IL91194A - 3-piperazinylbenzazole derivatives, their preparation and pharmaceutical compositions containing them - Google Patents

3-piperazinylbenzazole derivatives, their preparation and pharmaceutical compositions containing them

Info

Publication number: IL91194A
Authority: IL; Israel
Prior art keywords: formula; hydrogen; 6alkyl; parts; alk
Prior art date: 1988-08-05

Application number

IL9119489A

Other languages

English (en)

Other versions

IL91194A0 (en

Original Assignee

Janssen Pharmaceutica Nv

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.)

1988-08-05

Filing date

1989-08-03

Publication date

1994-04-12

1989-08-03 Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv

1989-08-03 Priority to IL10559489A priority Critical patent/IL105594A/en

1990-03-19 Publication of IL91194A0 publication Critical patent/IL91194A0/xx

1993-05-04 Priority to IL105594A priority patent/IL105594A0/xx

1994-04-12 Publication of IL91194A publication Critical patent/IL91194A/en

Links

239000008194 pharmaceutical composition Substances 0.000 title abstract description 8
238000002360 preparation method Methods 0.000 title description 18
VASVHOLFOSSBKT-UHFFFAOYSA-N 3-piperazin-1-yl-1h-indole Chemical class C1CNCCN1C1=CNC2=CC=CC=C12 VASVHOLFOSSBKT-UHFFFAOYSA-N 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 89
239000001257 hydrogen Substances 0.000 claims abstract description 42
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 42
238000000034 method Methods 0.000 claims abstract description 25
239000002253 acid Substances 0.000 claims abstract description 21
150000003839 salts Chemical class 0.000 claims abstract description 18
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 17
229910052760 oxygen Inorganic materials 0.000 claims abstract description 15
229910052717 sulfur Inorganic materials 0.000 claims abstract description 7
239000004480 active ingredient Substances 0.000 claims abstract description 5
239000000203 mixture Substances 0.000 claims description 56
-1 cyano, hydroxy Chemical group 0.000 claims description 37
125000005843 halogen group Chemical group 0.000 claims description 20
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
239000002585 base Substances 0.000 claims description 17
239000003153 chemical reaction reagent Substances 0.000 claims description 17
150000002431 hydrogen Chemical class 0.000 claims description 16
238000003756 stirring Methods 0.000 claims description 14
125000003118 aryl group Chemical group 0.000 claims description 11
241001465754 Metazoa Species 0.000 claims description 10
239000012442 inert solvent Substances 0.000 claims description 9
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
239000001301 oxygen Substances 0.000 claims description 7
239000003513 alkali Substances 0.000 claims description 6
230000002152 alkylating effect Effects 0.000 claims description 6
208000028017 Psychotic disease Diseases 0.000 claims description 5
230000000561 anti-psychotic effect Effects 0.000 claims description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 4
125000001153 fluoro group Chemical group F* 0.000 claims description 4
229910001516 alkali metal iodide Inorganic materials 0.000 claims description 3
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 3
239000003960 organic solvent Substances 0.000 claims description 3
125000001424 substituent group Chemical group 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
239000012458 free base Substances 0.000 claims description 2
231100000252 nontoxic Toxicity 0.000 claims description 2
230000003000 nontoxic effect Effects 0.000 claims description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
150000004885 piperazines Chemical class 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
125000004356 hydroxy functional group Chemical group O* 0.000 abstract description 7
239000000164 antipsychotic agent Substances 0.000 abstract description 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 2
125000001475 halogen functional group Chemical group 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
239000000243 solution Substances 0.000 description 31
239000000543 intermediate Substances 0.000 description 29
239000003480 eluent Substances 0.000 description 26
239000011541 reaction mixture Substances 0.000 description 24
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
229960001701 chloroform Drugs 0.000 description 22
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
150000003254 radicals Chemical group 0.000 description 20
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
239000000047 product Substances 0.000 description 18
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
238000010992 reflux Methods 0.000 description 16
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
238000006243 chemical reaction Methods 0.000 description 15
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 14
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
239000000741 silica gel Substances 0.000 description 14
229910002027 silica gel Inorganic materials 0.000 description 14
238000004440 column chromatography Methods 0.000 description 13
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
238000007363 ring formation reaction Methods 0.000 description 11
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
238000001816 cooling Methods 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 9
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 9
229960004046 apomorphine Drugs 0.000 description 9
239000000706 filtrate Substances 0.000 description 9
APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 9
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 8
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
239000000284 extract Substances 0.000 description 8
239000002904 solvent Substances 0.000 description 8
239000003826 tablet Substances 0.000 description 8
SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
150000001412 amines Chemical class 0.000 description 7
229960002748 norepinephrine Drugs 0.000 description 7
SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 7
229910000029 sodium carbonate Inorganic materials 0.000 description 7
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
150000004945 aromatic hydrocarbons Chemical class 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical class O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 5
125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 5
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
239000000010 aprotic solvent Substances 0.000 description 5
125000001309 chloro group Chemical group Cl* 0.000 description 5
229960004592 isopropanol Drugs 0.000 description 5
229910052751 metal Inorganic materials 0.000 description 5
239000002184 metal Substances 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
239000002202 Polyethylene glycol Substances 0.000 description 4
241000700159 Rattus Species 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
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 4
150000007513 acids Chemical class 0.000 description 4
125000001246 bromo group Chemical group Br* 0.000 description 4
239000002775 capsule Substances 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
239000003937 drug carrier Substances 0.000 description 4
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
239000010410 layer Substances 0.000 description 4
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
150000002923 oximes Chemical class 0.000 description 4
229920001223 polyethylene glycol Polymers 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 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
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
239000000725 suspension Substances 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
WCGPCBACLBHDCI-UHFFFAOYSA-N 2,4-difluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C(F)=C1 WCGPCBACLBHDCI-UHFFFAOYSA-N 0.000 description 3
HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
239000000654 additive Substances 0.000 description 3
239000000908 ammonium hydroxide Substances 0.000 description 3
230000037396 body weight Effects 0.000 description 3
238000009835 boiling Methods 0.000 description 3
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
239000000843 powder Substances 0.000 description 3
239000000376 reactant Substances 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
239000012453 solvate Substances 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
239000012258 stirred mixture Substances 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 2
XRDTZJLJRAPNJG-UHFFFAOYSA-N 3-(4-benzylpiperazin-1-yl)-6-fluoro-1h-indazole Chemical compound N=1NC2=CC(F)=CC=C2C=1N(CC1)CCN1CC1=CC=CC=C1 XRDTZJLJRAPNJG-UHFFFAOYSA-N 0.000 description 2
OMQHDIHZSDEIFH-UHFFFAOYSA-N 3-Acetyldihydro-2(3H)-furanone Chemical compound CC(=O)C1CCOC1=O OMQHDIHZSDEIFH-UHFFFAOYSA-N 0.000 description 2
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
241000282472 Canis lupus familiaris Species 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
206010010904 Convulsion Diseases 0.000 description 2
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
206010020565 Hyperaemia Diseases 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
238000007126 N-alkylation reaction Methods 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
125000001931 aliphatic group Chemical group 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
150000001340 alkali metals Chemical class 0.000 description 2
150000004703 alkoxides Chemical class 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
230000000202 analgesic effect Effects 0.000 description 2
239000005557 antagonist Substances 0.000 description 2
229940082988 antihypertensives serotonin antagonists Drugs 0.000 description 2
239000003420 antiserotonin agent Substances 0.000 description 2
125000004104 aryloxy group Chemical group 0.000 description 2
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 2
150000004649 carbonic acid derivatives Chemical class 0.000 description 2
239000000969 carrier Substances 0.000 description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical group [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 2
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
239000003210 dopamine receptor blocking agent Substances 0.000 description 2
239000003814 drug Substances 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 2
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
VGJWQSVKJUBBRX-UHFFFAOYSA-N ethyl 4-(1,2-benzothiazol-3-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1C1=NSC2=CC=CC=C12 VGJWQSVKJUBBRX-UHFFFAOYSA-N 0.000 description 2
230000002496 gastric effect Effects 0.000 description 2
239000008103 glucose Substances 0.000 description 2
235000011187 glycerol Nutrition 0.000 description 2
230000002140 halogenating effect Effects 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
150000004678 hydrides Chemical class 0.000 description 2
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
229910000041 hydrogen chloride Inorganic materials 0.000 description 2
125000001841 imino group Chemical group [H]N=* 0.000 description 2
125000002346 iodo group Chemical group I* 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
235000014655 lactic acid Nutrition 0.000 description 2
239000008101 lactose Substances 0.000 description 2
239000007788 liquid Substances 0.000 description 2
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
230000000701 neuroleptic effect Effects 0.000 description 2
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
239000003921 oil Substances 0.000 description 2
235000019198 oils Nutrition 0.000 description 2
229940100688 oral solution Drugs 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
239000006187 pill Substances 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
229960003415 propylparaben Drugs 0.000 description 2
239000008213 purified water Substances 0.000 description 2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Thiazole And Isothizaole Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Hydrogenated Pyridines (AREA)

IL9119489A 1988-08-05 1989-08-03 3-piperazinylbenzazole derivatives, their preparation and pharmaceutical compositions containing them IL91194A (en)

Priority Applications (2)

Application Number	Priority Date	Filing Date	Title
IL10559489A IL105594A (en)	1988-08-05	1989-08-03	History of 3-piperazinylbenzperazole
IL105594A IL105594A0 (en)	1988-08-05	1993-05-04	3-piperazinyl-benzpyrazole derivatives

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US22841788A	1988-08-05	1988-08-05

Publications (2)

Publication Number	Publication Date
IL91194A0 IL91194A0 (en)	1990-03-19
IL91194A true IL91194A (en)	1994-04-12

Family

ID=22857091

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL9119489A IL91194A (en)	1988-08-05	1989-08-03	3-piperazinylbenzazole derivatives, their preparation and pharmaceutical compositions containing them

Country Status (20)

Country	Link
EP (1)	EP0353821B1 (de)
JP (1)	JP2779216B2 (de)
KR (1)	KR0145706B1 (de)
CN (1)	CN1023602C (de)
AT (1)	ATE122348T1 (de)
AU (1)	AU619877B2 (de)
CA (1)	CA1331609C (de)
DE (1)	DE68922537T2 (de)
DK (1)	DK175124B1 (de)
ES (1)	ES2074462T3 (de)
FI (1)	FI90238C (de)
HU (1)	HU206341B (de)
IE (1)	IE66198B1 (de)
IL (1)	IL91194A (de)
NO (1)	NO176051C (de)
NZ (1)	NZ230045A (de)
PH (1)	PH26550A (de)
PT (1)	PT91364B (de)
SU (1)	SU1687030A3 (de)
ZA (1)	ZA895978B (de)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5364866A (en)	1989-05-19	1994-11-15	Hoechst-Roussel Pharmaceuticals, Inc.	Heteroarylpiperidines, pyrrolidines and piperazines and their use as antipsychotics and analetics
US5561128A (en) *	1989-05-19	1996-10-01	Hoechst-Roussel Pharmaceuticals, Inc.	N-[(4-(heteroaryl)-1-piperidinyl)alkyl]-10,11-dihydro-5H-dibenz[B,F]azepines and related compounds and their therapeutic utility
US5776963A (en) *	1989-05-19	1998-07-07	Hoechst Marion Roussel, Inc.	3-(heteroaryl)-1- (2,3-dihydro-1h-isoindol-2-yl)alkyl!pyrrolidines and 3-(heteroaryl)-1- (2,3-dihydro-1h-indol-1-yl)alkyl!pyrrolidines and related compounds and their therapeutic untility
US4954503A (en) *	1989-09-11	1990-09-04	Hoechst-Roussel Pharmaceuticals, Inc.	3-(1-substituted-4-piperazinyl)-1H-indazoles
FR2671350A1 (fr) *	1991-01-08	1992-07-10	Adir	Nouveaux derives de benzisoxazole et de benzisothiazole, leur procede de preparation, et les compositions pharmaceutiques les renfermant.
US5041445A (en) *	1990-05-21	1991-08-20	Hoechst-Roussel Pharmaceuticals Incorporated	3-[1-thiazolidinylbutyl-4-piperazinyl]-1H-indazoles
CA2118936A1 (en) *	1991-09-25	1993-04-01	Gene M. Bright	Neuroleptic 2-substituted perhydro-1-h-pyrido[1,2-a]pyrazines
GB9202915D0 (en) *	1992-02-12	1992-03-25	Wellcome Found	Chemical compounds
EP0635506A4 (de) *	1993-02-04	1995-04-12	Meiji Seika Co	Verbindung mit antipsychotischerwirkung.
EP0794185A4 (de) *	1994-11-25	1998-03-25	Meiji Seika Co	Bizyklische thiazolverbindung
KR100315939B1 (ko) *	1995-11-07	2002-01-16	디. 제이. 우드, 스피겔 알렌 제이	3-(1-피페라지닐)-1,2-벤즈이소티아졸의제조방법및중간체
US6187774B1 (en) *	1996-03-04	2001-02-13	Yoshitomi Pharmaceutical Industries, Ltd.	Fused heterocyclic compounds and pharmaceutical applications thereof
HUP0400389A3 (en)	2001-03-29	2008-03-28	Schering Corp	Aryl oxime-piperazines useful as ccr5 antagonists and pharmaceutical compositions containing them
PL378120A1 (pl) *	2003-02-14	2006-03-06	Wyeth	Heterocyklilo-3-sulfonyloindazole jako ligandy 5-hydroksytryptaminy
EP2337783A1 (de) *	2008-09-23	2011-06-29	F. Hoffmann-La Roche AG	Als modulatoren von dopamin-d3-rezeptoren geeignete isoxazolo[4,5]pyridin-3-ylpiperazinderivate
US11676855B2 (en) *	2020-02-26	2023-06-13	Taiwan Semiconductor Manufacturing Co., Ltd.	Patterning interconnects and other structures by photo-sensitizing method
CN114634479B (zh) *	2020-12-16	2025-02-07	北京盈科瑞创新药物研究有限公司	一种派嗪衍生物、其制备方法及应用
CA3245085A1 (en) *	2022-01-11	2023-07-20	Suven Life Sciences Limited	HETEROCYCLIC DERIVATIVES AND THEIR USE IN THE TREATMENT OF DISORDERS OF THE CENTRAL NERVOUS SYSTEM

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4411901A (en) *	1981-12-23	1983-10-25	Mead Johnson & Company	Benzisothiazole and benzisoxazole piperazine derivatives
US4452799A (en)	1981-12-23	1984-06-05	Mead Johnson & Company	Benzisothiazole and benzisoxazole piperazine derivatives
HU198036B (en) *	1983-08-22	1989-07-28	Hoechst Roussel Pharma	Process for production of derivatives of 3-piperidil-/1h/-indasole and medical preparatives containing them
US4524206A (en)	1983-09-12	1985-06-18	Mead Johnson & Company	1-Heteroaryl-4-(2,5-pyrrolidinedion-1-yl)alkyl)piperazine derivatives
US4590196A (en)	1984-08-23	1986-05-20	Bristol-Myers Company	Analgesic 1,2-benzisothiazol-3-ylpiperazine derivatives
US4804663A (en) *	1985-03-27	1989-02-14	Janssen Pharmaceutica N.V.	3-piperidinyl-substituted 1,2-benzisoxazoles and 1,2-benzisothiazoles
EP0302423A3 (de)	1987-08-07	1991-01-09	Hoechst-Roussel Pharmaceuticals Incorporated	1-Phenyl-3-(1-piperazinyl)-1H-Indazole, Verfahren und Zwischenprodukte zu deren Herstellung und deren Anwendung als Arzneimittel

1989
- 1989-07-21 NZ NZ230045A patent/NZ230045A/en unknown
- 1989-07-26 SU SU894614564A patent/SU1687030A3/ru active
- 1989-07-28 AT AT89201981T patent/ATE122348T1/de not_active IP Right Cessation
- 1989-07-28 ES ES89201981T patent/ES2074462T3/es not_active Expired - Lifetime
- 1989-07-28 EP EP89201981A patent/EP0353821B1/de not_active Expired - Lifetime
- 1989-07-28 DE DE68922537T patent/DE68922537T2/de not_active Expired - Fee Related
- 1989-07-28 CA CA000606919A patent/CA1331609C/en not_active Expired - Fee Related
- 1989-08-01 AU AU39171/89A patent/AU619877B2/en not_active Ceased
- 1989-08-02 JP JP1199515A patent/JP2779216B2/ja not_active Expired - Fee Related
- 1989-08-03 IL IL9119489A patent/IL91194A/en not_active IP Right Cessation
- 1989-08-03 PT PT91364A patent/PT91364B/pt not_active IP Right Cessation
- 1989-08-04 ZA ZA895978A patent/ZA895978B/xx unknown
- 1989-08-04 FI FI893701A patent/FI90238C/fi not_active IP Right Cessation
- 1989-08-04 DK DK198903836A patent/DK175124B1/da not_active IP Right Cessation
- 1989-08-04 NO NO893168A patent/NO176051C/no unknown
- 1989-08-04 IE IE253589A patent/IE66198B1/en not_active IP Right Cessation
- 1989-08-04 HU HU893967A patent/HU206341B/hu not_active IP Right Cessation
- 1989-08-04 PH PH39057A patent/PH26550A/en unknown
- 1989-08-04 KR KR1019890011154A patent/KR0145706B1/ko not_active Expired - Fee Related
- 1989-08-05 CN CN89106438A patent/CN1023602C/zh not_active Expired - Fee Related

Also Published As

Publication number	Publication date
HU206341B (en)	1992-10-28
KR900003155A (ko)	1990-03-23
EP0353821A3 (de)	1991-07-17
CN1023602C (zh)	1994-01-26
KR0145706B1 (ko)	1998-08-17
FI893701A0 (fi)	1989-08-04
FI90238B (fi)	1993-09-30
DK383689D0 (da)	1989-08-04
DK383689A (da)	1990-02-06
IE66198B1 (en)	1995-12-13
CA1331609C (en)	1994-08-23
DE68922537T2 (de)	1995-09-14
HUT55385A (en)	1991-05-28
NO893168L (no)	1990-02-06
IE892535L (en)	1990-02-05
IL91194A0 (en)	1990-03-19
JPH0288572A (ja)	1990-03-28
PT91364A (pt)	1990-03-08
PT91364B (pt)	1995-03-31
DE68922537D1 (de)	1995-06-14
AU3917189A (en)	1990-03-08
AU619877B2 (en)	1992-02-06
JP2779216B2 (ja)	1998-07-23
DK175124B1 (da)	2004-06-07
NO176051B (no)	1994-10-17
NO176051C (no)	1995-01-25
ES2074462T3 (es)	1995-09-16
ZA895978B (en)	1991-04-24
EP0353821A2 (de)	1990-02-07
EP0353821B1 (de)	1995-05-10
FI893701L (fi)	1990-02-06
FI90238C (fi)	1994-01-10
CN1040194A (zh)	1990-03-07
NO893168D0 (no)	1989-08-04
NZ230045A (en)	1990-11-27
PH26550A (en)	1992-08-19
SU1687030A3 (ru)	1991-10-23
ATE122348T1 (de)	1995-05-15

Legal Events

Date	Code	Title
1999-12-31	KB	Patent renewed
2003-10-31	KB	Patent renewed
2008-04-13	MM9K	Patent not in force due to non-payment of renewal fees

Publication	Publication Date	Title
US4804663A (en)	1989-02-14	3-piperidinyl-substituted 1,2-benzisoxazoles and 1,2-benzisothiazoles
US4957916A (en)	1990-09-18	Antipsychotic 3-piperazinylbenzazole derivatives
EP0368388B1 (de)	1995-05-10	3-Piperidinyl-1,2-benzisoxazole
EP0353821B1 (de)	1995-05-10	Antipsychotische 3-Piperazinylbenzazolderivate
US5140029A (en)	1992-08-18	2-aminopyrimidinone derivatives
EP0378255A2 (de)	1990-07-18	2-Aminopyrimidinon-Derivate
EP0453042B1 (de)	1999-11-03	An den Positionen 2 und 9 substituierte 4H-pyrido-(1,2-a)pyrimidin-4-one
AU702931B2 (en)	1999-03-11	Antipsychotic 4-(1H-indolyl-1-yl)-1-substituted piperidine derivatives
US5015740A (en)	1991-05-14	Antipsychotic 3-piperazinylbenzazole derivatives
EP0357134B1 (de)	1995-06-28	Antihypertensive 3-Piperidinylindazol-Derivate
US5196425A (en)	1993-03-23	Antihypertensive 3-piperidinyl-indazole derivatives
US5284854A (en)	1994-02-08	2-aminopyrimidinone derivatives
US5321028A (en)	1994-06-14	Antihypertensive 3-piperidinyl-indazole derivatives
IL105594A (en)	1994-10-07	History of 3-piperazinylbenzperazole