JPH0556345B2 - - Google Patents

Info

Publication number: JPH0556345B2
Authority: JP; Japan
Prior art keywords: group; salt; fluorobenzoyl; piperidinyl; ethyl
Prior art date: 1983-03-09
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

Application number

JP8444220A

Other languages

English (en)

Japanese (ja)

Other versions

JPS59186959A (ja

Inventor

Sutoruni Angero

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Novartis AG

Original Assignee

Ciba Geigy AG

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.)

1983-03-09

Filing date

1984-03-09

Publication date

1993-08-19

1984-03-09 Application filed by Ciba Geigy AG filed Critical Ciba Geigy AG

1984-10-23 Publication of JPS59186959A publication Critical patent/JPS59186959A/ja

1993-08-19 Publication of JPH0556345B2 publication Critical patent/JPH0556345B2/ja

Status Granted legal-status Critical Current

Links

-1 cyano, carbamoyl Chemical group 0.000 claims description 133
150000001875 compounds Chemical class 0.000 claims description 117
150000003839 salts Chemical class 0.000 claims description 77
229910052736 halogen Inorganic materials 0.000 claims description 49
150000002367 halogens Chemical class 0.000 claims description 44
125000003545 alkoxy group Chemical group 0.000 claims description 40
125000004432 carbon atom Chemical group C* 0.000 claims description 39
125000000217 alkyl group Chemical group 0.000 claims description 27
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 23
239000001257 hydrogen Substances 0.000 claims description 23
229910052739 hydrogen Inorganic materials 0.000 claims description 23
125000001424 substituent group Chemical group 0.000 claims description 21
125000003282 alkyl amino group Chemical group 0.000 claims description 16
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 13
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 12
125000005551 pyridylene group Chemical group 0.000 claims description 12
125000002947 alkylene group Chemical group 0.000 claims description 11
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 11
125000004093 cyano group Chemical group *C#N 0.000 claims description 11
125000005843 halogen group Chemical group 0.000 claims description 11
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 10
239000004480 active ingredient Substances 0.000 claims description 9
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 9
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 6
125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 5
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
XMRWAAOHXNIGHP-UHFFFAOYSA-N 5-cyano-n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-methoxybenzamide Chemical compound COC1=CC=C(C#N)C=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 XMRWAAOHXNIGHP-UHFFFAOYSA-N 0.000 claims description 4
229910052701 rubidium Inorganic materials 0.000 claims description 4
DGHSVXGZTBSHHD-UHFFFAOYSA-N 3-bromo-4-fluoro-n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]benzamide Chemical compound C1=CC(F)=CC=C1C(=O)C1CCN(CCNC(=O)C=2C=C(Br)C(F)=CC=2)CC1 DGHSVXGZTBSHHD-UHFFFAOYSA-N 0.000 claims description 3
IHWSSUJVXAVJOK-UHFFFAOYSA-N 4-fluoro-n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]benzamide Chemical compound C1=CC(F)=CC=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 IHWSSUJVXAVJOK-UHFFFAOYSA-N 0.000 claims description 3
COOBIGBMMSAVJT-UHFFFAOYSA-N 5-cyano-n-[2-[4-[(4-fluorophenyl)-hydroxymethylidene]piperidin-1-yl]ethyl]-2-methoxybenzamide Chemical compound COC1=CC=C(C#N)C=C1C(=O)NCCN(CC1)CCC1=C(O)C1=CC=C(F)C=C1 COOBIGBMMSAVJT-UHFFFAOYSA-N 0.000 claims description 3
239000003814 drug Substances 0.000 claims description 3
OPWUWAVBEYJLKA-UHFFFAOYSA-N 2-bromo-4-fluoro-n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]benzamide Chemical compound C1=CC(F)=CC=C1C(=O)C1CCN(CCNC(=O)C=2C(=CC(F)=CC=2)Br)CC1 OPWUWAVBEYJLKA-UHFFFAOYSA-N 0.000 claims description 2
SQVMUOGSZMKXMJ-UHFFFAOYSA-N 3-bromo-n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-4-methoxybenzamide Chemical compound C1=C(Br)C(OC)=CC=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 SQVMUOGSZMKXMJ-UHFFFAOYSA-N 0.000 claims description 2
RWZRYNLTCOJMSO-UHFFFAOYSA-N 5-bromo-4-chloro-n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-methoxybenzamide Chemical compound COC1=CC(Cl)=C(Br)C=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 RWZRYNLTCOJMSO-UHFFFAOYSA-N 0.000 claims description 2
229910052705 radium Inorganic materials 0.000 claims description 2
229910052702 rhenium Inorganic materials 0.000 claims description 2
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 2
ZKKDSCWDKMGZGE-UHFFFAOYSA-N 3,5-dichloro-n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-methoxy-4-methylbenzamide Chemical compound COC1=C(Cl)C(C)=C(Cl)C=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 ZKKDSCWDKMGZGE-UHFFFAOYSA-N 0.000 claims 1
ZSIVELBPQANHFZ-UHFFFAOYSA-N 3-cyano-n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-4-methoxybenzamide Chemical compound C1=C(C#N)C(OC)=CC=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 ZSIVELBPQANHFZ-UHFFFAOYSA-N 0.000 claims 1
FRSNVCJKOCMYLN-UHFFFAOYSA-N 4-fluoro-n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-methoxybenzamide Chemical compound COC1=CC(F)=CC=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 FRSNVCJKOCMYLN-UHFFFAOYSA-N 0.000 claims 1
NGLIVDONXVSSFM-UHFFFAOYSA-N 5-bromo-4-fluoro-n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-methoxybenzamide Chemical compound COC1=CC(F)=C(Br)C=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 NGLIVDONXVSSFM-UHFFFAOYSA-N 0.000 claims 1
MHGNQCAGTSQBSS-UHFFFAOYSA-N 5-bromo-n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-methoxybenzamide Chemical compound COC1=CC=C(Br)C=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 MHGNQCAGTSQBSS-UHFFFAOYSA-N 0.000 claims 1
JPDSQDCQRCJEDV-UHFFFAOYSA-N 5-chloro-n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-methoxy-4-(methylaminosulfamoyl)benzamide Chemical compound C1=C(Cl)C(S(=O)(=O)NNC)=CC(OC)=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 JPDSQDCQRCJEDV-UHFFFAOYSA-N 0.000 claims 1
230000000561 anti-psychotic effect Effects 0.000 claims 1
229940079593 drug Drugs 0.000 claims 1
AXKXBPHUXOCHSD-UHFFFAOYSA-N n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2,6-dimethoxybenzamide Chemical compound COC1=CC=CC(OC)=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 AXKXBPHUXOCHSD-UHFFFAOYSA-N 0.000 claims 1
KATFLYVSUVZNDQ-UHFFFAOYSA-N n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-methoxy-5-methylsulfonylbenzamide Chemical compound COC1=CC=C(S(C)(=O)=O)C=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 KATFLYVSUVZNDQ-UHFFFAOYSA-N 0.000 claims 1
WQXGDTHNUALJKU-UHFFFAOYSA-N n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-methoxy-5-sulfamoylbenzamide Chemical compound COC1=CC=C(S(N)(=O)=O)C=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 WQXGDTHNUALJKU-UHFFFAOYSA-N 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 108
239000002253 acid Substances 0.000 description 61
238000000034 method Methods 0.000 description 54
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 45
239000000243 solution Substances 0.000 description 43
239000007858 starting material Substances 0.000 description 42
238000002844 melting Methods 0.000 description 41
230000008018 melting Effects 0.000 description 41
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
239000000203 mixture Substances 0.000 description 37
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 34
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 31
238000006243 chemical reaction Methods 0.000 description 31
239000002585 base Substances 0.000 description 29
125000002887 hydroxy group Chemical group [H]O* 0.000 description 27
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 24
238000003756 stirring Methods 0.000 description 20
238000011282 treatment Methods 0.000 description 19
150000007513 acids Chemical class 0.000 description 18
230000002829 reductive effect Effects 0.000 description 17
HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 16
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
ABERUOJGWHYBJL-UHFFFAOYSA-N (4-fluorophenyl)-piperidin-4-ylmethanone Chemical compound C1=CC(F)=CC=C1C(=O)C1CCNCC1 ABERUOJGWHYBJL-UHFFFAOYSA-N 0.000 description 15
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 14
125000003118 aryl group Chemical group 0.000 description 14
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 14
229910052794 bromium Inorganic materials 0.000 description 14
239000003054 catalyst Substances 0.000 description 13
239000002904 solvent Substances 0.000 description 13
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
239000013543 active substance Substances 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
235000011121 sodium hydroxide Nutrition 0.000 description 12
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
WJAXXWSZNSFVNG-UHFFFAOYSA-N 2-bromoethanamine;hydron;bromide Chemical compound [Br-].[NH3+]CCBr WJAXXWSZNSFVNG-UHFFFAOYSA-N 0.000 description 11
238000001816 cooling Methods 0.000 description 11
150000002148 esters Chemical class 0.000 description 11
150000004820 halides Chemical class 0.000 description 11
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
229910000041 hydrogen chloride Inorganic materials 0.000 description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
239000003795 chemical substances by application Substances 0.000 description 10
239000011541 reaction mixture Substances 0.000 description 10
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 9
229920002472 Starch Polymers 0.000 description 9
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical group OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
229960000583 acetic acid Drugs 0.000 description 9
150000001718 carbodiimides Chemical class 0.000 description 9
229910052731 fluorine Inorganic materials 0.000 description 9
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 9
239000003826 tablet Substances 0.000 description 9
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 8
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
229910052783 alkali metal Inorganic materials 0.000 description 8
150000001412 amines Chemical class 0.000 description 8
239000002775 capsule Substances 0.000 description 8
239000000460 chlorine Substances 0.000 description 8
229910052801 chlorine Inorganic materials 0.000 description 8
239000003085 diluting agent Substances 0.000 description 8
239000011737 fluorine Substances 0.000 description 8
229910052500 inorganic mineral Inorganic materials 0.000 description 8
229910052943 magnesium sulfate Inorganic materials 0.000 description 8
235000019341 magnesium sulphate Nutrition 0.000 description 8
235000010755 mineral Nutrition 0.000 description 8
239000011707 mineral Substances 0.000 description 8
239000000454 talc Substances 0.000 description 8
229910052623 talc Inorganic materials 0.000 description 8
235000012222 talc Nutrition 0.000 description 8
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 7
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 7
239000002841 Lewis acid Substances 0.000 description 7
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 7
125000003277 amino group Chemical group 0.000 description 7
150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
238000010438 heat treatment Methods 0.000 description 7
150000002431 hydrogen Chemical class 0.000 description 7
239000011261 inert gas Substances 0.000 description 7
239000008101 lactose Substances 0.000 description 7
150000007517 lewis acids Chemical class 0.000 description 7
239000007788 liquid Substances 0.000 description 7
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
230000007935 neutral effect Effects 0.000 description 7
235000019698 starch Nutrition 0.000 description 7
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
150000008044 alkali metal hydroxides Chemical class 0.000 description 6
229910021529 ammonia Inorganic materials 0.000 description 6
239000012298 atmosphere Substances 0.000 description 6
125000003917 carbamoyl group Chemical class [H]N([H])C(*)=O 0.000 description 6
238000009833 condensation Methods 0.000 description 6
230000005494 condensation Effects 0.000 description 6
230000007062 hydrolysis Effects 0.000 description 6
238000006460 hydrolysis reaction Methods 0.000 description 6
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
239000000463 material Substances 0.000 description 6
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 6
229910052757 nitrogen Inorganic materials 0.000 description 6
239000012074 organic phase Substances 0.000 description 6
239000000825 pharmaceutical preparation Substances 0.000 description 6
229920001223 polyethylene glycol Polymers 0.000 description 6
229910000027 potassium carbonate Inorganic materials 0.000 description 6
238000002360 preparation method Methods 0.000 description 6
239000000047 product Substances 0.000 description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
238000001953 recrystallisation Methods 0.000 description 6
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 6
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 5
NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 5
108010010803 Gelatin Proteins 0.000 description 5
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 5
KLGZORFFBKAAHL-UHFFFAOYSA-N [1-(2-aminoethyl)piperidin-4-yl]-(4-fluorophenyl)methanone;hydrochloride Chemical compound Cl.C1CN(CCN)CCC1C(=O)C1=CC=C(F)C=C1 KLGZORFFBKAAHL-UHFFFAOYSA-N 0.000 description 5
150000001340 alkali metals Chemical class 0.000 description 5
150000004649 carbonic acid derivatives Chemical class 0.000 description 5
150000001735 carboxylic acids Chemical class 0.000 description 5
238000009903 catalytic hydrogenation reaction Methods 0.000 description 5
238000000354 decomposition reaction Methods 0.000 description 5
239000008273 gelatin Substances 0.000 description 5
229920000159 gelatin Polymers 0.000 description 5
235000019322 gelatine Nutrition 0.000 description 5
235000011852 gelatine desserts Nutrition 0.000 description 5
150000004678 hydrides Chemical class 0.000 description 5
238000005984 hydrogenation reaction Methods 0.000 description 5
235000019359 magnesium stearate Nutrition 0.000 description 5
239000012299 nitrogen atmosphere Substances 0.000 description 5
229910052700 potassium Inorganic materials 0.000 description 5
239000011591 potassium Substances 0.000 description 5
239000008107 starch Substances 0.000 description 5
238000006467 substitution reaction Methods 0.000 description 5
239000000725 suspension Substances 0.000 description 5
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 4
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 4
239000005977 Ethylene Substances 0.000 description 4
238000007126 N-alkylation reaction Methods 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
125000004423 acyloxy group Chemical group 0.000 description 4
150000001298 alcohols Chemical class 0.000 description 4
125000005194 alkoxycarbonyloxy group Chemical group 0.000 description 4
125000005907 alkyl ester group Chemical group 0.000 description 4
150000003863 ammonium salts Chemical class 0.000 description 4
150000001450 anions Chemical class 0.000 description 4
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
239000013078 crystal Substances 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
239000012954 diazonium Substances 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical group [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 4
239000008298 dragée Substances 0.000 description 4
230000032050 esterification Effects 0.000 description 4
238000005886 esterification reaction Methods 0.000 description 4
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 4
230000001747 exhibiting effect Effects 0.000 description 4
239000012458 free base Substances 0.000 description 4
239000008187 granular material Substances 0.000 description 4
238000007912 intraperitoneal administration Methods 0.000 description 4
229910052740 iodine Inorganic materials 0.000 description 4
239000011630 iodine Substances 0.000 description 4
229910052751 metal Inorganic materials 0.000 description 4
239000002184 metal Substances 0.000 description 4
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 4
230000003647 oxidation Effects 0.000 description 4
238000007254 oxidation reaction Methods 0.000 description 4
229910000073 phosphorus hydride Inorganic materials 0.000 description 4
125000006239 protecting group Chemical group 0.000 description 4
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 4
239000000126 substance Substances 0.000 description 4
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
GPRLGFOHIHVRSI-UHFFFAOYSA-N (2,2-dimethylaziridin-1-yl)-(4-fluorophenyl)methanone Chemical compound CC1(C)CN1C(=O)C1=CC=C(F)C=C1 GPRLGFOHIHVRSI-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 3
RHAUXFLTGFZBPF-UHFFFAOYSA-N 3-(aziridine-1-carbonyl)-4-methoxybenzonitrile Chemical compound COC1=CC=C(C#N)C=C1C(=O)N1CC1 RHAUXFLTGFZBPF-UHFFFAOYSA-N 0.000 description 3
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
BYESISJSHDVTPA-UHFFFAOYSA-N 5-cyano-2-methoxybenzoyl chloride Chemical compound COC1=CC=C(C#N)C=C1C(Cl)=O BYESISJSHDVTPA-UHFFFAOYSA-N 0.000 description 3
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
229920002261 Corn starch Polymers 0.000 description 3
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 3
239000002202 Polyethylene glycol Substances 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
241000700159 Rattus Species 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
235000021355 Stearic acid Nutrition 0.000 description 3
239000012445 acidic reagent Substances 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
125000002252 acyl group Chemical group 0.000 description 3
238000005917 acylation reaction Methods 0.000 description 3
150000003973 alkyl amines Chemical class 0.000 description 3
150000001350 alkyl halides Chemical class 0.000 description 3
150000001408 amides Chemical class 0.000 description 3
239000000908 ammonium hydroxide Substances 0.000 description 3
150000008064 anhydrides Chemical class 0.000 description 3
239000000164 antipsychotic agent Substances 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
239000011230 binding agent Substances 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
238000003776 cleavage reaction Methods 0.000 description 3
238000000576 coating method Methods 0.000 description 3
239000008120 corn starch Substances 0.000 description 3
NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 3
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 3
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 3
238000006266 etherification reaction Methods 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
239000007789 gas Substances 0.000 description 3
150000002391 heterocyclic compounds Chemical class 0.000 description 3
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
238000002955 isolation Methods 0.000 description 3
239000000314 lubricant Substances 0.000 description 3
229940098779 methanesulfonic acid Drugs 0.000 description 3
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 3
150000007522 mineralic acids Chemical class 0.000 description 3
AJUXDFHPVZQOGF-UHFFFAOYSA-N n,n-dimethyl-1-naphthylamine Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1 AJUXDFHPVZQOGF-UHFFFAOYSA-N 0.000 description 3
UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
150000007524 organic acids Chemical class 0.000 description 3
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 3
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 3
229910003446 platinum oxide Inorganic materials 0.000 description 3
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
239000000843 powder Substances 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
230000007017 scission Effects 0.000 description 3
FDNAPBUWERUEDA-UHFFFAOYSA-N silicon tetrachloride Chemical compound Cl[Si](Cl)(Cl)Cl FDNAPBUWERUEDA-UHFFFAOYSA-N 0.000 description 3
239000012279 sodium borohydride Substances 0.000 description 3
229910000033 sodium borohydride Inorganic materials 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
239000000600 sorbitol Substances 0.000 description 3
239000003381 stabilizer Substances 0.000 description 3
239000008117 stearic acid Substances 0.000 description 3
150000003626 triacylglycerols Chemical class 0.000 description 3
IYGWDOXHCPQXKN-UHFFFAOYSA-N (4-chlorophenyl)-piperidin-4-ylmethanone Chemical compound C1=CC(Cl)=CC=C1C(=O)C1CCNCC1 IYGWDOXHCPQXKN-UHFFFAOYSA-N 0.000 description 2
GPKDBZQZPNOBGM-UHFFFAOYSA-N (4-fluorophenyl)-piperidin-4-ylmethanone;hydron;chloride Chemical compound [Cl-].C1=CC(F)=CC=C1C(=O)C1CC[NH2+]CC1 GPKDBZQZPNOBGM-UHFFFAOYSA-N 0.000 description 2
UABFDXDSFKGWJM-UHFFFAOYSA-N 2-(2-methoxyphenyl)-4,5-dihydro-1,3-oxazole Chemical compound COC1=CC=CC=C1C1=NCCO1 UABFDXDSFKGWJM-UHFFFAOYSA-N 0.000 description 2
MSMHDJPCXSJKSY-UHFFFAOYSA-N 2-[4-(4-fluorobenzoyl)piperidin-1-yl]acetonitrile Chemical compound C1=CC(F)=CC=C1C(=O)C1CCN(CC#N)CC1 MSMHDJPCXSJKSY-UHFFFAOYSA-N 0.000 description 2
KEKXCNOFDWCQSJ-UHFFFAOYSA-N 2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]ethanamine;hydrochloride Chemical compound Cl.C1CN(CCN)CCC1CC1=CC=C(F)C=C1 KEKXCNOFDWCQSJ-UHFFFAOYSA-N 0.000 description 2
JGLJEWMZORMIDX-UHFFFAOYSA-N 3-(4,5-dihydro-1,3-oxazol-2-yl)-4-methoxy-n,n-dimethylbenzenesulfonamide Chemical compound COC1=CC=C(S(=O)(=O)N(C)C)C=C1C1=NCCO1 JGLJEWMZORMIDX-UHFFFAOYSA-N 0.000 description 2
KBYZFTMBSZCYGM-UHFFFAOYSA-N 4-chloro-5-cyano-2-methoxybenzoic acid Chemical compound COC1=CC(Cl)=C(C#N)C=C1C(O)=O KBYZFTMBSZCYGM-UHFFFAOYSA-N 0.000 description 2
LTVIGJUDBNCHPV-UHFFFAOYSA-N 4-chloro-5-cyano-n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-methoxybenzamide Chemical compound COC1=CC(Cl)=C(C#N)C=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 LTVIGJUDBNCHPV-UHFFFAOYSA-N 0.000 description 2
DLTGYPSSHXBNQG-UHFFFAOYSA-N 5-bromo-4-chloro-2-methoxybenzoic acid Chemical compound COC1=CC(Cl)=C(Br)C=C1C(O)=O DLTGYPSSHXBNQG-UHFFFAOYSA-N 0.000 description 2
YKMJSNNJDXFSEW-UHFFFAOYSA-N 5-bromo-4-chloro-2-methoxybenzoyl chloride Chemical group COC1=CC(Cl)=C(Br)C=C1C(Cl)=O YKMJSNNJDXFSEW-UHFFFAOYSA-N 0.000 description 2
YIMIWSDSUBSUSY-UHFFFAOYSA-N 5-bromo-n-(2-bromoethyl)-4-chloro-2-methoxybenzamide Chemical compound COC1=CC(Cl)=C(Br)C=C1C(=O)NCCBr YIMIWSDSUBSUSY-UHFFFAOYSA-N 0.000 description 2
MHQCWMUUWOKZJY-UHFFFAOYSA-N 5-bromo-n-(2-bromoethyl)-4-fluoro-2-methoxybenzamide Chemical compound COC1=CC(F)=C(Br)C=C1C(=O)NCCBr MHQCWMUUWOKZJY-UHFFFAOYSA-N 0.000 description 2
SPBDISKDQOUELJ-UHFFFAOYSA-N 5-cyano-n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-methoxybenzamide;hydrochloride Chemical compound Cl.COC1=CC=C(C#N)C=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 SPBDISKDQOUELJ-UHFFFAOYSA-N 0.000 description 2
229910015900 BF3 Inorganic materials 0.000 description 2
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 2
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 2
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
238000005727 Friedel-Crafts reaction Methods 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
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
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 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical group [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
230000006181 N-acylation Effects 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 2
ILUJQPXNXACGAN-UHFFFAOYSA-N O-methylsalicylic acid Chemical compound COC1=CC=CC=C1C(O)=O ILUJQPXNXACGAN-UHFFFAOYSA-N 0.000 description 2
KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
238000000297 Sandmeyer reaction Methods 0.000 description 2
BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
HRPNWDSBOOAPPG-UHFFFAOYSA-N [1-(2-aminoethyl)piperidin-4-yl]-(4-fluorophenyl)methanone;dihydrochloride Chemical compound Cl.Cl.C1CN(CCN)CCC1C(=O)C1=CC=C(F)C=C1 HRPNWDSBOOAPPG-UHFFFAOYSA-N 0.000 description 2
150000008065 acid anhydrides Chemical class 0.000 description 2
230000010933 acylation Effects 0.000 description 2
230000006978 adaptation Effects 0.000 description 2
125000004414 alkyl thio group Chemical group 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
125000004429 atom Chemical group 0.000 description 2
WJMOWGFGRONZPA-UHFFFAOYSA-N aziridin-1-yl-(4-fluorophenyl)methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1CC1 WJMOWGFGRONZPA-UHFFFAOYSA-N 0.000 description 2
150000008107 benzenesulfonic acids Chemical class 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 description 2
NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
238000009835 boiling Methods 0.000 description 2
GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
150000001805 chlorine compounds Chemical class 0.000 description 2
239000010949 copper Substances 0.000 description 2
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 2
239000012043 crude product Substances 0.000 description 2
239000012024 dehydrating agents‎ Substances 0.000 description 2
125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 2
150000001989 diazonium salts Chemical class 0.000 description 2
238000006193 diazotization reaction Methods 0.000 description 2
WFPZPJSADLPSON-UHFFFAOYSA-N dinitrogen tetraoxide Chemical compound [O-][N+](=O)[N+]([O-])=O WFPZPJSADLPSON-UHFFFAOYSA-N 0.000 description 2
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
FNODWEPAWIJGPM-UHFFFAOYSA-N ethyl 2-methoxybenzoate Chemical compound CCOC(=O)C1=CC=CC=C1OC FNODWEPAWIJGPM-UHFFFAOYSA-N 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
239000003925 fat Substances 0.000 description 2
239000000945 filler Substances 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
125000001153 fluoro group Chemical group F* 0.000 description 2
125000004997 halocarbonyl group Chemical group 0.000 description 2
230000002140 halogenating effect Effects 0.000 description 2
229930195733 hydrocarbon Natural products 0.000 description 2
150000002430 hydrocarbons Chemical class 0.000 description 2
229940071870 hydroiodic acid Drugs 0.000 description 2
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
125000003010 ionic group Chemical group 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
229910052744 lithium Inorganic materials 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
VPWFFXHRQFUOFL-UHFFFAOYSA-N n-(2-bromoethyl)-2-methoxy-5-sulfamoylbenzamide Chemical compound COC1=CC=C(S(N)(=O)=O)C=C1C(=O)NCCBr VPWFFXHRQFUOFL-UHFFFAOYSA-N 0.000 description 2
WSAMZZRCRBIXQN-UHFFFAOYSA-N n-(2-bromoethyl)-4-fluoro-2-methoxybenzamide Chemical compound COC1=CC(F)=CC=C1C(=O)NCCBr WSAMZZRCRBIXQN-UHFFFAOYSA-N 0.000 description 2
AJWXBCFNKBLFTQ-UHFFFAOYSA-N n-(2-bromoethyl)-5-cyano-2-methoxybenzamide Chemical compound COC1=CC=C(C#N)C=C1C(=O)NCCBr AJWXBCFNKBLFTQ-UHFFFAOYSA-N 0.000 description 2
BTXVRERBMIYNRF-UHFFFAOYSA-N n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2,6-dimethoxypyridine-3-carboxamide Chemical compound COC1=NC(OC)=CC=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 BTXVRERBMIYNRF-UHFFFAOYSA-N 0.000 description 2
229910017604 nitric acid Inorganic materials 0.000 description 2
239000003921 oil Substances 0.000 description 2
235000019198 oils Nutrition 0.000 description 2
239000003791 organic solvent mixture Substances 0.000 description 2
239000007800 oxidant agent Substances 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 2
229920001592 potato starch Polymers 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
230000000069 prophylactic effect Effects 0.000 description 2
229940001470 psychoactive drug Drugs 0.000 description 2
239000004089 psychotropic agent Substances 0.000 description 2
238000000746 purification Methods 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
229910000077 silane Inorganic materials 0.000 description 2
125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
159000000000 sodium salts Chemical class 0.000 description 2
239000007787 solid Substances 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
150000003460 sulfonic acids Chemical class 0.000 description 2
DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
230000001225 therapeutic effect Effects 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
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
HVLLSGMXQDNUAL-UHFFFAOYSA-N triphenyl phosphite Chemical compound C=1C=CC=CC=1OP(OC=1C=CC=CC=1)OC1=CC=CC=C1 HVLLSGMXQDNUAL-UHFFFAOYSA-N 0.000 description 2
229940100445 wheat starch Drugs 0.000 description 2
239000011592 zinc chloride Substances 0.000 description 2
235000005074 zinc chloride Nutrition 0.000 description 2
XIGPWKKSFLEKSM-UHFFFAOYSA-N (4-fluoropiperidin-1-yl)-phenylmethanone Chemical compound C1CC(F)CCN1C(=O)C1=CC=CC=C1 XIGPWKKSFLEKSM-UHFFFAOYSA-N 0.000 description 1
KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
XGINAUQXFXVBND-UHFFFAOYSA-N 1,2,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrimidine Chemical compound N1CC=CN2CCCC21 XGINAUQXFXVBND-UHFFFAOYSA-N 0.000 description 1
YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 1
DTLTUUJDCNTTSN-UHFFFAOYSA-N 1,4-dioxane;molecular bromine Chemical compound BrBr.C1COCCO1 DTLTUUJDCNTTSN-UHFFFAOYSA-N 0.000 description 1
125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 description 1
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
XYPISWUKQGWYGX-UHFFFAOYSA-N 2,2,2-trifluoroethaneperoxoic acid Chemical compound OOC(=O)C(F)(F)F XYPISWUKQGWYGX-UHFFFAOYSA-N 0.000 description 1
NJQJGRGGIUNVAB-UHFFFAOYSA-N 2,4,4,6-tetrabromocyclohexa-2,5-dien-1-one Chemical compound BrC1=CC(Br)(Br)C=C(Br)C1=O NJQJGRGGIUNVAB-UHFFFAOYSA-N 0.000 description 1
QDPPCXKAAZEBQO-UHFFFAOYSA-N 2-(2,6-dimethoxypyrimidin-4-yl)-4,5-dihydro-1,3-oxazole Chemical compound COC1=NC(OC)=CC(C=2OCCN=2)=N1 QDPPCXKAAZEBQO-UHFFFAOYSA-N 0.000 description 1
RTPGQSBRNXEZGV-UHFFFAOYSA-N 2-(3-bromo-4-methoxyphenyl)-4,5-dihydro-1,3-oxazole Chemical compound C1=C(Br)C(OC)=CC=C1C1=NCCO1 RTPGQSBRNXEZGV-UHFFFAOYSA-N 0.000 description 1
IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
PZKVXLLNZGVYAJ-UHFFFAOYSA-N 2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]acetonitrile;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1CC1CCN(CC#N)CC1 PZKVXLLNZGVYAJ-UHFFFAOYSA-N 0.000 description 1
RRKPMLZRLKTDQV-UHFFFAOYSA-N 2-bromo-4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1Br RRKPMLZRLKTDQV-UHFFFAOYSA-N 0.000 description 1
AXZRUTPBQMAWLP-UHFFFAOYSA-N 2-bromo-4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C(Br)=C1 AXZRUTPBQMAWLP-UHFFFAOYSA-N 0.000 description 1
MARXMDRWROUXMD-UHFFFAOYSA-N 2-bromoisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(Br)C(=O)C2=C1 MARXMDRWROUXMD-UHFFFAOYSA-N 0.000 description 1
NCDLFYLLYQXPCS-UHFFFAOYSA-N 2-chloro-1-methylpiperidine Chemical compound CN1CCCCC1Cl NCDLFYLLYQXPCS-UHFFFAOYSA-N 0.000 description 1
UNBTYFIWJDCOJU-UHFFFAOYSA-N 2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)-5-methoxy-n-methylaniline Chemical compound C1=C(Cl)C(NC)=CC(OC)=C1C1=NCCO1 UNBTYFIWJDCOJU-UHFFFAOYSA-N 0.000 description 1
VIHVLDUNSNGDLU-UHFFFAOYSA-N 2-methoxy-5-methylsulfanylbenzoyl chloride Chemical compound COC1=CC=C(SC)C=C1C(Cl)=O VIHVLDUNSNGDLU-UHFFFAOYSA-N 0.000 description 1
XQPPSAOBIFDIGU-UHFFFAOYSA-N 2-methoxy-5-methylsulfinylbenzoic acid Chemical compound COC1=CC=C(S(C)=O)C=C1C(O)=O XQPPSAOBIFDIGU-UHFFFAOYSA-N 0.000 description 1
RCFGFTLCCWRMTI-UHFFFAOYSA-N 2-methoxy-5-methylsulfonylbenzoyl chloride Chemical compound COC1=CC=C(S(C)(=O)=O)C=C1C(Cl)=O RCFGFTLCCWRMTI-UHFFFAOYSA-N 0.000 description 1
XFZMCFJADJFEBB-UHFFFAOYSA-N 2-methoxy-5-sulfamoylbenzoyl chloride Chemical compound COC1=CC=C(S(N)(=O)=O)C=C1C(Cl)=O XFZMCFJADJFEBB-UHFFFAOYSA-N 0.000 description 1
MNWSGMTUGXNYHJ-UHFFFAOYSA-N 2-methoxybenzamide Chemical compound COC1=CC=CC=C1C(N)=O MNWSGMTUGXNYHJ-UHFFFAOYSA-N 0.000 description 1
LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical compound NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 1
YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 description 1
BIFVRQZFKXPQCB-UHFFFAOYSA-N 3-(chloromethyl)-2,6-dimethoxypyridine Chemical compound COC1=CC=C(CCl)C(OC)=N1 BIFVRQZFKXPQCB-UHFFFAOYSA-N 0.000 description 1
XBGXGCOLWCMVOI-UHFFFAOYSA-N 3-(trifluoromethyl)benzamide Chemical compound NC(=O)C1=CC=CC(C(F)(F)F)=C1 XBGXGCOLWCMVOI-UHFFFAOYSA-N 0.000 description 1
ONELILMJNOWXSA-UHFFFAOYSA-N 3-bromo-4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C(Br)=C1 ONELILMJNOWXSA-UHFFFAOYSA-N 0.000 description 1
HPHZOCIBMCWXCQ-UHFFFAOYSA-N 3-bromo-4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1Br HPHZOCIBMCWXCQ-UHFFFAOYSA-N 0.000 description 1
BBPZABXVRBFWGD-UHFFFAOYSA-N 3-bromo-4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1Br BBPZABXVRBFWGD-UHFFFAOYSA-N 0.000 description 1
TZIZSHYTTRIQEU-UHFFFAOYSA-N 3-bromo-n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-4-methoxybenzamide;methanesulfonic acid Chemical compound CS(O)(=O)=O.C1=C(Br)C(OC)=CC=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 TZIZSHYTTRIQEU-UHFFFAOYSA-N 0.000 description 1
KWYCYTBGNRBJNO-UHFFFAOYSA-N 3-cyano-2-methoxybenzamide Chemical compound COC1=C(C(=O)N)C=CC=C1C#N KWYCYTBGNRBJNO-UHFFFAOYSA-N 0.000 description 1
KZJFPTMKPSNCDL-UHFFFAOYSA-N 3-cyano-4-methoxybenzoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1C#N KZJFPTMKPSNCDL-UHFFFAOYSA-N 0.000 description 1
KESAGUFJMGMNHP-UHFFFAOYSA-N 3-cyano-n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-4-methoxybenzamide;hydrochloride Chemical compound Cl.C1=C(C#N)C(OC)=CC=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 KESAGUFJMGMNHP-UHFFFAOYSA-N 0.000 description 1
RKGVNFPHEWAMEI-UHFFFAOYSA-N 3-fluoro-2-methoxybenzamide Chemical compound COC1=C(F)C=CC=C1C(N)=O RKGVNFPHEWAMEI-UHFFFAOYSA-N 0.000 description 1
MEOOXZGGYVXUSG-UHFFFAOYSA-N 3-fluoro-2-methoxybenzoic acid Chemical compound COC1=C(F)C=CC=C1C(O)=O MEOOXZGGYVXUSG-UHFFFAOYSA-N 0.000 description 1
PKLFZYXTNBIKKN-UHFFFAOYSA-N 3-n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-4-methoxybenzene-1,3-dicarboxamide;hydrochloride Chemical compound Cl.COC1=CC=C(C(N)=O)C=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 PKLFZYXTNBIKKN-UHFFFAOYSA-N 0.000 description 1
QGXQKGLWWDUOEY-UHFFFAOYSA-N 3-n-hydroxybicyclo[2.2.1]hept-5-ene-2,3-dicarboxamide Chemical compound C1C2C=CC1C(C(=O)N)C2C(=O)NO QGXQKGLWWDUOEY-UHFFFAOYSA-N 0.000 description 1
ROLMZTIHUMKEAI-UHFFFAOYSA-N 4,5-difluoro-2-hydroxybenzonitrile Chemical compound OC1=CC(F)=C(F)C=C1C#N ROLMZTIHUMKEAI-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
OJKWWANXBGLGQN-UHFFFAOYSA-N 4-[(4-fluorophenyl)methyl]piperidine;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1CC1CCNCC1 OJKWWANXBGLGQN-UHFFFAOYSA-N 0.000 description 1
UFEYMXHWIHFRBX-UHFFFAOYSA-N 4-chloro-2-methoxybenzoic acid Chemical compound COC1=CC(Cl)=CC=C1C(O)=O UFEYMXHWIHFRBX-UHFFFAOYSA-N 0.000 description 1
PSFBAEIWEFWPQA-UHFFFAOYSA-N 4-chloro-5-cyano-2-methoxybenzoyl chloride Chemical compound COC1=CC(Cl)=C(C#N)C=C1C(Cl)=O PSFBAEIWEFWPQA-UHFFFAOYSA-N 0.000 description 1
UBJDJZAFWVMMFA-UHFFFAOYSA-N 4-chloro-5-cyano-n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-methoxybenzamide;methanesulfonic acid Chemical compound CS(O)(=O)=O.COC1=CC(Cl)=C(C#N)C=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 UBJDJZAFWVMMFA-UHFFFAOYSA-N 0.000 description 1
UUQDNAPKWPKHMK-UHFFFAOYSA-N 4-fluoro-2-methoxybenzoic acid Chemical compound COC1=CC(F)=CC=C1C(O)=O UUQDNAPKWPKHMK-UHFFFAOYSA-N 0.000 description 1
KOHPYCKBINGPFW-UHFFFAOYSA-N 4-fluoro-2-methoxybenzoyl chloride Chemical compound COC1=CC(F)=CC=C1C(Cl)=O KOHPYCKBINGPFW-UHFFFAOYSA-N 0.000 description 1
GTVJBNYKJBCXEO-UHFFFAOYSA-N 4-fluoro-n-[2-[4-(thiophene-2-carbonyl)piperidin-1-yl]ethyl]benzamide;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1C(=O)NCCN1CCC(C(=O)C=2SC=CC=2)CC1 GTVJBNYKJBCXEO-UHFFFAOYSA-N 0.000 description 1
NRTZADONRRKSHX-UHFFFAOYSA-N 4-fluoro-n-[3-[4-(4-fluorobenzoyl)piperidin-1-yl]-2-methylpropyl]benzamide;hydrochloride Chemical compound Cl.C1CC(C(=O)C=2C=CC(F)=CC=2)CCN1CC(C)CNC(=O)C1=CC=C(F)C=C1 NRTZADONRRKSHX-UHFFFAOYSA-N 0.000 description 1
CZKLEJHVLCMVQR-UHFFFAOYSA-N 4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1 CZKLEJHVLCMVQR-UHFFFAOYSA-N 0.000 description 1
NQUVCRCCRXRJCK-UHFFFAOYSA-N 4-methylbenzoyl chloride Chemical compound CC1=CC=C(C(Cl)=O)C=C1 NQUVCRCCRXRJCK-UHFFFAOYSA-N 0.000 description 1
CNPSPVQFRPLAIK-UHFFFAOYSA-N 5-(aziridine-1-carbonyl)-2-methoxybenzonitrile Chemical compound C1=C(C#N)C(OC)=CC=C1C(=O)N1CC1 CNPSPVQFRPLAIK-UHFFFAOYSA-N 0.000 description 1
HJMBACRULXCTRQ-UHFFFAOYSA-N 5-(dimethylsulfamoyl)-2-methoxybenzoic acid Chemical compound COC1=CC=C(S(=O)(=O)N(C)C)C=C1C(O)=O HJMBACRULXCTRQ-UHFFFAOYSA-N 0.000 description 1
OQXNSLHCYIUEDO-UHFFFAOYSA-N 5-bromo-4-fluoro-2-methoxybenzoic acid Chemical compound COC1=CC(F)=C(Br)C=C1C(O)=O OQXNSLHCYIUEDO-UHFFFAOYSA-N 0.000 description 1
WXNOOZGCXYZWLB-UHFFFAOYSA-N 5-bromo-4-fluoro-2-methoxybenzoyl chloride Chemical compound COC1=CC(F)=C(Br)C=C1C(Cl)=O WXNOOZGCXYZWLB-UHFFFAOYSA-N 0.000 description 1
MFSNBQDZHAORBU-UHFFFAOYSA-N 5-chloro-n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-methoxy-4-(methylamino)benzamide Chemical compound C1=C(Cl)C(NC)=CC(OC)=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 MFSNBQDZHAORBU-UHFFFAOYSA-N 0.000 description 1
LBGOULWHGBIJBZ-UHFFFAOYSA-N 5-chloro-n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-methoxy-4-(methylamino)benzamide;hydrochloride Chemical compound Cl.C1=C(Cl)C(NC)=CC(OC)=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 LBGOULWHGBIJBZ-UHFFFAOYSA-N 0.000 description 1
XIHQLVNPKUKVGH-UHFFFAOYSA-N 5-cyano-n-[2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]ethyl]-2-methoxybenzamide;hydrochloride Chemical compound Cl.COC1=CC=C(C#N)C=C1C(=O)NCCN1CCC(CC=2C=CC(F)=CC=2)CC1 XIHQLVNPKUKVGH-UHFFFAOYSA-N 0.000 description 1
OGVFDBIHDFFEBW-UHFFFAOYSA-N 5-cyano-n-[3-[4-(4-fluorobenzoyl)piperidin-1-yl]propyl]-2-methoxybenzamide Chemical compound COC1=CC=C(C#N)C=C1C(=O)NCCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 OGVFDBIHDFFEBW-UHFFFAOYSA-N 0.000 description 1
244000215068 Acacia senegal Species 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
244000186140 Asperula odorata Species 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical group CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
108050004812 Dopamine receptor Proteins 0.000 description 1
102000015554 Dopamine receptor Human genes 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
LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
238000003547 Friedel-Crafts alkylation reaction Methods 0.000 description 1
235000008526 Galium odoratum Nutrition 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 1
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
YXLXNENXOJSQEI-UHFFFAOYSA-L Oxine-copper Chemical compound [Cu+2].C1=CN=C2C([O-])=CC=CC2=C1.C1=CN=C2C([O-])=CC=CC2=C1 YXLXNENXOJSQEI-UHFFFAOYSA-L 0.000 description 1
239000005662 Paraffin oil Substances 0.000 description 1
GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
208000028017 Psychotic disease Diseases 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
238000006350 Schiemann fluorination reaction Methods 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-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
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
239000004902 Softening Agent Substances 0.000 description 1
206010042008 Stereotypy Diseases 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
SMEGJBVQLJJKKX-HOTMZDKISA-N [(2R,3S,4S,5R,6R)-5-acetyloxy-3,4,6-trihydroxyoxan-2-yl]methyl acetate Chemical compound CC(=O)OC[C@@H]1[C@H]([C@@H]([C@H]([C@@H](O1)O)OC(=O)C)O)O SMEGJBVQLJJKKX-HOTMZDKISA-N 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
239000000205 acacia gum Substances 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
229940081735 acetylcellulose Drugs 0.000 description 1
231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
238000011047 acute toxicity test Methods 0.000 description 1
239000003463 adsorbent Substances 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
HAXFWIACAGNFHA-UHFFFAOYSA-N aldrithiol Chemical compound C=1C=CC=NC=1SSC1=CC=CC=N1 HAXFWIACAGNFHA-UHFFFAOYSA-N 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
150000001335 aliphatic alkanes Chemical class 0.000 description 1
229910001854 alkali hydroxide Inorganic materials 0.000 description 1
229910001508 alkali metal halide Inorganic materials 0.000 description 1
150000008045 alkali metal halides Chemical class 0.000 description 1
229910000102 alkali metal hydride Inorganic materials 0.000 description 1
150000008046 alkali metal hydrides Chemical class 0.000 description 1
229910000272 alkali metal oxide Inorganic materials 0.000 description 1
229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
125000003342 alkenyl group Chemical group 0.000 description 1
230000009435 amidation Effects 0.000 description 1
238000007112 amidation reaction Methods 0.000 description 1
229940025084 amphetamine Drugs 0.000 description 1
230000003042 antagnostic effect Effects 0.000 description 1
FAPDDOBMIUGHIN-UHFFFAOYSA-K antimony trichloride Chemical compound Cl[Sb](Cl)Cl FAPDDOBMIUGHIN-UHFFFAOYSA-K 0.000 description 1
229940005529 antipsychotics Drugs 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
125000005333 aroyloxy group Chemical group 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
JWCRKKRGKXHPQO-UHFFFAOYSA-N aziridin-1-yl-(5-bromo-2-methoxyphenyl)methanone Chemical compound COC1=CC=C(Br)C=C1C(=O)N1CC1 JWCRKKRGKXHPQO-UHFFFAOYSA-N 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class 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
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
239000000920 calcium hydroxide Substances 0.000 description 1
229910001861 calcium hydroxide Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
235000013539 calcium stearate Nutrition 0.000 description 1
239000008116 calcium stearate Substances 0.000 description 1
229910000394 calcium triphosphate Inorganic materials 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
150000001728 carbonyl compounds Chemical group 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
239000012876 carrier material Substances 0.000 description 1
229920002301 cellulose acetate Polymers 0.000 description 1
KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
230000001055 chewing effect Effects 0.000 description 1
238000005660 chlorination reaction Methods 0.000 description 1
NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 description 1
AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 1
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
229940075614 colloidal silicon dioxide Drugs 0.000 description 1
239000000084 colloidal system Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
150000001879 copper Chemical class 0.000 description 1
150000003983 crown ethers Chemical class 0.000 description 1
YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical compound CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 description 1
230000034994 death Effects 0.000 description 1
231100000517 death Toxicity 0.000 description 1
238000005661 deetherification reaction Methods 0.000 description 1
239000008367 deionised water Substances 0.000 description 1
229910021641 deionized water Inorganic materials 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
235000019700 dicalcium phosphate Nutrition 0.000 description 1
150000001991 dicarboxylic acids Chemical class 0.000 description 1
SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 1
FDSGHYHRLSWSLQ-UHFFFAOYSA-N dichloromethane;propan-2-one Chemical compound ClCCl.CC(C)=O FDSGHYHRLSWSLQ-UHFFFAOYSA-N 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
QUNALZGLMQIJHN-UHFFFAOYSA-N diethylphosphorylcyanamide Chemical compound CCP(=O)(CC)NC#N QUNALZGLMQIJHN-UHFFFAOYSA-N 0.000 description 1
229910001873 dinitrogen Inorganic materials 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
239000007884 disintegrant Substances 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000012374 esterification agent Substances 0.000 description 1
PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
KCCLMESCYFWIGA-UHFFFAOYSA-N ethyl 3-cyano-2-methoxybenzoate Chemical compound CCOC(=O)C1=CC=CC(C#N)=C1OC KCCLMESCYFWIGA-UHFFFAOYSA-N 0.000 description 1
QFTBGVQIVQMULK-UHFFFAOYSA-N ethyl 4-chloro-5-cyano-2-methoxybenzoate Chemical compound CCOC(=O)C1=CC(C#N)=C(Cl)C=C1OC QFTBGVQIVQMULK-UHFFFAOYSA-N 0.000 description 1
MGWGUIKIDQGYJO-UHFFFAOYSA-N ethyl 5-bromo-4-chloro-2-methoxybenzoate Chemical compound CCOC(=O)C1=CC(Br)=C(Cl)C=C1OC MGWGUIKIDQGYJO-UHFFFAOYSA-N 0.000 description 1
229960003750 ethyl chloride Drugs 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
229940093471 ethyl oleate Drugs 0.000 description 1
WMYNMYVRWWCRPS-UHFFFAOYSA-N ethynoxyethane Chemical group CCOC#C WMYNMYVRWWCRPS-UHFFFAOYSA-N 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
125000001207 fluorophenyl group Chemical group 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
238000004508 fractional distillation Methods 0.000 description 1
238000007710 freezing Methods 0.000 description 1
230000008014 freezing Effects 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000005446 heptyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
210000001320 hippocampus Anatomy 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
150000002440 hydroxy compounds Chemical class 0.000 description 1
JGJLWPGRMCADHB-UHFFFAOYSA-N hypobromite Inorganic materials Br[O-] JGJLWPGRMCADHB-UHFFFAOYSA-N 0.000 description 1
CUILPNURFADTPE-UHFFFAOYSA-N hypobromous acid Chemical compound BrO CUILPNURFADTPE-UHFFFAOYSA-N 0.000 description 1
239000005457 ice water Substances 0.000 description 1
150000002460 imidazoles Chemical class 0.000 description 1
JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
150000004966 inorganic peroxy acids Chemical class 0.000 description 1
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
FBAFATDZDUQKNH-UHFFFAOYSA-M iron chloride Chemical compound [Cl-].[Fe] FBAFATDZDUQKNH-UHFFFAOYSA-M 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000004922 lacquer Substances 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
229910052749 magnesium Inorganic materials 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
235000010355 mannitol Nutrition 0.000 description 1
229910052987 metal hydride Inorganic materials 0.000 description 1
150000004681 metal hydrides Chemical class 0.000 description 1
229910000000 metal hydroxide Inorganic materials 0.000 description 1
150000004692 metal hydroxides Chemical class 0.000 description 1
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
MNDFXDXRMYURMC-UHFFFAOYSA-N methyl 3-carbamoylbenzoate Chemical compound COC(=O)C1=CC=CC(C(N)=O)=C1 MNDFXDXRMYURMC-UHFFFAOYSA-N 0.000 description 1
VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical group COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 1
229940102396 methyl bromide Drugs 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
MBABOKRGFJTBAE-UHFFFAOYSA-N methyl methanesulfonate Chemical compound COS(C)(=O)=O MBABOKRGFJTBAE-UHFFFAOYSA-N 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
244000005700 microbiome Species 0.000 description 1
238000002156 mixing Methods 0.000 description 1
229910052750 molybdenum Inorganic materials 0.000 description 1
239000011733 molybdenum Substances 0.000 description 1
UHAAFJWANJYDIS-UHFFFAOYSA-N n,n'-diethylmethanediimine Chemical compound CCN=C=NCC UHAAFJWANJYDIS-UHFFFAOYSA-N 0.000 description 1
CFKVVQJIHBHPQC-UHFFFAOYSA-N n-(2-bromoethyl)-2-methoxy-5-(trifluoromethyl)benzamide Chemical compound COC1=CC=C(C(F)(F)F)C=C1C(=O)NCCBr CFKVVQJIHBHPQC-UHFFFAOYSA-N 0.000 description 1
USSCXDBIFDPAHR-UHFFFAOYSA-N n-(2-bromoethyl)-4-fluorobenzamide Chemical compound FC1=CC=C(C(=O)NCCBr)C=C1 USSCXDBIFDPAHR-UHFFFAOYSA-N 0.000 description 1
JWDAZJGCVQCSRD-UHFFFAOYSA-N n-(3-chloropropyl)-5-cyano-2-methoxybenzamide Chemical compound COC1=CC=C(C#N)C=C1C(=O)NCCCCl JWDAZJGCVQCSRD-UHFFFAOYSA-N 0.000 description 1
YPRSLNMANLEHPJ-UHFFFAOYSA-N n-[2-[4-(4-chlorobenzoyl)piperidin-1-yl]ethyl]-4-fluorobenzamide;methanesulfonic acid Chemical compound CS(O)(=O)=O.C1=CC(F)=CC=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(Cl)=CC=2)CC1 YPRSLNMANLEHPJ-UHFFFAOYSA-N 0.000 description 1
GREJOAOEUDOVLN-UHFFFAOYSA-N n-[2-[4-(4-chlorobenzoyl)piperidin-1-yl]ethyl]-5-cyano-2-methoxybenzamide;methanesulfonic acid Chemical compound CS(O)(=O)=O.COC1=CC=C(C#N)C=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(Cl)=CC=2)CC1 GREJOAOEUDOVLN-UHFFFAOYSA-N 0.000 description 1
JENHLCXFTWKWBT-UHFFFAOYSA-N n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2,6-dimethoxybenzamide;hydrochloride Chemical compound Cl.COC1=CC=CC(OC)=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 JENHLCXFTWKWBT-UHFFFAOYSA-N 0.000 description 1
FYNMPZRSPFKECC-UHFFFAOYSA-N n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-methoxy-5-(trifluoromethyl)benzamide;hydrochloride Chemical compound Cl.COC1=CC=C(C(F)(F)F)C=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 FYNMPZRSPFKECC-UHFFFAOYSA-N 0.000 description 1
VZMKRPSYXQJBHX-UHFFFAOYSA-N n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-methoxy-5-methylsulfanylbenzamide;hydrochloride Chemical compound Cl.COC1=CC=C(SC)C=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 VZMKRPSYXQJBHX-UHFFFAOYSA-N 0.000 description 1
HRYGIOAFOZWXKH-UHFFFAOYSA-N n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-methoxy-5-methylsulfinylbenzamide Chemical compound COC1=CC=C(S(C)=O)C=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 HRYGIOAFOZWXKH-UHFFFAOYSA-N 0.000 description 1
HLCMRXKTEKTMKP-UHFFFAOYSA-N n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-methoxy-5-methylsulfinylbenzamide;hydrochloride Chemical compound Cl.COC1=CC=C(S(C)=O)C=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 HLCMRXKTEKTMKP-UHFFFAOYSA-N 0.000 description 1
GZSVCPLRLFNQGJ-UHFFFAOYSA-N n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-methoxy-5-methylsulfonylbenzamide;hydrochloride Chemical compound Cl.COC1=CC=C(S(C)(=O)=O)C=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 GZSVCPLRLFNQGJ-UHFFFAOYSA-N 0.000 description 1
ZNSJDGINLCMMHM-UHFFFAOYSA-N n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-methoxybenzamide;hydrochloride Chemical compound Cl.COC1=CC=CC=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 ZNSJDGINLCMMHM-UHFFFAOYSA-N 0.000 description 1
VBTQNRFWXBXZQR-UHFFFAOYSA-N n-bromoacetamide Chemical compound CC(=O)NBr VBTQNRFWXBXZQR-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
229910000510 noble metal Inorganic materials 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000005526 organic bromine compounds Chemical class 0.000 description 1
150000004967 organic peroxy acids Chemical class 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
RFWLACFDYFIVMC-UHFFFAOYSA-D pentacalcium;[oxido(phosphonatooxy)phosphoryl] phosphate Chemical compound [Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O.[O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O RFWLACFDYFIVMC-UHFFFAOYSA-D 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
230000000737 periodic effect Effects 0.000 description 1
150000004965 peroxy acids Chemical class 0.000 description 1
150000004968 peroxymonosulfuric acids Chemical class 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
150000003003 phosphines Chemical class 0.000 description 1
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 1
239000000049 pigment Substances 0.000 description 1
QBJGQECJNLNPLJ-UHFFFAOYSA-N piperidin-4-yl(thiophen-2-yl)methanone Chemical compound C=1C=CSC=1C(=O)C1CCNCC1 QBJGQECJNLNPLJ-UHFFFAOYSA-N 0.000 description 1
229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
238000012545 processing Methods 0.000 description 1
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
238000011160 research Methods 0.000 description 1
229940100486 rice starch Drugs 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
229910052710 silicon Inorganic materials 0.000 description 1
239000010703 silicon Substances 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
239000010802 sludge Substances 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000004317 sodium nitrate Substances 0.000 description 1
235000010344 sodium nitrate Nutrition 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
239000012265 solid product Substances 0.000 description 1
238000003797 solvolysis reaction Methods 0.000 description 1
241000894007 species Species 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
238000009495 sugar coating Methods 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
150000003457 sulfones Chemical class 0.000 description 1
150000003459 sulfonic acid esters Chemical class 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000002511 suppository base Substances 0.000 description 1
239000013076 target substance Substances 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 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
238000012360 testing method Methods 0.000 description 1
238000005979 thermal decomposition reaction Methods 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
238000012546 transfer Methods 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
150000003624 transition metals Chemical class 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
ZDHXKXAHOVTTAH-UHFFFAOYSA-N trichlorosilane Chemical compound Cl[SiH](Cl)Cl ZDHXKXAHOVTTAH-UHFFFAOYSA-N 0.000 description 1
239000005052 trichlorosilane Substances 0.000 description 1
125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
229910052721 tungsten Inorganic materials 0.000 description 1
239000010937 tungsten Substances 0.000 description 1
229910052720 vanadium Inorganic materials 0.000 description 1
GPPXJZIENCGNKB-UHFFFAOYSA-N vanadium Chemical compound [V]#[V] GPPXJZIENCGNKB-UHFFFAOYSA-N 0.000 description 1
229920001567 vinyl ester resin Polymers 0.000 description 1
238000005303 weighing Methods 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Landscapes

Pyridine Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Hydrogenated Pyridines (AREA)

JP4422084A 1983-03-09 1984-03-09 Ｎ―（ピペリジニル―アルキル）―カルボキサミド類およびそれを含む向精神病薬 Granted JPS59186959A (ja)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
CH125883		1983-03-09
CH1258/83-4		1983-03-09
CH3925/83-5		1983-07-18

Publications (2)

Publication Number	Publication Date
JPS59186959A JPS59186959A (ja)	1984-10-23
JPH0556345B2 true JPH0556345B2 (da)	1993-08-19

Family

ID=4206177

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP4422084A Granted JPS59186959A (ja)	1983-03-09	1984-03-09	Ｎ―（ピペリジニル―アルキル）―カルボキサミド類およびそれを含む向精神病薬

Country Status (3)

Country	Link
JP (1)	JPS59186959A (da)
AR (1)	AR242025A1 (da)
ZA (1)	ZA841728B (da)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6770659B2 (en) *	2002-08-26	2004-08-03	Sk Corporation	Benzoyl piperidine compounds

Citations (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS5223080A (en) *	1975-08-13	1977-02-21	Janssen Pharmaceutica Nv	New nn*11piperidinylalkyl* aryl carboxysamide derivative
US4110449A (en) *	1977-05-23	1978-08-29	E. R. Squibb & Sons, Inc.	2-substituted benzisothiazol-3-ones
JPS55105679A (en) *	1979-01-08	1980-08-13	Janssen Pharmaceutica Nv	Novel piperidinylalkylquinazoline derivative
JPS5890552A (ja) *	1981-10-01	1983-05-30	ジヤンセン・フア−マシユ−チカ・ナ−ムロ−ゼ・フエンノ−トシヤツプ	新規なｎ−（３−ヒドロキシ−４−ピペリジニル）ベンズアミド誘導体

1984
- 1984-03-08 ZA ZA841728A patent/ZA841728B/xx unknown
- 1984-03-09 JP JP4422084A patent/JPS59186959A/ja active Granted
1986
- 1986-08-08 AR AR30484786A patent/AR242025A1/es active

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS5223080A (en) *	1975-08-13	1977-02-21	Janssen Pharmaceutica Nv	New nn*11piperidinylalkyl* aryl carboxysamide derivative
US4110449A (en) *	1977-05-23	1978-08-29	E. R. Squibb & Sons, Inc.	2-substituted benzisothiazol-3-ones
JPS55105679A (en) *	1979-01-08	1980-08-13	Janssen Pharmaceutica Nv	Novel piperidinylalkylquinazoline derivative
JPS5890552A (ja) *	1981-10-01	1983-05-30	ジヤンセン・フア−マシユ−チカ・ナ−ムロ−ゼ・フエンノ−トシヤツプ	新規なｎ−（３−ヒドロキシ−４−ピペリジニル）ベンズアミド誘導体

Also Published As

Publication number	Publication date
ZA841728B (en)	1984-11-28
JPS59186959A (ja)	1984-10-23
AR242025A1 (es)	1993-02-26

Publication	Publication Date	Title
US4140789A (en)	1979-02-20	Etherified hydroxy-benzodiheterocyclic compounds
US5395839A (en)	1995-03-07	Imidazopyridine derivatives and their use
US4559349A (en)	1985-12-17	Carboxamides
EP0912550A1 (en)	1999-05-06	Sulfonamide derivatives as 5ht7 receptor antagonists
WO1998050346A2 (en)	1998-11-12	Acetamide and urea derivatives, process for their preparation and their use in the treatment of cns disorders
JPS59507B2 (ja)	1984-01-07	新規な複素環式化合物の製造方法
PL119641B1 (en)	1982-01-30	Process for preparing novel,condensed derivatives of pyrimidine pirimidina
US4377576A (en)	1983-03-22	5-(Heterocyclic amino-propionyl)-5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-ones
WO2002042293A1 (en)	2002-05-30	Isoquinoline derivatives useful in the treatment of cns disorders
EP0597112A1 (en)	1994-05-18	Novel imidazole derivative, pharmaceutical use thereof, and intermediate therefor
JPH02138266A (ja)	1990-05-28	６‐フェニル‐３‐（ピペラジニルアルキル）‐２，４（１ｈ，３ｈ）‐ピリミジンジオン誘導体
HU202508B (en)	1991-03-28	Process for producing new 1,4-disubstituted piperazine derivatives and pharmaceutical compositions containing them as active components
EP0015615B1 (en)	1983-01-12	Phenyl piperazine derivatives, their preparation and antiagressive medicines containing them
US4325953A (en)	1982-04-20	4-Aryl-4-aryloxypiperidines
JPS6047255B2 (ja)	1985-10-21	２−アミノ−５−スルフアモイル−安息香酸アミドの製法
US4505913A (en)	1985-03-19	Substituted anthranilamides and pharmaceutical preparations containing these compounds
BG63336B1 (bg)	2001-10-31	Нови производни на хидроксамови киселини, фармацевтични състави на тяхна основа и метод за получаването им
JPH0556345B2 (da)	1993-08-19
JPH01151561A (ja)	1989-06-14	フタラジン化合物、その製造方法、ならびにこの化合物を含有する心血管疾患および腫瘍の治療剤
JPS6126992B2 (da)	1986-06-23
JPH11508588A (ja)	1999-07-27	キナゾリン誘導体
US3511839A (en)	1970-05-12	Substituted benzoic acid esters of certain dibenz(b,f)azepine derivatives
JP2781277B2 (ja)	1998-07-30	ベンズアゼピン誘導体及びその医薬組成物並びに中間体
JP2003507463A (ja)	2003-02-25	置換ピペラジン誘導体、その調製及びその薬物としての使用
JPS62292763A (ja)	1987-12-19	アルアルキルイミダゾ−ル誘導体