CA2107009A1

CA2107009A1 - 6-(heterocyclo)-4-amino-1,2,2a,3,4,5-hexahydrobenz[cd]indoles pour le traitement du mal des transports et des vomissements

6-(heterocyclo)-4-amino-1,2,2a,3,4,5-hexahydrobenz[cd]indoles pour le traitement du mal des transports et des vomissements

Info

Publication number: CA2107009A1
Authority: CA; Canada
Prior art keywords: alkyl; compound; hexahydrobenz; indole; hydrogen
Prior art date: 1992-09-30
Legal status : Abandoned

Application number

CA 2107009

Other languages

English (en)

Inventor

Richard Nolan Booher

Michael Edward Flaugh

David Ernest Lawhorn

Michael John Martinelli

Charles John Junior Paget

John Mehnert Schaus

Current Assignee

Eli Lilly and Co

Original Assignee

Individual

Priority date

1992-09-30

Filing date

1993-09-27

Publication date

1994-03-31

1993-09-27 Application filed by Individual filed Critical Individual

1994-03-31 Publication of CA2107009A1 publication Critical patent/CA2107009A1/fr

Status Abandoned legal-status Critical Current

Links

206010047700 Vomiting Diseases 0.000 title claims abstract description 25
201000003152 motion sickness Diseases 0.000 title claims abstract description 24
150000002475 indoles Chemical class 0.000 title abstract description 5
230000008673 vomiting Effects 0.000 title description 4
150000001875 compounds Chemical class 0.000 claims abstract description 130
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
229910052739 hydrogen Inorganic materials 0.000 claims description 48
239000001257 hydrogen Substances 0.000 claims description 47
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 27
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 25
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 22
150000003839 salts Chemical class 0.000 claims description 19
239000003054 catalyst Substances 0.000 claims description 18
229910052757 nitrogen Inorganic materials 0.000 claims description 17
125000003118 aryl group Chemical group 0.000 claims description 16
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
125000003831 tetrazolyl group Chemical group 0.000 claims description 15
239000002253 acid Substances 0.000 claims description 12
125000000753 cycloalkyl group Chemical group 0.000 claims description 11
229910052717 sulfur Inorganic materials 0.000 claims description 11
239000011135 tin Chemical group 0.000 claims description 11
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
239000001301 oxygen Substances 0.000 claims description 10
229910052760 oxygen Inorganic materials 0.000 claims description 10
239000000546 pharmaceutical excipient Substances 0.000 claims description 10
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 10
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical group [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 9
125000003342 alkenyl group Chemical group 0.000 claims description 9
239000011593 sulfur Substances 0.000 claims description 9
229910052718 tin Inorganic materials 0.000 claims description 9
MFVFAPQCEUCUSG-UHFFFAOYSA-N 1,2,2a,3,4,5-hexahydrobenzo[cd]indole Chemical class C1CCC2CNC3=CC=CC1=C32 MFVFAPQCEUCUSG-UHFFFAOYSA-N 0.000 claims description 8
230000000903 blocking effect Effects 0.000 claims description 8
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 8
239000003814 drug Substances 0.000 claims description 8
125000006239 protecting group Chemical group 0.000 claims description 8
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 7
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical group [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
125000005843 halogen group Chemical group 0.000 claims description 7
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical group [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 6
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical group [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 6
229910052744 lithium Inorganic materials 0.000 claims description 6
125000002524 organometallic group Chemical group 0.000 claims description 6
229910052725 zinc Inorganic materials 0.000 claims description 6
239000011701 zinc Chemical group 0.000 claims description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
229910052799 carbon Inorganic materials 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 5
239000011777 magnesium Chemical group 0.000 claims description 5
229910052749 magnesium Inorganic materials 0.000 claims description 5
QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical group [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 claims description 5
229910052753 mercury Inorganic materials 0.000 claims description 5
238000011282 treatment Methods 0.000 claims description 5
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 4
ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical group OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 3
125000005842 heteroatom Chemical group 0.000 claims description 3
150000002391 heterocyclic compounds Chemical class 0.000 claims description 3
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 3
MEWUHSSDGFRFMO-UHFFFAOYSA-N 6-(1,2-oxazol-3-yl)-n,n-dipropyl-1,2,2a,3,4,5-hexahydrobenzo[cd]indol-4-amine Chemical compound C12=C3CC(N(CCC)CCC)CC2CNC1=CC=C3C=1C=CON=1 MEWUHSSDGFRFMO-UHFFFAOYSA-N 0.000 claims description 2
208000035475 disorder Diseases 0.000 claims description 2
125000000842 isoxazolyl group Chemical group 0.000 claims description 2
150000007522 mineralic acids Chemical class 0.000 claims description 2
JPGQICRHIHFAEB-UHFFFAOYSA-N n,n-dipropyl-6-pyridin-4-yl-1,2,2a,3,4,5-hexahydrobenzo[cd]indol-4-amine Chemical compound C12=C3CC(N(CCC)CCC)CC2CNC1=CC=C3C1=CC=NC=C1 JPGQICRHIHFAEB-UHFFFAOYSA-N 0.000 claims description 2
150000002825 nitriles Chemical class 0.000 claims description 2
229940076279 serotonin Drugs 0.000 claims description 2
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 3
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 3
SAFOURHKMHCNJA-UHFFFAOYSA-N 6-(1,3-oxazol-2-yl)-n,n-dipropyl-1,2,2a,3,4,5-hexahydrobenzo[cd]indol-4-amine Chemical compound C12=C3CC(N(CCC)CCC)CC2CNC1=CC=C3C1=NC=CO1 SAFOURHKMHCNJA-UHFFFAOYSA-N 0.000 claims 2
RKZZDPJDNOUAAC-UHFFFAOYSA-N 6-(1,3-oxazol-5-yl)-n,n-dipropyl-1,2,2a,3,4,5-hexahydrobenzo[cd]indol-4-amine Chemical compound C12=C3CC(N(CCC)CCC)CC2CNC1=CC=C3C1=CN=CO1 RKZZDPJDNOUAAC-UHFFFAOYSA-N 0.000 claims 2
150000001540 azides Chemical class 0.000 claims 2
KJSKKCWDKUCPJA-UHFFFAOYSA-N 6-(1,2-oxazol-5-yl)-n,n-dipropyl-1,2,2a,3,4,5-hexahydrobenzo[cd]indol-4-amine Chemical compound C12=C3CC(N(CCC)CCC)CC2CNC1=CC=C3C1=CC=NO1 KJSKKCWDKUCPJA-UHFFFAOYSA-N 0.000 claims 1
OMBQNQPVGWBWEK-UHFFFAOYSA-N 6-(3h-oxadiazol-2-yl)-n,n-dipropyl-1,2,2a,3,4,5-hexahydrobenzo[cd]indol-4-amine Chemical compound C12=C3CC(N(CCC)CCC)CC2CNC1=CC=C3N1NC=CO1 OMBQNQPVGWBWEK-UHFFFAOYSA-N 0.000 claims 1
FMJQYKDJZKDETC-UHFFFAOYSA-N 6-(furan-3-yl)-n,n-dipropyl-1,2,2a,3,4,5-hexahydrobenzo[cd]indol-4-amine Chemical compound C12=C3CC(N(CCC)CCC)CC2CNC1=CC=C3C=1C=COC=1 FMJQYKDJZKDETC-UHFFFAOYSA-N 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
ZZFKKNWHTDHUJB-UHFFFAOYSA-N n,n-dimethyl-6-(1h-pyrazol-4-yl)-1,2,2a,3,4,5-hexahydrobenzo[cd]indol-4-amine Chemical compound C12=C3CC(N(C)C)CC2CNC1=CC=C3C=1C=NNC=1 ZZFKKNWHTDHUJB-UHFFFAOYSA-N 0.000 claims 1
XFUGUKQQCFFOSM-UHFFFAOYSA-N n,n-dipropyl-6-(1,3-thiazol-2-yl)-1,2,2a,3,4,5-hexahydrobenzo[cd]indol-4-amine Chemical compound C12=C3CC(N(CCC)CCC)CC2CNC1=CC=C3C1=NC=CS1 XFUGUKQQCFFOSM-UHFFFAOYSA-N 0.000 claims 1
SVKSZPMEILPDEB-UHFFFAOYSA-N n,n-dipropyl-6-(1,3-thiazol-5-yl)-1,2,2a,3,4,5-hexahydrobenzo[cd]indol-4-amine Chemical compound C12=C3CC(N(CCC)CCC)CC2CNC1=CC=C3C1=CN=CS1 SVKSZPMEILPDEB-UHFFFAOYSA-N 0.000 claims 1
MYEZCQNPZZGLFO-UHFFFAOYSA-N n,n-dipropyl-6-(1h-pyrazol-5-yl)-1,2,2a,3,4,5-hexahydrobenzo[cd]indol-4-amine Chemical compound C12=C3CC(N(CCC)CCC)CC2CNC1=CC=C3C=1C=CNN=1 MYEZCQNPZZGLFO-UHFFFAOYSA-N 0.000 claims 1
DIKORSGOJRLITP-UHFFFAOYSA-N n,n-dipropyl-6-pyridin-2-yl-1,2,2a,3,4,5-hexahydrobenzo[cd]indol-4-amine Chemical compound C12=C3CC(N(CCC)CCC)CC2CNC1=CC=C3C1=CC=CC=N1 DIKORSGOJRLITP-UHFFFAOYSA-N 0.000 claims 1
IILUFARIIXEASK-UHFFFAOYSA-N n,n-dipropyl-6-pyridin-3-yl-1,2,2a,3,4,5-hexahydrobenzo[cd]indol-4-amine Chemical compound C12=C3CC(N(CCC)CCC)CC2CNC1=CC=C3C1=CC=CN=C1 IILUFARIIXEASK-UHFFFAOYSA-N 0.000 claims 1
238000000034 method Methods 0.000 abstract description 70
230000008569 process Effects 0.000 abstract description 9
239000000243 solution Substances 0.000 description 170
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 137
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 85
239000003921 oil Substances 0.000 description 60
235000019198 oils Nutrition 0.000 description 60
239000000203 mixture Substances 0.000 description 55
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 54
125000000217 alkyl group Chemical group 0.000 description 53
239000011541 reaction mixture Substances 0.000 description 52
-1 sec.-butyl Chemical group 0.000 description 52
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 51
235000019439 ethyl acetate Nutrition 0.000 description 47
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 44
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 44
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 32
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
238000006243 chemical reaction Methods 0.000 description 30
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
238000002360 preparation method Methods 0.000 description 28
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
229910052943 magnesium sulfate Inorganic materials 0.000 description 26
239000000047 product Substances 0.000 description 26
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 24
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 23
235000019341 magnesium sulphate Nutrition 0.000 description 22
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 20
239000000741 silica gel Substances 0.000 description 20
229910002027 silica gel Inorganic materials 0.000 description 20
150000002431 hydrogen Chemical class 0.000 description 16
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
239000002904 solvent Substances 0.000 description 14
238000007327 hydrogenolysis reaction Methods 0.000 description 13
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
239000003929 acidic solution Substances 0.000 description 12
238000004458 analytical method Methods 0.000 description 12
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 12
229960000583 acetic acid Drugs 0.000 description 11
125000000623 heterocyclic group Chemical group 0.000 description 11
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 10
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 10
229920002472 Starch Polymers 0.000 description 10
239000004480 active ingredient Substances 0.000 description 10
239000012267 brine Substances 0.000 description 10
239000003153 chemical reaction reagent Substances 0.000 description 10
239000000284 extract Substances 0.000 description 10
238000009472 formulation Methods 0.000 description 10
239000012528 membrane Substances 0.000 description 10
235000019698 starch Nutrition 0.000 description 10
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 10
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 9
239000008107 starch Substances 0.000 description 9
BKAWJIRCKVUVED-UHFFFAOYSA-N 5-(2-hydroxyethyl)-4-methylthiazole Chemical compound CC=1N=CSC=1CCO BKAWJIRCKVUVED-UHFFFAOYSA-N 0.000 description 8
NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
229910017974 NH40H Inorganic materials 0.000 description 8
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
150000001414 amino alcohols Chemical class 0.000 description 8
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
230000027455 binding Effects 0.000 description 8
239000000706 filtrate Substances 0.000 description 8
235000019359 magnesium stearate Nutrition 0.000 description 8
238000000159 protein binding assay Methods 0.000 description 8
150000003335 secondary amines Chemical class 0.000 description 8
239000000872 buffer Substances 0.000 description 7
238000004587 chromatography analysis Methods 0.000 description 7
238000002425 crystallisation Methods 0.000 description 7
230000008025 crystallization Effects 0.000 description 7
239000003480 eluent Substances 0.000 description 7
150000002118 epoxides Chemical class 0.000 description 7
150000002367 halogens Chemical class 0.000 description 7
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [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 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
229910052736 halogen Inorganic materials 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
102000005962 receptors Human genes 0.000 description 6
108020003175 receptors Proteins 0.000 description 6
238000010992 reflux Methods 0.000 description 6
230000000707 stereoselective effect Effects 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
239000003826 tablet Substances 0.000 description 6
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 5
108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 5
ASXGJMSKWNBENU-UHFFFAOYSA-N 8-OH-DPAT Chemical compound C1=CC(O)=C2CC(N(CCC)CCC)CCC2=C1 ASXGJMSKWNBENU-UHFFFAOYSA-N 0.000 description 5
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
239000007818 Grignard reagent Substances 0.000 description 5
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 5
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 5
241000124008 Mammalia Species 0.000 description 5
IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 5
NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [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 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
125000003545 alkoxy group Chemical group 0.000 description 5
235000011114 ammonium hydroxide Nutrition 0.000 description 5
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 5
239000012043 crude product Substances 0.000 description 5
125000004093 cyano group Chemical group *C#N 0.000 description 5
201000010099 disease Diseases 0.000 description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
239000007903 gelatin capsule Substances 0.000 description 5
150000004795 grignard reagents Chemical class 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
239000010410 layer Substances 0.000 description 5
239000012299 nitrogen atmosphere Substances 0.000 description 5
229910052763 palladium Inorganic materials 0.000 description 5
229910052938 sodium sulfate Inorganic materials 0.000 description 5
235000011152 sodium sulphate Nutrition 0.000 description 5
238000003756 stirring Methods 0.000 description 5
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 5
238000005303 weighing Methods 0.000 description 5
QZAYGJVTTNCVMB-PZFLKRBQSA-N 3-(2-amino-1,2-ditritioethyl)-1h-indol-5-ol Chemical compound C1=C(O)C=C2C(C([3H])C(N)[3H])=CNC2=C1 QZAYGJVTTNCVMB-PZFLKRBQSA-N 0.000 description 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
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