KR100341190B1 - 피페리딘및피페라진 - Google Patents
피페리딘및피페라진 Download PDFInfo
- Publication number
- KR100341190B1 KR100341190B1 KR1019940024737A KR19940024737A KR100341190B1 KR 100341190 B1 KR100341190 B1 KR 100341190B1 KR 1019940024737 A KR1019940024737 A KR 1019940024737A KR 19940024737 A KR19940024737 A KR 19940024737A KR 100341190 B1 KR100341190 B1 KR 100341190B1
- Authority
- KR
- South Korea
- Prior art keywords
- piperazine
- butyl
- formula
- group
- chroman
- 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.)
- Expired - Lifetime
Links
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 title claims abstract description 18
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 title claims description 18
- -1 2,3-dihydrobenzofuran-5-yl Chemical group 0.000 claims abstract description 60
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 11
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 9
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 9
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 8
- 150000004885 piperazines Chemical class 0.000 claims abstract description 8
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 claims abstract description 8
- 125000004533 benzofuran-5-yl group Chemical group O1C=CC2=C1C=CC(=C2)* 0.000 claims abstract description 7
- 230000000694 effects Effects 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 5
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 78
- 239000002253 acid Substances 0.000 claims description 22
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 239000003638 chemical reducing agent Substances 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 238000003797 solvolysis reaction Methods 0.000 claims description 4
- FBORTSDQSNZPLD-UHFFFAOYSA-N 3-[4-[4-(2,3-dihydro-1-benzofuran-5-yl)piperazin-1-yl]butyl]-5-methoxy-1h-indole Chemical compound C1=C2OCCC2=CC(N2CCN(CC2)CCCCC2=CNC3=CC=C(C=C32)OC)=C1 FBORTSDQSNZPLD-UHFFFAOYSA-N 0.000 claims description 3
- NCZDFXRMIXGJIE-UHFFFAOYSA-N 3-[4-[4-(3,4-dihydro-2h-chromen-6-yl)piperazin-1-yl]butyl]-1h-indol-5-ol Chemical compound O1CCCC2=CC(N3CCN(CC3)CCCCC3=CNC4=CC=C(C=C43)O)=CC=C21 NCZDFXRMIXGJIE-UHFFFAOYSA-N 0.000 claims description 3
- KFNBERZIJGZUQL-UHFFFAOYSA-N 3-[4-[4-(3,4-dihydro-2h-chromen-6-yl)piperazin-1-yl]butyl]-5-methoxy-1h-indole Chemical compound O1CCCC2=CC(N3CCN(CC3)CCCCC3=CNC4=CC=C(C=C43)OC)=CC=C21 KFNBERZIJGZUQL-UHFFFAOYSA-N 0.000 claims description 3
- 239000000935 antidepressant agent Substances 0.000 claims description 3
- 229940005513 antidepressants Drugs 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 125000000524 functional group Chemical group 0.000 claims description 3
- 230000004048 modification Effects 0.000 claims description 3
- 238000012986 modification Methods 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
- VMAVRHPRKKYXEE-UHFFFAOYSA-N 3-[4-[4-(2,3-dihydro-1-benzofuran-5-yl)-4-hydroxypiperidin-1-yl]butyl]-1h-indole-5-carboxamide Chemical compound C1=C2OCCC2=CC(C2(O)CCN(CC2)CCCCC2=CNC3=CC=C(C=C32)C(=O)N)=C1 VMAVRHPRKKYXEE-UHFFFAOYSA-N 0.000 claims description 2
- WPEMBCYQSJWMGL-UHFFFAOYSA-N 3-[4-[4-(2,3-dihydro-1-benzofuran-5-yl)piperidin-1-yl]butyl]-1h-indole-5-carboxamide Chemical compound C1=C2OCCC2=CC(C2CCN(CC2)CCCCC2=CNC3=CC=C(C=C32)C(=O)N)=C1 WPEMBCYQSJWMGL-UHFFFAOYSA-N 0.000 claims description 2
- 229940030600 antihypertensive agent Drugs 0.000 claims description 2
- 239000002220 antihypertensive agent Substances 0.000 claims description 2
- 239000000164 antipsychotic agent Substances 0.000 claims description 2
- 229940005529 antipsychotics Drugs 0.000 claims description 2
- 239000002249 anxiolytic agent Substances 0.000 claims description 2
- 230000000949 anxiolytic effect Effects 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 230000001430 anti-depressive effect Effects 0.000 claims 2
- 230000003276 anti-hypertensive effect Effects 0.000 claims 1
- 230000000561 anti-psychotic effect Effects 0.000 claims 1
- NEAYFBXORWZSFT-UHFFFAOYSA-N ethyl 5-[4-[4-(5-cyano-1h-indol-3-yl)butyl]piperazin-1-yl]-1-benzofuran-2-carboxylate Chemical compound C1=C(C#N)C=C2C(CCCCN3CCN(CC3)C=3C=C4C=C(OC4=CC=3)C(=O)OCC)=CNC2=C1 NEAYFBXORWZSFT-UHFFFAOYSA-N 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 239000003176 neuroleptic agent Substances 0.000 claims 1
- 230000000701 neuroleptic effect Effects 0.000 claims 1
- 239000003723 serotonin 1A agonist Substances 0.000 claims 1
- SGEGOXDYSFKCPT-UHFFFAOYSA-N vilazodone Chemical compound C1=C(C#N)C=C2C(CCCCN3CCN(CC3)C=3C=C4C=C(OC4=CC=3)C(=O)N)=CNC2=C1 SGEGOXDYSFKCPT-UHFFFAOYSA-N 0.000 claims 1
- 210000003169 central nervous system Anatomy 0.000 abstract description 3
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 abstract description 2
- 238000006243 chemical reaction Methods 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 239000004480 active ingredient Substances 0.000 description 16
- 238000006722 reduction reaction Methods 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- 238000011282 treatment Methods 0.000 description 15
- 238000000034 method Methods 0.000 description 14
- 230000009467 reduction Effects 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 238000002844 melting Methods 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- XOVUXHKCSWGUJC-UHFFFAOYSA-N n,n-bis(2-chloroethyl)-1-benzofuran-5-amine Chemical compound ClCCN(CCCl)C1=CC=C2OC=CC2=C1 XOVUXHKCSWGUJC-UHFFFAOYSA-N 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- WVLFSMOGFARRCQ-UHFFFAOYSA-N 1-(3,4-dihydro-2h-chromen-6-yl)piperazine Chemical compound C1=C2CCCOC2=CC=C1N1CCNCC1 WVLFSMOGFARRCQ-UHFFFAOYSA-N 0.000 description 7
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 7
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- DWCOQZFEBZCIDZ-UHFFFAOYSA-N methyl 3-(4-chlorobutyl)-1h-indole-5-carboxylate Chemical compound COC(=O)C1=CC=C2NC=C(CCCCCl)C2=C1 DWCOQZFEBZCIDZ-UHFFFAOYSA-N 0.000 description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Substances CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 7
- FEZCEOAYHYBMFP-UHFFFAOYSA-N 3-(4-chlorobutyl)-5-methoxy-1h-indole Chemical compound COC1=CC=C2NC=C(CCCCCl)C2=C1 FEZCEOAYHYBMFP-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- DVVCESKEEKGQDK-UHFFFAOYSA-N 1-(2,3-dihydro-1-benzofuran-5-yl)piperazine Chemical compound C=1C=C2OCCC2=CC=1N1CCNCC1 DVVCESKEEKGQDK-UHFFFAOYSA-N 0.000 description 5
- 239000003513 alkali Substances 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- DGHYFKBJNPDQGI-UHFFFAOYSA-N 3-[4-[4-(2,3-dihydro-1-benzofuran-5-yl)piperazin-1-yl]butyl]-1h-indole-5-carboxylic acid Chemical compound C1=C2OCCC2=CC(N2CCN(CC2)CCCCC2=CNC3=CC=C(C=C32)C(=O)O)=C1 DGHYFKBJNPDQGI-UHFFFAOYSA-N 0.000 description 4
- ZEMJUXNZPZQBEG-UHFFFAOYSA-N 3-[4-[4-(3,4-dihydro-2h-chromen-6-yl)piperazin-1-yl]butyl]-1h-indole-5-carboxylic acid Chemical compound O1CCCC2=CC(N3CCN(CC3)CCCCC3=CNC4=CC=C(C=C43)C(=O)O)=CC=C21 ZEMJUXNZPZQBEG-UHFFFAOYSA-N 0.000 description 4
- RWYQAAAIONZWGU-UHFFFAOYSA-N 6-piperazin-1-ylchromen-4-one Chemical compound C1=C2C(=O)C=COC2=CC=C1N1CCNCC1 RWYQAAAIONZWGU-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 150000002170 ethers Chemical class 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- PFVBSYOXPYKRAW-UHFFFAOYSA-N methyl 3-[4-[4-(3,4-dihydro-2h-chromen-6-yl)piperazin-1-yl]butyl]-1h-indole-5-carboxylate Chemical compound O1CCCC2=CC(N3CCN(CC3)CCCCC3=CNC4=CC=C(C=C43)C(=O)OC)=CC=C21 PFVBSYOXPYKRAW-UHFFFAOYSA-N 0.000 description 4
- UBYLCMRMRHJXES-UHFFFAOYSA-N methyl 3-[4-[4-(4-oxochromen-6-yl)piperazin-1-yl]butyl]-1h-indole-5-carboxylate Chemical compound O1C=CC(=O)C2=CC(N3CCN(CC3)CCCCC3=CNC4=CC=C(C=C43)C(=O)OC)=CC=C21 UBYLCMRMRHJXES-UHFFFAOYSA-N 0.000 description 4
- 150000002825 nitriles Chemical class 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- NJJWMEJWFYRORL-UHFFFAOYSA-N 3-(4-chlorobutyl)-1h-indole-5-carbonitrile Chemical compound C1=C(C#N)C=C2C(CCCCCl)=CNC2=C1 NJJWMEJWFYRORL-UHFFFAOYSA-N 0.000 description 3
- ZHGWCRLFEMSSCW-UHFFFAOYSA-N 3-(4-chlorobutyl)-5,6-dimethoxy-1h-indole Chemical compound C1=C(OC)C(OC)=CC2=C1C(CCCCCl)=CN2 ZHGWCRLFEMSSCW-UHFFFAOYSA-N 0.000 description 3
- DEKRNBPLWBLQJA-UHFFFAOYSA-N 3-[2-[4-(1-benzofuran-5-yl)piperazin-1-yl]ethyl]-5-methoxy-1h-indole Chemical compound C1=C2OC=CC2=CC(N2CCN(CC2)CCC2=CNC3=CC=C(C=C32)OC)=C1 DEKRNBPLWBLQJA-UHFFFAOYSA-N 0.000 description 3
- UGYAOPMKVGMXFD-UHFFFAOYSA-N 3-[4-[4-(2,3-dihydro-1-benzofuran-5-yl)-4-hydroxypiperidin-1-yl]butyl]-1h-indole-5-carboxylic acid Chemical compound C1=C2OCCC2=CC(C2(O)CCN(CC2)CCCCC2=CNC3=CC=C(C=C32)C(=O)O)=C1 UGYAOPMKVGMXFD-UHFFFAOYSA-N 0.000 description 3
- RSXUEYFLDNUILS-UHFFFAOYSA-N 5-[4-[4-(5-cyano-1h-indol-3-yl)butyl]piperazin-4-ium-1-yl]-1-benzofuran-2-carboxylate Chemical compound C1=C(C#N)C=C2C(CCCCN3CCN(CC3)C=3C=C4C=C(OC4=CC=3)C(=O)O)=CNC2=C1 RSXUEYFLDNUILS-UHFFFAOYSA-N 0.000 description 3
- JTEJPPKMYBDEMY-UHFFFAOYSA-N 5-methoxytryptamine Chemical compound COC1=CC=C2NC=C(CCN)C2=C1 JTEJPPKMYBDEMY-UHFFFAOYSA-N 0.000 description 3
- XSDYUFFJOJVGMF-UHFFFAOYSA-N 5-piperazin-1-yl-1-benzofuran-2-carboxylic acid Chemical compound C=1C=C2OC(C(=O)O)=CC2=CC=1N1CCNCC1 XSDYUFFJOJVGMF-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 3
- 206010010904 Convulsion Diseases 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 3
- 239000003708 ampul Substances 0.000 description 3
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 3
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 3
- TXFLGZOGNOOEFZ-UHFFFAOYSA-N bis(2-chloroethyl)amine Chemical group ClCCNCCCl TXFLGZOGNOOEFZ-UHFFFAOYSA-N 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 206010008118 cerebral infarction Diseases 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 150000002475 indoles Chemical class 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- RZMJYUDWAZUQKC-UHFFFAOYSA-N methyl 3-[4-[4-(2,3-dihydro-1-benzofuran-5-yl)-4-hydroxypiperidin-1-yl]butyl]-1h-indole-5-carboxylate Chemical compound C1=C2OCCC2=CC(C2(O)CCN(CC2)CCCCC2=CNC3=CC=C(C=C32)C(=O)OC)=C1 RZMJYUDWAZUQKC-UHFFFAOYSA-N 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N p-toluenesulfonic acid Substances CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 150000003335 secondary amines Chemical class 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 3
- PYUFUUDEYQJLPV-UHFFFAOYSA-N 1-(1-benzofuran-5-yl)piperazine Chemical compound C1CNCCN1C1=CC=C(OC=C2)C2=C1 PYUFUUDEYQJLPV-UHFFFAOYSA-N 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 2
- YHYLDEVWYOFIJK-UHFFFAOYSA-N 1h-indole-5-carbonitrile Chemical compound N#CC1=CC=C2NC=CC2=C1 YHYLDEVWYOFIJK-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- MMUWHDVLRAINGJ-UHFFFAOYSA-M 2-chloro-1-methylpyridin-1-ium;methanesulfonate Chemical compound CS([O-])(=O)=O.C[N+]1=CC=CC=C1Cl MMUWHDVLRAINGJ-UHFFFAOYSA-M 0.000 description 2
- OBXWGWGUXIQLSG-UHFFFAOYSA-N 3-(3-aminopropyl)-1h-indol-5-ol Chemical compound C1=C(O)C=C2C(CCCN)=CNC2=C1 OBXWGWGUXIQLSG-UHFFFAOYSA-N 0.000 description 2
- GRGCCVWDHCWPTH-UHFFFAOYSA-N 3-(3-aminopropyl)-1h-indole-5-carbonitrile Chemical compound C1=C(C#N)C=C2C(CCCN)=CNC2=C1 GRGCCVWDHCWPTH-UHFFFAOYSA-N 0.000 description 2
- BTPKXLJPAUCHOW-UHFFFAOYSA-N 3-[2-[4-(1-benzofuran-5-yl)piperazin-1-yl]ethyl]-1h-indol-5-ol Chemical compound C1=C2OC=CC2=CC(N2CCN(CC2)CCC2=CNC3=CC=C(C=C32)O)=C1 BTPKXLJPAUCHOW-UHFFFAOYSA-N 0.000 description 2
- AQXBDWSDNDWYEN-UHFFFAOYSA-N 3-[4-[4-(1-benzofuran-5-yl)piperazin-1-yl]butyl]-5-methoxy-1h-indole Chemical compound C1=C2OC=CC2=CC(N2CCN(CC2)CCCCC2=CNC3=CC=C(C=C32)OC)=C1 AQXBDWSDNDWYEN-UHFFFAOYSA-N 0.000 description 2
- BLAKFOADRSDPNY-UHFFFAOYSA-N 3-[4-[4-(3,4-dihydro-2h-chromen-6-yl)piperazin-1-yl]butyl]-5,6-dimethoxy-1h-indole Chemical compound O1CCCC2=CC(N3CCN(CC3)CCCCC3=CNC=4C=C(C(=CC=43)OC)OC)=CC=C21 BLAKFOADRSDPNY-UHFFFAOYSA-N 0.000 description 2
- SQBLZOZDHPIMMX-UHFFFAOYSA-N 3-[4-[4-(4-oxochromen-6-yl)piperazin-1-yl]butyl]-1h-indole-5-carboxylic acid Chemical compound O1C=CC(=O)C2=CC(N3CCN(CC3)CCCCC3=CNC4=CC=C(C=C43)C(=O)O)=CC=C21 SQBLZOZDHPIMMX-UHFFFAOYSA-N 0.000 description 2
- PMRAIFHQGIJTTP-UHFFFAOYSA-N 4-(5-fluoro-1h-indol-3-yl)butan-1-amine Chemical compound C1=C(F)C=C2C(CCCCN)=CNC2=C1 PMRAIFHQGIJTTP-UHFFFAOYSA-N 0.000 description 2
- BIPSFKGKOMDMFB-UHFFFAOYSA-N 4-[5-(methoxymethyl)-1h-indol-3-yl]butan-1-amine Chemical compound COCC1=CC=C2NC=C(CCCCN)C2=C1 BIPSFKGKOMDMFB-UHFFFAOYSA-N 0.000 description 2
- VHCPFZDWRAIJKA-UHFFFAOYSA-N 5-(4-hydroxypiperidin-4-yl)-1-benzofuran-3-carboxylic acid Chemical compound C1=C2C(C(=O)O)=COC2=CC=C1C1(O)CCNCC1 VHCPFZDWRAIJKA-UHFFFAOYSA-N 0.000 description 2
- JBKKMOYEFSXQEE-UHFFFAOYSA-N 5-piperazin-1-yl-1-benzofuran-2-carbonitrile Chemical compound C=1C=C2OC(C#N)=CC2=CC=1N1CCNCC1 JBKKMOYEFSXQEE-UHFFFAOYSA-N 0.000 description 2
- MBBFNMNVDPOREX-UHFFFAOYSA-N 6-aminochromen-4-one Chemical group O1C=CC(=O)C2=CC(N)=CC=C21 MBBFNMNVDPOREX-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-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
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- RFPSMDQRWIJYQK-UHFFFAOYSA-N ethyl 3-(2-aminoethyl)-1h-indole-5-carboxylate Chemical compound CCOC(=O)C1=CC=C2NC=C(CCN)C2=C1 RFPSMDQRWIJYQK-UHFFFAOYSA-N 0.000 description 2
- KTVKGYUGDLUAJB-UHFFFAOYSA-N ethyl 3-[4-[4-(1-benzofuran-5-yl)piperazin-1-yl]butyl]-1h-indole-5-carboxylate Chemical compound C1=C2OC=CC2=CC(N2CCN(CC2)CCCCC2=CNC3=CC=C(C=C32)C(=O)OCC)=C1 KTVKGYUGDLUAJB-UHFFFAOYSA-N 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052987 metal hydride Inorganic materials 0.000 description 2
- 150000004681 metal hydrides Chemical class 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- AUENRBJHFYRCNJ-UHFFFAOYSA-N methyl 3-(3-aminopropyl)-1h-indole-5-carboxylate Chemical compound COC(=O)C1=CC=C2NC=C(CCCN)C2=C1 AUENRBJHFYRCNJ-UHFFFAOYSA-N 0.000 description 2
- FZJZRWDOGCSPEV-UHFFFAOYSA-N methyl 3-(4-chlorobutyl)-1h-indole-6-carboxylate Chemical compound COC(=O)C1=CC=C2C(CCCCCl)=CNC2=C1 FZJZRWDOGCSPEV-UHFFFAOYSA-N 0.000 description 2
- XHXHFFHBAHXAAJ-UHFFFAOYSA-N methyl 3-[4-[4-(2,3-dihydro-1-benzofuran-5-yl)piperazin-1-yl]butyl]-1h-indole-5-carboxylate Chemical compound C1=C2OCCC2=CC(N2CCN(CC2)CCCCC2=CNC3=CC=C(C=C32)C(=O)OC)=C1 XHXHFFHBAHXAAJ-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- 235000011007 phosphoric acid Nutrition 0.000 description 2
- WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 150000003138 primary alcohols Chemical class 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 238000011200 topical administration Methods 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
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- OFBBHAJLVVKTDS-UHFFFAOYSA-N (5-amino-1-benzofuran-2-yl)methanol Chemical compound NC1=CC=C2OC(CO)=CC2=C1 OFBBHAJLVVKTDS-UHFFFAOYSA-N 0.000 description 1
- HQVNLCGWZRUFOH-UHFFFAOYSA-N (5-piperazin-1-yl-1-benzofuran-2-yl)methanol Chemical compound C=1C=C2OC(CO)=CC2=CC=1N1CCNCC1 HQVNLCGWZRUFOH-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- GMOLCSICTCPZCU-UHFFFAOYSA-N 1-benzofuran-5-amine Chemical group NC1=CC=C2OC=CC2=C1 GMOLCSICTCPZCU-UHFFFAOYSA-N 0.000 description 1
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 1
- CBTITARLOCZPDU-UHFFFAOYSA-N 1h-indole-2-carbonitrile Chemical compound C1=CC=C2NC(C#N)=CC2=C1 CBTITARLOCZPDU-UHFFFAOYSA-N 0.000 description 1
- YJMADHMYUJFMQE-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-5-amine Chemical group NC1=CC=C2OCCC2=C1 YJMADHMYUJFMQE-UHFFFAOYSA-N 0.000 description 1
- OXQGTIUCKGYOAA-UHFFFAOYSA-N 2-Ethylbutanoic acid Chemical compound CCC(CC)C(O)=O OXQGTIUCKGYOAA-UHFFFAOYSA-N 0.000 description 1
- YMDZDFSUDFLGMX-UHFFFAOYSA-N 2-chloro-n-(2-chloroethyl)ethanamine;hydron;chloride Chemical group [Cl-].ClCC[NH2+]CCCl YMDZDFSUDFLGMX-UHFFFAOYSA-N 0.000 description 1
- NYEZIGVQPDFDQF-UHFFFAOYSA-N 3-(2-aminoethyl)-1h-indole-5-carbonitrile Chemical compound C1=C(C#N)C=C2C(CCN)=CNC2=C1 NYEZIGVQPDFDQF-UHFFFAOYSA-N 0.000 description 1
- BLEBTHHPYINQMI-UHFFFAOYSA-N 3-(2-chloroacetyl)-1h-indole-5-carbonitrile Chemical compound C1=C(C#N)C=C2C(C(=O)CCl)=CNC2=C1 BLEBTHHPYINQMI-UHFFFAOYSA-N 0.000 description 1
- YQUFFGIQZBPPCV-UHFFFAOYSA-N 3-(2-chloroethyl)-1h-indole-5-carbonitrile Chemical compound C1=C(C#N)C=C2C(CCCl)=CNC2=C1 YQUFFGIQZBPPCV-UHFFFAOYSA-N 0.000 description 1
- OGVRYSMQZMUUCU-UHFFFAOYSA-N 3-(4-chlorobutyl)-1h-indol-5-ol Chemical compound OC1=CC=C2NC=C(CCCCCl)C2=C1 OGVRYSMQZMUUCU-UHFFFAOYSA-N 0.000 description 1
- OIOXCPTYEYEJHJ-UHFFFAOYSA-N 3-(4-chlorobutyl)-5,6-difluoro-1h-indole Chemical compound C1=C(F)C(F)=CC2=C1C(CCCCCl)=CN2 OIOXCPTYEYEJHJ-UHFFFAOYSA-N 0.000 description 1
- XWKXQKUUXBPOEI-UHFFFAOYSA-N 3-(4-chlorobutyl)-5-fluoro-1h-indole Chemical compound FC1=CC=C2NC=C(CCCCCl)C2=C1 XWKXQKUUXBPOEI-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- MOSOXTNQFNGKHZ-UHFFFAOYSA-N 3-[2-[4-(1-benzofuran-5-yl)piperazin-1-yl]ethyl]-1h-indole-5-carbonitrile Chemical compound C1=C2OC=CC2=CC(N2CCN(CC2)CCC2=CNC3=CC=C(C=C32)C#N)=C1 MOSOXTNQFNGKHZ-UHFFFAOYSA-N 0.000 description 1
- VMZIVUKCLDWEEP-UHFFFAOYSA-N 3-[2-[4-(4-oxochromen-6-yl)piperazin-1-yl]ethyl]-1h-indole-5-carbonitrile Chemical compound C1=C(C#N)C=C2C(CCN3CCN(CC3)C3=CC=C4OC=CC(C4=C3)=O)=CNC2=C1 VMZIVUKCLDWEEP-UHFFFAOYSA-N 0.000 description 1
- ZKNOKEPJPGXOKZ-UHFFFAOYSA-N 3-[3-[4-(1-benzofuran-5-yl)piperazin-1-yl]propyl]-1h-indol-5-ol Chemical compound C1=C2OC=CC2=CC(N2CCN(CC2)CCCC2=CNC3=CC=C(C=C32)O)=C1 ZKNOKEPJPGXOKZ-UHFFFAOYSA-N 0.000 description 1
- HHCAPAKSPAUEMT-UHFFFAOYSA-N 3-[3-[4-(3,4-dihydro-2h-chromen-6-yl)piperazin-1-yl]propyl]-1h-indol-5-ol Chemical compound O1CCCC2=CC(N3CCN(CC3)CCCC3=CNC4=CC=C(C=C43)O)=CC=C21 HHCAPAKSPAUEMT-UHFFFAOYSA-N 0.000 description 1
- NEYVQESKPQYYIE-UHFFFAOYSA-N 3-[4-[4-(1-benzofuran-5-yl)piperazin-1-yl]butyl]-1h-indol-5-ol Chemical compound C1=C2OC=CC2=CC(N2CCN(CC2)CCCCC2=CNC3=CC=C(C=C32)O)=C1 NEYVQESKPQYYIE-UHFFFAOYSA-N 0.000 description 1
- YDTVHBKHQVLUJL-UHFFFAOYSA-N 3-[4-[4-(1-benzofuran-5-yl)piperazin-1-yl]butyl]-1h-indole-5-carboxylic acid Chemical compound C1=C2OC=CC2=CC(N2CCN(CC2)CCCCC2=CNC3=CC=C(C=C32)C(=O)O)=C1 YDTVHBKHQVLUJL-UHFFFAOYSA-N 0.000 description 1
- KNTGQPJYKVSUFX-UHFFFAOYSA-N 3-[4-[4-(1-benzofuran-5-yl)piperazin-1-yl]butyl]-5-(methoxymethyl)-1h-indole Chemical compound C1=C2OC=CC2=CC(N2CCN(CC2)CCCCC2=CNC3=CC=C(C=C32)COC)=C1 KNTGQPJYKVSUFX-UHFFFAOYSA-N 0.000 description 1
- FYBWQOUVFNWYIZ-UHFFFAOYSA-N 3-[4-[4-(1-benzofuran-5-yl)piperazin-1-yl]butyl]-5-fluoro-1h-indole Chemical compound C1=C2OC=CC2=CC(N2CCN(CC2)CCCCC2=CNC3=CC=C(C=C32)F)=C1 FYBWQOUVFNWYIZ-UHFFFAOYSA-N 0.000 description 1
- SXGVIZMAMIXWPF-UHFFFAOYSA-N 3-[4-[4-(2,3-dihydro-1-benzofuran-5-yl)piperazin-1-yl]butyl]-1h-indol-5-ol Chemical compound C1=C2OCCC2=CC(N2CCN(CC2)CCCCC2=CNC3=CC=C(C=C32)O)=C1 SXGVIZMAMIXWPF-UHFFFAOYSA-N 0.000 description 1
- UMXKZXWFCNSZOX-UHFFFAOYSA-N 3-[4-[4-(2,3-dihydro-1-benzofuran-5-yl)piperazin-1-yl]butyl]-1h-indole-5-carboxamide Chemical compound C1=C2OCCC2=CC(N2CCN(CC2)CCCCC2=CNC3=CC=C(C=C32)C(=O)N)=C1 UMXKZXWFCNSZOX-UHFFFAOYSA-N 0.000 description 1
- IBXHSXIXJZECAX-UHFFFAOYSA-N 3-[4-[4-(2,3-dihydro-1-benzofuran-5-yl)piperazin-1-yl]butyl]-6-fluoro-1h-indole Chemical compound C1=C2OCCC2=CC(N2CCN(CC2)CCCCC=2C3=CC=C(C=C3NC=2)F)=C1 IBXHSXIXJZECAX-UHFFFAOYSA-N 0.000 description 1
- VMTVDMPBNHSHFK-UHFFFAOYSA-N 3-[4-[4-(2,3-dihydro-1-benzofuran-5-yl)piperidin-1-yl]butyl]-1h-indole-5-carboxylic acid Chemical compound C1=C2OCCC2=CC(C2CCN(CC2)CCCCC2=CNC3=CC=C(C=C32)C(=O)O)=C1 VMTVDMPBNHSHFK-UHFFFAOYSA-N 0.000 description 1
- ZOTMPHLOFULIPB-UHFFFAOYSA-N 3-[4-[4-(3,4-dihydro-2h-chromen-6-yl)piperazin-1-yl]butyl]-1h-indole-5-carboxamide Chemical compound O1CCCC2=CC(N3CCN(CC3)CCCCC3=CNC4=CC=C(C=C43)C(=O)N)=CC=C21 ZOTMPHLOFULIPB-UHFFFAOYSA-N 0.000 description 1
- ZFHTZNCQARDMJL-UHFFFAOYSA-N 3-[4-[4-(3,4-dihydro-2h-chromen-6-yl)piperazin-1-yl]butyl]-5,6-difluoro-1h-indole Chemical compound O1CCCC2=CC(N3CCN(CC3)CCCCC3=CNC=4C=C(C(=CC=43)F)F)=CC=C21 ZFHTZNCQARDMJL-UHFFFAOYSA-N 0.000 description 1
- LJZIXWRFMRNXKE-UHFFFAOYSA-N 3-[4-[4-(3,4-dihydro-2h-chromen-6-yl)piperazin-1-yl]butyl]-5-(methoxymethyl)-1h-indole Chemical compound O1CCCC2=CC(N3CCN(CC3)CCCCC3=CNC4=CC=C(C=C43)COC)=CC=C21 LJZIXWRFMRNXKE-UHFFFAOYSA-N 0.000 description 1
- MVZRFLITYKMNOB-UHFFFAOYSA-N 3-[4-[4-(3,4-dihydro-2h-chromen-6-yl)piperazin-1-yl]butyl]-5-fluoro-1h-indole Chemical compound O1CCCC2=CC(N3CCN(CC3)CCCCC3=CNC4=CC=C(C=C43)F)=CC=C21 MVZRFLITYKMNOB-UHFFFAOYSA-N 0.000 description 1
- ACMKRHSLVYGGMJ-UHFFFAOYSA-N 3-[4-[4-(4-oxochromen-6-yl)piperazin-1-yl]butyl]-1h-indole-5-carbonitrile Chemical compound C1=C(C#N)C=C2C(CCCCN3CCN(CC3)C3=CC=C4OC=CC(C4=C3)=O)=CNC2=C1 ACMKRHSLVYGGMJ-UHFFFAOYSA-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
- IYCLYGPFQYBFSX-UHFFFAOYSA-N 4-(2,3-dihydro-1-benzofuran-5-yl)piperidin-4-ol Chemical compound C=1C=C2OCCC2=CC=1C1(O)CCNCC1 IYCLYGPFQYBFSX-UHFFFAOYSA-N 0.000 description 1
- AZLWTTVWXMJMGZ-UHFFFAOYSA-N 4-(2,3-dihydro-1-benzofuran-5-yl)piperidine Chemical compound C=1C=C2OCCC2=CC=1C1CCNCC1 AZLWTTVWXMJMGZ-UHFFFAOYSA-N 0.000 description 1
- RTWVAPUYIFGXIS-UHFFFAOYSA-N 4-(2-ethoxycarbonyl-1h-indol-3-yl)butanoic acid Chemical compound C1=CC=C2C(CCCC(O)=O)=C(C(=O)OCC)NC2=C1 RTWVAPUYIFGXIS-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- KYPZSCNPVLPUSF-UHFFFAOYSA-N 5,6-dichloro-3-(2-chloroethyl)-1h-indole Chemical compound ClC1=C(Cl)C=C2C(CCCl)=CNC2=C1 KYPZSCNPVLPUSF-UHFFFAOYSA-N 0.000 description 1
- LMRMNMLGNKFLNH-UHFFFAOYSA-N 5,6-dichloro-3-[2-[4-(2,3-dihydro-1-benzofuran-5-yl)piperazin-1-yl]ethyl]-1h-indole Chemical compound C1=C2OCCC2=CC(N2CCN(CC2)CCC2=CNC=3C=C(C(=CC=32)Cl)Cl)=C1 LMRMNMLGNKFLNH-UHFFFAOYSA-N 0.000 description 1
- XORLHLFUDFQYPD-UHFFFAOYSA-N 5-[4-[2-(5-methoxycarbonyl-1h-indol-3-yl)ethyl]piperazin-1-yl]-1-benzofuran-2-carboxylic acid Chemical compound C1=C2OC(C(O)=O)=CC2=CC(N2CCN(CC2)CCC2=CNC3=CC=C(C=C32)C(=O)OC)=C1 XORLHLFUDFQYPD-UHFFFAOYSA-N 0.000 description 1
- HUIQQCKIXGMQKB-UHFFFAOYSA-N 5-[4-[3-(5-cyano-1h-indol-3-yl)propyl]piperazin-1-yl]-1-benzofuran-2-carboxylic acid Chemical compound C1=C(C#N)C=C2C(CCCN3CCN(CC3)C=3C=C4C=C(OC4=CC=3)C(=O)O)=CNC2=C1 HUIQQCKIXGMQKB-UHFFFAOYSA-N 0.000 description 1
- NKZMCDJRVAYBTC-UHFFFAOYSA-N 5-[4-[4-(5,6-dimethoxy-1h-indol-3-yl)butyl]piperazin-1-yl]-1-benzofuran-2-carboxylic acid Chemical compound C1=C2OC(C(O)=O)=CC2=CC(N2CCN(CC2)CCCCC2=CNC=3C=C(C(=CC=32)OC)OC)=C1 NKZMCDJRVAYBTC-UHFFFAOYSA-N 0.000 description 1
- SCDSPUPSVOBHQX-UHFFFAOYSA-N 5-[4-[4-(5-methoxy-1h-indol-3-yl)butyl]piperazin-1-yl]-1-benzofuran-2-carbonitrile Chemical compound C1=C2OC(C#N)=CC2=CC(N2CCN(CC2)CCCCC2=CNC3=CC=C(C=C32)OC)=C1 SCDSPUPSVOBHQX-UHFFFAOYSA-N 0.000 description 1
- HIQVRSZLSIXTIG-UHFFFAOYSA-N 5-[4-hydroxy-1-[4-(7-methoxycarbonyl-1h-indol-3-yl)butyl]piperidin-4-yl]-1-benzofuran-3-carboxylic acid Chemical compound C1=C2OC=C(C(O)=O)C2=CC(C2(O)CCN(CC2)CCCCC=2C=3C=CC=C(C=3NC=2)C(=O)OC)=C1 HIQVRSZLSIXTIG-UHFFFAOYSA-N 0.000 description 1
- SRTPSDCZLBCSCE-UHFFFAOYSA-N 5-chloro-3-(4-chlorobutyl)-1h-indole Chemical compound C1=C(Cl)C=C2C(CCCCCl)=CNC2=C1 SRTPSDCZLBCSCE-UHFFFAOYSA-N 0.000 description 1
- QWCCOWNLLWQGIA-UHFFFAOYSA-N 5-chloro-3-[4-[4-(2,3-dihydro-1-benzofuran-5-yl)piperazin-1-yl]butyl]-1h-indole Chemical compound C1=C2OCCC2=CC(N2CCN(CC2)CCCCC2=CNC3=CC=C(C=C32)Cl)=C1 QWCCOWNLLWQGIA-UHFFFAOYSA-N 0.000 description 1
- LDCYZAJDBXYCGN-VIFPVBQESA-N 5-hydroxy-L-tryptophan Chemical compound C1=C(O)C=C2C(C[C@H](N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-VIFPVBQESA-N 0.000 description 1
- QBAYIBBJZXGIHK-UHFFFAOYSA-N 5-piperidin-4-yl-1-benzofuran-2-carboxylic acid Chemical compound C=1C=C2OC(C(=O)O)=CC2=CC=1C1CCNCC1 QBAYIBBJZXGIHK-UHFFFAOYSA-N 0.000 description 1
- ROJKLVNWCRLHOT-UHFFFAOYSA-N 6-[4-[4-(6-chloro-1h-indol-3-yl)butyl]piperazin-1-yl]chromen-4-one Chemical compound O1C=CC(=O)C2=CC(N3CCN(CC3)CCCCC=3C4=CC=C(C=C4NC=3)Cl)=CC=C21 ROJKLVNWCRLHOT-UHFFFAOYSA-N 0.000 description 1
- NPGKKMDMOCZRQH-UHFFFAOYSA-N 6-[4-[4-[5-(hydroxymethyl)-1h-indol-3-yl]butyl]piperazin-1-yl]chromen-4-one Chemical compound O1C=CC(=O)C2=CC(N3CCN(CC3)CCCCC3=CNC4=CC=C(C=C43)CO)=CC=C21 NPGKKMDMOCZRQH-UHFFFAOYSA-N 0.000 description 1
- OXBMVHLTZIGJEO-UHFFFAOYSA-N 6-chloro-3-(4-chlorobutyl)-1h-indole Chemical compound ClC1=CC=C2C(CCCCCl)=CNC2=C1 OXBMVHLTZIGJEO-UHFFFAOYSA-N 0.000 description 1
- 206010000599 Acromegaly Diseases 0.000 description 1
- 229910000761 Aluminium amalgam Inorganic materials 0.000 description 1
- 201000000736 Amenorrhea Diseases 0.000 description 1
- 206010001928 Amenorrhoea Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 101100283604 Caenorhabditis elegans pigk-1 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 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
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical compound [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 description 1
- 206010058359 Hypogonadism Diseases 0.000 description 1
- 238000006147 Japp-Klingemann synthesis reaction Methods 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
- 241001465754 Metazoa Species 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
- 229910000990 Ni alloy Inorganic materials 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 241000700159 Rattus Species 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
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 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
- 229920001615 Tragacanth Polymers 0.000 description 1
- 238000006856 Wolf-Kishner-Huang Minlon reduction reaction Methods 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- NSQSTEXVDPCLAE-UHFFFAOYSA-N [3-[2-[4-(3,4-dihydro-2h-chromen-6-yl)piperidin-1-yl]ethyl]-1h-indol-5-yl]methanol Chemical compound O1CCCC2=CC(C3CCN(CC3)CCC3=CNC4=CC=C(C=C43)CO)=CC=C21 NSQSTEXVDPCLAE-UHFFFAOYSA-N 0.000 description 1
- JJJDGTSDJSWIAT-UHFFFAOYSA-N [3-[3-[4-(3,4-dihydro-2h-chromen-6-yl)piperidin-1-yl]propyl]-1h-indol-5-yl]methanol Chemical compound O1CCCC2=CC(C3CCN(CC3)CCCC3=CNC4=CC=C(C=C43)CO)=CC=C21 JJJDGTSDJSWIAT-UHFFFAOYSA-N 0.000 description 1
- GRNSFCRBZKEXOM-UHFFFAOYSA-N [3-[4-[4-(1-benzofuran-5-yl)piperazin-1-yl]butyl]-1h-indol-5-yl]methanol Chemical compound C1=C2OC=CC2=CC(N2CCN(CC2)CCCCC2=CNC3=CC=C(C=C32)CO)=C1 GRNSFCRBZKEXOM-UHFFFAOYSA-N 0.000 description 1
- IHDMMRAUUYNYIP-UHFFFAOYSA-N [3-[4-[4-(3,4-dihydro-2h-chromen-6-yl)piperazin-1-yl]butyl]-1h-indol-5-yl]methanol Chemical compound O1CCCC2=CC(N3CCN(CC3)CCCCC3=CNC4=CC=C(C=C43)CO)=CC=C21 IHDMMRAUUYNYIP-UHFFFAOYSA-N 0.000 description 1
- FHIMDRZPLBYUOF-UHFFFAOYSA-N [5-[4-[4-(5-methoxy-1h-indol-3-yl)butyl]piperazin-1-yl]-1-benzofuran-2-yl]methanol Chemical compound C1=C2OC(CO)=CC2=CC(N2CCN(CC2)CCCCC2=CNC3=CC=C(C=C32)OC)=C1 FHIMDRZPLBYUOF-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- CJCSPKMFHVPWAR-JTQLQIEISA-N alpha-methyl-L-dopa Chemical compound OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 CJCSPKMFHVPWAR-JTQLQIEISA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 231100000540 amenorrhea Toxicity 0.000 description 1
- 230000002862 amidating effect Effects 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 229940125684 antimigraine agent Drugs 0.000 description 1
- 239000002282 antimigraine agent Substances 0.000 description 1
- 239000003420 antiserotonin agent Substances 0.000 description 1
- 229940005530 anxiolytics Drugs 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process 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
- 230000036772 blood pressure Effects 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 description 1
- 229960002802 bromocriptine Drugs 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 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
- MHUWZNTUIIFHAS-CLFAGFIQSA-N dioleoyl phosphatidic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(O)=O)OC(=O)CCCCCCC\C=C/CCCCCCCC MHUWZNTUIIFHAS-CLFAGFIQSA-N 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229960003133 ergot alkaloid Drugs 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- FGSGHBPKHFDJOP-UHFFFAOYSA-N ethyl 2-oxocyclohexane-1-carboxylate Chemical compound CCOC(=O)C1CCCCC1=O FGSGHBPKHFDJOP-UHFFFAOYSA-N 0.000 description 1
- GHZCDGWNEWZXMR-UHFFFAOYSA-N ethyl 3-(3-chloropropyl)-1h-indole-6-carboxylate Chemical compound CCOC(=O)C1=CC=C2C(CCCCl)=CNC2=C1 GHZCDGWNEWZXMR-UHFFFAOYSA-N 0.000 description 1
- XCSDYWCVUBZGBS-UHFFFAOYSA-N ethyl 3-[2-[4-(1-benzofuran-5-yl)piperazin-1-yl]ethyl]-1h-indole-5-carboxylate Chemical compound C1=C2OC=CC2=CC(N2CCN(CC2)CCC2=CNC3=CC=C(C=C32)C(=O)OCC)=C1 XCSDYWCVUBZGBS-UHFFFAOYSA-N 0.000 description 1
- LFTLXTMCSPONRY-UHFFFAOYSA-N ethyl 3-[2-[4-(3,4-dihydro-2h-chromen-6-yl)piperazin-1-yl]ethyl]-1h-indole-5-carboxylate Chemical compound O1CCCC2=CC(N3CCN(CC3)CCC3=CNC4=CC=C(C=C43)C(=O)OCC)=CC=C21 LFTLXTMCSPONRY-UHFFFAOYSA-N 0.000 description 1
- YFOIJNRCGYTEQC-UHFFFAOYSA-N ethyl 3-[3-[4-(2-cyano-1-benzofuran-5-yl)piperazin-1-yl]propyl]-1h-indole-6-carboxylate Chemical compound C1=C2OC(C#N)=CC2=CC(N2CCN(CC2)CCCC=2C3=CC=C(C=C3NC=2)C(=O)OCC)=C1 YFOIJNRCGYTEQC-UHFFFAOYSA-N 0.000 description 1
- YFFLLDHEEWSHQG-UHFFFAOYSA-N ethyl 5-amino-1-benzofuran-2-carboxylate Chemical compound NC1=CC=C2OC(C(=O)OCC)=CC2=C1 YFFLLDHEEWSHQG-UHFFFAOYSA-N 0.000 description 1
- ZKLDXJIVWKPASZ-UHFFFAOYSA-N ethyl 5-piperazin-1-yl-1-benzofuran-2-carboxylate Chemical compound C=1C=C2OC(C(=O)OCC)=CC2=CC=1N1CCNCC1 ZKLDXJIVWKPASZ-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229950006191 gluconic acid Drugs 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 150000002366 halogen compounds Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- YPGCWEMNNLXISK-UHFFFAOYSA-N hydratropic acid Chemical compound OC(=O)C(C)C1=CC=CC=C1 YPGCWEMNNLXISK-UHFFFAOYSA-N 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 150000002497 iodine compounds Chemical class 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960004502 levodopa Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- MJGFBOZCAJSGQW-UHFFFAOYSA-N mercury sodium Chemical compound [Na].[Hg] MJGFBOZCAJSGQW-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- ORDVHOHCTUHXBX-UHFFFAOYSA-M methanesulfonate;1-methylpyridin-1-ium Chemical compound CS([O-])(=O)=O.C[N+]1=CC=CC=C1 ORDVHOHCTUHXBX-UHFFFAOYSA-M 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- KSYFUOTTYSLEHU-UHFFFAOYSA-N methyl 3-(2-chloroethyl)-1h-indole-5-carboxylate Chemical compound COC(=O)C1=CC=C2NC=C(CCCl)C2=C1 KSYFUOTTYSLEHU-UHFFFAOYSA-N 0.000 description 1
- ZSMAUHHQPNQOTK-UHFFFAOYSA-N methyl 3-(4-chlorobutyl)-1h-indole-7-carboxylate Chemical compound COC(=O)C1=CC=CC2=C1NC=C2CCCCCl ZSMAUHHQPNQOTK-UHFFFAOYSA-N 0.000 description 1
- MYYRGZUDMVVZMA-UHFFFAOYSA-N methyl 3-[3-[4-(1-benzofuran-5-yl)piperazin-1-yl]propyl]-1h-indole-5-carboxylate Chemical compound C1=C2OC=CC2=CC(N2CCN(CC2)CCCC2=CNC3=CC=C(C=C32)C(=O)OC)=C1 MYYRGZUDMVVZMA-UHFFFAOYSA-N 0.000 description 1
- VFMMHMFMBJWXIO-UHFFFAOYSA-N methyl 3-[3-[4-(3,4-dihydro-2h-chromen-6-yl)piperazin-1-yl]propyl]-1h-indole-5-carboxylate Chemical compound O1CCCC2=CC(N3CCN(CC3)CCCC3=CNC4=CC=C(C=C43)C(=O)OC)=CC=C21 VFMMHMFMBJWXIO-UHFFFAOYSA-N 0.000 description 1
- CUZZMXQWSWJQEY-UHFFFAOYSA-N methyl 3-[3-[4-(3,4-dihydro-2h-chromen-6-yl)piperidin-1-yl]propyl]-1h-indole-5-carboxylate Chemical compound O1CCCC2=CC(C3CCN(CC3)CCCC3=CNC4=CC=C(C=C43)C(=O)OC)=CC=C21 CUZZMXQWSWJQEY-UHFFFAOYSA-N 0.000 description 1
- CNOWNFYBGWSHBZ-UHFFFAOYSA-N methyl 3-[4-[4-(2,3-dihydro-1-benzofuran-5-yl)piperidin-1-yl]butyl]-1h-indole-5-carboxylate Chemical compound C1=C2OCCC2=CC(C2CCN(CC2)CCCCC2=CNC3=CC=C(C=C32)C(=O)OC)=C1 CNOWNFYBGWSHBZ-UHFFFAOYSA-N 0.000 description 1
- JMJVWORWWIGVMK-UHFFFAOYSA-N methyl 3-[4-[4-(3,4-dihydro-2h-chromen-6-yl)piperazin-1-yl]butyl]-1h-indole-6-carboxylate Chemical compound O1CCCC2=CC(N3CCN(CC3)CCCCC=3C4=CC=C(C=C4NC=3)C(=O)OC)=CC=C21 JMJVWORWWIGVMK-UHFFFAOYSA-N 0.000 description 1
- NAXYPJOGTVVGFR-UHFFFAOYSA-N methyl 5-[4-[4-(5-cyano-1h-indol-3-yl)butyl]piperazin-1-yl]-1-benzofuran-2-carboxylate Chemical compound C1=C(C#N)C=C2C(CCCCN3CCN(CC3)C=3C=C4C=C(OC4=CC=3)C(=O)OC)=CNC2=C1 NAXYPJOGTVVGFR-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-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
- 210000001577 neostriatum Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
- YLLIGHVCTUPGEH-UHFFFAOYSA-M potassium;ethanol;hydroxide Chemical compound [OH-].[K+].CCO YLLIGHVCTUPGEH-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 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
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000000952 serotonin receptor agonist Substances 0.000 description 1
- 229910001023 sodium amalgam Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000006318 tert-butyl amino group Chemical group [H]N(*)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 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
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 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
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- C07D405/14—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 three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Anesthesiology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4333254A DE4333254A1 (de) | 1993-09-30 | 1993-09-30 | Piperidine und Piperazine |
| DEP4333254.4 | 1993-09-30 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR950008510A KR950008510A (ko) | 1995-04-17 |
| KR100341190B1 true KR100341190B1 (ko) | 2002-11-13 |
Family
ID=6499013
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019940024737A Expired - Lifetime KR100341190B1 (ko) | 1993-09-30 | 1994-09-29 | 피페리딘및피페라진 |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US5532241A (enExample) |
| EP (1) | EP0648767B1 (enExample) |
| JP (2) | JP4065034B2 (enExample) |
| KR (1) | KR100341190B1 (enExample) |
| CN (1) | CN1056610C (enExample) |
| AT (1) | ATE153663T1 (enExample) |
| AU (1) | AU679774B2 (enExample) |
| CA (1) | CA2133152C (enExample) |
| CZ (1) | CZ293558B6 (enExample) |
| DE (2) | DE4333254A1 (enExample) |
| DK (1) | DK0648767T3 (enExample) |
| ES (1) | ES2105454T3 (enExample) |
| GR (1) | GR3024551T3 (enExample) |
| HU (1) | HU218918B (enExample) |
| NO (1) | NO306948B1 (enExample) |
| PL (1) | PL178137B1 (enExample) |
| RU (1) | RU2132848C1 (enExample) |
| SK (1) | SK281793B6 (enExample) |
| TW (1) | TW313569B (enExample) |
| UA (1) | UA34449C2 (enExample) |
| ZA (1) | ZA947622B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101310191B1 (ko) | 2005-04-26 | 2013-09-24 | 메르크 파텐트 게엠베하 | ５-(４-[４-(５-시아노-３-인돌일)-부틸]-１-피페라진일)-벤조퓨란-２-카르복사미드의 제조 방법 |
Families Citing this family (85)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4333254A1 (de) * | 1993-09-30 | 1995-04-06 | Merck Patent Gmbh | Piperidine und Piperazine |
| GB9321221D0 (en) * | 1993-10-14 | 1993-12-01 | Glaxo Spa | Heterocyclic compounds |
| FR2712591B1 (fr) * | 1993-11-19 | 1996-02-09 | Pf Medicament | Nouvelles arylpipérazines dérivées d'indole, leur préparation et leur utilisation thérapeutique. |
| GB9501865D0 (en) * | 1995-01-31 | 1995-03-22 | Merck Sharp & Dohme | Therapeutic agents |
| DE19514567A1 (de) * | 1995-04-20 | 1996-10-24 | Merck Patent Gmbh | Benzofurane |
| US6436940B2 (en) * | 1996-12-20 | 2002-08-20 | H. Lundbeck A/S | Indane or dihydroindole derivatives |
| DE19730989A1 (de) * | 1997-07-18 | 1999-01-21 | Merck Patent Gmbh | Piperazin-Derivate |
| KR100545329B1 (ko) | 1997-07-25 | 2006-01-24 | 하. 룬트벡 아크티에 셀스카브 | 인돌 및 2,3-디히드로인돌 유도체, 그들의 제조방법 및 사용 |
| US6004982A (en) * | 1997-09-15 | 1999-12-21 | Hoechst Marion Roussel, Inc. | 4-piperidinyl) H-2-benzopyran derivatives useful as antipsychotic agents |
| US7189753B1 (en) | 1997-11-06 | 2007-03-13 | Cady Roger K | Preemptive prophylaxis of migraine |
| US6303627B1 (en) * | 1998-06-19 | 2001-10-16 | Eli Lilly And Company | Inhibitors of serotonin reuptake |
| DE19858340A1 (de) * | 1998-12-17 | 2000-06-21 | Merck Patent Gmbh | Verfahren zur Herstellung von 3-Alkanoyl- und 3-Alkylindolen |
| RU2278115C2 (ru) * | 1999-05-21 | 2006-06-20 | Сайос Инк. | ПРОИЗВОДНЫЕ ИНДОЛЬНОГО РЯДА В КАЧЕСТВЕ ИНГИБИТОРОВ p38 КИНАЗЫ |
| IL146309A (en) * | 1999-05-21 | 2008-03-20 | Scios Inc | Derivatives of the indole type and pharmaceutical preparations containing them as inhibitors of kinase p38 |
| TW518218B (en) * | 1999-05-27 | 2003-01-21 | Merck Patent Gmbh | Pharmaceutical compositions comprising 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoylbenzofuran-5-yl)piperazine or its physiologically acceptable salts for use in the treatment of sub-type anxiety disorders |
| US20120077825A1 (en) * | 1999-05-27 | 2012-03-29 | Merck Patentgesellschaft | Novel use of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine and its physiologically acceptable salts |
| DE19932314A1 (de) * | 1999-07-10 | 2001-01-11 | Merck Patent Gmbh | Benzofuranderivate |
| SK287018B6 (sk) * | 1999-08-23 | 2009-09-07 | Solvay Pharmaceuticals B. V. | Deriváty fenylpiperazínov, spôsob ich prípravy, farmaceutická kompozícia s ich obsahom a ich použitie |
| CA2428511C (en) * | 2000-11-14 | 2009-12-29 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Novel uses of combined 5-ht1a agonists and serotonin reuptake inhibitors |
| UA76130C2 (en) * | 2000-11-20 | 2006-07-17 | Merck Patent Gmbh | Use of compounds combining properties of selective inhibitors of serotonin re-uptake and agonists of 5-ht1a receptor for treatment of irritable bowel syndrome |
| GB2370270A (en) * | 2000-12-20 | 2002-06-26 | Lilly Co Eli | Pharmaceutical compounds |
| AR032712A1 (es) | 2001-02-21 | 2003-11-19 | Solvay Pharm Bv | Un mesilato de derivados de fenilpiperazina y composiciones farmaceuticas que lo contienen |
| DE10112151A1 (de) | 2001-03-14 | 2002-09-19 | Merck Patent Gmbh | Substituierte Benzofuran-2-carbonsäureamide |
| US6656950B2 (en) * | 2001-04-25 | 2003-12-02 | Wyeth | Antidepressant azaheterocyclylmethyl derivatives of 1,4-dioxino[2,3-b]pyridine |
| UA76758C2 (uk) | 2001-06-19 | 2006-09-15 | Мерк Патент Гмбх | Поліморфні форми гідрохлориду 1-'4-(5-ціаноіндол-3-іл)бутил-4-(2-карбамоїлбензофуран-5-іл)піперазину |
| DE10217006A1 (de) * | 2002-04-16 | 2003-11-06 | Merck Patent Gmbh | Substituierte Indole |
| RU2347784C2 (ru) * | 2002-05-29 | 2009-02-27 | Мершан Корпорейшн | Макроциклические соединения, лекарственное средство на их основе и их применение |
| DE10259244A1 (de) * | 2002-12-17 | 2004-07-01 | Merck Patent Gmbh | N-(Indolethyl-)cycloamin-Verbindungen |
| WO2004056769A2 (en) * | 2002-12-20 | 2004-07-08 | Ciba Specialty Chemicals Holding Inc. | Synthesis of amines and intermediates for the synthesis thereof |
| DE10305739A1 (de) * | 2003-02-11 | 2004-08-19 | Merck Patent Gmbh | Benzofuranderivate |
| DE10306941A1 (de) * | 2003-02-18 | 2004-08-26 | Merck Patent Gmbh | Benzofuranoxyethylamine |
| DE10315285A1 (de) | 2003-04-04 | 2004-10-14 | Merck Patent Gmbh | Chromenonindole |
| DE10326939A1 (de) * | 2003-06-16 | 2005-01-05 | Merck Patent Gmbh | Indol-Derivate |
| DE10326940A1 (de) * | 2003-06-16 | 2005-01-05 | Merck Patent Gmbh | Indol-Derivate |
| DE102004063797A1 (de) * | 2004-12-30 | 2006-07-13 | Schwarz Pharma Ag | Sauerstoffhaltige annelierte Phenylpiperazin- und Phenyldiazepancarboxamide |
| EP2110374A1 (en) * | 2008-04-18 | 2009-10-21 | Merck Sante | Benzofurane, benzothiophene, benzothiazol derivatives as FXR modulators |
| MA33159B1 (fr) | 2009-03-10 | 2012-03-01 | Takeda Pharmaceutical | Derives de la coumarone |
| US8877778B2 (en) * | 2010-12-15 | 2014-11-04 | Hoffmann-La Roche Inc. | Benzofurane compounds |
| US9708300B2 (en) | 2011-03-20 | 2017-07-18 | Cadila Healthcare Limited | Amorphous form of vilazodone hydrochloride and process for its preparation |
| CN102219783B (zh) * | 2011-05-05 | 2013-07-03 | 天津市汉康医药生物技术有限公司 | 盐酸维拉佐酮及其组合物 |
| CN102267985B (zh) * | 2011-06-15 | 2015-12-09 | 上海医药工业研究院 | 维拉佐酮或其盐酸盐的制备方法 |
| CN102267932A (zh) * | 2011-06-15 | 2011-12-07 | 上海医药工业研究院 | 4-(5-氰基-1h-吲哚-3-基)丁基取代磺酸酯类化合物及其应用 |
| CN102949364A (zh) * | 2011-08-30 | 2013-03-06 | 天津药物研究院 | 一种含有效成分盐酸维拉佐酮的缓释片 |
| WO2013078361A1 (en) | 2011-11-23 | 2013-05-30 | Assia Chemical Industries Ltd. | Solid state forms of vilazodone and vilazodone hydrochloride |
| AU2012354150A1 (en) | 2011-12-12 | 2014-07-03 | Ranbaxy Laboratories Limited | Amorphous vilazodone hydrochloride, a process for its preparation and pharmaceutical compositions thereof |
| ITMI20120531A1 (it) | 2012-04-02 | 2013-10-03 | Erregierre Spa | Procedimento per la preparazione di vilazodone cloridrato |
| WO2013153492A2 (en) * | 2012-04-12 | 2013-10-17 | Alembic Pharmaceuticals Limited | Process for the preparation of vilazodone hydrochloride and its amorphous form |
| US20150073148A1 (en) | 2012-04-16 | 2015-03-12 | Ranbaxy Laboratories Limited | Process for the preparation of crystalline vilazodone hydrochloride |
| WO2013164794A1 (en) | 2012-05-04 | 2013-11-07 | Ranbaxy Laboratories Limited | Crystalline forms of vilazodone hydrochloride |
| CN102659660B (zh) * | 2012-05-11 | 2014-07-02 | 杭州和泽医药科技有限公司 | 3-(4-氯丁基)-1h-吲哚-5-氰基的制备方法及其应用 |
| WO2013175361A1 (en) | 2012-05-24 | 2013-11-28 | Ranbaxy Laboratories Limited | Process for the preparation of vilazodone hydrochloride |
| US8835635B2 (en) | 2012-06-05 | 2014-09-16 | Symed Labs Limited | Amorphous form of vilazodone hydrochloride substantially free of crystalline forms |
| WO2013182946A2 (en) * | 2012-06-06 | 2013-12-12 | Ranbaxy Laboratories Limited | Process for the preparation of vilazodone hydrochloride |
| AU2013273868A1 (en) | 2012-06-13 | 2015-02-05 | Apotex Inc. | Forms of Vilazodone and processes for the preparation thereof |
| WO2014005134A2 (en) * | 2012-06-29 | 2014-01-03 | Forest Laboratories Holdings Limited | 4-(2-(6-substituted-hexylidene) hydrazinyl)benzonitrile and preparation thereof |
| US9399630B2 (en) | 2012-07-02 | 2016-07-26 | Symed Labs Limited | Process for preparing benzofuran-2-carboxamide derivatives |
| CN102796037B (zh) * | 2012-08-09 | 2013-11-06 | 成都苑东药业有限公司 | 一种3-(4-(4-取代哌嗪)-1-丁酰基)吲哚-5-甲腈及其用途 |
| WO2014028473A1 (en) | 2012-08-13 | 2014-02-20 | Assia Chemical Industries Ltd. | New salts of vilazodone and solid state forms thereof |
| US9533949B2 (en) | 2012-09-12 | 2017-01-03 | Apotex Pharmachem Inc. | Processes for the preparation of 3-alkyl indoles |
| WO2014049609A2 (en) | 2012-09-26 | 2014-04-03 | Cadila Healthcare Limited | Novel salts of vilazodone |
| WO2014061000A1 (en) | 2012-10-19 | 2014-04-24 | Ranbaxy Laboratories Limited | Process for the preparation of vilazodone or pharmaceutically acceptable salt thereof |
| WO2014061004A2 (en) | 2012-10-19 | 2014-04-24 | Ranbaxy Laboratories Limited | Process for the preparation of vilazodone or pharmaceutically acceptable salt thereof |
| WO2014064715A2 (en) | 2012-10-22 | 2014-05-01 | Cadila Healthcare Limited | Amorphous form of vilazodone hydrochloride and process for preparing thereof |
| CN102977083A (zh) * | 2012-12-17 | 2013-03-20 | 南京海纳医药科技有限公司 | 1-[4-(5-氰基吲哚-3-基)丁基]-4-(2-氨甲酰-苯并呋喃-5-基)-哌嗪盐酸盐的新晶型xⅶ及其制备方法 |
| CN102993186B (zh) * | 2012-12-20 | 2015-11-18 | 北京海步国际医药科技发展有限公司 | 一种新型的哌嗪衍生物 |
| ITMI20130392A1 (it) | 2013-03-15 | 2014-09-16 | Dipharma Francis Srl | Sintesi di un inibitore della ricaptazione della serotonina |
| CN104098552A (zh) * | 2013-04-02 | 2014-10-15 | 上海医药工业研究院 | 维拉佐酮的制备方法 |
| WO2014178013A1 (en) | 2013-04-30 | 2014-11-06 | Ranbaxy Laboratories Limited | Vilazodone impurities, process for their preparation, and their use as reference standards |
| WO2014199313A1 (en) | 2013-06-12 | 2014-12-18 | Lupin Limited | Substantially pure vilazodone hydrochloride and a process thereof |
| EP2824104A1 (en) | 2013-07-12 | 2015-01-14 | Sandoz AG | Process for the preparation of form III of Vilazodone hydrochloride |
| CN103360373B (zh) * | 2013-07-12 | 2016-06-15 | 苏州永健生物医药有限公司 | 维拉唑酮中间体及其盐的合成方法 |
| US9598401B2 (en) | 2013-07-29 | 2017-03-21 | Sunshine Lake Pharma Co., Ltd. | Substituted heteroaryl compounds and methods of use thereof |
| WO2015019237A1 (en) | 2013-08-06 | 2015-02-12 | Ranbaxy Laboratories Limited | Pharmaceutical composition of vilazodone |
| WO2015019256A1 (en) | 2013-08-06 | 2015-02-12 | Ranbaxy Laboratories Limited | Pharmaceutical composition of vilazodone and processes of preparation thereof |
| EP3083589B1 (en) | 2013-12-20 | 2019-12-18 | Sunshine Lake Pharma Co., Ltd. | Substituted piperazine compounds and methods of use thereof |
| CN103709089B (zh) * | 2013-12-31 | 2015-08-19 | 南通恒盛精细化工有限公司 | 一种制备3-(4’-氯丁基)-5-氰基吲哚的方法 |
| WO2016128987A1 (en) * | 2015-02-13 | 2016-08-18 | Harman Finochem Limited | A process for preparation of 2-benzofurancarboxamide, 5-[4-[4-(5cyano-1h-indol-3-yl)butyl]-1-piperazinyl] free base and its hydrochloride salt |
| WO2016142952A1 (en) * | 2015-03-10 | 2016-09-15 | Nosch Labs Private Limited | Process for preparation of vilazodone and its novel intermediates |
| US10316025B2 (en) | 2015-06-03 | 2019-06-11 | Sunshine Lake Pharma Co., Ltd. | Substituted piperazine compounds and methods of use and use thereof |
| US12171761B2 (en) | 2016-11-02 | 2024-12-24 | Sunshine Lake Pharma Co., Ltd. | Vilazodone inclusion complexes, compositions and preparation thereof |
| WO2018082557A1 (en) | 2016-11-02 | 2018-05-11 | Sunshine Lake Pharma Co., Ltd. | Vilazodone inclusion complexes, compositions and preparation thereof |
| TR201702104A2 (tr) | 2017-02-13 | 2018-08-27 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | Vi̇lazodon hi̇droklorür farmasöti̇k bi̇leşi̇mleri̇ |
| TR201702103A2 (tr) | 2017-02-13 | 2018-08-27 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | Vilazodon hi̇droklorürün tablet formlari |
| ES2974248T3 (es) | 2017-09-29 | 2024-06-26 | Sunshine Lake Pharma Co Ltd | Compuesto de pirimidin-piperazina sustituido y uso del mismo |
| CN111454250B (zh) * | 2019-01-21 | 2021-05-07 | 华东理工大学 | 多靶点活性化合物及其用途 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1075156A (en) * | 1963-08-27 | 1967-07-12 | Luso Farmaco Inst | Substituted piperazines |
| US3468882A (en) * | 1966-10-07 | 1969-09-23 | Sterling Drug Inc | Phenylhydrazone derivatives as intermediates for preparing indoles |
| GB8830312D0 (en) * | 1988-12-28 | 1989-02-22 | Lundbeck & Co As H | Heterocyclic compounds |
| DE3907974A1 (de) * | 1989-03-11 | 1990-09-13 | Merck Patent Gmbh | Indolderivate |
| JPH0465034A (ja) * | 1990-07-02 | 1992-03-02 | Mitsubishi Electric Corp | 酸化物超電導線材の製造方法 |
| FR2670491B1 (fr) | 1990-12-14 | 1993-02-05 | Adir | Nouvelles piperazines 1,4-disubstituees, leur procede de preparation et les compositions pharmaceutiques les renfermant. |
| DE4101686A1 (de) * | 1991-01-22 | 1992-07-23 | Merck Patent Gmbh | Indolderivate |
| DE4127849A1 (de) * | 1991-08-22 | 1993-02-25 | Merck Patent Gmbh | Benzodioxanderivate |
| DK148392D0 (da) * | 1992-12-09 | 1992-12-09 | Lundbeck & Co As H | Heterocykliske forbindelser |
| DE4333254A1 (de) * | 1993-09-30 | 1995-04-06 | Merck Patent Gmbh | Piperidine und Piperazine |
-
1993
- 1993-09-30 DE DE4333254A patent/DE4333254A1/de not_active Withdrawn
-
1994
- 1994-08-01 UA UA94085681A patent/UA34449C2/uk unknown
- 1994-09-20 DE DE59402902T patent/DE59402902D1/de not_active Expired - Lifetime
- 1994-09-20 ES ES94114798T patent/ES2105454T3/es not_active Expired - Lifetime
- 1994-09-20 EP EP94114798A patent/EP0648767B1/de not_active Expired - Lifetime
- 1994-09-20 DK DK94114798.5T patent/DK0648767T3/da active
- 1994-09-20 AT AT94114798T patent/ATE153663T1/de active
- 1994-09-27 TW TW083108965A patent/TW313569B/zh not_active IP Right Cessation
- 1994-09-27 AU AU74244/94A patent/AU679774B2/en not_active Expired
- 1994-09-27 CN CN94116585A patent/CN1056610C/zh not_active Expired - Lifetime
- 1994-09-28 CZ CZ19942370A patent/CZ293558B6/cs not_active IP Right Cessation
- 1994-09-28 JP JP23353894A patent/JP4065034B2/ja not_active Expired - Lifetime
- 1994-09-28 PL PL94305216A patent/PL178137B1/pl unknown
- 1994-09-28 CA CA002133152A patent/CA2133152C/en not_active Expired - Fee Related
- 1994-09-29 ZA ZA947622A patent/ZA947622B/xx unknown
- 1994-09-29 RU RU94035660A patent/RU2132848C1/ru active
- 1994-09-29 HU HU9402806A patent/HU218918B/hu unknown
- 1994-09-29 US US08/314,734 patent/US5532241A/en not_active Expired - Lifetime
- 1994-09-29 SK SK1184-94A patent/SK281793B6/sk not_active IP Right Cessation
- 1994-09-29 KR KR1019940024737A patent/KR100341190B1/ko not_active Expired - Lifetime
- 1994-09-29 NO NO943616A patent/NO306948B1/no not_active IP Right Cessation
-
1997
- 1997-08-27 GR GR970402190T patent/GR3024551T3/el unknown
-
2007
- 2007-02-15 JP JP2007034671A patent/JP4700017B2/ja not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101310191B1 (ko) | 2005-04-26 | 2013-09-24 | 메르크 파텐트 게엠베하 | ５-(４-[４-(５-시아노-３-인돌일)-부틸]-１-피페라진일)-벤조퓨란-２-카르복사미드의 제조 방법 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR100341190B1 (ko) | 피페리딘및피페라진 | |
| US5693655A (en) | 3-indolylpiperidines | |
| KR100528684B1 (ko) | 피페라진 유도체 | |
| US5242925A (en) | Piperazinylbenzodioxane derivatives | |
| JP3327473B2 (ja) | インドール誘導体 | |
| JP3834098B2 (ja) | ベンゾニトリル類およびベンゾフルオリド類 | |
| SK4396A3 (en) | Indolepiperidine derivative, preparation method thereof and pharmaceutical composition containing its | |
| US5106850A (en) | Indole derivatives | |
| HU180873B (en) | Process for preparing indolyl-alkyl-amine derivatives and pharmaceutical preparations containing such compounds as active substances | |
| JPH047745B2 (enExample) | ||
| US6333339B1 (en) | 3-Benzylpiperidine | |
| JPH02273672A (ja) | インドール誘導体類 | |
| CZ450999A3 (cs) | Derivát 3-benzylpiperidinu, způsob jeho přípravy a farmaceutický prostředek, který ho obsahuje | |
| JPS62263181A (ja) | インド−ル誘導体 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0109 | Patent application |
Patent event code: PA01091R01D Comment text: Patent Application Patent event date: 19940929 |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 19990928 Comment text: Request for Examination of Application Patent event code: PA02011R01I Patent event date: 19940929 Comment text: Patent Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20011123 Patent event code: PE09021S01D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20020416 |
|
| GRNT | Written decision to grant | ||
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20020605 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 20020607 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration | ||
| PR1001 | Payment of annual fee |
Payment date: 20050524 Start annual number: 4 End annual number: 4 |
|
| PR1001 | Payment of annual fee |
Payment date: 20060525 Start annual number: 5 End annual number: 5 |
|
| PR1001 | Payment of annual fee |
Payment date: 20070523 Start annual number: 6 End annual number: 6 |
|
| PR1001 | Payment of annual fee |
Payment date: 20080522 Start annual number: 7 End annual number: 7 |
|
| PR1001 | Payment of annual fee |
Payment date: 20090525 Start annual number: 8 End annual number: 8 |
|
| PR1001 | Payment of annual fee |
Payment date: 20100525 Start annual number: 9 End annual number: 9 |
|
| PR1001 | Payment of annual fee |
Payment date: 20110502 Start annual number: 10 End annual number: 10 |
|
| PR1001 | Payment of annual fee |
Payment date: 20120518 Start annual number: 11 End annual number: 11 |
|
| FPAY | Annual fee payment |
Payment date: 20130520 Year of fee payment: 12 |
|
| PR1001 | Payment of annual fee |
Payment date: 20130520 Start annual number: 12 End annual number: 12 |
|
| FPAY | Annual fee payment |
Payment date: 20140522 Year of fee payment: 13 |
|
| PR1001 | Payment of annual fee |
Payment date: 20140522 Start annual number: 13 End annual number: 13 |
|
| EXPY | Expiration of term | ||
| PC1801 | Expiration of term |
Termination date: 20150329 Termination category: Expiration of duration |