SK9442002A3 - Substituted phenyl-piperazine derivatives, their preparation and use - Google Patents

Substituted phenyl-piperazine derivatives, their preparation and use Download PDF

Info

Publication number: SK9442002A3
Authority: SK; Slovakia
Prior art keywords: piperazine; phenyl; indol; propyl; yloxy
Prior art date: 1999-12-30

Application number

SK944-2002A

Other languages

English (en)

Slovak (sk)

Inventor

Thomas Ruhland

Christian Krog-Jensen

Mario Rottlander

Gitte Mikkelsen

Ejner Knud Moltzen

Kim Andersen

Original Assignee

Lundbeck & Co As H

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.)

1999-12-30

Filing date

2000-12-20

Publication date

2002-11-06

2000-12-20 Application filed by Lundbeck & Co As H filed Critical Lundbeck & Co As H

2002-11-06 Publication of SK9442002A3 publication Critical patent/SK9442002A3/sk

Links

YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical class C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 title claims description 18
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 101
-1 1-homopiperidinyl Chemical group 0.000 claims description 74
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 48
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 38
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 32
229910052739 hydrogen Inorganic materials 0.000 claims description 27
239000001257 hydrogen Substances 0.000 claims description 25
150000002431 hydrogen Chemical class 0.000 claims description 14
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
239000002253 acid Substances 0.000 claims description 10
125000000217 alkyl group Chemical group 0.000 claims description 10
150000003839 salts Chemical class 0.000 claims description 10
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 8
229910052736 halogen Inorganic materials 0.000 claims description 8
150000002367 halogens Chemical class 0.000 claims description 8
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 8
125000003118 aryl group Chemical group 0.000 claims description 7
208000012902 Nervous system disease Diseases 0.000 claims description 6
208000025966 Neurological disease Diseases 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
208000024827 Alzheimer disease Diseases 0.000 claims description 5
208000028017 Psychotic disease Diseases 0.000 claims description 5
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 5
229910052757 nitrogen Inorganic materials 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 5
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 4
JCXYIZHUALZKGZ-UHFFFAOYSA-N 3-[3-[4-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)phenyl]piperazin-1-yl]propyl]-5-fluoro-1h-indole Chemical compound O1CCOC2=C1C=CC=C2OC1=CC=CC=C1N(CC1)CCN1CCCC1=CNC2=CC=C(F)C=C21 JCXYIZHUALZKGZ-UHFFFAOYSA-N 0.000 claims description 4
208000019901 Anxiety disease Diseases 0.000 claims description 4
208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 4
206010039966 Senile dementia Diseases 0.000 claims description 4
206010041250 Social phobia Diseases 0.000 claims description 4
229910052799 carbon Inorganic materials 0.000 claims description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
208000028867 ischemia Diseases 0.000 claims description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
229940002612 prodrug Drugs 0.000 claims description 4
239000000651 prodrug Substances 0.000 claims description 4
229940076279 serotonin Drugs 0.000 claims description 4
229910052717 sulfur Inorganic materials 0.000 claims description 4
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 3
125000002252 acyl group Chemical group 0.000 claims description 3
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
125000000753 cycloalkyl group Chemical group 0.000 claims description 3
201000010099 disease Diseases 0.000 claims description 3
125000001072 heteroaryl group Chemical group 0.000 claims description 3
125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
HNDDEJSHBYUIQF-UHFFFAOYSA-N 3-[1-[4-[2-(1h-indol-3-yl)ethyl]piperazin-1-yl]cyclohexa-2,4-dien-1-yl]oxy-n,n-dimethylaniline Chemical compound CN(C)C1=CC=CC(OC2(C=CC=CC2)N2CCN(CCC=3C4=CC=CC=C4NC=3)CC2)=C1 HNDDEJSHBYUIQF-UHFFFAOYSA-N 0.000 claims description 2
GAWDQCKEXSAHTB-UHFFFAOYSA-N 3-[1-[4-[3-(1h-indol-3-yl)propyl]piperazin-1-yl]cyclohexa-2,4-dien-1-yl]oxy-n,n-dimethylaniline Chemical compound CN(C)C1=CC=CC(OC2(C=CC=CC2)N2CCN(CCCC=3C4=CC=CC=C4NC=3)CC2)=C1 GAWDQCKEXSAHTB-UHFFFAOYSA-N 0.000 claims description 2
XHYDHLYHMNFUCR-UHFFFAOYSA-N 3-[2-[4-[3-(5-fluoro-1h-indol-3-yl)propyl]piperazin-1-yl]phenoxy]-n,n-dimethylaniline Chemical compound CN(C)C1=CC=CC(OC=2C(=CC=CC=2)N2CCN(CCCC=3C4=CC(F)=CC=C4NC=3)CC2)=C1 XHYDHLYHMNFUCR-UHFFFAOYSA-N 0.000 claims description 2
MZFKVLBXPSVKGQ-UHFFFAOYSA-N 3-[3-[4-[2-(1,3-benzodioxol-5-yloxy)phenyl]piperazin-1-yl]propyl]-6-chloro-1h-indole Chemical compound C1=C2OCOC2=CC(OC2=CC=CC=C2N2CCN(CC2)CCCC=2C3=CC=C(C=C3NC=2)Cl)=C1 MZFKVLBXPSVKGQ-UHFFFAOYSA-N 0.000 claims description 2
NRGTXEUWAJRJMT-UHFFFAOYSA-N 3-[3-[4-[2-(2,3-dihydro-1,4-benzodioxin-6-yloxy)phenyl]piperazin-1-yl]propyl]-1h-indole Chemical compound C1=CC=C2C(CCCN3CCN(CC3)C=3C(=CC=CC=3)OC=3C=C4OCCOC4=CC=3)=CNC2=C1 NRGTXEUWAJRJMT-UHFFFAOYSA-N 0.000 claims description 2
TVRRHNHAQUPMKC-UHFFFAOYSA-N 3-[3-[4-[2-(3-methoxyphenoxy)phenyl]piperazin-1-yl]propyl]-1h-pyrrolo[3,2-h]quinoline Chemical compound COC1=CC=CC(OC=2C(=CC=CC=2)N2CCN(CCCC=3C4=C(C5=NC=CC=C5C=C4)NC=3)CC2)=C1 TVRRHNHAQUPMKC-UHFFFAOYSA-N 0.000 claims description 2
FVIHVLPVKPYXBS-UHFFFAOYSA-N 3-[3-[4-[2-(4-methoxyphenoxy)phenyl]piperazin-1-yl]propyl]-1h-indole Chemical compound C1=CC(OC)=CC=C1OC1=CC=CC=C1N1CCN(CCCC=2C3=CC=CC=C3NC=2)CC1 FVIHVLPVKPYXBS-UHFFFAOYSA-N 0.000 claims description 2
ITUPHCUEMUPHHZ-UHFFFAOYSA-N 5-bromo-3-[3-[4-[2-(2-methoxyphenoxy)phenyl]piperazin-1-yl]propyl]-1h-indole Chemical compound COC1=CC=CC=C1OC1=CC=CC=C1N1CCN(CCCC=2C3=CC(Br)=CC=C3NC=2)CC1 ITUPHCUEMUPHHZ-UHFFFAOYSA-N 0.000 claims description 2
BYPGLVLRQYFMDE-UHFFFAOYSA-N 5-chloro-3-[3-[4-[2-(2-methoxyphenoxy)phenyl]piperazin-1-yl]propyl]-1h-indole Chemical compound COC1=CC=CC=C1OC1=CC=CC=C1N1CCN(CCCC=2C3=CC(Cl)=CC=C3NC=2)CC1 BYPGLVLRQYFMDE-UHFFFAOYSA-N 0.000 claims description 2
DDYLGNDOBMGFCI-UHFFFAOYSA-N 7-fluoro-3-[3-[4-[2-(3-methoxyphenoxy)phenyl]piperazin-1-yl]propyl]-1h-indole Chemical compound COC1=CC=CC(OC=2C(=CC=CC=2)N2CCN(CCCC=3C4=CC=CC(F)=C4NC=3)CC2)=C1 DDYLGNDOBMGFCI-UHFFFAOYSA-N 0.000 claims description 2
208000017194 Affective disease Diseases 0.000 claims description 2
230000005856 abnormality Effects 0.000 claims description 2
230000016571 aggressive behavior Effects 0.000 claims description 2
125000003545 alkoxy group Chemical group 0.000 claims description 2
210000003169 central nervous system Anatomy 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
125000005322 morpholin-1-yl group Chemical group 0.000 claims description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
208000019906 panic disease Diseases 0.000 claims description 2
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
125000003226 pyrazolyl group Chemical group 0.000 claims description 2
125000004076 pyridyl group Chemical group 0.000 claims description 2
125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 2
LUJPWQVJKPZNSK-UHFFFAOYSA-N 3-[2-[4-[1-(1,3-benzodioxol-5-yloxy)cyclohexa-2,4-dien-1-yl]piperazin-1-yl]ethyl]-1h-indole Chemical compound C=1NC2=CC=CC=C2C=1CCN(CC1)CCN1C1(OC=2C=C3OCOC3=CC=2)CC=CC=C1 LUJPWQVJKPZNSK-UHFFFAOYSA-N 0.000 claims 1
OWEYIAFRYKPGTI-UHFFFAOYSA-N 3-[2-[4-[2-(1,3-benzodioxol-5-yloxy)phenyl]piperazin-1-yl]ethyl]-6-chloro-1h-indole Chemical compound C1=C2OCOC2=CC(OC2=CC=CC=C2N2CCN(CC2)CCC=2C3=CC=C(C=C3NC=2)Cl)=C1 OWEYIAFRYKPGTI-UHFFFAOYSA-N 0.000 claims 1
IWCRVEQTMBSESW-UHFFFAOYSA-N 3-[3-[4-[2-(1,3-benzodioxol-5-yloxy)phenyl]piperazin-1-yl]propyl]-1h-pyrrolo[3,2-h]quinoline Chemical compound C1=CC2=CC=CN=C2C2=C1C(CCCN1CCN(CC1)C=1C(=CC=CC=1)OC=1C=C3OCOC3=CC=1)=CN2 IWCRVEQTMBSESW-UHFFFAOYSA-N 0.000 claims 1
SJNOCZFKZOJIQV-UHFFFAOYSA-N 3-[3-[4-[2-(1,3-benzodioxol-5-yloxy)phenyl]piperazin-1-yl]propyl]-5-bromo-1h-indole Chemical compound C1=C2OCOC2=CC(OC2=CC=CC=C2N2CCN(CC2)CCCC2=CNC3=CC=C(C=C32)Br)=C1 SJNOCZFKZOJIQV-UHFFFAOYSA-N 0.000 claims 1
HXXYEEZKEAZAQO-UHFFFAOYSA-N 3-[3-[4-[2-(1,3-benzodioxol-5-yloxy)phenyl]piperazin-1-yl]propyl]-5-iodo-1h-indole Chemical compound C1=C2OCOC2=CC(OC2=CC=CC=C2N2CCN(CC2)CCCC2=CNC3=CC=C(C=C32)I)=C1 HXXYEEZKEAZAQO-UHFFFAOYSA-N 0.000 claims 1
XEPRNSDBSCSQII-UHFFFAOYSA-N 3-[3-[4-[2-(1,3-benzodioxol-5-yloxy)phenyl]piperazin-1-yl]propyl]-7-bromo-1h-indole Chemical compound C1=C2OCOC2=CC(OC2=CC=CC=C2N2CCN(CC2)CCCC=2C=3C=CC=C(C=3NC=2)Br)=C1 XEPRNSDBSCSQII-UHFFFAOYSA-N 0.000 claims 1
OSBODECQQSOMJP-UHFFFAOYSA-N 3-[3-[4-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)phenyl]piperazin-1-yl]propyl]-1h-indole Chemical compound C1=CC=C2C(CCCN3CCN(CC3)C=3C(=CC=CC=3)OC=3C=4OCCOC=4C=CC=3)=CNC2=C1 OSBODECQQSOMJP-UHFFFAOYSA-N 0.000 claims 1
YWFVVSIGTZAXMZ-UHFFFAOYSA-N 3-[3-[4-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)phenyl]piperazin-1-yl]propyl]-5-methyl-1h-indole Chemical compound O1CCOC2=C1C=CC=C2OC1=CC=CC=C1N(CC1)CCN1CCCC1=CNC2=CC=C(C)C=C21 YWFVVSIGTZAXMZ-UHFFFAOYSA-N 0.000 claims 1
HRVYGCMPBMUWFJ-UHFFFAOYSA-N 3-[3-[4-[2-(2,6-dimethoxyphenoxy)phenyl]piperazin-1-yl]propyl]-5-fluoro-1h-indole Chemical compound COC1=CC=CC(OC)=C1OC1=CC=CC=C1N1CCN(CCCC=2C3=CC(F)=CC=C3NC=2)CC1 HRVYGCMPBMUWFJ-UHFFFAOYSA-N 0.000 claims 1
QEZZAYHWJOLDBB-UHFFFAOYSA-N 3-[4-[4-(2-phenoxyphenyl)piperazin-1-yl]butyl]-1h-indole Chemical compound C=1NC2=CC=CC=C2C=1CCCCN(CC1)CCN1C1=CC=CC=C1OC1=CC=CC=C1 QEZZAYHWJOLDBB-UHFFFAOYSA-N 0.000 claims 1
AWVHHHMYGYTECD-UHFFFAOYSA-N 3-[4-[4-[2-(1,3-benzodioxol-5-yloxy)phenyl]piperazin-1-yl]butyl]-1h-indole Chemical compound C1=C2OCOC2=CC(OC2=CC=CC=C2N2CCN(CC2)CCCCC=2C3=CC=CC=C3NC=2)=C1 AWVHHHMYGYTECD-UHFFFAOYSA-N 0.000 claims 1
SPZHZXUYAUSLEZ-UHFFFAOYSA-N 5,7-difluoro-3-[3-[4-(2-phenoxyphenyl)piperazin-1-yl]propyl]-1h-indole Chemical compound C12=CC(F)=CC(F)=C2NC=C1CCCN(CC1)CCN1C1=CC=CC=C1OC1=CC=CC=C1 SPZHZXUYAUSLEZ-UHFFFAOYSA-N 0.000 claims 1
ZQCXOBLVWVJECD-UHFFFAOYSA-N 5-chloro-3-[3-[4-[2-(2,6-dimethoxyphenoxy)phenyl]piperazin-1-yl]propyl]-1h-indole Chemical compound COC1=CC=CC(OC)=C1OC1=CC=CC=C1N1CCN(CCCC=2C3=CC(Cl)=CC=C3NC=2)CC1 ZQCXOBLVWVJECD-UHFFFAOYSA-N 0.000 claims 1
OINDAPWTNMMZPX-UHFFFAOYSA-N 5-iodo-3-[3-[4-(2-phenoxyphenyl)piperazin-1-yl]propyl]-1h-indole Chemical compound C12=CC(I)=CC=C2NC=C1CCCN(CC1)CCN1C1=CC=CC=C1OC1=CC=CC=C1 OINDAPWTNMMZPX-UHFFFAOYSA-N 0.000 claims 1
UKTVNKZIUFMCFK-UHFFFAOYSA-N 6-chloro-3-[2-[4-(2-phenoxyphenyl)piperazin-1-yl]ethyl]-1h-indole Chemical compound C=1NC2=CC(Cl)=CC=C2C=1CCN(CC1)CCN1C1=CC=CC=C1OC1=CC=CC=C1 UKTVNKZIUFMCFK-UHFFFAOYSA-N 0.000 claims 1
SNUOPPWSZMNHHF-UHFFFAOYSA-N 6-chloro-3-[3-[4-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)phenyl]piperazin-1-yl]propyl]-1h-indole Chemical compound O1CCOC2=C1C=CC=C2OC1=CC=CC=C1N(CC1)CCN1CCCC1=CNC2=CC(Cl)=CC=C21 SNUOPPWSZMNHHF-UHFFFAOYSA-N 0.000 claims 1
CAURJXXIHPFLBP-UHFFFAOYSA-N 6-chloro-3-[3-[4-[2-(2,3-dihydro-1,4-benzodioxin-6-yloxy)phenyl]piperazin-1-yl]propyl]-1h-indole Chemical compound O1CCOC2=CC(OC3=CC=CC=C3N3CCN(CC3)CCCC=3C4=CC=C(C=C4NC=3)Cl)=CC=C21 CAURJXXIHPFLBP-UHFFFAOYSA-N 0.000 claims 1
HRIZKEVNKGMQNZ-UHFFFAOYSA-N 6-chloro-3-[3-[4-[2-(3-methoxyphenoxy)phenyl]piperazin-1-yl]propyl]-1h-indole Chemical compound COC1=CC=CC(OC=2C(=CC=CC=2)N2CCN(CCCC=3C4=CC=C(Cl)C=C4NC=3)CC2)=C1 HRIZKEVNKGMQNZ-UHFFFAOYSA-N 0.000 claims 1
KIFNFFBTSDIOQZ-UHFFFAOYSA-N 7-bromo-3-[3-[4-[2-(2-methoxyphenoxy)phenyl]piperazin-1-yl]propyl]-1h-indole Chemical compound COC1=CC=CC=C1OC1=CC=CC=C1N1CCN(CCCC=2C3=CC=CC(Br)=C3NC=2)CC1 KIFNFFBTSDIOQZ-UHFFFAOYSA-N 0.000 claims 1
TWVWLMZPWYEJMU-UHFFFAOYSA-N 7-chloro-3-[3-[4-(2-phenoxyphenyl)piperazin-1-yl]propyl]-1h-indole Chemical compound C=1NC=2C(Cl)=CC=CC=2C=1CCCN(CC1)CCN1C1=CC=CC=C1OC1=CC=CC=C1 TWVWLMZPWYEJMU-UHFFFAOYSA-N 0.000 claims 1
208000007848 Alcoholism Diseases 0.000 claims 1
201000007930 alcohol dependence Diseases 0.000 claims 1
239000000969 carrier Substances 0.000 claims 1
208000035475 disorder Diseases 0.000 claims 1
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
150000001875 compounds Chemical class 0.000 abstract description 51
101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 abstract description 4
102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 abstract description 4
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 64
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
238000000034 method Methods 0.000 description 38
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
229920005989 resin Polymers 0.000 description 33
239000011347 resin Substances 0.000 description 33
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 31
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 22
108020003175 receptors Proteins 0.000 description 22
102000005962 receptors Human genes 0.000 description 22
230000005764 inhibitory process Effects 0.000 description 17
239000000243 solution Substances 0.000 description 17
239000002904 solvent Substances 0.000 description 17
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
239000000203 mixture Substances 0.000 description 16
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
239000011541 reaction mixture Substances 0.000 description 14
239000005557 antagonist Substances 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
229960003638 dopamine Drugs 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 10
230000000694 effects Effects 0.000 description 10
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
229910000027 potassium carbonate Inorganic materials 0.000 description 8
150000003335 secondary amines Chemical class 0.000 description 8
230000000561 anti-psychotic effect Effects 0.000 description 7
210000004556 brain Anatomy 0.000 description 7
238000001816 cooling Methods 0.000 description 7
239000003814 drug Substances 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
230000027455 binding Effects 0.000 description 6
229940079593 drug Drugs 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
239000003446 ligand Substances 0.000 description 6
230000003287 optical effect Effects 0.000 description 6
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
239000002464 receptor antagonist Substances 0.000 description 6
229940044551 receptor antagonist Drugs 0.000 description 6
239000004793 Polystyrene Substances 0.000 description 5
238000010828 elution Methods 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
229920002223 polystyrene Polymers 0.000 description 5
238000010992 reflux Methods 0.000 description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
OTVPWGHMBHYUAX-UHFFFAOYSA-N [Fe].[CH]1C=CC=C1 Chemical compound [Fe].[CH]1C=CC=C1 OTVPWGHMBHYUAX-UHFFFAOYSA-N 0.000 description 4
150000001241 acetals Chemical class 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
239000007791 liquid phase Substances 0.000 description 4
239000012038 nucleophile Substances 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
238000010898 silica gel chromatography Methods 0.000 description 4
239000007787 solid Substances 0.000 description 4
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical class OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
102000017911 HTR1A Human genes 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical class CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
150000001408 amides Chemical class 0.000 description 3
239000000010 aprotic solvent Substances 0.000 description 3
238000003556 assay Methods 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
210000004027 cell Anatomy 0.000 description 3
230000007278 cognition impairment Effects 0.000 description 3
239000002245 particle Substances 0.000 description 3
230000008569 process Effects 0.000 description 3
239000000047 product Substances 0.000 description 3
238000012552 review Methods 0.000 description 3
201000000980 schizophrenia Diseases 0.000 description 3
238000000926 separation method Methods 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
239000000725 suspension Substances 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
LYPSVQXMCZIRGP-UHFFFAOYSA-N 3-(1h-indol-3-yl)propan-1-ol Chemical compound C1=CC=C2C(CCCO)=CNC2=C1 LYPSVQXMCZIRGP-UHFFFAOYSA-N 0.000 description 2
YUBXEUBNYOBJMQ-UHFFFAOYSA-N 3-(3-bromopropyl)-1h-indole Chemical compound C1=CC=C2C(CCCBr)=CNC2=C1 YUBXEUBNYOBJMQ-UHFFFAOYSA-N 0.000 description 2
NBNANZDPAUVZCM-UHFFFAOYSA-N 3-[3-[4-(2-phenoxyphenyl)piperazin-1-yl]propyl]-1h-indole Chemical compound C=1NC2=CC=CC=C2C=1CCCN(CC1)CCN1C1=CC=CC=C1OC1=CC=CC=C1 NBNANZDPAUVZCM-UHFFFAOYSA-N 0.000 description 2
VHWXQDZLKFTBDL-UHFFFAOYSA-N 3-[3-[4-[2-(2-methoxyphenoxy)phenyl]piperazin-1-yl]propyl]-1h-indole Chemical compound COC1=CC=CC=C1OC1=CC=CC=C1N1CCN(CCCC=2C3=CC=CC=C3NC=2)CC1 VHWXQDZLKFTBDL-UHFFFAOYSA-N 0.000 description 2
YCXQDIPLCFFZRS-UHFFFAOYSA-N 4-[3-[2-[4-[3-(5-bromo-1h-indol-3-yl)propyl]piperazin-1-yl]phenoxy]phenyl]morpholine Chemical compound C12=CC(Br)=CC=C2NC=C1CCCN(CC1)CCN1C1=CC=CC=C1OC(C=1)=CC=CC=1N1CCOCC1 YCXQDIPLCFFZRS-UHFFFAOYSA-N 0.000 description 2
ZNLHWEDEIKEQDK-UHFFFAOYSA-N 5-chloropentanal Chemical compound ClCCCCC=O ZNLHWEDEIKEQDK-UHFFFAOYSA-N 0.000 description 2
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 2
QCHDGUBAWVJQTF-UHFFFAOYSA-N C(C(=O)O)(=O)O.CN(C=1C=C(OC2=C(C=CC=C2)N2CCN(CC2)CCC2=CNC3=CC=CC=C23)C=CC1)C Chemical compound C(C(=O)O)(=O)O.CN(C=1C=C(OC2=C(C=CC=C2)N2CCN(CC2)CCC2=CNC3=CC=CC=C23)C=CC1)C QCHDGUBAWVJQTF-UHFFFAOYSA-N 0.000 description 2
TWJOFWFXXQEALX-UHFFFAOYSA-N C(C(=O)O)(=O)O.O1COC2=C1C=CC(=C2)OC2=C(C=CC=C2)N2CCN(CC2)CCC2=CNC1=CC=CC=C21 Chemical compound C(C(=O)O)(=O)O.O1COC2=C1C=CC(=C2)OC2=C(C=CC=C2)N2CCN(CC2)CCC2=CNC1=CC=CC=C21 TWJOFWFXXQEALX-UHFFFAOYSA-N 0.000 description 2
ZKMHJOBROVWUKS-UHFFFAOYSA-N C(C(=O)O)(=O)O.O1COC2=C1C=CC(=C2)OC2=C(C=CC=C2)N2CCN(CC2)CCCC2=CNC1=CC=CC=C21 Chemical compound C(C(=O)O)(=O)O.O1COC2=C1C=CC(=C2)OC2=C(C=CC=C2)N2CCN(CC2)CCCC2=CNC1=CC=CC=C21 ZKMHJOBROVWUKS-UHFFFAOYSA-N 0.000 description 2
XQITVWOBLATGPY-UHFFFAOYSA-N COC=1C=C(OC2=C(C=CC=C2)N2CCN(CC2)CCCC2=CNC=3C2=NC=2C=CC=CC2C3)C=CC1 Chemical compound COC=1C=C(OC2=C(C=CC=C2)N2CCN(CC2)CCCC2=CNC=3C2=NC=2C=CC=CC2C3)C=CC1 XQITVWOBLATGPY-UHFFFAOYSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
WPHVZYBDVDBGEM-UHFFFAOYSA-N Cl.Cl.COC1=C(OC2=C(C=CC=C2)N2CCN(CC2)CCCC2=CNC3=CC=C(C=C23)F)C=CC=C1 Chemical compound Cl.Cl.COC1=C(OC2=C(C=CC=C2)N2CCN(CC2)CCCC2=CNC3=CC=C(C=C23)F)C=CC=C1 WPHVZYBDVDBGEM-UHFFFAOYSA-N 0.000 description 2
OTEKRWJYGAAJRF-UHFFFAOYSA-N Cl.O1COC2=C1C=CC(=C2)OC2=C(C=CC=C2)N2CCN(CC2)CCCC2=CNC1=CC(=CC=C21)Cl Chemical compound Cl.O1COC2=C1C=CC(=C2)OC2=C(C=CC=C2)N2CCN(CC2)CCCC2=CNC1=CC(=CC=C21)Cl OTEKRWJYGAAJRF-UHFFFAOYSA-N 0.000 description 2
208000020401 Depressive disease Diseases 0.000 description 2
208000030814 Eating disease Diseases 0.000 description 2
208000019454 Feeding and Eating disease Diseases 0.000 description 2
101000822895 Homo sapiens 5-hydroxytryptamine receptor 1A Proteins 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
208000019022 Mood disease Diseases 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 2
239000002168 alkylating agent Substances 0.000 description 2
229940100198 alkylating agent Drugs 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
230000008485 antagonism Effects 0.000 description 2
230000009286 beneficial effect Effects 0.000 description 2
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 2
229960004170 clozapine Drugs 0.000 description 2
238000004040 coloring Methods 0.000 description 2
230000001143 conditioned effect Effects 0.000 description 2
239000012043 crude product Substances 0.000 description 2
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 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
150000002009 diols Chemical class 0.000 description 2
235000014632 disordered eating Nutrition 0.000 description 2
238000001914 filtration Methods 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
150000002475 indoles Chemical class 0.000 description 2
238000005342 ion exchange Methods 0.000 description 2
230000002197 limbic effect Effects 0.000 description 2
239000000463 material Substances 0.000 description 2
239000012528 membrane Substances 0.000 description 2
XKQRIBXKPQGCPO-UHFFFAOYSA-N n,n-dimethyl-3-(2-piperazin-1-ylphenoxy)aniline Chemical compound CN(C)C1=CC=CC(OC=2C(=CC=CC=2)N2CCNCC2)=C1 XKQRIBXKPQGCPO-UHFFFAOYSA-N 0.000 description 2
239000003176 neuroleptic agent Substances 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
125000004193 piperazinyl group Chemical group 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
230000009467 reduction Effects 0.000 description 2
238000011160 research Methods 0.000 description 2
239000003727 serotonin 1A antagonist Substances 0.000 description 2
230000000697 serotonin reuptake Effects 0.000 description 2
239000003772 serotonin uptake inhibitor Substances 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 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
239000007858 starting material Substances 0.000 description 2
239000000126 substance Substances 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
210000003568 synaptosome Anatomy 0.000 description 2
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
238000012360 testing method Methods 0.000 description 2
HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
230000001225 therapeutic effect Effects 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
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
238000005406 washing Methods 0.000 description 2
239000011592 zinc chloride Substances 0.000 description 2
235000005074 zinc chloride Nutrition 0.000 description 2
KRVOJOCLBAAKSJ-RDTXWAMCSA-N (2R,3R)-nemonapride Chemical compound C1=C(Cl)C(NC)=CC(OC)=C1C(=O)N[C@H]1[C@@H](C)N(CC=2C=CC=CC=2)CC1 KRVOJOCLBAAKSJ-RDTXWAMCSA-N 0.000 description 1
FEKUXLUOKFSMRO-UHFFFAOYSA-N (4-fluorophenyl)hydrazine;hydron;chloride Chemical compound Cl.NNC1=CC=C(F)C=C1 FEKUXLUOKFSMRO-UHFFFAOYSA-N 0.000 description 1
VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 1
BFCFYVKQTRLZHA-UHFFFAOYSA-N 1-chloro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1Cl BFCFYVKQTRLZHA-UHFFFAOYSA-N 0.000 description 1
PWKNBLFSJAVFAB-UHFFFAOYSA-N 1-fluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1F PWKNBLFSJAVFAB-UHFFFAOYSA-N 0.000 description 1
IGXSSRPZRAIXQF-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxin-5-ol Chemical compound O1CCOC2=C1C=CC=C2O IGXSSRPZRAIXQF-UHFFFAOYSA-N 0.000 description 1
YMDZDFSUDFLGMX-UHFFFAOYSA-N 2-chloro-n-(2-chloroethyl)ethanamine;hydron;chloride Chemical compound [Cl-].ClCC[NH2+]CCCl YMDZDFSUDFLGMX-UHFFFAOYSA-N 0.000 description 1
HBAHZZVIEFRTEY-UHFFFAOYSA-N 2-heptylcyclohex-2-en-1-one Chemical compound CCCCCCCC1=CCCCC1=O HBAHZZVIEFRTEY-UHFFFAOYSA-N 0.000 description 1
GOLXRNDWAUTYKT-UHFFFAOYSA-N 3-(1H-indol-3-yl)propanoic acid Chemical compound C1=CC=C2C(CCC(=O)O)=CNC2=C1 GOLXRNDWAUTYKT-UHFFFAOYSA-N 0.000 description 1
MESJRHHDBDCQTH-UHFFFAOYSA-N 3-(dimethylamino)phenol Chemical compound CN(C)C1=CC=CC(O)=C1 MESJRHHDBDCQTH-UHFFFAOYSA-N 0.000 description 1
JJWGGTBCCAPKEC-UHFFFAOYSA-N 3-[2-[4-[2-(6-chloro-1h-indol-3-yl)ethyl]piperazin-1-yl]phenoxy]-n,n-dimethylaniline Chemical compound CN(C)C1=CC=CC(OC=2C(=CC=CC=2)N2CCN(CCC=3C4=CC=C(Cl)C=C4NC=3)CC2)=C1 JJWGGTBCCAPKEC-UHFFFAOYSA-N 0.000 description 1
XTNQUASOAVCWFR-UHFFFAOYSA-N 3-[3-[4-[1-(1,3-benzodioxol-5-yloxy)cyclohexa-2,4-dien-1-yl]piperazin-1-yl]propyl]-1h-indole Chemical compound C=1NC2=CC=CC=C2C=1CCCN(CC1)CCN1C1(OC=2C=C3OCOC3=CC=2)CC=CC=C1 XTNQUASOAVCWFR-UHFFFAOYSA-N 0.000 description 1
HCGIKUSNRRBOND-UHFFFAOYSA-N 3-[3-[4-[2-(2,6-dimethoxyphenoxy)phenyl]piperazin-1-yl]propyl]-5-iodo-1h-indole Chemical compound COC1=CC=CC(OC)=C1OC1=CC=CC=C1N1CCN(CCCC=2C3=CC(I)=CC=C3NC=2)CC1 HCGIKUSNRRBOND-UHFFFAOYSA-N 0.000 description 1
HGGGPQXRYFVAIT-UHFFFAOYSA-N 3-[3-[4-[2-(2,6-dimethoxyphenoxy)phenyl]piperazin-1-yl]propyl]-5-methyl-1h-indole Chemical compound COC1=CC=CC(OC)=C1OC1=CC=CC=C1N1CCN(CCCC=2C3=CC(C)=CC=C3NC=2)CC1 HGGGPQXRYFVAIT-UHFFFAOYSA-N 0.000 description 1
FEMNAJICUFEEAB-UHFFFAOYSA-N 3-[3-[4-[2-(3-ethoxyphenoxy)phenyl]piperazin-1-yl]propyl]-5-methyl-1h-indole Chemical compound CCOC1=CC=CC(OC=2C(=CC=CC=2)N2CCN(CCCC=3C4=CC(C)=CC=C4NC=3)CC2)=C1 FEMNAJICUFEEAB-UHFFFAOYSA-N 0.000 description 1
KQXNDOJNIPWLPE-UHFFFAOYSA-N 3-[4-[4-[2-(2-methoxyphenoxy)phenyl]piperazin-1-yl]butyl]-1h-indole Chemical compound COC1=CC=CC=C1OC1=CC=CC=C1N1CCN(CCCCC=2C3=CC=CC=C3NC=2)CC1 KQXNDOJNIPWLPE-UHFFFAOYSA-N 0.000 description 1
QHIPGMYRQRWNRR-UHFFFAOYSA-N 4-[3-[2-[4-[3-(5-fluoro-1h-indol-3-yl)propyl]piperazin-1-yl]phenoxy]phenyl]morpholine Chemical compound C12=CC(F)=CC=C2NC=C1CCCN(CC1)CCN1C1=CC=CC=C1OC(C=1)=CC=CC=1N1CCOCC1 QHIPGMYRQRWNRR-UHFFFAOYSA-N 0.000 description 1
DOQLCJMCQWQQHK-UHFFFAOYSA-N 4-chlorobutanal Chemical compound ClCCCC=O DOQLCJMCQWQQHK-UHFFFAOYSA-N 0.000 description 1
CSMJLNZSFBNWGG-UHFFFAOYSA-N 5,7-dimethyl-3-[3-[4-(2-phenoxyphenyl)piperazin-1-yl]propyl]-1h-indole Chemical compound C12=CC(C)=CC(C)=C2NC=C1CCCN(CC1)CCN1C1=CC=CC=C1OC1=CC=CC=C1 CSMJLNZSFBNWGG-UHFFFAOYSA-N 0.000 description 1
RBEAPCNJKIRGQK-UHFFFAOYSA-N 5-bromo-3-[3-[4-[2-(2,6-dimethoxyphenoxy)phenyl]piperazin-1-yl]propyl]-1h-indole Chemical compound COC1=CC=CC(OC)=C1OC1=CC=CC=C1N1CCN(CCCC=2C3=CC(Br)=CC=C3NC=2)CC1 RBEAPCNJKIRGQK-UHFFFAOYSA-N 0.000 description 1
IMMGOHFIDQMRJW-UHFFFAOYSA-N 5-chloro-3-[3-[4-[2-(3-methoxyphenoxy)phenyl]piperazin-1-yl]propyl]-1h-indole Chemical compound COC1=CC=CC(OC=2C(=CC=CC=2)N2CCN(CCCC=3C4=CC(Cl)=CC=C4NC=3)CC2)=C1 IMMGOHFIDQMRJW-UHFFFAOYSA-N 0.000 description 1
YULASTKKEXFGFD-UHFFFAOYSA-N 5-fluoro-3-[3-[4-[2-(2-methoxyphenoxy)phenyl]piperazin-1-yl]propyl]-1h-indole Chemical compound COC1=CC=CC=C1OC1=CC=CC=C1N1CCN(CCCC=2C3=CC(F)=CC=C3NC=2)CC1 YULASTKKEXFGFD-UHFFFAOYSA-N 0.000 description 1
BJNYRUIABYCUEN-UHFFFAOYSA-N 5-methyl-3-[3-[4-(2-phenoxyphenyl)piperazin-1-yl]propyl]-1h-indole Chemical compound C12=CC(C)=CC=C2NC=C1CCCN(CC1)CCN1C1=CC=CC=C1OC1=CC=CC=C1 BJNYRUIABYCUEN-UHFFFAOYSA-N 0.000 description 1
DJMWBNWFBCHEOX-UHFFFAOYSA-N 6-chloro-3-[2-[4-[2-(2-methoxyphenoxy)phenyl]piperazin-1-yl]ethyl]-1h-indole Chemical compound COC1=CC=CC=C1OC1=CC=CC=C1N1CCN(CCC=2C3=CC=C(Cl)C=C3NC=2)CC1 DJMWBNWFBCHEOX-UHFFFAOYSA-N 0.000 description 1
ZAGYUVDFLFKSSF-UHFFFAOYSA-N 6-chloro-3-[3-[4-[2-(2-methoxyphenoxy)phenyl]piperazin-1-yl]propyl]-1h-indole Chemical compound COC1=CC=CC=C1OC1=CC=CC=C1N1CCN(CCCC=2C3=CC=C(Cl)C=C3NC=2)CC1 ZAGYUVDFLFKSSF-UHFFFAOYSA-N 0.000 description 1
GVIQYWPEJQUXLX-UHFFFAOYSA-N 6-chlorohexanal Chemical compound ClCCCCCC=O GVIQYWPEJQUXLX-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
SKTFQHRVFFOHTQ-UHFFFAOYSA-N 8-bromo-1,3-dimethyl-7h-purine-2,6-dione Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC(Br)=N2 SKTFQHRVFFOHTQ-UHFFFAOYSA-N 0.000 description 1
229910015900 BF3 Inorganic materials 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
244000025254 Cannabis sativa Species 0.000 description 1
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
244000223760 Cinnamomum zeylanicum Species 0.000 description 1
206010012289 Dementia Diseases 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
208000012661 Dyskinesia Diseases 0.000 description 1
238000006783 Fischer indole synthesis reaction Methods 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
101150015707 HTR1A gene Proteins 0.000 description 1
241000282412 Homo Species 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 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
229910010082 LiAlH Inorganic materials 0.000 description 1
229920001367 Merrifield resin Polymers 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
208000018737 Parkinson disease Diseases 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
239000003875 Wang resin Substances 0.000 description 1
NERFNHBZJXXFGY-UHFFFAOYSA-N [4-[(4-methylphenyl)methoxy]phenyl]methanol Chemical compound C1=CC(C)=CC=C1COC1=CC=C(CO)C=C1 NERFNHBZJXXFGY-UHFFFAOYSA-N 0.000 description 1
230000009102 absorption Effects 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
230000009471 action Effects 0.000 description 1
239000008186 active pharmaceutical agent Substances 0.000 description 1
239000000556 agonist Substances 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
150000001448 anilines Chemical class 0.000 description 1
230000003042 antagnostic effect Effects 0.000 description 1
239000000935 antidepressant agent Substances 0.000 description 1
229940054051 antipsychotic indole derivative Drugs 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O 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
125000002619 bicyclic group Chemical group 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical class C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
235000017803 cinnamon Nutrition 0.000 description 1
238000011260 co-administration Methods 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
229940126214 compound 3 Drugs 0.000 description 1
229940125898 compound 5 Drugs 0.000 description 1
235000021438 curry Nutrition 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
238000013461 design Methods 0.000 description 1
238000001514 detection method Methods 0.000 description 1
CCAFPWNGIUBUSD-UHFFFAOYSA-N diethyl sulfoxide Chemical compound CCS(=O)CC CCAFPWNGIUBUSD-UHFFFAOYSA-N 0.000 description 1
125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
PUSKHXMZPOMNTQ-UHFFFAOYSA-N ethyl 2,1,3-benzoselenadiazole-5-carboxylate Chemical compound CCOC(=O)C1=CC=C2N=[Se]=NC2=C1 PUSKHXMZPOMNTQ-UHFFFAOYSA-N 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
230000003054 hormonal effect Effects 0.000 description 1
150000007857 hydrazones Chemical class 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
239000002917 insecticide Substances 0.000 description 1
230000010354 integration Effects 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
238000004255 ion exchange chromatography Methods 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000011968 lewis acid catalyst Substances 0.000 description 1
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
230000003340 mental effect Effects 0.000 description 1
229950002475 mesilate Drugs 0.000 description 1
WZHJKEUHNJHDLS-QTGUNEKASA-N metergoline Chemical compound C([C@H]1CN([C@H]2[C@@H](C=3C=CC=C4N(C)C=C(C=34)C2)C1)C)NC(=O)OCC1=CC=CC=C1 WZHJKEUHNJHDLS-QTGUNEKASA-N 0.000 description 1
229960004650 metergoline Drugs 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
238000007040 multi-step synthesis reaction Methods 0.000 description 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class 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
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
238000006386 neutralization reaction Methods 0.000 description 1
150000002828 nitro derivatives Chemical class 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
210000001009 nucleus accumben Anatomy 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
239000012071 phase Substances 0.000 description 1
229920000642 polymer Chemical class 0.000 description 1
210000002442 prefrontal cortex Anatomy 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
208000020016 psychiatric disease Diseases 0.000 description 1
238000000746 purification Methods 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
238000004445 quantitative analysis Methods 0.000 description 1
238000012207 quantitative assay Methods 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
230000009103 reabsorption Effects 0.000 description 1
239000000376 reactant Substances 0.000 description 1
239000000018 receptor agonist Substances 0.000 description 1
229940044601 receptor agonist Drugs 0.000 description 1
238000004366 reverse phase liquid chromatography Methods 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
230000000698 schizophrenic effect Effects 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
239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
238000003756 stirring Methods 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229960000278 theophylline Drugs 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
150000003577 thiophenes Chemical class 0.000 description 1
238000004448 titration Methods 0.000 description 1
229950004288 tosilate Drugs 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
238000001429 visible spectrum Methods 0.000 description 1
239000003643 water by type Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- 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
- C07D405/12—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 linked by a chain containing hetero atoms as chain links
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
- 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
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems

Landscapes

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

SK944-2002A 1999-12-30 2000-12-20 Substituted phenyl-piperazine derivatives, their preparation and use SK9442002A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DKPA199901885		1999-12-30
PCT/DK2000/000721 WO2001049678A1 (en)	1999-12-30	2000-12-20	Substituted phenyl-piperazine derivatives, their preparation and use

Publications (1)

Publication Number	Publication Date
SK9442002A3 true SK9442002A3 (en)	2002-11-06

Family

ID=8108803

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK944-2002A SK9442002A3 (en)	1999-12-30	2000-12-20	Substituted phenyl-piperazine derivatives, their preparation and use

Country Status (28)

Country	Link
US (1)	US6699864B2 (pl)
EP (1)	EP1246816B1 (pl)
JP (1)	JP2003519224A (pl)
KR (1)	KR100790916B1 (pl)
CN (1)	CN1230432C (pl)
AR (1)	AR029428A1 (pl)
AT (1)	ATE261959T1 (pl)
AU (1)	AU2152101A (pl)
BG (1)	BG65262B1 (pl)
BR (1)	BR0016952A (pl)
CA (1)	CA2395705C (pl)
CZ (1)	CZ20022319A3 (pl)
DE (1)	DE60009155T2 (pl)
EA (1)	EA006071B1 (pl)
ES (1)	ES2213634T3 (pl)
HU (1)	HUP0203722A3 (pl)
IL (2)	IL150241A0 (pl)
IS (1)	IS2174B (pl)
MX (1)	MXPA02006223A (pl)
NO (1)	NO322666B1 (pl)
NZ (1)	NZ519647A (pl)
PL (1)	PL199351B1 (pl)
PT (1)	PT1246816E (pl)
SK (1)	SK9442002A3 (pl)
TR (2)	TR200400645T4 (pl)
UA (1)	UA72948C2 (pl)
WO (1)	WO2001049678A1 (pl)
ZA (1)	ZA200204814B (pl)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
UA81749C2 (uk) *	2001-10-04	2008-02-11	Х. Луннбек А/С	Фенілпіперазинові похідні як інгібітори зворотного захоплення серотоніну
DE10259244A1 (de) *	2002-12-17	2004-07-01	Merck Patent Gmbh	N-(Indolethyl-)cycloamin-Verbindungen
UA81300C2 (en) *	2003-04-04	2007-12-25	Lundbeck & Co As H	Derivates of 4-(2-fenilsulfanilfenil)-1,2,3,6-tetrahydropiridin as retarding agents of serotonin recapture
WO2004087156A1 (en)	2003-04-04	2004-10-14	H. Lundbeck A/S	4-(2-phenylsulfanyl-phenyl)-piperidine derivatives as serotonin reuptake inhibitors
EP1701940B1 (en)	2003-12-23	2008-05-28	H.Lundbeck A/S	2-(1h-indolylsulfanyl)-benzyl amine derivatives as ssri
SE0400441D0 (sv)	2004-02-25	2004-02-25	Active Biotech Ab	Novel Benzofurans and Indols
AR052308A1 (es)	2004-07-16	2007-03-14	Lundbeck & Co As H	Derivados de 2-(1h-indolilsulfanil)-arilamina y una composicion farmaceutica que contiene al compuesto
US7629473B2 (en)	2005-06-17	2009-12-08	H. Lundbeck A/S	2-(1H-indolylsulfanyl)-aryl amine derivatives
AR054393A1 (es)	2005-06-17	2007-06-20	Lundbeck & Co As H	Derivados de benzo(b)furano y benzo(b)tiofeno, composiciones farmaceuticas que los contienen y su uso en la fabricacion de un medicamento para el tratamiento de enfermedades mediadas por la inhibicion de la reabsorcion de neurotransmisores de amina biogenicos.
MY150647A (en)	2006-06-16	2014-02-14	Lundbeck & Co As H	1-[2-(2,4-dimethylphenylsulfanyl)-phenyl] piperazine as a compound with combined serotonin reuptake, 5-ht3 and 5-ht1a activity for the treatment of cognitive impairment
EP2209380A4 (en) *	2007-10-09	2011-09-14	Mark T Hamann	METHOD OF USE OF COMPOSITIONS WITH ANTIDEPRESSIVE EFFICACY, MOOD EFFICACY AND OTHER NEUROLOGICAL EFFECTIVENESS AND COMPOSITIONS THEREOF
WO2009112139A1 (en) *	2008-03-14	2009-09-17	Merck Patent Gmbh,	Azaindole compounds for treatment of central nervous system disorders
CN105283442B (zh) *	2013-04-04	2018-04-13	斯洛文尼亚莱柯制药股份有限公司	用于合成1‑(2‑((2,4‑二甲基苯基)硫代)苯基)哌嗪的方法
WO2015169180A1 (en) *	2014-05-04	2015-11-12	Sunshine Lake Pharma Co., Ltd.	Substituted piperazine compounds and methods and use thereof
CN105085491B (zh) *	2014-05-05	2019-06-25	广东东阳光药业有限公司	取代的吲哚化合物及其使用方法和用途
CN106243088B (zh)	2015-06-03	2019-01-04	广东东阳光药业有限公司	取代的哌嗪化合物及其使用方法和用途
WO2017012579A1 (zh) *	2015-07-23	2017-01-26	广东东阳光药业有限公司	取代的吲哚化合物及其使用方法和用途
US11285153B2 (en)	2017-09-29	2022-03-29	Sunshine Lake Pharma Co., Ltd.	Substituted pyrimidine piperazine compound and use thereof
CN111518012A (zh) *	2020-05-27	2020-08-11	中国药科大学	含苯硫醚结构的化合物或其药学上可接受的盐、制备方法和用途

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE2138865A1 (de) *	1970-08-15	1973-02-22	Sumitomo Chemical Co	3-indolylpiperazine, verfahren zu ihrer herstellung und arzneimittel
GB8830312D0 (en) *	1988-12-28	1989-02-22	Lundbeck & Co As H	Heterocyclic compounds
AU6435594A (en) *	1993-04-15	1994-11-08	Merck Sharp & Dohme Limited	Indole derivatives as dopamine d4 antagonists
FR2712591B1 (fr) *	1993-11-19	1996-02-09	Pf Medicament	Nouvelles arylpipérazines dérivées d'indole, leur préparation et leur utilisation thérapeutique.
WO1997019039A1 (en)	1995-11-17	1997-05-29	Novartis Ag	Solid phase synthesis of heterocyclic compounds and combinatorial compound library
USH2007H1 (en) *	1996-01-19	2001-12-04	Fmc Corporation	Insecticidal N-heterocyclylalkyl-or N-[(polycyclyl)alkyl]-N′substituted piperazines
ES2128266B1 (es) *	1997-07-08	2000-01-16	Vita Invest Sa	Compuestos derivados de tiofeno y benzotiofeno y utilizacion y composicion correspondientes.
DE60034571T2 (de)	1999-06-15	2007-12-27	Aventis Pharmaceuticals Inc.	Festphasensynthese von n,n-disubstituierten diazacycloalkylcarboxy-derivaten
JP2003519227A (ja) *	1999-12-30	2003-06-17	ハー・ルンドベック・アクチエゼルスカベット	置換されたベンゼン誘導体の製造方法

2000
- 2000-12-20 WO PCT/DK2000/000721 patent/WO2001049678A1/en not_active Ceased
- 2000-12-20 PT PT00984924T patent/PT1246816E/pt unknown
- 2000-12-20 EA EA200200732A patent/EA006071B1/ru not_active IP Right Cessation
- 2000-12-20 TR TR2004/00645T patent/TR200400645T4/xx unknown
- 2000-12-20 DE DE60009155T patent/DE60009155T2/de not_active Expired - Fee Related
- 2000-12-20 TR TR2002/01683T patent/TR200201683T2/xx unknown
- 2000-12-20 AT AT00984924T patent/ATE261959T1/de not_active IP Right Cessation
- 2000-12-20 PL PL355539A patent/PL199351B1/pl not_active IP Right Cessation
- 2000-12-20 CN CNB008192057A patent/CN1230432C/zh not_active Expired - Fee Related
- 2000-12-20 CZ CZ20022319A patent/CZ20022319A3/cs unknown
- 2000-12-20 IL IL15024100A patent/IL150241A0/xx unknown
- 2000-12-20 SK SK944-2002A patent/SK9442002A3/sk unknown
- 2000-12-20 JP JP2001550218A patent/JP2003519224A/ja active Pending
- 2000-12-20 HU HU0203722A patent/HUP0203722A3/hu unknown
- 2000-12-20 MX MXPA02006223A patent/MXPA02006223A/es active IP Right Grant
- 2000-12-20 ES ES00984924T patent/ES2213634T3/es not_active Expired - Lifetime
- 2000-12-20 UA UA2002065260A patent/UA72948C2/uk unknown
- 2000-12-20 NZ NZ519647A patent/NZ519647A/en unknown
- 2000-12-20 CA CA002395705A patent/CA2395705C/en not_active Expired - Fee Related
- 2000-12-20 KR KR1020027008608A patent/KR100790916B1/ko not_active Expired - Fee Related
- 2000-12-20 AU AU21521/01A patent/AU2152101A/en not_active Abandoned
- 2000-12-20 BR BR0016952-8A patent/BR0016952A/pt not_active Application Discontinuation
- 2000-12-20 EP EP00984924A patent/EP1246816B1/en not_active Expired - Lifetime
- 2000-12-28 AR ARP000106987A patent/AR029428A1/es unknown
2002
- 2002-06-13 IS IS6420A patent/IS2174B/is unknown
- 2002-06-14 ZA ZA200204814A patent/ZA200204814B/xx unknown
- 2002-06-16 IL IL150241A patent/IL150241A/en not_active IP Right Cessation
- 2002-06-20 US US10/177,261 patent/US6699864B2/en not_active Expired - Fee Related
- 2002-06-28 NO NO20023146A patent/NO322666B1/no not_active IP Right Cessation
- 2002-07-17 BG BG106930A patent/BG65262B1/bg unknown

Also Published As

Publication number	Publication date
HUP0203722A3 (en)	2005-03-29
ZA200204814B (en)	2003-08-27
EP1246816B1 (en)	2004-03-17
IS6420A (is)	2002-06-13
PT1246816E (pt)	2004-08-31
JP2003519224A (ja)	2003-06-17
ES2213634T3 (es)	2004-09-01
US20030125320A1 (en)	2003-07-03
PL199351B1 (pl)	2008-09-30
BG65262B1 (bg)	2007-10-31
AU2152101A (en)	2001-07-16
IS2174B (is)	2006-11-15
NO322666B1 (no)	2006-11-13
ATE261959T1 (de)	2004-04-15
TR200201683T2 (tr)	2002-12-23
NZ519647A (en)	2004-02-27
EP1246816A1 (en)	2002-10-09
WO2001049678A1 (en)	2001-07-12
CA2395705A1 (en)	2001-07-12
CN1437597A (zh)	2003-08-20
US6699864B2 (en)	2004-03-02
EA200200732A1 (ru)	2003-02-27
EA006071B1 (ru)	2005-08-25
BG106930A (en)	2003-04-30
DE60009155D1 (de)	2004-04-22
BR0016952A (pt)	2002-10-08
PL355539A1 (pl)	2004-05-04
CZ20022319A3 (cs)	2002-10-16
KR100790916B1 (ko)	2008-01-03
MXPA02006223A (es)	2002-12-05
UA72948C2 (uk)	2005-05-16
AR029428A1 (es)	2003-06-25
IL150241A (en)	2008-12-29
NO20023146L (no)	2002-06-28
HUP0203722A2 (hu)	2003-03-28
TR200400645T4 (tr)	2004-06-21
KR20020063287A (ko)	2002-08-01
IL150241A0 (en)	2002-12-01
CA2395705C (en)	2006-10-17
WO2001049678A9 (en)	2002-10-10
DE60009155T2 (de)	2005-01-05
CN1230432C (zh)	2005-12-07
NO20023146D0 (no)	2002-06-28

Publication	Publication Date	Title
EP1246816B1 (en)	2004-03-17	Substituted phenyl-piperazine derivatives, their preparation and use
EP1246815B1 (en)	2004-03-17	Phenylpiperazinyl derivatives
ES2223628T3 (es)	2005-03-01	Derivados de 4-fenil-1-piperazinilo, -piperidinilo y -tetrahidropiridilo.
SK9452002A3 (en)	2002-11-06	Indole derivatives, pharmaceutical composition containing the same and their use
HUP0301735A2 (hu)	2003-08-28	A központi idegrendszer megbetegedéseinek kezelésére alkalmas indolszármazékok, ezeket tartalmazó gyógyszerkészítmények és alkalmazásuk
AU761122B2 (en)	2003-05-29	Aryl-(4-flouro-4-((2-pyridin-2-yl-ethylamino)-methyl)- piperidin-1-yl)-methanone derivatives as 5-HT1 receptor antagonists
EP1468996B1 (en)	2007-09-26	Indole derivatives for the treatment of CNS disorders
SK402003A3 (en)	2003-07-01	Indole derivatives, pharmaceutical composition comprising same and their use