DE3535929A1 - 1,2-disubstituierte ergolinderivate - Google Patents
1,2-disubstituierte ergolinderivateInfo
- Publication number
- DE3535929A1 DE3535929A1 DE19853535929 DE3535929A DE3535929A1 DE 3535929 A1 DE3535929 A1 DE 3535929A1 DE 19853535929 DE19853535929 DE 19853535929 DE 3535929 A DE3535929 A DE 3535929A DE 3535929 A1 DE3535929 A1 DE 3535929A1
- Authority
- DE
- Germany
- Prior art keywords
- ergolinyl
- urea
- diethyl
- methyl
- dimethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 35
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 24
- 239000002253 acid Substances 0.000 claims abstract description 17
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- 125000002252 acyl group Chemical group 0.000 claims abstract description 8
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 7
- 239000001257 hydrogen Substances 0.000 claims abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 6
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 6
- AWFDCTXCTHGORH-HGHGUNKESA-N 6-[4-[(6ar,9r,10ar)-5-bromo-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-carbonyl]piperazin-1-yl]-1-methylpyridin-2-one Chemical class O=C([C@H]1CN([C@H]2[C@@H](C=3C=CC=C4NC(Br)=C(C=34)C2)C1)C)N(CC1)CCN1C1=CC=CC(=O)N1C AWFDCTXCTHGORH-HGHGUNKESA-N 0.000 claims abstract description 5
- 125000003118 aryl group Chemical group 0.000 claims abstract description 5
- 229910052717 sulfur Chemical group 0.000 claims abstract description 5
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
- 239000001301 oxygen Substances 0.000 claims abstract description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 3
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 3
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims abstract description 3
- -1 1,1-Diethyl-3- [2- (1,3-dithiolan-2-yl) -1,6-dimethyl-8α-ergolinyl] urea 1,1-diethyl-3- (1,2,6-trimethyl-8α-ergolinyl) urea 1,1-diethyl-3- (6-methyl-2-formyl-8α-ergolinyl) urea Chemical compound 0.000 claims description 33
- 238000000034 method Methods 0.000 claims description 12
- 239000003054 catalyst Substances 0.000 claims description 10
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 6
- 239000004202 carbamide Substances 0.000 claims description 5
- 239000012039 electrophile Substances 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 150000003585 thioureas Chemical class 0.000 claims description 3
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
- 150000004662 dithiols Chemical class 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- 230000022244 formylation Effects 0.000 claims description 2
- 238000006170 formylation reaction Methods 0.000 claims description 2
- KIVMUXPQKLRPFI-QZBAPJRNSA-N C(C)N(C(=O)N[C@@H]1CN([C@@H]2CC3=C(N(C4=CC=CC([C@H]2C1)=C34)C)C#CC)C)CC.C(C)N(C(=O)N[C@@H]3CN([C@@H]4CC1=C(N(C2=CC=CC([C@H]4C3)=C12)CCC)C#C)C)CC Chemical compound C(C)N(C(=O)N[C@@H]1CN([C@@H]2CC3=C(N(C4=CC=CC([C@H]2C1)=C34)C)C#CC)C)CC.C(C)N(C(=O)N[C@@H]3CN([C@@H]4CC1=C(N(C2=CC=CC([C@H]4C3)=C12)CCC)C#C)C)CC KIVMUXPQKLRPFI-QZBAPJRNSA-N 0.000 claims 1
- AGIDQSAEEZRHLH-QSIGMZKWSA-N C(C)N(C(=O)N[C@@H]1CN([C@@H]2CC3=C(N(C4=CC=CC([C@H]2C1)=C34)C)CCC3=CC=CC=C3)C)CC.C(C)N(C(=O)N[C@@H]3CN([C@@H]4CC1=C(N(C2=CC=CC([C@H]4C3)=C12)CCC)CC)C)CC.C(C)N(C(=O)N[C@@H]1CN([C@@H]2CC3=C(N(C4=CC=CC([C@H]2C1)=C34)C)C#C)C)CC Chemical compound C(C)N(C(=O)N[C@@H]1CN([C@@H]2CC3=C(N(C4=CC=CC([C@H]2C1)=C34)C)CCC3=CC=CC=C3)C)CC.C(C)N(C(=O)N[C@@H]3CN([C@@H]4CC1=C(N(C2=CC=CC([C@H]4C3)=C12)CCC)CC)C)CC.C(C)N(C(=O)N[C@@H]1CN([C@@H]2CC3=C(N(C4=CC=CC([C@H]2C1)=C34)C)C#C)C)CC AGIDQSAEEZRHLH-QSIGMZKWSA-N 0.000 claims 1
- WAUZSPIZSRFRMM-CKEPXIACSA-N C(C)N(C(=O)N[C@@H]1CN([C@@H]2CC3=C(N(C4=CC=CC([C@H]2C1)=C34)CCC)I)C)CC.BrC3=C4C[C@H]1N(C[C@H](C[C@@H]1C=1C=CC=C(N3C)C14)NC(N(CC)CC)=O)CCC.BrC1=C4C[C@H]3N(C[C@H](C[C@@H]3C=3C=CC=C(N1C)C34)NC(N(CC)CC)=O)C Chemical compound C(C)N(C(=O)N[C@@H]1CN([C@@H]2CC3=C(N(C4=CC=CC([C@H]2C1)=C34)CCC)I)C)CC.BrC3=C4C[C@H]1N(C[C@H](C[C@@H]1C=1C=CC=C(N3C)C14)NC(N(CC)CC)=O)CCC.BrC1=C4C[C@H]3N(C[C@H](C[C@@H]3C=3C=CC=C(N1C)C34)NC(N(CC)CC)=O)C WAUZSPIZSRFRMM-CKEPXIACSA-N 0.000 claims 1
- JIQHWZMAFNPLBW-HVMFLUNKSA-N C(C1=CC=CC=C1)SC1=C2C[C@H]3N(C[C@H](C[C@@H]3C=3C=CC=C(N1C)C32)NC(N(CC)CC)=O)C.C(C)N(C(=O)N[C@@H]3CN([C@@H]2CC1=C(N(C4=CC=CC([C@H]2C3)=C14)C)SC1=CC=CC=C1)C)CC.BrC1=C4C[C@H]3N(C[C@H](C=C3C=3C=CC=C(N1C)C34)NC(N(CC)CC)=O)C Chemical compound C(C1=CC=CC=C1)SC1=C2C[C@H]3N(C[C@H](C[C@@H]3C=3C=CC=C(N1C)C32)NC(N(CC)CC)=O)C.C(C)N(C(=O)N[C@@H]3CN([C@@H]2CC1=C(N(C4=CC=CC([C@H]2C3)=C14)C)SC1=CC=CC=C1)C)CC.BrC1=C4C[C@H]3N(C[C@H](C=C3C=3C=CC=C(N1C)C34)NC(N(CC)CC)=O)C JIQHWZMAFNPLBW-HVMFLUNKSA-N 0.000 claims 1
- OLTWCZGVKOGJFX-FGNMRCHZSA-N CN1C(=C2C[C@H]3N(C[C@H](C=C3C=3C=CC=C1C32)NC(N(CC)CC)=O)C)SC.C(C)N(C(=O)N[C@@H]3CN([C@@H]2CC1=C(N(C4=CC=CC([C@H]2C3)=C14)C)SC)C)CC.NC(=O)N Chemical compound CN1C(=C2C[C@H]3N(C[C@H](C=C3C=3C=CC=C1C32)NC(N(CC)CC)=O)C)SC.C(C)N(C(=O)N[C@@H]3CN([C@@H]2CC1=C(N(C4=CC=CC([C@H]2C3)=C14)C)SC)C)CC.NC(=O)N OLTWCZGVKOGJFX-FGNMRCHZSA-N 0.000 claims 1
- TVBBWAHXCUFDBH-ZKPJOOANSA-N CN1C(=C2C[C@H]3N(C[C@H](C=C3C=3C=CC=C1C32)NC(N(CC)CC)=O)C)SC3=CC=CC=C3.C(C)N(C(=O)N[C@@H]3CN([C@@H]2CC1=C(N(C4=CC=CC([C@H]2C3)=C14)C)SCCC)C)CC Chemical compound CN1C(=C2C[C@H]3N(C[C@H](C=C3C=3C=CC=C1C32)NC(N(CC)CC)=O)C)SC3=CC=CC=C3.C(C)N(C(=O)N[C@@H]3CN([C@@H]2CC1=C(N(C4=CC=CC([C@H]2C3)=C14)C)SCCC)C)CC TVBBWAHXCUFDBH-ZKPJOOANSA-N 0.000 claims 1
- KLJJVFILQIFUMB-VDFMLGTDSA-N CN1C[C@H](C[C@@H]2C=3C=CC=C4N(C(=C(C[C@@H]12)C34)CC)CCC)NC(N(CC)CC)=S.C(C)N(C(=O)N[C@@H]3CN([C@@H]4CC1=C(N(C2=CC=CC([C@H]4C3)=C12)CCC)CC)C)CC.C(C)N(C(=O)N[C@@H]1CN([C@@H]2CC3=C(N(C4=CC=CC([C@H]2C1)=C34)CCC)C=C)C)CC.NC(=O)N Chemical compound CN1C[C@H](C[C@@H]2C=3C=CC=C4N(C(=C(C[C@@H]12)C34)CC)CCC)NC(N(CC)CC)=S.C(C)N(C(=O)N[C@@H]3CN([C@@H]4CC1=C(N(C2=CC=CC([C@H]4C3)=C12)CCC)CC)C)CC.C(C)N(C(=O)N[C@@H]1CN([C@@H]2CC3=C(N(C4=CC=CC([C@H]2C1)=C34)CCC)C=C)C)CC.NC(=O)N KLJJVFILQIFUMB-VDFMLGTDSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 abstract 1
- 125000004430 oxygen atom Chemical group O* 0.000 abstract 1
- 230000000144 pharmacologic effect Effects 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 239000000203 mixture Substances 0.000 description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 229910052786 argon Inorganic materials 0.000 description 8
- 239000012442 inert solvent Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- GUUVPOWQJOLRAS-UHFFFAOYSA-N Diphenyl disulfide Chemical compound C=1C=CC=CC=1SSC1=CC=CC=C1 GUUVPOWQJOLRAS-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
- 239000007868 Raney catalyst Substances 0.000 description 5
- 229910000564 Raney nickel Inorganic materials 0.000 description 5
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 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 5
- 229960004046 apomorphine Drugs 0.000 description 5
- 235000013877 carbamide Nutrition 0.000 description 5
- 150000002170 ethers Chemical class 0.000 description 5
- 229910052744 lithium Inorganic materials 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 239000000010 aprotic solvent Substances 0.000 description 4
- 229960002896 clonidine Drugs 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- GVPWHKZIJBODOX-UHFFFAOYSA-N dibenzyl disulfide Chemical compound C=1C=CC=CC=1CSSCC1=CC=CC=C1 GVPWHKZIJBODOX-UHFFFAOYSA-N 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 230000002631 hypothermal effect Effects 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- DCOKFNWIRJKEEG-GEQKSPFYSA-N 3-[(6ar,9s,10ar)-5-ethenyl-7-methyl-4-propyl-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C1([C@@H]2[C@H](N(C[C@H](C2)NC(=O)N(CC)CC)C)C2)=CC=CC3=C1C2=C(C=C)N3CCC DCOKFNWIRJKEEG-GEQKSPFYSA-N 0.000 description 3
- IIPUPWJBJXAVRT-GEQKSPFYSA-N 3-[(6ar,9s,10ar)-5-ethyl-7-methyl-4-propyl-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C1([C@@H]2[C@H](N(C[C@H](C2)NC(=O)N(CC)CC)C)C2)=CC=CC3=C1C2=C(CC)N3CCC IIPUPWJBJXAVRT-GEQKSPFYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 150000001350 alkyl halides Chemical class 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 229910052757 nitrogen Chemical group 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- YNWIDURWQZKLSX-GEQKSPFYSA-N 3-[(6aR,9S,10aR)-5-ethyl-7-methyl-4-propyl-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinolin-9-yl]-1,1-diethylthiourea Chemical compound CN1C[C@H](C[C@@H]2C=3C=CC=C4N(C(=C(C[C@@H]12)C=34)CC)CCC)NC(N(CC)CC)=S YNWIDURWQZKLSX-GEQKSPFYSA-N 0.000 description 2
- VBJKKKOUSCYKOY-SCLBCKFNSA-N 3-[(6ar,9s)-5-bromo-4,7-dimethyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C1=CC(C=2[C@H](N(C)C[C@H](C=2)NC(=O)N(CC)CC)C2)=C3C2=C(Br)N(C)C3=C1 VBJKKKOUSCYKOY-SCLBCKFNSA-N 0.000 description 2
- NLVAIIPKQLHJOX-KVSKMBFKSA-N 3-[(6ar,9s,10ar)-4,7-dimethyl-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NC(=O)N(CC)CC)=C3C2=CN(C)C3=C1 NLVAIIPKQLHJOX-KVSKMBFKSA-N 0.000 description 2
- JDVFAPYYBYASMQ-ZSZQSSIHSA-N 3-[(6ar,9s,10ar)-4-acetyl-5-iodo-7-methyl-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NC(=O)N(CC)CC)=C3C2=C(I)N(C(C)=O)C3=C1 JDVFAPYYBYASMQ-ZSZQSSIHSA-N 0.000 description 2
- GHBBCXWKTFQMRR-XAUMDUMWSA-N 3-[(6ar,9s,10ar)-5-(1,3-dithiolan-2-yl)-4,7-dimethyl-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C([C@@H]1[C@@H](C=2C=CC=C(C3=2)N2C)C[C@@H](CN1C)NC(=O)N(CC)CC)C3=C2C1SCCS1 GHBBCXWKTFQMRR-XAUMDUMWSA-N 0.000 description 2
- BVBAHRBRBODPHA-JCKWVBRZSA-N 3-[(6ar,9s,10ar)-5-bromo-4,7-dimethyl-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NC(=O)N(CC)CC)=C3C2=C(Br)N(C)C3=C1 BVBAHRBRBODPHA-JCKWVBRZSA-N 0.000 description 2
- PNNAMFACCXPDEC-GEQKSPFYSA-N 3-[(6ar,9s,10ar)-5-ethynyl-7-methyl-4-propyl-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C1([C@@H]2[C@H](N(C[C@H](C2)NC(=O)N(CC)CC)C)C2)=CC=CC3=C1C2=C(C#C)N3CCC PNNAMFACCXPDEC-GEQKSPFYSA-N 0.000 description 2
- CINUROYQMZAVEH-XAUMDUMWSA-N 3-[(6ar,9s,10ar)-5-iodo-7-methyl-4-propyl-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C1([C@@H]2[C@H](N(C[C@H](C2)NC(=O)N(CC)CC)C)C2)=CC=CC3=C1C2=C(I)N3CCC CINUROYQMZAVEH-XAUMDUMWSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- QMKYVKHSZKWPIP-HNAYVOBHSA-N CN1C=C2C[C@H]3N(C[C@H](C=C3C=3C=CC=C1C=32)NC(N(CC)CC)=O)C Chemical compound CN1C=C2C[C@H]3N(C[C@H](C=C3C=3C=CC=C1C=32)NC(N(CC)CC)=O)C QMKYVKHSZKWPIP-HNAYVOBHSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-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
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- 238000011785 NMRI mouse Methods 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- XYONNSVDNIRXKZ-UHFFFAOYSA-N S-methyl methanethiosulfonate Chemical compound CSS(C)(=O)=O XYONNSVDNIRXKZ-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 150000001263 acyl chlorides Chemical class 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 150000002940 palladium Chemical class 0.000 description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- JCBJVAJGLKENNC-UHFFFAOYSA-M potassium ethyl xanthate Chemical compound [K+].CCOC([S-])=S JCBJVAJGLKENNC-UHFFFAOYSA-M 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000011593 sulfur Chemical group 0.000 description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000028016 temperature homeostasis Effects 0.000 description 2
- 238000006177 thiolation reaction Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 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
- 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 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- DHBXNPKRAUYBTH-UHFFFAOYSA-N 1,1-ethanedithiol Chemical compound CC(S)S DHBXNPKRAUYBTH-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- HGNXDVMCNWPAGR-IFXJQAMLSA-N 3-[(6aR,9S)-4,7-dimethyl-5-methylsulfanyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinolin-9-yl]-1,1-diethylurea Chemical compound CN1C(=C2C[C@H]3N(C[C@H](C=C3C=3C=CC=C1C=32)NC(N(CC)CC)=O)C)SC HGNXDVMCNWPAGR-IFXJQAMLSA-N 0.000 description 1
- WAMHTUYTFLGRFJ-YRISNDGFSA-N 3-[(6aR,9S,10aR)-4,7-dimethyl-5-propylsulfanyl-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinolin-9-yl]-1,1-diethylurea Chemical compound C(C)N(C(=O)N[C@@H]1CN([C@@H]2CC3=C(N(C4=CC=CC([C@H]2C1)=C34)C)SCCC)C)CC WAMHTUYTFLGRFJ-YRISNDGFSA-N 0.000 description 1
- ZTMOXMKJSVWGKB-LUQKVYGDSA-N 3-[(6aR,9S,10aR)-5-ethynyl-4,7-dimethyl-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinolin-9-yl]-1,1-diethylurea Chemical compound C(#C)C1=C2C[C@H]3N(C[C@H](C[C@@H]3C=3C=CC=C(N1C)C=32)NC(N(CC)CC)=O)C ZTMOXMKJSVWGKB-LUQKVYGDSA-N 0.000 description 1
- ZOIOAUYNHZYECT-MHECFPHRSA-N 3-[(6ar,9s)-4,7-dimethyl-5-phenylsulfanyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C([C@H]1N(C)C[C@H](C=C1C=1C=CC=C(C2=1)N1C)NC(=O)N(CC)CC)C2=C1SC1=CC=CC=C1 ZOIOAUYNHZYECT-MHECFPHRSA-N 0.000 description 1
- WYSBQPVFIGKKFZ-QKYXUNIQSA-N 3-[(6ar,9s,10ar)-4,5,7-trimethyl-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NC(=O)N(CC)CC)=C3C2=C(C)N(C)C3=C1 WYSBQPVFIGKKFZ-QKYXUNIQSA-N 0.000 description 1
- UZHCOMMZWXIOOK-ZSZQSSIHSA-N 3-[(6ar,9s,10ar)-4,7-dimethyl-5-methylsulfanyl-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NC(=O)N(CC)CC)=C3C2=C(SC)N(C)C3=C1 UZHCOMMZWXIOOK-ZSZQSSIHSA-N 0.000 description 1
- QXSIWAZJRZCMQS-SNYIIPAISA-N 3-[(6ar,9s,10ar)-4,7-dimethyl-5-phenylsulfanyl-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C([C@@H]1[C@@H](C=2C=CC=C(C3=2)N2C)C[C@@H](CN1C)NC(=O)N(CC)CC)C3=C2SC1=CC=CC=C1 QXSIWAZJRZCMQS-SNYIIPAISA-N 0.000 description 1
- SJWINRAKFZCGOG-ZSZQSSIHSA-N 3-[(6ar,9s,10ar)-5-(1,3-dithiolan-2-yl)-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C([C@@H]1[C@@H](C=2C=CC=C(C3=2)N2)C[C@@H](CN1C)NC(=O)N(CC)CC)C3=C2C1SCCS1 SJWINRAKFZCGOG-ZSZQSSIHSA-N 0.000 description 1
- USTFQHKVBGAUPX-ZSZQSSIHSA-N 3-[(6ar,9s,10ar)-5-(hydroxymethyl)-4,7-dimethyl-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NC(=O)N(CC)CC)=C3C2=C(CO)N(C)C3=C1 USTFQHKVBGAUPX-ZSZQSSIHSA-N 0.000 description 1
- RBWCIISTHHFJOI-DXCKQFNASA-N 3-[(6ar,9s,10ar)-5-bromo-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NC(=O)N(CC)CC)=C3C2=C(Br)NC3=C1 RBWCIISTHHFJOI-DXCKQFNASA-N 0.000 description 1
- ALLGYPURAPDKMY-ZSZQSSIHSA-N 3-[(6ar,9s,10ar)-5-bromo-7-propyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C1=CC([C@H]2C[C@@H](CN([C@@H]2C2)CCC)NC(=O)N(CC)CC)=C3C2=C(Br)NC3=C1 ALLGYPURAPDKMY-ZSZQSSIHSA-N 0.000 description 1
- ZMADCGSDJKHDCB-YYFZDKIDSA-N 3-[(6ar,9s,10ar)-5-ethynyl-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NC(=O)N(CC)CC)=C3C2=C(C#C)NC3=C1 ZMADCGSDJKHDCB-YYFZDKIDSA-N 0.000 description 1
- OCSZQRFNOQGEPK-ZSZQSSIHSA-N 3-[(6ar,9s,10ar)-5-formyl-4,7-dimethyl-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NC(=O)N(CC)CC)=C3C2=C(C=O)N(C)C3=C1 OCSZQRFNOQGEPK-ZSZQSSIHSA-N 0.000 description 1
- HNWWGVFBTYUAPJ-ZBQZNYHESA-N 3-[(6ar,9s,10ar)-5-formyl-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NC(=O)N(CC)CC)=C3C2=C(C=O)NC3=C1 HNWWGVFBTYUAPJ-ZBQZNYHESA-N 0.000 description 1
- JUAFFCYJDFGDSA-DXCKQFNASA-N 3-[(6ar,9s,10ar)-5-iodo-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NC(=O)N(CC)CC)=C3C2=C(I)NC3=C1 JUAFFCYJDFGDSA-DXCKQFNASA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 1
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 235000011437 Amygdalus communis Nutrition 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- TUJLXCVSKUCDRD-AQOAWAETSA-N C(C)N(C(=O)N[C@@H]1CN([C@@H]2CC3=C(N(C4=CC=CC([C@H]2C1)=C34)C)C#CC)C)CC Chemical compound C(C)N(C(=O)N[C@@H]1CN([C@@H]2CC3=C(N(C4=CC=CC([C@H]2C1)=C34)C)C#CC)C)CC TUJLXCVSKUCDRD-AQOAWAETSA-N 0.000 description 1
- ILQRUTUTDSAZHF-UHFFFAOYSA-N C(C)SS(=O)=O.CC1=CC=CC=C1 Chemical compound C(C)SS(=O)=O.CC1=CC=CC=C1 ILQRUTUTDSAZHF-UHFFFAOYSA-N 0.000 description 1
- LYPIGYXPYTYOOM-NIRIFSCTSA-N C(C1=CC=CC=C1)SC1=C2C[C@H]3N(C[C@H](C[C@@H]3C=3C=CC=C(N1C)C=32)NC(N(CC)CC)=O)C Chemical compound C(C1=CC=CC=C1)SC1=C2C[C@H]3N(C[C@H](C[C@@H]3C=3C=CC=C(N1C)C=32)NC(N(CC)CC)=O)C LYPIGYXPYTYOOM-NIRIFSCTSA-N 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
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- 102000015554 Dopamine receptor Human genes 0.000 description 1
- 108050004812 Dopamine receptor Proteins 0.000 description 1
- 229940098778 Dopamine receptor agonist Drugs 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 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
- 239000005909 Kieselgur Substances 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-L PdCl2(PPh3)2 Substances [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 241000220304 Prunus dulcis Species 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- BKRGVLQUQGGVSM-KBXCAEBGSA-N Revanil Chemical compound C1=CC(C=2[C@H](N(C)C[C@H](C=2)NC(=O)N(CC)CC)C2)=C3C2=CNC3=C1 BKRGVLQUQGGVSM-KBXCAEBGSA-N 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 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
- 241001061127 Thione Species 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- ZZXDRXVIRVJQBT-UHFFFAOYSA-M Xylenesulfonate Chemical compound CC1=CC=CC(S([O-])(=O)=O)=C1C ZZXDRXVIRVJQBT-UHFFFAOYSA-M 0.000 description 1
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N acetic acid;palladium Chemical compound [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- 150000000475 acetylene derivatives Chemical class 0.000 description 1
- YTIVTFGABIZHHX-UHFFFAOYSA-L acetylenedicarboxylate(2-) Chemical compound [O-]C(=O)C#CC([O-])=O YTIVTFGABIZHHX-UHFFFAOYSA-L 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000001347 alkyl bromides Chemical class 0.000 description 1
- 150000001343 alkyl silanes Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 235000020224 almond Nutrition 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001090 anti-dopaminergic effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- GDBGRCLUSRPBEH-UHFFFAOYSA-N argon chloroform Chemical compound [Ar].C(Cl)(Cl)Cl GDBGRCLUSRPBEH-UHFFFAOYSA-N 0.000 description 1
- 159000000032 aromatic acids Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 235000015895 biscuits Nutrition 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- JOYKCMAPFCSKNO-UHFFFAOYSA-N chloro benzenesulfonate Chemical compound ClOS(=O)(=O)C1=CC=CC=C1 JOYKCMAPFCSKNO-UHFFFAOYSA-N 0.000 description 1
- KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 235000014510 cooky Nutrition 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 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
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- RQKYPMNUYSOMOD-UHFFFAOYSA-N dimethyl(methylsulfanyl)sulfanium Chemical compound CS[S+](C)C RQKYPMNUYSOMOD-UHFFFAOYSA-N 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000007336 electrophilic substitution reaction Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- RHGUXDUPXYFCTE-ZWNOBZJWSA-N ergoline Chemical class C1=CC([C@@H]2[C@H](NCCC2)C2)=C3C2=CNC3=C1 RHGUXDUPXYFCTE-ZWNOBZJWSA-N 0.000 description 1
- GCSJLQSCSDMKTP-UHFFFAOYSA-N ethenyl(trimethyl)silane Chemical compound C[Si](C)(C)C=C GCSJLQSCSDMKTP-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- KKLGDUSGQMHBPB-UHFFFAOYSA-N hex-2-ynedioic acid Chemical compound OC(=O)CCC#CC(O)=O KKLGDUSGQMHBPB-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-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
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229960003587 lisuride Drugs 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 229940049920 malate Drugs 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
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 125000005341 metaphosphate group Chemical group 0.000 description 1
- IZYBEMGNIUSSAX-UHFFFAOYSA-N methyl benzenecarboperoxoate Chemical compound COOC(=O)C1=CC=CC=C1 IZYBEMGNIUSSAX-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 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
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 150000002941 palladium compounds Chemical class 0.000 description 1
- OTYPIDNRISCWQY-UHFFFAOYSA-L palladium(2+);tris(2-methylphenyl)phosphane;dichloride Chemical compound Cl[Pd]Cl.CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C.CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C OTYPIDNRISCWQY-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
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical compound CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
- 229940049953 phenylacetate Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 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
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-M propynoate Chemical compound [O-]C(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-M 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 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
- 150000003254 radicals Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 230000000698 schizophrenic effect Effects 0.000 description 1
- 229940116351 sebacate Drugs 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
- 150000004756 silanes Chemical class 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- ORGHESHFQPYLAO-UHFFFAOYSA-N vinyl radical Chemical compound C=[CH] ORGHESHFQPYLAO-UHFFFAOYSA-N 0.000 description 1
- 229940071104 xylenesulfonate Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D457/00—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid
- C07D457/10—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid with hetero atoms directly attached in position 8
- C07D457/12—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychiatry (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Priority Applications (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19853535929 DE3535929A1 (de) | 1985-10-04 | 1985-10-04 | 1,2-disubstituierte ergolinderivate |
| JP61234693A JPH0670051B2 (ja) | 1985-10-04 | 1986-10-03 | １，２−置換されたエルゴリン誘導体、該製法及び該誘導体を含有する精神分裂同型団精神病及び抑うつ症治療剤 |
| AT86730153T ATE74919T1 (de) | 1985-10-04 | 1986-10-03 | 1,2-disubstituierte ergolinderivate. |
| CS867154A CS259893B2 (en) | 1985-10-04 | 1986-10-03 | Method of ergoline's 1,2-disubstituted derivatives production |
| ES86730153T ES2051694T3 (es) | 1985-10-04 | 1986-10-03 | Derivados de ergolina disustituidos en posiciones 1,2. |
| EP86730153A EP0217736B1 (de) | 1985-10-04 | 1986-10-03 | 1,2-Disubstituierte Ergolinderivate |
| DE8686730153T DE3684855D1 (de) | 1985-10-04 | 1986-10-03 | 1,2-disubstituierte ergolinderivate. |
| US06/915,358 US4874768A (en) | 1985-10-04 | 1986-10-06 | 1,2-disubstituted ergolines useful for producing central antidopanminergic or α2-receptor-blocking activity |
| CS874031A CS259899B2 (cs) | 1985-10-04 | 1987-06-02 | Způsob výroby nových 1,2-disubstituovaných derivátů ergolinu |
| CS874030A CS259898B2 (en) | 1985-10-04 | 1987-06-02 | Method of ergoline's new 1,2-disubstituted derivatives production |
| GR920401190T GR3005135T3 (enExample) | 1985-10-04 | 1992-07-10 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19853535929 DE3535929A1 (de) | 1985-10-04 | 1985-10-04 | 1,2-disubstituierte ergolinderivate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE3535929A1 true DE3535929A1 (de) | 1987-04-09 |
Family
ID=6283084
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19853535929 Withdrawn DE3535929A1 (de) | 1985-10-04 | 1985-10-04 | 1,2-disubstituierte ergolinderivate |
| DE8686730153T Expired - Lifetime DE3684855D1 (de) | 1985-10-04 | 1986-10-03 | 1,2-disubstituierte ergolinderivate. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE8686730153T Expired - Lifetime DE3684855D1 (de) | 1985-10-04 | 1986-10-03 | 1,2-disubstituierte ergolinderivate. |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US4874768A (enExample) |
| EP (1) | EP0217736B1 (enExample) |
| JP (1) | JPH0670051B2 (enExample) |
| AT (1) | ATE74919T1 (enExample) |
| CS (1) | CS259893B2 (enExample) |
| DE (2) | DE3535929A1 (enExample) |
| ES (1) | ES2051694T3 (enExample) |
| GR (1) | GR3005135T3 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3620293A1 (de) * | 1986-06-16 | 1987-12-17 | Schering Ag | 1-und/oder 2-substituierte ergolinderivate |
| DE3824659A1 (de) * | 1988-07-15 | 1990-02-08 | Schering Ag | 2-, 12- oder 13-substituierte 3-(8'(alpha)-ergolinyl)-1,1-diethylharnstoffe, ihre herstellung und verwendung in arzneimitteln |
| DK338789A (da) * | 1988-07-15 | 1990-01-16 | Schering Ag | 2-substituerede ergolinylurinstofderivater og fremgangsmaade til fremstilling deraf, deres anvendelse som laegemidler samt mellemprodukter til fremstilling deraf |
| TW252979B (enExample) * | 1992-12-24 | 1995-08-01 | Erba Carlo Spa | |
| DE10041478A1 (de) | 2000-08-24 | 2002-03-14 | Sanol Arznei Schwarz Gmbh | Neue pharmazeutische Zusammensetzung |
| DE10334188B4 (de) * | 2003-07-26 | 2007-07-05 | Schwarz Pharma Ag | Verwendung von Rotigotin zur Behandlung von Depressionen |
| DE10334187A1 (de) * | 2003-07-26 | 2005-03-03 | Schwarz Pharma Ag | Substituierte 2-Aminotetraline zur Behandlung von Depressionen |
| EP2083008A1 (en) * | 2007-12-07 | 2009-07-29 | Axxonis Pharma AG | Ergoline derivatives as selective radical scavengers for neurons |
| BR112017015487A2 (pt) | 2015-01-20 | 2018-01-30 | Xoc Pharmaceuticals Inc | Composto; composição; método de tratamento e/ou prevenção de enxaqueca, als, doença de alzheimer, doença de parkinson, distúrbios extrapirimidais, depressão, náusea, êmese, síndrome das pernas inquietas, insônia, agressão, doença de huntington, doença cardiopulmonar, fibrogênese, hipertensão arterial pulmonar, ansiedade, dependências a drogas, distonia, parassonia ou hiperlactinemia em um indivíduo; métodos de agonização dos receptores d2, 5-ht1d, 5-ht1a e 5-ht2c, em um indivíduo; método de antagonização do receptor d3 em um indivíduo; métodos de agonização seletiva dos receptores 5 -ht1d, e 5-ht2c, método de fornecimento de atividade de antagonista funcional no receptor 5 -ht2b ou no receptor 5-ht7, ou em ambos, em um indivíduo; método de fornecimento de atividade de antagonista funcional nos receptores adrenérgicos em um indivíduo |
| CA3064274A1 (en) | 2017-06-01 | 2018-12-06 | Xoc Pharmaceuticals, Inc. | Ergoline derivatives for use in medicine |
| EP4423084A4 (en) * | 2021-10-26 | 2025-12-10 | Diamond Therapeutics Inc | 5-HT2A RECEPTOR ERGOLINE-DERIVED AGONISTS |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3151912A1 (de) * | 1981-12-23 | 1983-06-30 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Neue ergolin-aminoderivate, verfahren zu ihrer herstellung und deren verwendung als arzneimittel |
| DE3309493A1 (de) * | 1983-03-14 | 1984-09-20 | Schering AG, 1000 Berlin und 4709 Bergkamen | Neue ergolin-derivate, verfahren zu ihrer herstellung sowie verwendung als arzneimittel |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2656344A1 (de) * | 1975-12-23 | 1977-07-07 | Sandoz Ag | Ergolinderivate, ihre verwendung und herstellung |
| CH622518A5 (en) * | 1976-12-14 | 1981-04-15 | Sandoz Ag | Process for the preparation of novel ergoline compounds |
| DE3101535A1 (de) * | 1981-01-14 | 1982-08-12 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Neue (2-halogen-ergolinyl)-n'.n'-diethyl-harnstoffderivate, verfahren zu ihrer herstellung und deren verwendung als arzneimittel |
| PH21123A (en) * | 1983-04-28 | 1987-07-27 | Erba Farmitalia | Ergoline derivatives |
| DE3413659A1 (de) * | 1984-04-09 | 1985-10-17 | Schering AG, 1000 Berlin und 4709 Bergkamen | Neue 2-substituierte ergolin-derivate |
| EP0160842B1 (de) * | 1984-04-09 | 1994-06-22 | Schering Aktiengesellschaft | 2-substituierte Ergolin-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| DE3533675A1 (de) * | 1985-09-19 | 1987-03-26 | Schering Ag | Neue 12- und 13-brom-ergolinderivate |
-
1985
- 1985-10-04 DE DE19853535929 patent/DE3535929A1/de not_active Withdrawn
-
1986
- 1986-10-03 ES ES86730153T patent/ES2051694T3/es not_active Expired - Lifetime
- 1986-10-03 CS CS867154A patent/CS259893B2/cs unknown
- 1986-10-03 DE DE8686730153T patent/DE3684855D1/de not_active Expired - Lifetime
- 1986-10-03 AT AT86730153T patent/ATE74919T1/de not_active IP Right Cessation
- 1986-10-03 EP EP86730153A patent/EP0217736B1/de not_active Expired - Lifetime
- 1986-10-03 JP JP61234693A patent/JPH0670051B2/ja not_active Expired - Lifetime
- 1986-10-06 US US06/915,358 patent/US4874768A/en not_active Expired - Fee Related
-
1992
- 1992-07-10 GR GR920401190T patent/GR3005135T3/el unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3151912A1 (de) * | 1981-12-23 | 1983-06-30 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Neue ergolin-aminoderivate, verfahren zu ihrer herstellung und deren verwendung als arzneimittel |
| DE3309493A1 (de) * | 1983-03-14 | 1984-09-20 | Schering AG, 1000 Berlin und 4709 Bergkamen | Neue ergolin-derivate, verfahren zu ihrer herstellung sowie verwendung als arzneimittel |
Also Published As
| Publication number | Publication date |
|---|---|
| ATE74919T1 (de) | 1992-05-15 |
| JPS62174075A (ja) | 1987-07-30 |
| DE3684855D1 (de) | 1992-05-21 |
| CS259893B2 (en) | 1988-11-15 |
| EP0217736A3 (en) | 1989-03-22 |
| JPH0670051B2 (ja) | 1994-09-07 |
| US4874768A (en) | 1989-10-17 |
| ES2051694T3 (es) | 1994-07-01 |
| CS715486A2 (en) | 1988-03-15 |
| EP0217736A2 (de) | 1987-04-08 |
| GR3005135T3 (enExample) | 1993-05-24 |
| EP0217736B1 (de) | 1992-04-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0160842B1 (de) | 2-substituierte Ergolin-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel | |
| EP0021206B1 (de) | Neue (Ergolin-yl)-N', N'-diäthylharnstoff-Derivate, ihre Herstellung und sie enthaltende Arzneimittel | |
| DE3525564A1 (de) | Tricyclische verbindungen mit indolstruktur, verfahren zu ihrer herstellung und deren verwendung als arzneimittel | |
| EP0217736B1 (de) | 1,2-Disubstituierte Ergolinderivate | |
| EP0118848B1 (de) | Neue Ergolin-Derivate, Verfahren zu ihrer Herstellung sowie Verwendung als Arzneimittel | |
| DE3535927A1 (de) | 3-vinyl- und 3-ethinyl-ss-carbolinderivate, ihre herstellung und ihre verwendung als arzneimittel | |
| EP0351352B1 (de) | 2-Substituierte Ergoline, ihre Herstellung und Verwendung | |
| EP0307786A2 (de) | Deutero-Cholecalciferolderivate, ihre Herstellung und pharmazeutische Anwendung | |
| EP0217734B1 (de) | 12- und 13-Brom-Ergolinderivate | |
| DE3413657A1 (de) | Neue ergoline | |
| WO1993001185A1 (de) | 2,14-disubstituierte ergoline, deren herstellung und verwendung in arzneimitteln | |
| EP0220129B1 (de) | 12- und 13-substituierte Ergolinderivate | |
| DE3535930A1 (de) | Neue 2-substituierte ergolinderivate | |
| DE3620293A1 (de) | 1-und/oder 2-substituierte ergolinderivate | |
| DE3413659A1 (de) | Neue 2-substituierte ergolin-derivate | |
| EP0213062B1 (de) | 1-Alkyl-ergolinyl-thioharnstoffderivate | |
| DE3413660C2 (enExample) | ||
| DE3824659A1 (de) | 2-, 12- oder 13-substituierte 3-(8'(alpha)-ergolinyl)-1,1-diethylharnstoffe, ihre herstellung und verwendung in arzneimitteln | |
| EP0252873A1 (de) | 1-Aryl-ergolinyl-harnstoffderivate, Verfahren zu deren Herstellung sowie die Verwendung dieser Verbindungen als Arzneimittel | |
| DE3635798A1 (de) | 10-substituierte ergolinylharnstoffderivate, ihre herstellung und ihre verwendung als arzneimittel | |
| CS259898B2 (en) | Method of ergoline's new 1,2-disubstituted derivatives production | |
| DE2927050A1 (de) | Bibenzylderivate | |
| DE3917268A1 (de) | 2-substituierte ergoline, ihre herstellung und verwendung | |
| NO172390B (no) | Analogifremgangsmaate for stereospesifikk fremstilling av terapeutisk aktive furo(3,4-c)-pyridin-enantiomerer | |
| DE3824661A1 (de) | 2'-substituierte 3-(8'(alpha)-ergolinyl)-1,1-diethylharnstoffe bzw. -thioharnstoffe, ihre herstellung und verwendung als zwischenprodukte sowie in arzneimitteln |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8110 | Request for examination paragraph 44 | ||
| 8130 | Withdrawal |