEQHHKVTDYZTD-OAQYLSRUSA-N 0.000 claims description 3
- LLJAVORZMBIMFM-OAQYLSRUSA-N 4-n,4-n-dimethyl-1-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzene-1,4-dicarboxamide Chemical compound C1=CC(C(=O)N(C)C)=CC=C1C(=O)N[C@H]1CC2=C(N3CCN(C)CC3)C=CC=C2CC1 LLJAVORZMBIMFM-OAQYLSRUSA-N 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 208000013403 hyperactivity Diseases 0.000 claims description 3
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 3
- FTCLFWOUOUOQEH-HSZRJFAPSA-N n-[(2r)-8-(4-ethylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound C1CN(CC)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)N1CCOCC1)CC2 FTCLFWOUOUOQEH-HSZRJFAPSA-N 0.000 claims description 3
- HWSWMVFTXFBDRW-JOCHJYFZSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)N1CCOCC1)CC2 HWSWMVFTXFBDRW-JOCHJYFZSA-N 0.000 claims description 3
- KRMMIFCAVIETMC-HSZRJFAPSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-piperidin-1-ylbenzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)N1CCCCC1)CC2 KRMMIFCAVIETMC-HSZRJFAPSA-N 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- YKDQCDUROQIJOK-XMMPIXPASA-N 4-(4-hydroxyphenyl)-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)C=1C=CC(O)=CC=1)CC2 YKDQCDUROQIJOK-XMMPIXPASA-N 0.000 claims description 2
- RDORRCFUBBXXPQ-XMMPIXPASA-N 4-(dipropylsulfamoyl)-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1=CC(S(=O)(=O)N(CCC)CCC)=CC=C1C(=O)N[C@H]1CC2=C(N3CCN(C)CC3)C=CC=C2CC1 RDORRCFUBBXXPQ-XMMPIXPASA-N 0.000 claims description 2
- MMPDQFMVQQHORI-LJQANCHMSA-N 4-fluoro-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(F)=CC=1)CC2 MMPDQFMVQQHORI-LJQANCHMSA-N 0.000 claims description 2
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- 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 claims description 2
- VAQKVUSLQYAUDJ-JOCHJYFZSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-thiomorpholin-4-ylbenzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)N1CCSCC1)CC2 VAQKVUSLQYAUDJ-JOCHJYFZSA-N 0.000 claims description 2
- 125000006606 n-butoxy group Chemical group 0.000 claims description 2
- 125000004928 piperidonyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 206010036618 Premenstrual syndrome Diseases 0.000 claims 3
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- XRTVUDGKOMELHO-RUZDIDTESA-N 4-cyclohexyl-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)C1CCCCC1)CC2 XRTVUDGKOMELHO-RUZDIDTESA-N 0.000 claims 1
- 230000009036 growth inhibition Effects 0.000 claims 1
- 150000003460 sulfonic acids Chemical class 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 462
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 450
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 286
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 216
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 216
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 186
- 239000002904 solvent Substances 0.000 description 175
- 239000000243 solution Substances 0.000 description 151
- 239000011541 reaction mixture Substances 0.000 description 134
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 131
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 121
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 117
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 114
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 111
- 239000003480 eluent Substances 0.000 description 107
- 239000000741 silica gel Substances 0.000 description 97
- 229910002027 silica gel Inorganic materials 0.000 description 97
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 96
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 88
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 84
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 82
- 229910001868 water Inorganic materials 0.000 description 81
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 74
- 239000012074 organic phase Substances 0.000 description 74
- 239000011734 sodium Substances 0.000 description 74
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 73
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 72
- 239000013078 crystal Substances 0.000 description 68
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 66
- 239000000203 mixture Substances 0.000 description 62
- 239000012071 phase Substances 0.000 description 57
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 56
- 229920006395 saturated elastomer Polymers 0.000 description 56
- 239000003921 oil Substances 0.000 description 54
- 235000019198 oils Nutrition 0.000 description 54
- 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 48
- 238000010992 reflux Methods 0.000 description 47
- 239000012043 crude product Substances 0.000 description 46
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 46
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 41
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
- 235000011121 sodium hydroxide Nutrition 0.000 description 38
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 36
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 36
- 239000000908 ammonium hydroxide Substances 0.000 description 36
- 239000002585 base Substances 0.000 description 36
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 35
- 229910052757 nitrogen Inorganic materials 0.000 description 35
- 238000000746 purification Methods 0.000 description 33
- PLUBXMRUUVWRLT-UHFFFAOYSA-N Ethyl methanesulfonate Chemical compound CCOS(C)(=O)=O PLUBXMRUUVWRLT-UHFFFAOYSA-N 0.000 description 30
- 229910052763 palladium Inorganic materials 0.000 description 30
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 29
- 235000017557 sodium bicarbonate Nutrition 0.000 description 28
- 229910052727 yttrium Inorganic materials 0.000 description 28
- 229960000583 acetic acid Drugs 0.000 description 25
- 239000002253 acid Substances 0.000 description 25
- 229910000027 potassium carbonate Inorganic materials 0.000 description 25
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 24
- 239000007787 solid Substances 0.000 description 23
- 239000000047 product Substances 0.000 description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- 235000011054 acetic acid Nutrition 0.000 description 21
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 20
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 20
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 19
- 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 19
- 239000003054 catalyst Substances 0.000 description 19
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 19
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 18
- 229910021529 ammonia Inorganic materials 0.000 description 18
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 18
- 102000005962 receptors Human genes 0.000 description 17
- 108020003175 receptors Proteins 0.000 description 17
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- 239000003153 chemical reaction reagent Substances 0.000 description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 14
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 14
- 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 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 13
- 235000011167 hydrochloric acid Nutrition 0.000 description 13
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 13
- 239000012044 organic layer Substances 0.000 description 13
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical group C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 12
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 12
- 235000011181 potassium carbonates Nutrition 0.000 description 12
- 239000000377 silicon dioxide Substances 0.000 description 12
- 125000005270 trialkylamine group Chemical group 0.000 description 12
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 235000015320 potassium carbonate Nutrition 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- 239000012280 lithium aluminium hydride Substances 0.000 description 10
- 229910052759 nickel Inorganic materials 0.000 description 10
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 9
- 239000012346 acetyl chloride Substances 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 9
- 239000001569 carbon dioxide Substances 0.000 description 9
- 229910002092 carbon dioxide Inorganic materials 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- 230000007062 hydrolysis Effects 0.000 description 9
- 238000006460 hydrolysis reaction Methods 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
- 239000012299 nitrogen atmosphere Substances 0.000 description 9
- 229910052697 platinum Inorganic materials 0.000 description 9
- 229910052703 rhodium Inorganic materials 0.000 description 9
- 239000010948 rhodium Substances 0.000 description 9
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 9
- 230000000638 stimulation Effects 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 8
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
- 239000007832 Na2SO4 Substances 0.000 description 8
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 239000013543 active substance Substances 0.000 description 8
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 8
- 230000008025 crystallization Effects 0.000 description 8
- 235000011118 potassium hydroxide Nutrition 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 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 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 230000002378 acidificating effect Effects 0.000 description 7
- 239000000010 aprotic solvent Substances 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 230000003197 catalytic effect Effects 0.000 description 7
- 238000003818 flash chromatography Methods 0.000 description 7
- 210000005036 nerve Anatomy 0.000 description 7
- 239000012279 sodium borohydride Substances 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- BWZVCCNYKMEVEX-UHFFFAOYSA-N 2,4,6-Trimethylpyridine Chemical compound CC1=CC(C)=NC(C)=C1 BWZVCCNYKMEVEX-UHFFFAOYSA-N 0.000 description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 238000005984 hydrogenation reaction Methods 0.000 description 6
- 239000011630 iodine Substances 0.000 description 6
- 229910052740 iodine Inorganic materials 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 6
- 229940076279 serotonin Drugs 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 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 6
- 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 6
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 5
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 5
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- RRORBOQSFYQTQA-CQSZACIVSA-N (2r)-8-(1-methylpiperidin-4-yl)-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1CN(C)CCC1C1=CC=CC2=C1C[C@H](N)CC2 RRORBOQSFYQTQA-CQSZACIVSA-N 0.000 description 4
- 102000007527 Autoreceptors Human genes 0.000 description 4
- 108010071131 Autoreceptors Proteins 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 150000001335 aliphatic alkanes Chemical class 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 238000006264 debenzylation reaction Methods 0.000 description 4
- 230000017858 demethylation Effects 0.000 description 4
- 238000010520 demethylation reaction Methods 0.000 description 4
- 150000002081 enamines Chemical class 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 4
- 150000002466 imines Chemical class 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 150000003891 oxalate salts Chemical class 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 238000005932 reductive alkylation reaction Methods 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 4
- 230000005062 synaptic transmission Effects 0.000 description 4
- RECYBWRPTJBIGA-OAHLLOKOSA-N tert-butyl 4-[(7r)-7-amino-5,6,7,8-tetrahydronaphthalen-1-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=CC2=C1C[C@H](N)CC2 RECYBWRPTJBIGA-OAHLLOKOSA-N 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- CEIXLQVWHRUUMJ-CYBMUJFWSA-N (2r)-5-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=C1CC[C@@H](N)C2 CEIXLQVWHRUUMJ-CYBMUJFWSA-N 0.000 description 3
- AUHZEENZYGFFBQ-UHFFFAOYSA-N 1,3,5-Me3C6H3 Natural products CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 3
- HUUPVABNAQUEJW-UHFFFAOYSA-N 1-methylpiperidin-4-one Chemical compound CN1CCC(=O)CC1 HUUPVABNAQUEJW-UHFFFAOYSA-N 0.000 description 3
- XVAJKPNTGSKZSQ-UHFFFAOYSA-N 4-morpholinobenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1N1CCOCC1 XVAJKPNTGSKZSQ-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- 241000700198 Cavia Species 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 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 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 239000012445 acidic reagent Substances 0.000 description 3
- 230000002152 alkylating effect Effects 0.000 description 3
- 230000036506 anxiety Effects 0.000 description 3
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 3
- 229940073608 benzyl chloride Drugs 0.000 description 3
- 238000005574 benzylation reaction Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 238000001035 drying Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 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
- 239000013067 intermediate product Substances 0.000 description 3
- 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 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 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 3
- MVWZZXSPDHCPMY-UHFFFAOYSA-N n-ethyl-n-tributylstannylethanamine Chemical compound CCCC[Sn](CCCC)(CCCC)N(CC)CC MVWZZXSPDHCPMY-UHFFFAOYSA-N 0.000 description 3
- 229910017604 nitric acid Inorganic materials 0.000 description 3
- 239000012434 nucleophilic reagent Substances 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
- 238000012746 preparative thin layer chromatography Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 235000011149 sulphuric acid Nutrition 0.000 description 3
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 2
- URELKYOTTZSFOB-MRXNPFEDSA-N (2r)-8-(4-butylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1CN(CCCC)CCN1C1=CC=CC2=C1C[C@H](N)CC2 URELKYOTTZSFOB-MRXNPFEDSA-N 0.000 description 2
- AJBUFPNTLXQNRA-GOSISDBHSA-N (2r)-8-(4-hexylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1CN(CCCCCC)CCN1C1=CC=CC2=C1C[C@H](N)CC2 AJBUFPNTLXQNRA-GOSISDBHSA-N 0.000 description 2
- FARLAZDPQKRHIZ-QGZVFWFLSA-N (2r)-8-(4-pentylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1CN(CCCCC)CCN1C1=CC=CC2=C1C[C@H](N)CC2 FARLAZDPQKRHIZ-QGZVFWFLSA-N 0.000 description 2
- KHUZEPKPTDYLCM-SSDOTTSWSA-N (2r)-8-bromo-5-methoxy-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1[C@H](N)CCC2=C1C(Br)=CC=C2OC KHUZEPKPTDYLCM-SSDOTTSWSA-N 0.000 description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 2
- XWSGEVNYFYKXCP-UHFFFAOYSA-N 2-[carboxymethyl(methyl)amino]acetic acid Chemical compound OC(=O)CN(C)CC(O)=O XWSGEVNYFYKXCP-UHFFFAOYSA-N 0.000 description 2
- WTRIMJTZOOLIFZ-UHFFFAOYSA-N 2-bromo-2-methylpropanamide Chemical compound CC(C)(Br)C(N)=O WTRIMJTZOOLIFZ-UHFFFAOYSA-N 0.000 description 2
- NXEXOUAKEVFMBA-LJQANCHMSA-N 2-methyl-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C(=CC=CC=1)C)CC2 NXEXOUAKEVFMBA-LJQANCHMSA-N 0.000 description 2
- LSBDFXRDZJMBSC-UHFFFAOYSA-N 2-phenylacetamide Chemical compound NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-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
- NGLCRBTYPOFKBV-GOSISDBHSA-N 3-hydroxy-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=C(O)C=CC=1)CC2 NGLCRBTYPOFKBV-GOSISDBHSA-N 0.000 description 2
- WFJKSKWRBZDCKE-UHFFFAOYSA-N 3-methyl-4-morpholin-4-ylbenzoic acid Chemical compound CC1=CC(C(O)=O)=CC=C1N1CCOCC1 WFJKSKWRBZDCKE-UHFFFAOYSA-N 0.000 description 2
- VSWWMWRTKMCYSJ-HSZRJFAPSA-N 3-methyl-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=C(C)C(N3CCOCC3)=CC=1)CC2 VSWWMWRTKMCYSJ-HSZRJFAPSA-N 0.000 description 2
- NXTDJHZGHOFSQG-UHFFFAOYSA-N 3-phenoxybenzoic acid Chemical compound OC(=O)C1=CC=CC(OC=2C=CC=CC=2)=C1 NXTDJHZGHOFSQG-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
- QJJKANMUMBXTQE-UHFFFAOYSA-N 4-(4-benzylpiperazin-1-yl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1N1CCN(CC=2C=CC=CC=2)CC1 QJJKANMUMBXTQE-UHFFFAOYSA-N 0.000 description 2
- HLZACPQJCRXAQY-UHFFFAOYSA-N 4-(4-benzylpiperazin-4-ium-1-yl)benzoate Chemical compound C1=CC(C(=O)O)=CC=C1N1CCN(CC=2C=CC=CC=2)CC1 HLZACPQJCRXAQY-UHFFFAOYSA-N 0.000 description 2
- 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 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-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
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 2
- KSVCMEXDUHLOAR-UHFFFAOYSA-N 4-thiomorpholin-4-ylbenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1N1CCSCC1 KSVCMEXDUHLOAR-UHFFFAOYSA-N 0.000 description 2
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 2
- ADLDUYRIBVNUFQ-UHFFFAOYSA-N 8-(4-methylpiperazin-1-yl)-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1CN(C)CCN1C1=CC=CC2=C1CC(=O)CC2 ADLDUYRIBVNUFQ-UHFFFAOYSA-N 0.000 description 2
- KEHTUNIANGTXGP-UHFFFAOYSA-N 8-(4-methylpiperazin-1-yl)-3,4-dihydronaphthalene-2-carbonitrile Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C=C(C#N)CC2 KEHTUNIANGTXGP-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-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
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 229910015845 BBr3 Inorganic materials 0.000 description 2
- 239000005711 Benzoic acid Substances 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-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 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-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
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 2
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-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
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-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
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 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
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- ALXWSBFDLAKXDA-LJQANCHMSA-N [3-[[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamoyl]phenyl] methanesulfonate Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=C(OS(C)(=O)=O)C=CC=1)CC2 ALXWSBFDLAKXDA-LJQANCHMSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 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
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 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 2
- ZDKRMIJRCHPKLW-UHFFFAOYSA-N benzyl methanesulfonate Chemical compound CS(=O)(=O)OCC1=CC=CC=C1 ZDKRMIJRCHPKLW-UHFFFAOYSA-N 0.000 description 2
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 230000005684 electric field Effects 0.000 description 2
- 238000007336 electrophilic substitution reaction Methods 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
- 239000006260 foam Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 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
- 238000011534 incubation Methods 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
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 229940050176 methyl chloride Drugs 0.000 description 2
- SXBQPRGLUJQYIZ-HSZRJFAPSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-3-phenoxybenzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=C(OC=3C=CC=CC=3)C=CC=1)CC2 SXBQPRGLUJQYIZ-HSZRJFAPSA-N 0.000 description 2
- XGQVXNZFGIJQPT-MRXNPFEDSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]butanamide Chemical compound C([C@H](CC1=2)NC(=O)CCC)CC1=CC=CC=2N1CCN(C)CC1 XGQVXNZFGIJQPT-MRXNPFEDSA-N 0.000 description 2
- FUHRMGJITOPUFT-CQSZACIVSA-N n-[(2r)-8-piperazin-1-yl-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide Chemical compound C([C@H](CC1=2)NC(=O)C)CC1=CC=CC=2N1CCNCC1 FUHRMGJITOPUFT-CQSZACIVSA-N 0.000 description 2
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 238000006396 nitration reaction Methods 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
- 239000004031 partial agonist Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000001953 recrystallisation Methods 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
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 235000009518 sodium iodide Nutrition 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
- 238000003756 stirring Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000000946 synaptic effect Effects 0.000 description 2
- MEMUIPXIMAJPLJ-XMMPIXPASA-N tert-butyl 4-[(7r)-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=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)N1CCOCC1)CC2 MEMUIPXIMAJPLJ-XMMPIXPASA-N 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-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
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- DSGKWFGEUBCEIE-UHFFFAOYSA-N (2-carbonochloridoylphenyl) acetate Chemical compound CC(=O)OC1=CC=CC=C1C(Cl)=O DSGKWFGEUBCEIE-UHFFFAOYSA-N 0.000 description 1
- CGLCAQWQPIFKRX-SBSPUUFOSA-N (2r)-5-methoxy-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.C1[C@H](N)CCC2=C1C=CC=C2OC CGLCAQWQPIFKRX-SBSPUUFOSA-N 0.000 description 1
- ITNFMVBDTGJGKV-OAHLLOKOSA-N (2r)-8-(4-propylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1CN(CCC)CCN1C1=CC=CC2=C1C[C@H](N)CC2 ITNFMVBDTGJGKV-OAHLLOKOSA-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
- 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 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
- CEIXLQVWHRUUMJ-ZDUSSCGKSA-N (2s)-5-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=C1CC[C@H](N)C2 CEIXLQVWHRUUMJ-ZDUSSCGKSA-N 0.000 description 1
- JKOKSUARGAQGCX-ZDUSSCGKSA-N (2s)-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-ZDUSSCGKSA-N 0.000 description 1
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 description 1
- 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 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-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
- IBXMKLPFLZYRQZ-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 IBXMKLPFLZYRQZ-UHFFFAOYSA-N 0.000 description 1
- IKSNDOVDVVPSMA-UHFFFAOYSA-N 1-(bromomethyl)-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(CBr)C=C1 IKSNDOVDVVPSMA-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
- IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical compound C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 description 1
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 1
- MNDIARAMWBIKFW-UHFFFAOYSA-N 1-bromohexane Chemical compound CCCCCCBr MNDIARAMWBIKFW-UHFFFAOYSA-N 0.000 description 1
- YZWKKMVJZFACSU-UHFFFAOYSA-N 1-bromopentane Chemical compound CCCCCBr YZWKKMVJZFACSU-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
- NSWUGSKMMMROCB-CYBMUJFWSA-N 2,2,2-trifluoro-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C(F)(F)F)CC2 NSWUGSKMMMROCB-CYBMUJFWSA-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
- YMDZDFSUDFLGMX-UHFFFAOYSA-N 2-chloro-n-(2-chloroethyl)ethanamine;hydron;chloride Chemical compound [Cl-].ClCC[NH2+]CCCl YMDZDFSUDFLGMX-UHFFFAOYSA-N 0.000 description 1
- HNPSZFOWFAAFNC-LJQANCHMSA-N 2-ethoxy-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound CCOC1=CC=CC=C1C(=O)N[C@H]1CC2=C(N3CCN(C)CC3)C=CC=C2CC1 HNPSZFOWFAAFNC-LJQANCHMSA-N 0.000 description 1
- MDKAAWDKKBFSTK-UHFFFAOYSA-N 2-ethoxybenzoyl chloride Chemical compound CCOC1=CC=CC=C1C(Cl)=O MDKAAWDKKBFSTK-UHFFFAOYSA-N 0.000 description 1
- GPZXFICWCMCQPF-UHFFFAOYSA-N 2-methylbenzoyl chloride Chemical compound CC1=CC=CC=C1C(Cl)=O GPZXFICWCMCQPF-UHFFFAOYSA-N 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- LZBOSTUKSJTISB-UHFFFAOYSA-N 2-methylsulfonyloxybenzoic acid Chemical compound CS(=O)(=O)OC1=CC=CC=C1C(O)=O LZBOSTUKSJTISB-UHFFFAOYSA-N 0.000 description 1
- IBUSLNJQKLZPNR-UHFFFAOYSA-N 2-phenyl-1,3-thiazole-4-carboxylic acid Chemical compound OC(=O)C1=CSC(C=2C=CC=CC=2)=N1 IBUSLNJQKLZPNR-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
- VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 1
- COOQMBOJAAZEIR-UHFFFAOYSA-N 2-pyridin-4-yl-1,3-thiazole-4-carboxylic acid Chemical compound OC(=O)C1=CSC(C=2C=CN=CC=2)=N1 COOQMBOJAAZEIR-UHFFFAOYSA-N 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- RUJYJCANMOTJMO-UHFFFAOYSA-N 3-(trifluoromethyl)benzoyl chloride Chemical compound FC(F)(F)C1=CC=CC(C(Cl)=O)=C1 RUJYJCANMOTJMO-UHFFFAOYSA-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
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
- NGMYCWFGNSXLMP-UHFFFAOYSA-N 3-acetyloxybenzoic acid Chemical compound CC(=O)OC1=CC=CC(C(O)=O)=C1 NGMYCWFGNSXLMP-UHFFFAOYSA-N 0.000 description 1
- GYZZYRVWTDPJTH-UHFFFAOYSA-N 3-methyl-4-morpholin-4-ylbenzonitrile Chemical compound CC1=CC(C#N)=CC=C1N1CCOCC1 GYZZYRVWTDPJTH-UHFFFAOYSA-N 0.000 description 1
- ZPAAWIRZMZDWIS-UHFFFAOYSA-N 3-methylsulfonyloxybenzoic acid Chemical compound CS(=O)(=O)OC1=CC=CC(C(O)=O)=C1 ZPAAWIRZMZDWIS-UHFFFAOYSA-N 0.000 description 1
- MFEILWXBDBCWKF-UHFFFAOYSA-N 3-phenylpropanoyl chloride Chemical compound ClC(=O)CCC1=CC=CC=C1 MFEILWXBDBCWKF-UHFFFAOYSA-N 0.000 description 1
- SCEBDBNGUCNRCE-UHFFFAOYSA-N 4-(4-ethylphenyl)benzoic acid Chemical compound C1=CC(CC)=CC=C1C1=CC=C(C(O)=O)C=C1 SCEBDBNGUCNRCE-UHFFFAOYSA-N 0.000 description 1
- JTGCXYYDAVPSFD-UHFFFAOYSA-N 4-(4-hydroxyphenyl)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=C(O)C=C1 JTGCXYYDAVPSFD-UHFFFAOYSA-N 0.000 description 1
- LNYTUARMNSFFBE-UHFFFAOYSA-N 4-(diethylazaniumyl)benzoate Chemical compound CCN(CC)C1=CC=C(C(O)=O)C=C1 LNYTUARMNSFFBE-UHFFFAOYSA-N 0.000 description 1
- LHIJETBHEKJGOK-UHFFFAOYSA-N 4-(dimethylcarbamoyl)benzoic acid Chemical compound CN(C)C(=O)C1=CC=C(C(O)=O)C=C1 LHIJETBHEKJGOK-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
- GDNBJWVBQHSCTJ-UHFFFAOYSA-N 4-(trifluoromethylsulfonyloxy)benzoic acid Chemical compound OC(=O)C1=CC=C(OS(=O)(=O)C(F)(F)F)C=C1 GDNBJWVBQHSCTJ-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- GDBUZIKSJGRBJP-UHFFFAOYSA-M 4-acetyloxybenzoate Chemical compound CC(=O)OC1=CC=C(C([O-])=O)C=C1 GDBUZIKSJGRBJP-UHFFFAOYSA-M 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
- ZGGNKNJKYIDKIQ-RUZDIDTESA-N 4-benzoyl-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)C(=O)C=1C=CC=CC=1)CC2 ZGGNKNJKYIDKIQ-RUZDIDTESA-N 0.000 description 1
- IFQUPKAISSPFTE-UHFFFAOYSA-N 4-benzoylbenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C(=O)C1=CC=CC=C1 IFQUPKAISSPFTE-UHFFFAOYSA-N 0.000 description 1
- FCWPHAVLBGGGRV-AREMUKBSSA-N 4-benzyl-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(CC=3C=CC=CC=3)=CC=1)CC2 FCWPHAVLBGGGRV-AREMUKBSSA-N 0.000 description 1
- FPHVRPCVNPHPBH-UHFFFAOYSA-N 4-benzylbenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1CC1=CC=CC=C1 FPHVRPCVNPHPBH-UHFFFAOYSA-N 0.000 description 1
- SKXUZFJOLNNWIG-UHFFFAOYSA-N 4-bromo-3-methylbenzonitrile Chemical compound CC1=CC(C#N)=CC=C1Br SKXUZFJOLNNWIG-UHFFFAOYSA-N 0.000 description 1
- RSKIXKRJBQWLQD-LJQANCHMSA-N 4-bromo-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(Br)=CC=1)CC2 RSKIXKRJBQWLQD-LJQANCHMSA-N 0.000 description 1
- DENKGPBHLYFNGK-UHFFFAOYSA-N 4-bromobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Br)C=C1 DENKGPBHLYFNGK-UHFFFAOYSA-N 0.000 description 1
- KIQMQOUKDSGEPJ-HSZRJFAPSA-N 4-butoxy-n-[(2r)-8-(1-methylpiperidin-4-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1=CC(OCCCC)=CC=C1C(=O)N[C@H]1CC2=C(C3CCN(C)CC3)C=CC=C2CC1 KIQMQOUKDSGEPJ-HSZRJFAPSA-N 0.000 description 1
- RZGVRNVEYZRHRR-QFIPXVFZSA-N 4-butoxy-n-[(2s)-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=C2CC1 RZGVRNVEYZRHRR-QFIPXVFZSA-N 0.000 description 1
- LAUFPZPAKULAGB-UHFFFAOYSA-N 4-butoxybenzoic acid Chemical compound CCCCOC1=CC=C(C(O)=O)C=C1 LAUFPZPAKULAGB-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
- WPZKIJYFKPOMQB-LJQANCHMSA-N 4-chloro-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(Cl)=CC=1)CC2 WPZKIJYFKPOMQB-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
- USEDMAWWQDFMFY-UHFFFAOYSA-N 4-cyanobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(C#N)C=C1 USEDMAWWQDFMFY-UHFFFAOYSA-N 0.000 description 1
- QCIWHVKGVVQHIY-UHFFFAOYSA-N 4-cyclohexylbenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1CCCCC1 QCIWHVKGVVQHIY-UHFFFAOYSA-N 0.000 description 1
- OHBMHOHSRMWFSR-OAQYLSRUSA-N 4-ethyl-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1=CC(CC)=CC=C1C(=O)N[C@H]1CC2=C(N3CCN(C)CC3)C=CC=C2CC1 OHBMHOHSRMWFSR-OAQYLSRUSA-N 0.000 description 1
- AVTLLLZVYYPGFX-UHFFFAOYSA-N 4-ethylbenzoyl chloride Chemical compound CCC1=CC=C(C(Cl)=O)C=C1 AVTLLLZVYYPGFX-UHFFFAOYSA-N 0.000 description 1
- AEKVBBNGWBBYLL-UHFFFAOYSA-N 4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1 AEKVBBNGWBBYLL-UHFFFAOYSA-N 0.000 description 1
- CZKLEJHVLCMVQR-UHFFFAOYSA-N 4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1 CZKLEJHVLCMVQR-UHFFFAOYSA-N 0.000 description 1
- KJBQZZOBTGIDFW-GOSISDBHSA-N 4-hydroxy-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(O)=CC=1)CC2 KJBQZZOBTGIDFW-GOSISDBHSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- SVGIPFIEFKRFGG-LJQANCHMSA-N 4-methoxy-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1=CC(OC)=CC=C1C(=O)N[C@H]1CC2=C(N3CCN(C)CC3)C=CC=C2CC1 SVGIPFIEFKRFGG-LJQANCHMSA-N 0.000 description 1
- UVKXRNHMWWUFDS-UHFFFAOYSA-N 4-methylsulfonyloxybenzoic acid Chemical compound CS(=O)(=O)OC1=CC=C(C(O)=O)C=C1 UVKXRNHMWWUFDS-UHFFFAOYSA-N 0.000 description 1
- JPVUWCPKMYXOKW-UHFFFAOYSA-N 4-phenylbenzoyl chloride Chemical compound C1=CC(C(=O)Cl)=CC=C1C1=CC=CC=C1 JPVUWCPKMYXOKW-UHFFFAOYSA-N 0.000 description 1
- DGJNUESQBVPXAY-UHFFFAOYSA-N 4-piperidin-1-ylbenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1N1CCCCC1 DGJNUESQBVPXAY-UHFFFAOYSA-N 0.000 description 1
- IDDMJWJZSZMAOQ-UHFFFAOYSA-N 4-thiomorpholin-4-ylbenzonitrile Chemical compound C1=CC(C#N)=CC=C1N1CCSCC1 IDDMJWJZSZMAOQ-UHFFFAOYSA-N 0.000 description 1
- SWKPKONEIZGROQ-UHFFFAOYSA-N 4-trifluoromethylbenzoic acid Chemical compound OC(=O)C1=CC=C(C(F)(F)F)C=C1 SWKPKONEIZGROQ-UHFFFAOYSA-N 0.000 description 1
- QROOQGZOLRDGIW-UHFFFAOYSA-N 5'-bromospiro[1,3-dioxolane-2,3'-2,4-dihydro-1h-naphthalene] Chemical compound C1C=2C(Br)=CC=CC=2CCC21OCCO2 QROOQGZOLRDGIW-UHFFFAOYSA-N 0.000 description 1
- 210000002348 5-ht neuron Anatomy 0.000 description 1
- 102100036311 5-hydroxytryptamine receptor 1F Human genes 0.000 description 1
- 101710138086 5-hydroxytryptamine receptor 1F Proteins 0.000 description 1
- 102100036321 5-hydroxytryptamine receptor 2A Human genes 0.000 description 1
- 101710138091 5-hydroxytryptamine receptor 2A Proteins 0.000 description 1
- BYHDDXPKOZIZRV-UHFFFAOYSA-N 5-phenylpentanoic acid Chemical compound OC(=O)CCCCC1=CC=CC=C1 BYHDDXPKOZIZRV-UHFFFAOYSA-N 0.000 description 1
- ZEXYPLRLARKYLF-UHFFFAOYSA-N 6-(chloromethyl)-2-n-phenyl-1,3,5-triazine-2,4-diamine Chemical compound NC1=NC(CCl)=NC(NC=2C=CC=CC=2)=N1 ZEXYPLRLARKYLF-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 208000008811 Agoraphobia Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000700199 Cavia porcellus Species 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
- 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 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
- 208000019454 Feeding and Eating disease Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 101100134927 Gallus gallus COR8 gene Proteins 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
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 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
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010041250 Social phobia Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 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 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
- LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
- BULQAEPDJHOLIO-LJQANCHMSA-N [4-[[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamoyl]phenyl] methanesulfonate Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(OS(C)(=O)=O)=CC=1)CC2 BULQAEPDJHOLIO-LJQANCHMSA-N 0.000 description 1
- YABHVRJKXNUIGN-GOSISDBHSA-N [4-[[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamoyl]phenyl] trifluoromethanesulfonate Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(OS(=O)(=O)C(F)(F)F)=CC=1)CC2 YABHVRJKXNUIGN-GOSISDBHSA-N 0.000 description 1
- 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 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000007825 activation reagent Substances 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910001508 alkali metal halide Inorganic materials 0.000 description 1
- 150000008045 alkali metal halides Chemical class 0.000 description 1
- 229910001516 alkali metal iodide Inorganic materials 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229960004909 aminosalicylic acid Drugs 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 239000000538 analytical sample Substances 0.000 description 1
- MXMOTZIXVICDSD-UHFFFAOYSA-N anisoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1 MXMOTZIXVICDSD-UHFFFAOYSA-N 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000011260 aqueous acid Substances 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
- 229910052786 argon Inorganic materials 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
- 230000008901 benefit Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-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
- 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 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 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
- DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-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
- 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
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000000262 chemical ionisation mass spectrometry Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229960001653 citalopram Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 238000007333 cyanation reaction Methods 0.000 description 1
- 150000003997 cyclic ketones Chemical class 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- RVOJTCZRIKWHDX-UHFFFAOYSA-N cyclohexanecarbonyl chloride Chemical compound ClC(=O)C1CCCCC1 RVOJTCZRIKWHDX-UHFFFAOYSA-N 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 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
- 238000004090 dissolution Methods 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
- 208000024732 dysthymic disease Diseases 0.000 description 1
- 208000018334 ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome Diseases 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000005611 electricity Effects 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
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 208000029364 generalized anxiety disease Diseases 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 229950006191 gluconic acid Drugs 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229960004275 glycolic acid Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 208000031424 hyperprolactinemia Diseases 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-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
- 150000002576 ketones Chemical class 0.000 description 1
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 229910052744 lithium Inorganic materials 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
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 208000024714 major depressive disease Diseases 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 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
- 239000000463 material Substances 0.000 description 1
- QZIQJVCYUQZDIR-UHFFFAOYSA-N mechlorethamine hydrochloride Chemical compound Cl.ClCCN(C)CCCl QZIQJVCYUQZDIR-UHFFFAOYSA-N 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 235000013379 molasses Nutrition 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
- ZWIZCGYRSWZCJE-HSZRJFAPSA-N n-[(2r)-5-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-3-phenoxybenzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1CC[C@@H](NC(=O)C=1C=C(OC=3C=CC=CC=3)C=CC=1)C2 ZWIZCGYRSWZCJE-HSZRJFAPSA-N 0.000 description 1
- XBVQLBCTQHTBOR-JOCHJYFZSA-N n-[(2r)-5-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1CC[C@@H](NC(=O)C=1C=CC(=CC=1)N1CCOCC1)C2 XBVQLBCTQHTBOR-JOCHJYFZSA-N 0.000 description 1
- NFSLMNRJMXVMSP-HXUWFJFHSA-N n-[(2r)-8-(1-methylpiperidin-4-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-(trifluoromethyl)benzamide Chemical compound C1CN(C)CCC1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)C(F)(F)F)CC2 NFSLMNRJMXVMSP-HXUWFJFHSA-N 0.000 description 1
- XTMRQAXQZNCVSQ-GOSISDBHSA-N n-[(2r)-8-(4-butylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide Chemical compound C1CN(CCCC)CCN1C1=CC=CC2=C1C[C@H](NC(C)=O)CC2 XTMRQAXQZNCVSQ-GOSISDBHSA-N 0.000 description 1
- LRCFHICPVWKVHM-MRXNPFEDSA-N n-[(2r)-8-(4-ethylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide Chemical compound C1CN(CC)CCN1C1=CC=CC2=C1C[C@H](NC(C)=O)CC2 LRCFHICPVWKVHM-MRXNPFEDSA-N 0.000 description 1
- YMCQXJYNKVLBEP-HXUWFJFHSA-N n-[(2r)-8-(4-hexylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide Chemical compound C1CN(CCCCCC)CCN1C1=CC=CC2=C1C[C@H](NC(C)=O)CC2 YMCQXJYNKVLBEP-HXUWFJFHSA-N 0.000 description 1
- IETQXAXFPTUTML-HXUWFJFHSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-2-phenyl-1,3-thiazole-4-carboxamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1N=C(SC=1)C=1C=CC=CC=1)CC2 IETQXAXFPTUTML-HXUWFJFHSA-N 0.000 description 1
- ZHYHTIFAJAZKFX-LJQANCHMSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-2-pyridin-4-yl-1,3-thiazole-4-carboxamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1N=C(SC=1)C=1C=CN=CC=1)CC2 ZHYHTIFAJAZKFX-LJQANCHMSA-N 0.000 description 1
- AHDJLQQCPWZLSM-OAQYLSRUSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-3-phenylpropanamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)CCC=1C=CC=CC=1)CC2 AHDJLQQCPWZLSM-OAQYLSRUSA-N 0.000 description 1
- VZJRMDNSCFYSON-LJQANCHMSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-(2,2,2-trifluoroacetyl)benzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)C(=O)C(F)(F)F)CC2 VZJRMDNSCFYSON-LJQANCHMSA-N 0.000 description 1
- IQEMRBYSWQIPEI-RUZDIDTESA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-phenylbenzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)C=1C=CC=CC=1)CC2 IQEMRBYSWQIPEI-RUZDIDTESA-N 0.000 description 1
- ORQRTEMZFQGCLP-JOCHJYFZSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-phenylbutanamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)CCCC=1C=CC=CC=1)CC2 ORQRTEMZFQGCLP-JOCHJYFZSA-N 0.000 description 1
- ZKCBPHYKSQLXTR-JOCHJYFZSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-pyrrol-1-ylbenzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)N1C=CC=C1)CC2 ZKCBPHYKSQLXTR-JOCHJYFZSA-N 0.000 description 1
- NRKGAOSACUTWBU-HSZRJFAPSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-5-phenylpentanamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)CCCCC=1C=CC=CC=1)CC2 NRKGAOSACUTWBU-HSZRJFAPSA-N 0.000 description 1
- MFWHMORNUIJFHA-GOSISDBHSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-n-propan-2-ylacetamide Chemical compound C([C@H](CC1=2)N(C(C)C)C(C)=O)CC1=CC=CC=2N1CCN(C)CC1 MFWHMORNUIJFHA-GOSISDBHSA-N 0.000 description 1
- XVBGHLRTAVNIOZ-OAHLLOKOSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(C)=O)CC2 XVBGHLRTAVNIOZ-OAHLLOKOSA-N 0.000 description 1
- WLNSLSQQTPFNKF-LJQANCHMSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]cyclohexanecarboxamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C1CCCCC1)CC2 WLNSLSQQTPFNKF-LJQANCHMSA-N 0.000 description 1
- YYHYNKOILBLYBS-CQSZACIVSA-N n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]methanesulfonamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NS(C)(=O)=O)CC2 YYHYNKOILBLYBS-CQSZACIVSA-N 0.000 description 1
- MXQSFHYSPNHXQQ-LJQANCHMSA-N n-[(2r)-8-(4-pentylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide Chemical compound C1CN(CCCCC)CCN1C1=CC=CC2=C1C[C@H](NC(C)=O)CC2 MXQSFHYSPNHXQQ-LJQANCHMSA-N 0.000 description 1
- SQTCYINBELIFFC-QGZVFWFLSA-N n-[(2r)-8-(4-propylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide Chemical compound C1CN(CCC)CCN1C1=CC=CC2=C1C[C@H](NC(C)=O)CC2 SQTCYINBELIFFC-QGZVFWFLSA-N 0.000 description 1
- ZWIZCGYRSWZCJE-QHCPKHFHSA-N n-[(2s)-5-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-3-phenoxybenzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1CC[C@H](NC(=O)C=1C=C(OC=3C=CC=CC=3)C=CC=1)C2 ZWIZCGYRSWZCJE-QHCPKHFHSA-N 0.000 description 1
- CCUKQFHHPNQNAU-IBGZPJMESA-N n-[(2s)-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-IBGZPJMESA-N 0.000 description 1
- HWSWMVFTXFBDRW-QFIPXVFZSA-N n-[(2s)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@@H](NC(=O)C=1C=CC(=CC=1)N1CCOCC1)CC2 HWSWMVFTXFBDRW-QFIPXVFZSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- FLHUVRLPNXMCFX-LJQANCHMSA-N n-butyl-n-[(2r)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide Chemical compound C([C@H](CC1=2)N(CCCC)C(C)=O)CC1=CC=CC=2N1CCN(C)CC1 FLHUVRLPNXMCFX-LJQANCHMSA-N 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
- 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
- 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
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000021962 pH elevation Effects 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
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229950009215 phenylbutanoic acid Drugs 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
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 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
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 229940095574 propionic acid Drugs 0.000 description 1
- 239000003223 protective agent Substances 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
- 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
- 230000004044 response Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 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
- 239000000523 sample Substances 0.000 description 1
- 230000007017 scission Effects 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
- 230000009329 sexual behaviour Effects 0.000 description 1
- 238000005245 sintering Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 239000008259 solid foam Substances 0.000 description 1
- 201000001716 specific phobia Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 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
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical class OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 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
- 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
- CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 1
- PTMFUWGXPRYYMC-UHFFFAOYSA-N triethylazanium;formate Chemical compound OC=O.CCN(CC)CC PTMFUWGXPRYYMC-UHFFFAOYSA-N 0.000 description 1
- 229960003726 vasopressin Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000010626 work up procedure Methods 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
- C07D295/04—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
- C07D295/08—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 bound oxygen or sulfur atoms
- C07D295/096—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 bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61P25/22—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
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/26—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/04—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- 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
- C07D295/10—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 doubly bound oxygen or sulphur atoms
- C07D295/112—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 doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur 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
- C07D295/12—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
- 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
- C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/72—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 spiro-condensed with carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE9601110A SE9601110D0 (sv) | 1996-03-22 | 1996-03-22 | Substituted 1,2,3,4-tetrahydronaphthalene derivatives |
PCT/SE1997/000469 WO1997034883A1 (en) | 1996-03-22 | 1997-03-20 | Substituted 1,2,3,4-tetrahydronaphthalene derivatives |
Publications (3)
Publication Number | Publication Date |
---|---|
NO984385D0 NO984385D0 (no) | 1998-09-21 |
NO984385L NO984385L (no) | 1998-11-23 |
NO311803B1 true NO311803B1 (no) | 2002-01-28 |
Family
ID=20401907
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19984385A NO311803B1 (no) | 1996-03-22 | 1998-09-21 | Substituerte 1,2,3,4-tetrahydronaftalenderivater, farmasöytisk preparat inneholdende slike derivater, deresanvendelse, fremgangsmåte for deres fremstilling, og mellomprodukt |
Country Status (27)
Country | Link |
---|---|
US (2) | US6124283A (xx) |
EP (1) | EP0888319B1 (xx) |
JP (1) | JP2000506883A (xx) |
KR (1) | KR20000064751A (xx) |
CN (1) | CN1073101C (xx) |
AR (2) | AR006360A1 (xx) |
AT (1) | ATE231847T1 (xx) |
AU (1) | AU709856B2 (xx) |
BR (1) | BR9708093A (xx) |
CA (1) | CA2247940A1 (xx) |
CZ (1) | CZ301998A3 (xx) |
DE (1) | DE69718771T2 (xx) |
EE (1) | EE9800300A (xx) |
HR (1) | HRP970166A2 (xx) |
HU (1) | HUP9902454A3 (xx) |
ID (1) | ID16298A (xx) |
IL (2) | IL145681A0 (xx) |
IS (1) | IS4844A (xx) |
NO (1) | NO311803B1 (xx) |
NZ (1) | NZ331613A (xx) |
PL (1) | PL329121A1 (xx) |
SE (1) | SE9601110D0 (xx) |
SK (1) | SK282359B6 (xx) |
TR (1) | TR199801868T2 (xx) |
WO (1) | WO1997034883A1 (xx) |
YU (1) | YU40998A (xx) |
ZA (1) | ZA972056B (xx) |
Families Citing this family (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE9900190D0 (sv) * | 1999-01-22 | 1999-01-22 | Astra Ab | New compounds |
SE9702799D0 (sv) * | 1997-07-25 | 1997-07-25 | Astra Ab | New compounds |
SE9703375D0 (sv) * | 1997-09-18 | 1997-09-18 | Astra Ab | A new combination |
SE9703376D0 (sv) * | 1997-09-18 | 1997-09-18 | Astra Ab | A new combination |
SE9703374D0 (sv) * | 1997-09-18 | 1997-09-18 | Astra Ab | A new combination |
SE9703379D0 (sv) | 1997-09-18 | 1997-09-18 | Astra Ab | New compounds |
DK0952154T3 (da) | 1998-04-16 | 2004-12-13 | Pfizer Prod Inc | N-acyl- og N-aroylaralkylamider |
SE0002729D0 (sv) * | 2000-07-20 | 2000-07-20 | Astrazeneca Ab | Novel compound form |
CA2434152A1 (en) | 2001-01-16 | 2002-07-18 | Astrazeneca Ab | Therapeutic heterocyclic compounds |
IL156602A0 (en) | 2001-01-16 | 2004-01-04 | Astrazeneca Ab | Therapeutic chromone compounds |
WO2003007956A1 (en) | 2001-07-20 | 2003-01-30 | Psychogenics, Inc. | Treatment for attention-deficit hyperactivity disorder |
SE0301794D0 (sv) * | 2003-06-19 | 2003-06-19 | Astrazeneca Ab | New use III |
SE0301798D0 (sv) * | 2003-06-19 | 2003-06-19 | Astrazeneca Ab | New use IV |
CN101119965B (zh) * | 2004-12-21 | 2012-09-26 | 弗·哈夫曼-拉罗切有限公司 | 萘满和茚满衍生物及其用途 |
JP2009533325A (ja) * | 2006-03-17 | 2009-09-17 | アストラゼネカ・アクチエボラーグ | 5−ht6調節剤としての新規なテトラリン |
WO2008130319A2 (en) * | 2007-04-23 | 2008-10-30 | Astrazeneca Ab | Novel n-tetrahydronaphtalene or n-chromane carboxamide derivatives for the treatment of pain |
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 |
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 |
WO2008130323A1 (en) * | 2007-04-23 | 2008-10-30 | Astrazeneca Ab | Novel 8-piperazine-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 |
JP6888827B2 (ja) * | 2015-05-19 | 2021-06-16 | ノースイースタン ユニバーシティ | 末梢におけるセロトニン受容体をモジュレートするための化合物または方法 |
WO2020183011A1 (en) | 2019-03-14 | 2020-09-17 | Institut Curie | Htr1d inhibitors and uses thereof in the treatment of cancer |
Family Cites Families (14)
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 |
DE69218813T2 (de) * | 1991-02-08 | 1997-08-14 | Lilly Co Eli | Ringsubstituierte 2-Amino-1,2,3,4-tetrahydronaphthaline |
DE69232003T2 (de) * | 1991-09-18 | 2002-04-25 | Glaxo Group Ltd | Benzanilidderivate als 5-HT1D-Antagonisten |
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 |
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 |
CA2158457C (en) * | 1993-03-16 | 2001-04-17 | Bertrand Leo Chenard | Naphthalene derivatives |
SE9301732D0 (sv) * | 1993-05-18 | 1993-05-18 | Haakan Wilhelm Wikstroem | New centrally acting 5-,6-,7-, and 8-substituted sulphone esters of n-monosubstituted 2-aminotetralins |
JPH09503773A (ja) * | 1993-10-19 | 1997-04-15 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | 5ht−1dレセプター拮抗剤用のベンズアニリド誘導体 |
SE9702799D0 (sv) * | 1997-07-25 | 1997-07-25 | Astra Ab | New compounds |
SE9703374D0 (sv) * | 1997-09-18 | 1997-09-18 | Astra Ab | A new combination |
SE9703376D0 (sv) * | 1997-09-18 | 1997-09-18 | Astra Ab | A new combination |
SE9703375D0 (sv) * | 1997-09-18 | 1997-09-18 | Astra Ab | A new combination |
-
1996
- 1996-03-22 SE SE9601110A patent/SE9601110D0/xx unknown
-
1997
- 1997-03-10 ZA ZA9702056A patent/ZA972056B/xx unknown
- 1997-03-20 TR TR1998/01868T patent/TR199801868T2/xx unknown
- 1997-03-20 AT AT97914727T patent/ATE231847T1/de not_active IP Right Cessation
- 1997-03-20 WO PCT/SE1997/000469 patent/WO1997034883A1/en not_active Application Discontinuation
- 1997-03-20 US US08/836,004 patent/US6124283A/en not_active Expired - Fee Related
- 1997-03-20 NZ NZ331613A patent/NZ331613A/xx unknown
- 1997-03-20 BR BR9708093A patent/BR9708093A/pt unknown
- 1997-03-20 KR KR1019980707506A patent/KR20000064751A/ko not_active Application Discontinuation
- 1997-03-20 EP EP97914727A patent/EP0888319B1/en not_active Expired - Lifetime
- 1997-03-20 EE EE9800300A patent/EE9800300A/xx unknown
- 1997-03-20 DE DE69718771T patent/DE69718771T2/de not_active Expired - Fee Related
- 1997-03-20 IL IL14568197A patent/IL145681A0/xx unknown
- 1997-03-20 PL PL97329121A patent/PL329121A1/xx unknown
- 1997-03-20 IL IL12607097A patent/IL126070A0/xx unknown
- 1997-03-20 CN CN97194726A patent/CN1073101C/zh not_active Expired - Fee Related
- 1997-03-20 HU HU9902454A patent/HUP9902454A3/hu unknown
- 1997-03-20 JP JP9533410A patent/JP2000506883A/ja not_active Ceased
- 1997-03-20 CZ CZ983019A patent/CZ301998A3/cs unknown
- 1997-03-20 AU AU21865/97A patent/AU709856B2/en not_active Ceased
- 1997-03-20 CA CA002247940A patent/CA2247940A1/en not_active Abandoned
- 1997-03-20 SK SK1188-98A patent/SK282359B6/sk unknown
- 1997-03-21 ID IDP970931A patent/ID16298A/id unknown
- 1997-03-21 AR ARP970101163A patent/AR006360A1/es not_active Application Discontinuation
- 1997-03-21 HR HR9601110-1A patent/HRP970166A2/xx not_active Application Discontinuation
- 1997-12-02 AR ARP970105660A patent/AR010080A1/es unknown
-
1998
- 1998-09-09 IS IS4844A patent/IS4844A/is unknown
- 1998-09-21 NO NO19984385A patent/NO311803B1/no not_active IP Right Cessation
- 1998-09-22 YU YU40998A patent/YU40998A/sh unknown
-
2000
- 2000-08-31 US US09/653,427 patent/US6410530B1/en not_active Expired - Fee Related
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NO311803B1 (no) | Substituerte 1,2,3,4-tetrahydronaftalenderivater, farmasöytisk preparat inneholdende slike derivater, deresanvendelse, fremgangsmåte for deres fremstilling, og mellomprodukt | |
AU739569B2 (en) | Substituted 1,2,3,4-tetrahydronaphthalene derivatives | |
AU734580B2 (en) | Substituted chroman derivatives | |
EP1025094A1 (en) | Substituted indan derivatives | |
MXPA00000676A (en) | Substituted 1,2,3,4-tetrahydronaphthalene derivatives | |
CZ2000275A3 (cs) | Substituované 1,2,2,4-tetrahydronaftalenové deriváty |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM1K | Lapsed by not paying the annual fees |
Free format text: LAPSED IN SEPTEMBER 2003 |