IL111246A - Tricyclic heterocyclic toluamide derivatives and pharmaceutical compositions containing them - Google Patents

Tricyclic heterocyclic toluamide derivatives and pharmaceutical compositions containing them

Info

Publication number: IL111246A
Authority: IL; Israel
Prior art keywords: compound; disease; mmol; solution; nervous system
Prior art date: 1993-10-25

Application number

IL111246A

Other languages

English (en)

Other versions

IL111246A0 (en

Original Assignee

Ortho Pharma Corp

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.)

1993-10-25

Filing date

1994-10-11

Publication date

1998-01-04

1994-10-11 Application filed by Ortho Pharma Corp filed Critical Ortho Pharma Corp

1994-12-29 Publication of IL111246A0 publication Critical patent/IL111246A0/xx

1998-01-04 Publication of IL111246A publication Critical patent/IL111246A/en

Links

-1 heterocyclic toluamide derivatives Chemical class 0.000 title claims description 8
239000008194 pharmaceutical composition Substances 0.000 title claims description 5
150000001875 compounds Chemical class 0.000 claims abstract description 34
201000010099 disease Diseases 0.000 claims abstract description 10
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 10
210000003169 central nervous system Anatomy 0.000 claims abstract description 6
238000002360 preparation method Methods 0.000 claims description 8
150000003839 salts Chemical class 0.000 claims description 7
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 6
239000003814 drug Substances 0.000 claims description 6
238000000034 method Methods 0.000 claims description 6
229920006395 saturated elastomer Polymers 0.000 claims description 5
208000019901 Anxiety disease Diseases 0.000 claims description 4
239000002253 acid Substances 0.000 claims description 4
125000002252 acyl group Chemical group 0.000 claims description 4
230000036506 anxiety Effects 0.000 claims description 4
125000003118 aryl group Chemical group 0.000 claims description 4
229910052736 halogen Inorganic materials 0.000 claims description 4
150000002367 halogens Chemical class 0.000 claims description 4
241000282414 Homo sapiens Species 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 3
125000000217 alkyl group Chemical group 0.000 claims description 3
229910052799 carbon Inorganic materials 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000002619 bicyclic group Chemical group 0.000 claims description 2
208000015114 central nervous system disease Diseases 0.000 claims description 2
150000004677 hydrates Chemical class 0.000 claims description 2
229910052739 hydrogen Inorganic materials 0.000 claims description 2
125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 claims description 2
125000002950 monocyclic group Chemical group 0.000 claims description 2
229910052760 oxygen Inorganic materials 0.000 claims description 2
239000012453 solvate Substances 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
210000000653 nervous system Anatomy 0.000 claims 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
239000000243 solution Substances 0.000 description 38
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 36
239000011541 reaction mixture Substances 0.000 description 25
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 20
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 15
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 14
238000005481 NMR spectroscopy Methods 0.000 description 14
239000000463 material Substances 0.000 description 14
239000003921 oil Substances 0.000 description 13
239000007787 solid Substances 0.000 description 13
229910052757 nitrogen Inorganic materials 0.000 description 11
239000002026 chloroform extract Substances 0.000 description 10
239000006260 foam Substances 0.000 description 10
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
229910000027 potassium carbonate Inorganic materials 0.000 description 9
229910001868 water Inorganic materials 0.000 description 9
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 8
239000010410 layer Substances 0.000 description 8
239000000741 silica gel Substances 0.000 description 8
229910002027 silica gel Inorganic materials 0.000 description 8
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
230000027455 binding Effects 0.000 description 7
239000000843 powder Substances 0.000 description 7
238000000746 purification Methods 0.000 description 7
238000007792 addition Methods 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
102000005962 receptors Human genes 0.000 description 6
108020003175 receptors Proteins 0.000 description 6
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
239000000725 suspension Substances 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
BXLNHFVIUOMFIA-UHFFFAOYSA-N [3-(chloromethyl)phenyl]-piperidin-1-ylmethanone Chemical compound ClCC1=CC=CC(C(=O)N2CCCCC2)=C1 BXLNHFVIUOMFIA-UHFFFAOYSA-N 0.000 description 5
238000000921 elemental analysis Methods 0.000 description 5
239000000047 product Substances 0.000 description 5
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
238000003556 assay Methods 0.000 description 4
LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 4
150000003951 lactams Chemical class 0.000 description 4
239000003446 ligand Substances 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
125000001424 substituent group Chemical group 0.000 description 4
238000005160 1H NMR spectroscopy Methods 0.000 description 3
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
ZKLPQWVERHDLHR-UHFFFAOYSA-N [3-(chloromethyl)phenyl]-(2,3-dihydroindol-1-yl)methanone Chemical compound ClCC1=CC=CC(C(=O)N2C3=CC=CC=C3CC2)=C1 ZKLPQWVERHDLHR-UHFFFAOYSA-N 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
239000002585 base Substances 0.000 description 3
239000002775 capsule Substances 0.000 description 3
239000000969 carrier Substances 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
229940079593 drug Drugs 0.000 description 3
239000012259 ether extract Substances 0.000 description 3
238000003818 flash chromatography Methods 0.000 description 3
GEVPUGOOGXGPIO-UHFFFAOYSA-N oxalic acid;dihydrate Chemical compound O.O.OC(=O)C(O)=O GEVPUGOOGXGPIO-UHFFFAOYSA-N 0.000 description 3
238000010992 reflux Methods 0.000 description 3
239000002904 solvent Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
206010010904 Convulsion Diseases 0.000 description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
208000019695 Migraine disease Diseases 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
239000007868 Raney catalyst Substances 0.000 description 2
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
229910000564 Raney nickel Inorganic materials 0.000 description 2
208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
239000000654 additive Substances 0.000 description 2
230000001476 alcoholic effect Effects 0.000 description 2
239000000010 aprotic solvent Substances 0.000 description 2
KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
229940073608 benzyl chloride Drugs 0.000 description 2
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
VXIVSQZSERGHQP-UHFFFAOYSA-N chloroacetamide Chemical compound NC(=O)CCl VXIVSQZSERGHQP-UHFFFAOYSA-N 0.000 description 2
QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 2
229960004170 clozapine Drugs 0.000 description 2
238000009833 condensation Methods 0.000 description 2
230000005494 condensation Effects 0.000 description 2
230000036461 convulsion Effects 0.000 description 2
238000001816 cooling Methods 0.000 description 2
238000000354 decomposition reaction Methods 0.000 description 2
150000004985 diamines Chemical class 0.000 description 2
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
229960003878 haloperidol Drugs 0.000 description 2
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
238000011534 incubation Methods 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
206010022437 insomnia Diseases 0.000 description 2
239000007788 liquid Substances 0.000 description 2
239000000203 mixture Substances 0.000 description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
239000006186 oral dosage form Substances 0.000 description 2
239000003880 polar aprotic solvent Substances 0.000 description 2
239000008057 potassium phosphate buffer Substances 0.000 description 2
238000006722 reduction reaction Methods 0.000 description 2
201000000980 schizophrenia Diseases 0.000 description 2
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
229940076279 serotonin Drugs 0.000 description 2
230000009870 specific binding Effects 0.000 description 2
239000007858 starting material Substances 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
239000003826 tablet Substances 0.000 description 2
238000012360 testing method Methods 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
CFTOTSJVQRFXOF-UHFFFAOYSA-N 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole Chemical compound N1C2=CC=CC=C2C2=C1CNCC2 CFTOTSJVQRFXOF-UHFFFAOYSA-N 0.000 description 1
125000005273 2-acetoxybenzoic acid group Chemical group 0.000 description 1
125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
CMLFRMDBDNHMRA-UHFFFAOYSA-N 2h-1,2-benzoxazine Chemical compound C1=CC=C2C=CNOC2=C1 CMLFRMDBDNHMRA-UHFFFAOYSA-N 0.000 description 1
IXXUECVJJOVSJV-UHFFFAOYSA-N 2h-1,4-benzoxazin-3-ylmethanamine Chemical compound C1=CC=C2OCC(CN)=NC2=C1 IXXUECVJJOVSJV-UHFFFAOYSA-N 0.000 description 1
YCAIYRWHKSJKEB-UHFFFAOYSA-N 3-(chloromethyl)benzoyl chloride Chemical compound ClCC1=CC=CC(C(Cl)=O)=C1 YCAIYRWHKSJKEB-UHFFFAOYSA-N 0.000 description 1
125000005917 3-methylpentyl group Chemical group 0.000 description 1
102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 description 1
101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
208000024172 Cardiovascular disease Diseases 0.000 description 1
VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
241000282412 Homo Species 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
241000700157 Rattus norvegicus Species 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000016571 aggressive behavior Effects 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
150000001408 amides Chemical group 0.000 description 1
BVCZEBOGSOYJJT-UHFFFAOYSA-N ammonium carbamate Chemical compound [NH4+].NC([O-])=O BVCZEBOGSOYJJT-UHFFFAOYSA-N 0.000 description 1
239000002249 anxiolytic agent Substances 0.000 description 1
230000000949 anxiolytic effect Effects 0.000 description 1
125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
229910000085 borane Inorganic materials 0.000 description 1
QWCRAEMEVRGPNT-UHFFFAOYSA-N buspirone Chemical group C1C(=O)N(CCCCN2CCN(CC2)C=2N=CC=CN=2)C(=O)CC21CCCC2 QWCRAEMEVRGPNT-UHFFFAOYSA-N 0.000 description 1
229960002495 buspirone Drugs 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
210000003710 cerebral cortex Anatomy 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
239000003086 colorant Substances 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
229940126214 compound 3 Drugs 0.000 description 1
238000013329 compounding Methods 0.000 description 1
239000006071 cream Substances 0.000 description 1
WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
NMGSDTSOSIPXTN-UHFFFAOYSA-N cyclohexa-1,2-diene Chemical compound C1CC=C=CC1 NMGSDTSOSIPXTN-UHFFFAOYSA-N 0.000 description 1
UVJHQYIOXKWHFD-UHFFFAOYSA-N cyclohexa-1,4-diene Chemical compound C1C=CCC=C1 UVJHQYIOXKWHFD-UHFFFAOYSA-N 0.000 description 1
HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
229960003638 dopamine Drugs 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000002024 ethyl acetate extract Substances 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
239000012458 free base Substances 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
239000003979 granulating agent Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 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
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
239000012528 membrane Substances 0.000 description 1
GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
206010027599 migraine Diseases 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
210000001577 neostriatum Anatomy 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
239000004031 partial agonist Substances 0.000 description 1
MRBDMNSDAVCSSF-UHFFFAOYSA-N phentolamine Chemical compound C1=CC(C)=CC=C1N(C=1C=C(O)C=CC=1)CC1=NCCN1 MRBDMNSDAVCSSF-UHFFFAOYSA-N 0.000 description 1
229960001999 phentolamine Drugs 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
125000005544 phthalimido group Chemical group 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000004321 preservation Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
238000006798 ring closing metathesis reaction Methods 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
230000007017 scission Effects 0.000 description 1
125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
230000000862 serotonergic effect Effects 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
229950001675 spiperone Drugs 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
238000009901 transfer hydrogenation reaction Methods 0.000 description 1

Classifications

- 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
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
- A—HUMAN NECESSITIES
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- A61P25/08—Antiepileptics; Anticonvulsants
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
- A—HUMAN NECESSITIES
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- A61P25/22—Anxiolytics
- A—HUMAN NECESSITIES
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- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
- A—HUMAN NECESSITIES
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- 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

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Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Pain & Pain Management (AREA)
Psychiatry (AREA)
Anesthesiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Solid-Sorbent Or Filter-Aiding Compositions (AREA)

IL111246A 1993-10-25 1994-10-11 Tricyclic heterocyclic toluamide derivatives and pharmaceutical compositions containing them IL111246A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US08/142,748 US5512566A (en)	1993-10-25	1993-10-25	Tricyclic compounds having affinity for the 5-HT1A receptor

Publications (2)

Publication Number	Publication Date
IL111246A0 IL111246A0 (en)	1994-12-29
IL111246A true IL111246A (en)	1998-01-04

Family

ID=22501119

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL111246A IL111246A (en)	1993-10-25	1994-10-11	Tricyclic heterocyclic toluamide derivatives and pharmaceutical compositions containing them

Country Status (15)

Country	Link
US (1)	US5512566A (de)
EP (1)	EP0746556B1 (de)
JP (1)	JP3709203B2 (de)
AT (1)	ATE224895T1 (de)
AU (1)	AU680562B2 (de)
CA (1)	CA2174850A1 (de)
DE (1)	DE69431441T2 (de)
DK (1)	DK0746556T3 (de)
ES (1)	ES2183843T3 (de)
IL (1)	IL111246A (de)
NZ (1)	NZ275689A (de)
PT (1)	PT746556E (de)
SI (1)	SI0746556T1 (de)
WO (1)	WO1995011903A1 (de)
ZA (1)	ZA948354B (de)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5688950A (en) *	1996-04-23	1997-11-18	Neurogen Corporation	Tricyclic aminoalkylcarboxamides; novel dopamine D3 receptor subtype specific ligands
US7189753B1 (en)	1997-11-06	2007-03-13	Cady Roger K	Preemptive prophylaxis of migraine

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3755584A (en) *	1972-04-03	1973-08-28	Abbott Lab	Tranquilizers
IT1052009B (it) *	1975-12-30	1981-06-20	Erba Carlo Spa	Imidazo 4.3 c 1.4 benzossazino imidazo 4.3 c 1.4 benzotiazino pirazo 2.1 c 1.4 benzossazino e pirazo 2.1 c 1.4 benzotiazino derivati
ATE139230T1 (de) *	1988-12-15	1996-06-15	Abbott Lab	5-ht-selektive mittel
US5049564A (en) *	1989-11-17	1991-09-17	Abbott Laboratories	5-HT selective agents
US5244888A (en) *	1989-11-17	1993-09-14	Abbott Laboratories	5-HT selective agents
EP0510068B1 (de) *	1990-01-11	1999-04-14	PHARMACIA & UPJOHN COMPANY	6,7,8,9-tetrahydro-3h-benz(e)indolheterocyclen mit wirkung auf das zentrale nervensystem
WO1991013872A1 (en) *	1990-03-15	1991-09-19	The Upjohn Company	Therapeutically useful heterocyclic indole compounds
EP0539209A1 (de) *	1991-10-24	1993-04-28	The Upjohn Company	Benzo-Isochinoline Derivate und Analoge und ihre Anwendung in der Therapie
AU2559392A (en) *	1991-10-24	1993-05-21	Upjohn Company, The	Benzo-isoquinoline derivatives and analogs and their use in therapeutics

1993
- 1993-10-25 US US08/142,748 patent/US5512566A/en not_active Expired - Lifetime
1994
- 1994-10-11 DE DE69431441T patent/DE69431441T2/de not_active Expired - Fee Related
- 1994-10-11 CA CA002174850A patent/CA2174850A1/en not_active Abandoned
- 1994-10-11 IL IL111246A patent/IL111246A/en not_active IP Right Cessation
- 1994-10-11 ES ES94930720T patent/ES2183843T3/es not_active Expired - Lifetime
- 1994-10-11 NZ NZ275689A patent/NZ275689A/en unknown
- 1994-10-11 SI SI9430418T patent/SI0746556T1/xx unknown
- 1994-10-11 AU AU79757/94A patent/AU680562B2/en not_active Ceased
- 1994-10-11 WO PCT/US1994/011544 patent/WO1995011903A1/en not_active Ceased
- 1994-10-11 AT AT94930720T patent/ATE224895T1/de active
- 1994-10-11 PT PT94930720T patent/PT746556E/pt unknown
- 1994-10-11 JP JP51265995A patent/JP3709203B2/ja not_active Expired - Fee Related
- 1994-10-11 EP EP94930720A patent/EP0746556B1/de not_active Expired - Lifetime
- 1994-10-11 DK DK94930720T patent/DK0746556T3/da active
- 1994-10-24 ZA ZA948354A patent/ZA948354B/xx unknown

Also Published As

Publication number	Publication date
ZA948354B (en)	1996-04-24
EP0746556B1 (de)	2002-09-25
CA2174850A1 (en)	1995-05-04
EP0746556A1 (de)	1996-12-11
SI0746556T1 (en)	2003-02-28
JP3709203B2 (ja)	2005-10-26
NZ275689A (en)	1997-12-19
AU7975794A (en)	1995-05-22
WO1995011903A1 (en)	1995-05-04
DK0746556T3 (da)	2002-12-16
DE69431441D1 (de)	2002-10-31
AU680562B2 (en)	1997-07-31
JPH09504789A (ja)	1997-05-13
US5512566A (en)	1996-04-30
IL111246A0 (en)	1994-12-29
PT746556E (pt)	2002-12-31
DE69431441T2 (de)	2003-10-23
ATE224895T1 (de)	2002-10-15
ES2183843T3 (es)	2003-04-01

Legal Events

Date	Code	Title
1998-06-15	FF	Patent granted
1998-11-26	KB	Patent renewed
2001-04-30	KB	Patent renewed
2009-12-24	MM9K	Patent not in force due to non-payment of renewal fees

Publication	Publication Date	Title
EP1165558B1 (de)	2003-09-24	Pyrimido[6,1-a]isochinolinonderivate
US5834493A (en)	1998-11-10	Indole derivatives as 5-HT1A and/or 5-HT2 ligands
US5030640A (en)	1991-07-09	Novel β-adrenergic agonists and pharmaceutical compositions thereof
US8071786B2 (en)	2011-12-06	Indole compounds useful as serotonin selective agents
HUT70195A (en)	1995-09-28	Process for producing benzimidazolone derivatives and pharmaceutical preparations containing them
KR20010108025A (ko)	2001-12-07	5ＨＴ2Ｃ 효능제인2,3,4,4ａ-테트라하이드로-1Ｈ-피라지노(1,2-ａ)퀴녹살린-5(6Ｈ)온 유도체
SK106395A3 (en)	1995-12-06	Treating and treatment or prevention of mental diseases
EP2114878B1 (de)	2010-12-15	5-(heterocyclyl)alkyl-n-(arylsulfonyl)indolverbindungen und ihre verwendung als 5-ht6-liganden
KR101463190B1 (ko)	2014-11-18	５ｈｔ６ 수용체 리간드인 술폰 화합물
FI66611B (fi)	1984-07-31	Foerfarande foer framstaellning av nya terapeutiskt anvaendbara fenyl-kinolizidiner
US4672117A (en)	1987-06-09	Antipsychotic gamma-carbolines
EP2121602B1 (de)	2015-03-18	4-(heterocyclyl)alkyl-n-(arylsulfonyl)indolverbindungen und ihre verwendung als 5-ht6-liganden
US4778812A (en)	1988-10-18	2,3-dihydro-9-methyl-1H-pyrrolo[1,2-a]indol-1-amines and derivatives thereof
JPH05117273A (ja)	1993-05-14	医薬化合物
JP2001501949A (ja)	2001-02-13	中枢神経系疾患を処置することに有用な５―ヘテロ原子を含有するアルキル置換された―３―オキソ―ピリド（１，２―ａ）ベンゾイミダゾール―４―カルボキサミド誘導体
AU680562B2 (en)	1997-07-31	Tricyclic compounds having affinity for the 5-ht1a receptor
PL136930B1 (en)	1986-04-30	Method of obtaining novel derivatives of benzodiazepine
EA005071B1 (ru)	2004-10-28	ЗАМЕЩЕННЫЕ ПИРАЗОЛО[4,3-e]ДИАЗЕПИНЫ, ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ, СОДЕРЖАЩИЕ ИХ, И ПРИМЕНЕНИЕ В КАЧЕСТВЕ ЛЕКАРСТВЕННЫХ ПРОДУКТОВ
WO2009034581A1 (en)	2009-03-19	Substituted indolyl compounds and their use as 5-ht6 ligands
US4482714A (en)	1984-11-13	Pyrazino[2',3'-3,4]pyrido[1,2-a]indole derivatives
KR20000029564A (ko)	2000-05-25	5ＨＴ2ｃ길항제및Ｄ2길항제를함유하는약제학적조성물
MXPA04001810A (es)	2004-07-08	Compuestos de aminopirrol como agentes antiinflamatorios.
US5114944A (en)	1992-05-19	2-phenylpyrazolo[1,5-a]pyrimidine-3-acetic acid derivatives exhibiting therapeutic effects
US4515949A (en)	1985-05-07	[2-(1H-indol-1-yl)ethyl]-2-piperazine and pyrido[1,2-a]indol-9-one as intermediates for pyrazino(2,3-3,4)pyrido(1,2-a) indoles which are useful for treating hypertension in mammals
JPH09508637A (ja)	1997-09-02	５ｈｔ２ｂレセプタ拮抗薬縮合インドール