SK2996A3 - Methanoanthracenes substituted by piperidinyl group, preparation method thereof and their use as d1/d2-dopamine-antagonists and 5ht2-serotonin-antagonists - Google Patents

Methanoanthracenes substituted by piperidinyl group, preparation method thereof and their use as d1/d2-dopamine-antagonists and 5ht2-serotonin-antagonists Download PDF

Info

Publication number: SK2996A3
Authority: SK; Slovakia
Prior art keywords: compound; formula; group; alkyl; pharmaceutically acceptable
Prior art date: 1993-07-09

Application number

SK29-96A

Other languages

English (en)

Slovak (sk)

Inventor

Michael T Klimas

Marc O Terpko

Original Assignee

Zeneca Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1993-07-09

Filing date

1994-07-04

Publication date

1997-02-05

1994-07-04 Application filed by Zeneca Ltd filed Critical Zeneca Ltd

1997-02-05 Publication of SK2996A3 publication Critical patent/SK2996A3/sk

Links

239000003210 dopamine receptor blocking agent Substances 0.000 title claims abstract description 13
238000002360 preparation method Methods 0.000 title claims description 24
239000003420 antiserotonin agent Substances 0.000 title claims description 9
125000003386 piperidinyl group Chemical group 0.000 title abstract description 5
229940082988 antihypertensives serotonin antagonists Drugs 0.000 title description 4
150000001875 compounds Chemical class 0.000 claims abstract description 139
238000000034 method Methods 0.000 claims abstract description 54
150000003839 salts Chemical class 0.000 claims abstract description 29
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 26
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 21
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 20
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 20
230000008569 process Effects 0.000 claims abstract description 20
239000001257 hydrogen Substances 0.000 claims abstract description 19
150000003462 sulfoxides Chemical class 0.000 claims abstract description 18
125000001424 substituent group Chemical group 0.000 claims abstract description 16
150000002367 halogens Chemical class 0.000 claims abstract description 13
229910052736 halogen Inorganic materials 0.000 claims abstract description 12
125000005842 heteroatom Chemical group 0.000 claims abstract description 12
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 11
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 9
229910052760 oxygen Inorganic materials 0.000 claims abstract description 9
239000001301 oxygen Chemical group 0.000 claims abstract description 9
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 7
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 7
229910052717 sulfur Chemical group 0.000 claims abstract description 7
239000011593 sulfur Chemical group 0.000 claims abstract description 7
125000005843 halogen group Chemical group 0.000 claims abstract description 6
125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims abstract description 5
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims abstract description 5
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 5
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 5
208000020016 psychiatric disease Diseases 0.000 claims abstract description 4
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims abstract description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 81
-1 C 1 -C 6 -alkyl Chemical group 0.000 claims description 61
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 45
125000004432 carbon atom Chemical group C* 0.000 claims description 42
125000000217 alkyl group Chemical group 0.000 claims description 39
239000000203 mixture Substances 0.000 claims description 36
239000002904 solvent Substances 0.000 claims description 35
239000000243 solution Substances 0.000 claims description 30
239000002253 acid Substances 0.000 claims description 22
230000003647 oxidation Effects 0.000 claims description 21
238000007254 oxidation reaction Methods 0.000 claims description 21
CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 claims description 14
VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 claims description 14
239000008194 pharmaceutical composition Substances 0.000 claims description 12
239000007800 oxidant agent Substances 0.000 claims description 11
239000000126 substance Substances 0.000 claims description 10
208000028017 Psychotic disease Diseases 0.000 claims description 8
239000003638 chemical reducing agent Substances 0.000 claims description 8
LVMVFEHQMHETDS-UHFFFAOYSA-N dcl001042 Chemical compound CC[S+]([O-])C1=NC=CC=C1C1(O)CCN(CC23C4=CC=CC=C4C(C2)C=2C3=CC=CC=2)CC1 LVMVFEHQMHETDS-UHFFFAOYSA-N 0.000 claims description 8
239000003937 drug carrier Substances 0.000 claims description 8
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 7
YSAVZVORKRDODB-WDSKDSINSA-N diethyl tartrate Chemical compound CCOC(=O)[C@@H](O)[C@H](O)C(=O)OCC YSAVZVORKRDODB-WDSKDSINSA-N 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 7
239000010936 titanium Substances 0.000 claims description 7
229910052719 titanium Inorganic materials 0.000 claims description 7
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 6
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 6
150000001450 anions Chemical class 0.000 claims description 6
239000003085 diluting agent Substances 0.000 claims description 6
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
BBRKFUJIEXPDBJ-UHFFFAOYSA-N l008358 Chemical compound CCSC1=NC=CC=C1C1(O)CCN(CC23C4=CC=CC=C4C(C2)C=2C3=CC=CC=2)CC1 BBRKFUJIEXPDBJ-UHFFFAOYSA-N 0.000 claims description 6
238000002844 melting Methods 0.000 claims description 6
230000008018 melting Effects 0.000 claims description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
229940095064 tartrate Drugs 0.000 claims description 6
241000282412 Homo Species 0.000 claims description 5
150000001408 amides Chemical class 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
125000000623 heterocyclic group Chemical group 0.000 claims description 5
SJGALSBBFTYSBA-UHFFFAOYSA-N oxaziridine Chemical compound C1NO1 SJGALSBBFTYSBA-UHFFFAOYSA-N 0.000 claims description 5
125000004689 alkyl amino carbonyl alkyl group Chemical group 0.000 claims description 4
XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims description 4
150000001350 alkyl halides Chemical class 0.000 claims description 3
150000001768 cations Chemical class 0.000 claims description 3
150000002978 peroxides Chemical class 0.000 claims description 3
125000003375 sulfoxide group Chemical group 0.000 claims description 3
125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 2
239000000010 aprotic solvent Substances 0.000 claims description 2
239000012736 aqueous medium Substances 0.000 claims description 2
125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 2
125000004663 dialkyl amino group Chemical group 0.000 claims description 2
239000012457 nonaqueous media Substances 0.000 claims description 2
125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
150000002431 hydrogen Chemical class 0.000 abstract description 9
208000012902 Nervous system disease Diseases 0.000 abstract description 7
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 6
208000025966 Neurological disease Diseases 0.000 abstract description 6
239000000164 antipsychotic agent Substances 0.000 abstract description 5
125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 abstract description 3
230000000926 neurological effect Effects 0.000 abstract description 3
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 abstract description 3
125000002373 5 membered heterocyclic group Chemical group 0.000 abstract description 2
125000004070 6 membered heterocyclic group Chemical group 0.000 abstract description 2
201000000980 schizophrenia Diseases 0.000 abstract description 2
125000006563 (C1-3) alkylaminocarbonyl group Chemical group 0.000 abstract 1
125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 1
125000003282 alkyl amino group Chemical group 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
238000006243 chemical reaction Methods 0.000 description 22
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
239000007787 solid Substances 0.000 description 19
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
239000011541 reaction mixture Substances 0.000 description 16
VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 14
239000002585 base Substances 0.000 description 14
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
239000000047 product Substances 0.000 description 13
238000012360 testing method Methods 0.000 description 13
238000004809 thin layer chromatography Methods 0.000 description 13
HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
238000004128 high performance liquid chromatography Methods 0.000 description 11
239000000725 suspension Substances 0.000 description 11
238000004458 analytical method Methods 0.000 description 10
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
239000012948 isocyanate Substances 0.000 description 9
150000002513 isocyanates Chemical class 0.000 description 9
239000003921 oil Substances 0.000 description 9
239000000460 chlorine Substances 0.000 description 8
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 8
239000000284 extract Substances 0.000 description 8
230000009182 swimming Effects 0.000 description 8
101150049660 DRD2 gene Proteins 0.000 description 7
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 7
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 7
238000005481 NMR spectroscopy Methods 0.000 description 7
241000700159 Rattus Species 0.000 description 7
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 7
150000001412 amines Chemical class 0.000 description 7
230000008485 antagonism Effects 0.000 description 7
238000003818 flash chromatography Methods 0.000 description 7
125000006239 protecting group Chemical group 0.000 description 7
239000000741 silica gel Substances 0.000 description 7
229910002027 silica gel Inorganic materials 0.000 description 7
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 6
241000699666 Mus <mouse, genus> Species 0.000 description 6
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
239000004480 active ingredient Substances 0.000 description 6
125000003545 alkoxy group Chemical group 0.000 description 6
238000003556 assay Methods 0.000 description 6
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 5
229940121891 Dopamine receptor antagonist Drugs 0.000 description 5
241000699670 Mus sp. Species 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
150000001299 aldehydes Chemical class 0.000 description 5
125000004414 alkyl thio group Chemical group 0.000 description 5
230000003042 antagnostic effect Effects 0.000 description 5
239000005557 antagonist Substances 0.000 description 5
239000008346 aqueous phase Substances 0.000 description 5
238000009835 boiling Methods 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
230000009194 climbing Effects 0.000 description 5
229940126208 compound 22 Drugs 0.000 description 5
239000002552 dosage form Substances 0.000 description 5
229940079593 drug Drugs 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000003480 eluent Substances 0.000 description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
LKPFBGKZCCBZDK-UHFFFAOYSA-N n-hydroxypiperidine Chemical compound ON1CCCCC1 LKPFBGKZCCBZDK-UHFFFAOYSA-N 0.000 description 5
239000012299 nitrogen atmosphere Substances 0.000 description 5
102000005962 receptors Human genes 0.000 description 5
108020003175 receptors Proteins 0.000 description 5
238000001953 recrystallisation Methods 0.000 description 5
230000009467 reduction Effects 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
125000005270 trialkylamine group Chemical group 0.000 description 5
JUDKOGFHZYMDMF-UHFFFAOYSA-N 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol Chemical compound C1=2C=C(O)C(O)=CC=2CCNCC1C1=CC=CC=C1 JUDKOGFHZYMDMF-UHFFFAOYSA-N 0.000 description 4
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 4
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 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 4
230000000561 anti-psychotic effect Effects 0.000 description 4
150000001540 azides Chemical class 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 4
238000001816 cooling Methods 0.000 description 4
ZAELYRWEXINIKF-UHFFFAOYSA-N ctk2f1535 Chemical compound C12=CC=CC=C2C2(C=O)C3=CC=CC=C3C1C2 ZAELYRWEXINIKF-UHFFFAOYSA-N 0.000 description 4
229960003638 dopamine Drugs 0.000 description 4
DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 4
238000009472 formulation Methods 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
150000003141 primary amines Chemical class 0.000 description 4
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
238000004064 recycling Methods 0.000 description 4
239000011734 sodium Substances 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 4
230000001225 therapeutic effect Effects 0.000 description 4
239000003981 vehicle Substances 0.000 description 4
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
MTAODLNXWYIKSO-UHFFFAOYSA-N 2-fluoropyridine Chemical compound FC1=CC=CC=N1 MTAODLNXWYIKSO-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 3
125000004644 alkyl sulfinyl group Chemical group 0.000 description 3
229960004046 apomorphine Drugs 0.000 description 3
VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 3
230000006399 behavior Effects 0.000 description 3
230000027455 binding Effects 0.000 description 3
230000037396 body weight Effects 0.000 description 3
239000007795 chemical reaction product Substances 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
229940117975 chromium trioxide Drugs 0.000 description 3
GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 3
230000036461 convulsion Effects 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
238000006193 diazotization reaction Methods 0.000 description 3
MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 3
239000012458 free base Substances 0.000 description 3
150000004820 halides Chemical class 0.000 description 3
125000002768 hydroxyalkyl group Chemical group 0.000 description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
FPCCSQOGAWCVBH-UHFFFAOYSA-N ketanserin Chemical compound C1=CC(F)=CC=C1C(=O)C1CCN(CCN2C(C3=CC=CC=C3NC2=O)=O)CC1 FPCCSQOGAWCVBH-UHFFFAOYSA-N 0.000 description 3
239000012280 lithium aluminium hydride Substances 0.000 description 3
239000012528 membrane Substances 0.000 description 3
238000000159 protein binding assay Methods 0.000 description 3
229940044551 receptor antagonist Drugs 0.000 description 3
239000002464 receptor antagonist Substances 0.000 description 3
238000010992 reflux Methods 0.000 description 3
229940076279 serotonin Drugs 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
125000000101 thioether group Chemical group 0.000 description 3
WTNUJWCTVHBNEP-UHFFFAOYSA-N (9,10-dihydro-9,10-methanoanthracen-9-ylcarbonyl)piperidin-4-ol Chemical compound C1CC(O)CCN1C(=O)C1(C2=CC=CC=C22)C3=CC=CC=C3C2C1 WTNUJWCTVHBNEP-UHFFFAOYSA-N 0.000 description 2
ZOLDDQZVWZVZEJ-UHFFFAOYSA-N (9,10-dihydro-9,10-methanoanthracen-9-ylmethyl)-4-piperidinone Chemical compound C1CC(=O)CCN1CC1(C2=CC=CC=C22)C3=CC=CC=C3C2C1 ZOLDDQZVWZVZEJ-UHFFFAOYSA-N 0.000 description 2
HXDXYBOYGKEMQO-UHFFFAOYSA-N 1-(9,10-dihydro-9,10-methanoanthracen-9-ylmethyl)-4-(2-fluoro-3-pyridyl)-piperidin-4-ol Chemical compound C1CN(CC23C4=CC=CC=C4C(C2)C=2C3=CC=CC=2)CCC1(O)C1=CC=CN=C1F HXDXYBOYGKEMQO-UHFFFAOYSA-N 0.000 description 2
RLAWQNBRBDSSQS-UHFFFAOYSA-N 1h-cyclopropa[a]anthracene Chemical class C1=CC=CC2=CC3=C4CC4=CC=C3C=C21 RLAWQNBRBDSSQS-UHFFFAOYSA-N 0.000 description 2
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 2
NMSCHAVZGNIZJT-UHFFFAOYSA-N 9,10-dihydro-9,10-methano-9-anthracenecarboxylic acid Chemical compound C12=CC=CC=C2C2(C(=O)O)C3=CC=CC=C3C1C2 NMSCHAVZGNIZJT-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-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
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
229910004373 HOAc Inorganic materials 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
239000003810 Jones reagent Substances 0.000 description 2
239000005909 Kieselgur Substances 0.000 description 2
229930195725 Mannitol Natural products 0.000 description 2
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
229920005372 Plexiglas® Polymers 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
BZHJMEDXRYGGRV-UHFFFAOYSA-N Vinyl chloride Chemical compound ClC=C BZHJMEDXRYGGRV-UHFFFAOYSA-N 0.000 description 2
239000013543 active substance Substances 0.000 description 2
150000008044 alkali metal hydroxides Chemical class 0.000 description 2
125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
125000005196 alkyl carbonyloxy group Chemical group 0.000 description 2
235000010323 ascorbic acid Nutrition 0.000 description 2
239000011668 ascorbic acid Substances 0.000 description 2
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
239000002775 capsule Substances 0.000 description 2
238000009833 condensation Methods 0.000 description 2
230000005494 condensation Effects 0.000 description 2
210000001653 corpus striatum Anatomy 0.000 description 2
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
239000013078 crystal Substances 0.000 description 2
HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
238000000354 decomposition reaction Methods 0.000 description 2
238000010537 deprotonation reaction Methods 0.000 description 2
229940043279 diisopropylamine Drugs 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
238000001914 filtration Methods 0.000 description 2
150000004795 grignard reagents Chemical class 0.000 description 2
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
239000007924 injection Substances 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007927 intramuscular injection Substances 0.000 description 2
238000010255 intramuscular injection Methods 0.000 description 2
238000007912 intraperitoneal administration Methods 0.000 description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
229960005417 ketanserin Drugs 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
239000000594 mannitol Substances 0.000 description 2
235000010355 mannitol Nutrition 0.000 description 2
229910052763 palladium Inorganic materials 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
239000002243 precursor Substances 0.000 description 2
230000000069 prophylactic effect Effects 0.000 description 2
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
XRXDAJYKGWNHTQ-UHFFFAOYSA-N quipazine Chemical compound C1CNCCN1C1=CC=C(C=CC=C2)C2=N1 XRXDAJYKGWNHTQ-UHFFFAOYSA-N 0.000 description 2
229950002315 quipazine Drugs 0.000 description 2
239000002002 slurry Substances 0.000 description 2
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
DKGZKTPJOSAWFA-UHFFFAOYSA-N spiperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCC2(C(NCN2C=2C=CC=CC=2)=O)CC1 DKGZKTPJOSAWFA-UHFFFAOYSA-N 0.000 description 2
238000012289 standard assay Methods 0.000 description 2
239000007858 starting material Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
150000003457 sulfones Chemical class 0.000 description 2
IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 2
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 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
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
238000005303 weighing Methods 0.000 description 2
239000011701 zinc Substances 0.000 description 2
229910052725 zinc Inorganic materials 0.000 description 2
TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
GOTMKOSCLKVOGG-OAHLLOKOSA-N (5R)-8-chloro-3-methyl-5-phenyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol Chemical compound C1([C@@H]2C3=CC(O)=C(Cl)C=C3CCN(C2)C)=CC=CC=C1 GOTMKOSCLKVOGG-OAHLLOKOSA-N 0.000 description 1
SKYZYDSNJIOXRL-BTQNPOSSSA-N (6ar)-6-methyl-5,6,6a,7-tetrahydro-4h-dibenzo[de,g]quinoline-10,11-diol;hydrochloride Chemical compound Cl.C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 SKYZYDSNJIOXRL-BTQNPOSSSA-N 0.000 description 1
125000006699 (C1-C3) hydroxyalkyl group Chemical group 0.000 description 1
125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 description 1
KGMDODIDEQTIRA-UHFFFAOYSA-N 1,2-dihydrocyclobuta[a]anthracene Chemical compound C1=CC2=CC3=CC=CC=C3C=C2C2=C1CC2 KGMDODIDEQTIRA-UHFFFAOYSA-N 0.000 description 1
PKZNPHYUNGFAOO-UHFFFAOYSA-N 1-(9,10-dihydro-9,10-methanoanthracen-9-ylmethyl) piperidin-4-ol Chemical compound C1CC(O)CCN1CC1(C2=CC=CC=C22)C3=CC=CC=C3C2C1 PKZNPHYUNGFAOO-UHFFFAOYSA-N 0.000 description 1
125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 1
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 1
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
JLAKCHGEEBPDQI-UHFFFAOYSA-N 4-(4-fluorobenzyl)piperidine Chemical compound C1=CC(F)=CC=C1CC1CCNCC1 JLAKCHGEEBPDQI-UHFFFAOYSA-N 0.000 description 1
KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
206010002091 Anaesthesia Diseases 0.000 description 1
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
KTIJWHASRYGTCH-UHFFFAOYSA-N CC1(C(CCCN(CC2)CCC2(C2CCC(CS(N)=O)CCCC2)O)c2ccccc2C2)C2=CC=CC1 Chemical compound CC1(C(CCCN(CC2)CCC2(C2CCC(CS(N)=O)CCCC2)O)c2ccccc2C2)C2=CC=CC1 KTIJWHASRYGTCH-UHFFFAOYSA-N 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
108010035722 Chloride peroxidase Proteins 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
229920002261 Corn starch Polymers 0.000 description 1
238000005698 Diels-Alder reaction Methods 0.000 description 1
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
239000007818 Grignard reagent Substances 0.000 description 1
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
238000006809 Jones oxidation reaction Methods 0.000 description 1
WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 1
WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
ZZJYIKPMDIWRSN-HWBMXIPRSA-N LSM-20934 Chemical compound C12=CC=CC=C2CCC2=CC=CC3=C2[C@H]1CN1CC[C@](C(C)(C)C)(O)C[C@H]13 ZZJYIKPMDIWRSN-HWBMXIPRSA-N 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
206010028347 Muscle twitching Diseases 0.000 description 1
HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
108010064983 Ovomucin Proteins 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
229910052774 Proactinium Inorganic materials 0.000 description 1
GOTMKOSCLKVOGG-UHFFFAOYSA-N SCH 23390 Chemical compound C1N(C)CCC2=CC(Cl)=C(O)C=C2C1C1=CC=CC=C1 GOTMKOSCLKVOGG-UHFFFAOYSA-N 0.000 description 1
239000004809 Teflon Substances 0.000 description 1
229920006362 Teflon® Polymers 0.000 description 1
229910010413 TiO 2 Inorganic materials 0.000 description 1
229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000009471 action Effects 0.000 description 1
230000004913 activation Effects 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
230000000172 allergic effect Effects 0.000 description 1
AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
230000037005 anaesthesia Effects 0.000 description 1
PYKYMHQGRFAEBM-UHFFFAOYSA-N anthraquinone Natural products CCC(=O)c1c(O)c2C(=O)C3C(C=CC=C3O)C(=O)c2cc1CC(=O)OC PYKYMHQGRFAEBM-UHFFFAOYSA-N 0.000 description 1
150000004056 anthraquinones Chemical class 0.000 description 1
229940005529 antipsychotics Drugs 0.000 description 1
229960003990 apomorphine hydrochloride Drugs 0.000 description 1
239000006286 aqueous extract Substances 0.000 description 1
229940072107 ascorbate Drugs 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
208000010668 atopic eczema Diseases 0.000 description 1
238000007630 basic procedure Methods 0.000 description 1
BNQDCRGUHNALGH-UHFFFAOYSA-N benserazide Chemical compound OCC(N)C(=O)NNCC1=CC=C(O)C(O)=C1O BNQDCRGUHNALGH-UHFFFAOYSA-N 0.000 description 1
150000001555 benzenes Chemical class 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
239000012965 benzophenone Substances 0.000 description 1
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
JKIUUDJOCYHIGY-UHFFFAOYSA-N benzyl 4-hydroxypiperidine-1-carboxylate Chemical compound C1CC(O)CCN1C(=O)OCC1=CC=CC=C1 JKIUUDJOCYHIGY-UHFFFAOYSA-N 0.000 description 1
230000003851 biochemical process Effects 0.000 description 1
229910052796 boron Inorganic materials 0.000 description 1
MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 1
229940098773 bovine serum albumin Drugs 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
244000309464 bull Species 0.000 description 1
229950006479 butaclamol Drugs 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
239000007963 capsule composition Substances 0.000 description 1
235000011089 carbon dioxide Nutrition 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
238000001311 chemical methods and process Methods 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
150000001844 chromium Chemical class 0.000 description 1
229910000423 chromium oxide Inorganic materials 0.000 description 1
230000007012 clinical effect Effects 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
238000013501 data transformation Methods 0.000 description 1
239000003405 delayed action preparation Substances 0.000 description 1
230000005595 deprotonation Effects 0.000 description 1
230000006866 deterioration Effects 0.000 description 1
238000007865 diluting Methods 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
230000005593 dissociations Effects 0.000 description 1
239000000433 dopamine 1 receptor blocking agent Substances 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
238000012377 drug delivery Methods 0.000 description 1
230000009977 dual effect Effects 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
238000006911 enzymatic reaction Methods 0.000 description 1
QPUSANCBJDDXSA-UHFFFAOYSA-N ethanethiol;sodium Chemical compound [Na].CCS QPUSANCBJDDXSA-UHFFFAOYSA-N 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
239000000945 filler Substances 0.000 description 1
239000012065 filter cake Substances 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
210000005153 frontal cortex Anatomy 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000000499 gel Substances 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
238000002513 implantation Methods 0.000 description 1
230000006872 improvement Effects 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
239000011261 inert gas Substances 0.000 description 1
229940060367 inert ingredients Drugs 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
239000003446 ligand Substances 0.000 description 1
150000002642 lithium compounds Chemical class 0.000 description 1
230000014759 maintenance of location Effects 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
239000003550 marker Substances 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical group C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
JIKUXBYRTXDNIY-UHFFFAOYSA-N n-methyl-n-phenylformamide Chemical compound O=CN(C)C1=CC=CC=C1 JIKUXBYRTXDNIY-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
238000006386 neutralization reaction Methods 0.000 description 1
150000002823 nitrates Chemical class 0.000 description 1
230000000802 nitrating effect Effects 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
150000002829 nitrogen Chemical class 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
150000002900 organolithium compounds Chemical class 0.000 description 1
125000002524 organometallic group Chemical group 0.000 description 1
DIVDFFZHCJEHGG-UHFFFAOYSA-N oxidopamine Chemical compound NCCC1=CC(O)=C(O)C=C1O DIVDFFZHCJEHGG-UHFFFAOYSA-N 0.000 description 1
QCAJADRKKXQEGQ-UHFFFAOYSA-J oxolane;titanium(4+);tetrachloride Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Ti+4].C1CCOC1 QCAJADRKKXQEGQ-UHFFFAOYSA-J 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000008014 pharmaceutical binder Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
239000012071 phase Substances 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 1
HDOWRFHMPULYOA-PTQBSOBMSA-N piperidin-4-ol Chemical class OC1CC[15NH]CC1 HDOWRFHMPULYOA-PTQBSOBMSA-N 0.000 description 1
150000003053 piperidines Chemical class 0.000 description 1
230000036470 plasma concentration Effects 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
239000004926 polymethyl methacrylate Substances 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
238000000746 purification Methods 0.000 description 1
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
239000002287 radioligand Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
238000001525 receptor binding assay Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
239000013557 residual solvent Substances 0.000 description 1
230000004044 response Effects 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
238000003345 scintillation counting Methods 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
238000000926 separation method Methods 0.000 description 1
229940121356 serotonin receptor antagonist Drugs 0.000 description 1
AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000001119 stannous chloride Substances 0.000 description 1
235000011150 stannous chloride Nutrition 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
210000003523 substantia nigra Anatomy 0.000 description 1
239000000758 substrate Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000007916 tablet composition Substances 0.000 description 1
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
239000012414 tert-butyl nitrite Substances 0.000 description 1
150000003568 thioethers Chemical class 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
238000011144 upstream manufacturing Methods 0.000 description 1
229920001567 vinyl ester resin Polymers 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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
- C07D211/36—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 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
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/52—Oxygen atoms attached in position 4 having an aryl radical as the second substituent in position 4
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Psychiatry (AREA)
Plural Heterocyclic Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Hydrogenated Pyridines (AREA)

SK29-96A 1993-07-09 1994-07-04 Methanoanthracenes substituted by piperidinyl group, preparation method thereof and their use as d1/d2-dopamine-antagonists and 5ht2-serotonin-antagonists SK2996A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB939314250A GB9314250D0 (en)	1993-07-09	1993-07-09	Piperidinyl compounds
PCT/GB1994/001439 WO1995001974A1 (en)	1993-07-09	1994-07-04	Piperidinyl substituted methanoanthracenes as d1/d2-antagonists and 5ht2-serotanin-antagonists

Publications (1)

Publication Number	Publication Date
SK2996A3 true SK2996A3 (en)	1997-02-05

Family

ID=10738563

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK29-96A SK2996A3 (en)	1993-07-09	1994-07-04	Methanoanthracenes substituted by piperidinyl group, preparation method thereof and their use as d1/d2-dopamine-antagonists and 5ht2-serotonin-antagonists

Country Status (26)

Country	Link
EP (1)	EP0707579B1 (cs)
JP (1)	JP3031634B2 (cs)
AP (1)	AP521A (cs)
AT (1)	ATE175963T1 (cs)
AU (1)	AU687414B2 (cs)
CA (1)	CA2163994A1 (cs)
CZ (1)	CZ4496A3 (cs)
DE (1)	DE69416131T2 (cs)
DK (1)	DK0707579T3 (cs)
DZ (1)	DZ1796A1 (cs)
ES (1)	ES2128567T3 (cs)
FI (1)	FI960084A7 (cs)
GB (2)	GB9314250D0 (cs)
HR (1)	HRP940394A2 (cs)
HU (1)	HU219239B (cs)
IL (1)	IL110222A (cs)
MY (1)	MY111604A (cs)
NO (1)	NO960080D0 (cs)
NZ (1)	NZ268048A (cs)
PL (1)	PL312498A1 (cs)
RU (1)	RU2128178C1 (cs)
SG (1)	SG45425A1 (cs)
SI (1)	SI9400281A (cs)
SK (1)	SK2996A3 (cs)
WO (1)	WO1995001974A1 (cs)
ZA (1)	ZA944930B (cs)

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9117639D0 (en) *	1991-08-15	1991-10-02	Ici Plc	Therapeutic compounds

1993
- 1993-07-09 GB GB939314250A patent/GB9314250D0/en active Pending
1994
- 1994-06-30 AP APAP/P/1994/000652A patent/AP521A/en active
- 1994-07-01 GB GB9413235A patent/GB9413235D0/en active Pending
- 1994-07-04 JP JP7503893A patent/JP3031634B2/ja not_active Expired - Fee Related
- 1994-07-04 CA CA002163994A patent/CA2163994A1/en not_active Abandoned
- 1994-07-04 CZ CZ9644A patent/CZ4496A3/cs unknown
- 1994-07-04 DK DK94919752T patent/DK0707579T3/da active
- 1994-07-04 SG SG1996007272A patent/SG45425A1/en unknown
- 1994-07-04 DE DE69416131T patent/DE69416131T2/de not_active Expired - Lifetime
- 1994-07-04 PL PL94312498A patent/PL312498A1/xx unknown
- 1994-07-04 HU HU9503554A patent/HU219239B/hu not_active IP Right Cessation
- 1994-07-04 WO PCT/GB1994/001439 patent/WO1995001974A1/en not_active Ceased
- 1994-07-04 AT AT94919752T patent/ATE175963T1/de not_active IP Right Cessation
- 1994-07-04 NZ NZ268048A patent/NZ268048A/en unknown
- 1994-07-04 ES ES94919752T patent/ES2128567T3/es not_active Expired - Lifetime
- 1994-07-04 RU RU96102585A patent/RU2128178C1/ru active
- 1994-07-04 EP EP94919752A patent/EP0707579B1/en not_active Expired - Lifetime
- 1994-07-04 AU AU70779/94A patent/AU687414B2/en not_active Ceased
- 1994-07-04 SK SK29-96A patent/SK2996A3/sk unknown
- 1994-07-05 IL IL11022294A patent/IL110222A/xx not_active IP Right Cessation
- 1994-07-06 HR HR9314250.3A patent/HRP940394A2/xx not_active Application Discontinuation
- 1994-07-07 ZA ZA944930A patent/ZA944930B/xx unknown
- 1994-07-08 SI SI9400281A patent/SI9400281A/sl unknown
- 1994-07-09 DZ DZ940075A patent/DZ1796A1/fr active
- 1994-07-09 MY MYPI94001799A patent/MY111604A/en unknown
1996
- 1996-01-08 NO NO960080A patent/NO960080D0/no not_active Application Discontinuation
- 1996-01-08 FI FI960084A patent/FI960084A7/fi unknown

Also Published As

Publication number	Publication date
HU219239B (en)	2001-03-28
DE69416131T2 (de)	1999-06-10
IL110222A (en)	1999-09-22
CA2163994A1 (en)	1995-01-19
AP521A (en)	1996-08-05
SI9400281A (en)	1995-02-28
ZA944930B (en)	1995-01-16
ES2128567T3 (es)	1999-05-16
SG45425A1 (en)	1998-01-16
AU7077994A (en)	1995-02-06
HU9503554D0 (en)	1996-02-28
GB9413235D0 (en)	1994-08-24
ATE175963T1 (de)	1999-02-15
GB9314250D0 (en)	1993-08-18
DZ1796A1 (fr)	2002-02-17
NZ268048A (en)	1997-10-24
FI960084A0 (fi)	1996-01-08
JPH08512308A (ja)	1996-12-24
WO1995001974A1 (en)	1995-01-19
AU687414B2 (en)	1998-02-26
EP0707579B1 (en)	1999-01-20
PL312498A1 (en)	1996-04-29
AP9400652A0 (en)	1994-07-31
RU2128178C1 (ru)	1999-03-27
DK0707579T3 (da)	1999-09-13
IL110222A0 (en)	1994-10-21
MY111604A (en)	2000-09-27
NO960080L (no)	1996-01-08
JP3031634B2 (ja)	2000-04-10
FI960084A7 (fi)	1996-01-08
HUT75116A (en)	1997-04-28
NO960080D0 (no)	1996-01-08
EP0707579A1 (en)	1996-04-24
HRP940394A2 (en)	1996-12-31
DE69416131D1 (de)	1999-03-04
CZ4496A3 (en)	1996-06-12

Publication	Publication Date	Title
DE60129210T2 (de)	2008-03-20	Zyklische amid-derivate
US8487101B2 (en)	2013-07-16	Thieno-pyridine derivatives as MEK inhibitors
JPH0283375A (ja)	1990-03-23	２−置換ピペラジニル−２−（１，２−ベンズイソキサゾール−３−イル）酢酸誘導体
JPH11509541A (ja)	1999-08-24	新規なガランタミン誘導体、その製造方法、その医薬としての用途及びそれを含有する医薬組成物
HK83697A (en)	1997-06-27	Methanoanthracenes as dopamine antagonists
CZ292379B6 (cs)	2003-09-17	Tetrahydrochinolinové deriváty, způsob jejich výroby a farmaceutický prostředek s jejich obsahem
AU681601B2 (en)	1997-09-04	O-aryl ethers of morphinans
IE73874B1 (en)	1997-07-02	Substituted-4-amino-3-pyridinols a process for their preparation and their use as medicaments
EP2616460B1 (en)	2015-10-28	Heterocyclic compounds for treating or preventing disorders caused by reduced neurotransmission of serotonin, norephnephrine or dopamine.
CZ284789B6 (cs)	1999-03-17	Benzoxazinové deriváty, způsob jejich přípravy a farmaceutická kompozice tyto deriváty obsahující
US5512575A (en)	1996-04-30	Methanoanthraceneyl methyl piperidinyl compounds
CA2040107A1 (en)	1991-10-20	Amine derivatives
EP0326106A2 (en)	1989-08-02	Alkylene diamines
JP2003509494A (ja)	2003-03-11	ムスカリン拮抗薬
EP1440075A1 (fr)	2004-07-28	Nouveaux derives amides heteroaromatiques de 3beta-amino azabicyclooctane, leur procede de preparation et leurs applications en therapeutique
US5334594A (en)	1994-08-02	Amphoteric tricyclic compound
DE69813886T2 (de)	2004-01-08	Naphthalin derivate
US20110212976A1 (en)	2011-09-01	Deuterium-enriched risperidone
EP0201085A2 (en)	1986-11-12	6-Phenyl-1,2,3,4,4a,5,6,10b-octahydrobenz(h) isoquinolines
SK2996A3 (en)	1997-02-05	Methanoanthracenes substituted by piperidinyl group, preparation method thereof and their use as d1/d2-dopamine-antagonists and 5ht2-serotonin-antagonists
EP0401779B1 (en)	1995-05-03	4,5,5a,6-Tetrahydro-3H-isoxazolo (5,4,3-kl)acridines derivatives, a process for their preparation and their use as medicaments
CA2090635A1 (en)	1993-09-04	Substituted phenylquinazoline derivatives
SK120793A3 (en)	1994-11-09	4-heterocyclylsubstituted dihydropyridines
CS411291A3 (en)	1992-06-17	Pilocarpine derivatives, process of their preparation and a pharmaceutical comprising thereof
CN117480153A (zh)	2024-01-30	氮杂双环[3.1.0]己烷化合物