HRP970060A2 - Tetrahydroisoquinoline derivatives - Google Patents

Tetrahydroisoquinoline derivatives

Info

Publication number: HRP970060A2
Authority: HR; Croatia
Prior art keywords: disease; neurodegeneration; methyl; dimethoxy; phenyl
Prior art date: 1996-02-03

Application number

HR96101553.4A

Other languages

English (en)

Croatian (hr)

Inventor

Alexander Alanine

Anne Bourson

Bernd Buettelmann

Guenther Fischer

Marie-Paule Heitz Neidhart

Vincent Mutel

Emmanuel Pinard

Stephan Roever

Gerhard Trube

Rene Wyler

Original Assignee

Hoffmann La Roche

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.)

1996-02-03

Filing date

1997-01-31

Publication date

1998-04-30

1997-01-31 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1998-04-30 Publication of HRP970060A2 publication Critical patent/HRP970060A2/hr

Links

125000003039 tetrahydroisoquinolinyl group Chemical class C1(NCCC2=CC=CC=C12)* 0.000 title claims 2
150000001875 compounds Chemical class 0.000 claims description 33
230000004770 neurodegeneration Effects 0.000 claims description 18
238000000034 method Methods 0.000 claims description 15
108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims description 14
125000000217 alkyl group Chemical group 0.000 claims description 12
150000003839 salts Chemical class 0.000 claims description 10
230000001225 therapeutic effect Effects 0.000 claims description 9
102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 claims description 8
230000001154 acute effect Effects 0.000 claims description 7
230000001684 chronic effect Effects 0.000 claims description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
208000024827 Alzheimer disease Diseases 0.000 claims description 6
208000023105 Huntington disease Diseases 0.000 claims description 6
208000018737 Parkinson disease Diseases 0.000 claims description 6
208000030886 Traumatic Brain injury Diseases 0.000 claims description 6
125000003545 alkoxy group Chemical group 0.000 claims description 6
229910052739 hydrogen Inorganic materials 0.000 claims description 6
239000001257 hydrogen Substances 0.000 claims description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
208000019901 Anxiety disease Diseases 0.000 claims description 5
208000035143 Bacterial infection Diseases 0.000 claims description 5
208000036142 Viral infection Diseases 0.000 claims description 5
230000036506 anxiety Effects 0.000 claims description 5
230000001580 bacterial effect Effects 0.000 claims description 5
208000022362 bacterial infectious disease Diseases 0.000 claims description 5
201000010901 lateral sclerosis Diseases 0.000 claims description 5
238000004519 manufacturing process Methods 0.000 claims description 5
208000005264 motor neuron disease Diseases 0.000 claims description 5
201000000980 schizophrenia Diseases 0.000 claims description 5
238000011282 treatment Methods 0.000 claims description 5
230000009385 viral infection Effects 0.000 claims description 5
201000010099 disease Diseases 0.000 claims description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
125000003118 aryl group Chemical group 0.000 claims description 3
125000000753 cycloalkyl group Chemical group 0.000 claims description 3
229940079593 drug Drugs 0.000 claims description 3
MSXJZHUTIDWQBZ-UHFFFAOYSA-N 1-(4-chlorophenyl)-2-(6,7-dimethoxy-2-methyl-3,4-dihydro-1h-isoquinolin-1-yl)ethanol Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(C)C1CC(O)C1=CC=C(Cl)C=C1 MSXJZHUTIDWQBZ-UHFFFAOYSA-N 0.000 claims description 2
DSTWURHEHMZWEI-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)ethyl]-6-methoxy-2-methyl-3,4-dihydro-1H-isoquinolin-7-ol Chemical compound C1=2C=C(O)C(OC)=CC=2CCN(C)C1CCC1=CC=C(Cl)C=C1 DSTWURHEHMZWEI-UHFFFAOYSA-N 0.000 claims description 2
YANOZXMFEIQVAO-UHFFFAOYSA-N 2-(6,7-dimethoxy-2-methyl-3,4-dihydro-1h-isoquinolin-1-yl)-1-(4-methylphenyl)ethanol Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(C)C1CC(O)C1=CC=C(C)C=C1 YANOZXMFEIQVAO-UHFFFAOYSA-N 0.000 claims description 2
GDLPGKJBTVSYQJ-UHFFFAOYSA-N 2-(6,7-dimethoxy-2-methyl-3,4-dihydro-1h-isoquinolin-1-yl)-1-(4-nitrophenyl)ethanol Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(C)C1CC(O)C1=CC=C([N+]([O-])=O)C=C1 GDLPGKJBTVSYQJ-UHFFFAOYSA-N 0.000 claims description 2
OXTUHDQQPZHJLW-UHFFFAOYSA-N 6,7-dimethoxy-2-methyl-1-[2-(4-methylphenyl)ethyl]-3,4-dihydro-1h-isoquinoline Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(C)C1CCC1=CC=C(C)C=C1 OXTUHDQQPZHJLW-UHFFFAOYSA-N 0.000 claims description 2
OPKSZPOAUOROPP-UHFFFAOYSA-N 6-[2-(4-chlorophenyl)ethyl]-8,9-dimethoxy-1,2,3,4,4a,5,6,10b-octahydrophenanthridine Chemical compound N1C2CCCCC2C=2C=C(OC)C(OC)=CC=2C1CCC1=CC=C(Cl)C=C1 OPKSZPOAUOROPP-UHFFFAOYSA-N 0.000 claims description 2
ICOQDTUQBJNWLI-UHFFFAOYSA-N 6-[2-(4-chlorophenyl)ethyl]-8,9-dimethoxy-5-methyl-2,3,4,4a,6,10b-hexahydro-1h-phenanthridine Chemical compound CN1C2CCCCC2C=2C=C(OC)C(OC)=CC=2C1CCC1=CC=C(Cl)C=C1 ICOQDTUQBJNWLI-UHFFFAOYSA-N 0.000 claims description 2
SUWDPXLKWGGFJY-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)ethyl]-2-methyl-3,4-dihydro-1h-isoquinoline-6,7-diol Chemical compound CN1CCC2=CC(O)=C(O)C=C2C1CCC1=CC=C(Cl)C=C1 SUWDPXLKWGGFJY-UHFFFAOYSA-N 0.000 claims 1
230000006806 disease prevention Effects 0.000 claims 1
238000012360 testing method Methods 0.000 description 11
239000000203 mixture Substances 0.000 description 8
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 7
210000000287 oocyte Anatomy 0.000 description 7
239000000556 agonist Substances 0.000 description 6
239000000872 buffer Substances 0.000 description 6
-1 for example Chemical group 0.000 description 6
239000008187 granular material Substances 0.000 description 6
102000014649 NMDA glutamate receptor activity proteins Human genes 0.000 description 5
210000004556 brain Anatomy 0.000 description 5
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 4
239000002253 acid Substances 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
239000008188 pellet Substances 0.000 description 4
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
239000000243 solution Substances 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
150000001408 amides Chemical class 0.000 description 3
239000005557 antagonist Substances 0.000 description 3
230000027455 binding Effects 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
239000002775 capsule Substances 0.000 description 3
239000002299 complementary DNA Substances 0.000 description 3
230000000694 effects Effects 0.000 description 3
239000004615 ingredient Substances 0.000 description 3
238000007363 ring formation reaction Methods 0.000 description 3
239000012279 sodium borohydride Substances 0.000 description 3
229910000033 sodium borohydride Inorganic materials 0.000 description 3
UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
102100029458 Glutamate receptor ionotropic, NMDA 2A Human genes 0.000 description 2
102100022630 Glutamate receptor ionotropic, NMDA 2B Human genes 0.000 description 2
239000004471 Glycine Substances 0.000 description 2
108010084867 N-methyl D-aspartate receptor subtype 2A Proteins 0.000 description 2
229910019213 POCl3 Inorganic materials 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
239000003513 alkali Substances 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
238000001640 fractional crystallisation Methods 0.000 description 2
238000000227 grinding Methods 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
150000002367 halogens Chemical class 0.000 description 2
238000011534 incubation Methods 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
239000012528 membrane Substances 0.000 description 2
229910052987 metal hydride Inorganic materials 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
238000002360 preparation method Methods 0.000 description 2
239000008213 purified water Substances 0.000 description 2
102000005962 receptors Human genes 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
239000002904 solvent Substances 0.000 description 2
ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 description 2
239000000725 suspension Substances 0.000 description 2
239000007916 tablet composition Substances 0.000 description 2
239000011975 tartaric acid Substances 0.000 description 2
150000003526 tetrahydroisoquinolines Chemical class 0.000 description 2
238000005550 wet granulation Methods 0.000 description 2
LXAHHHIGZXPRKQ-UHFFFAOYSA-N 5-fluoro-2-methylpyridine Chemical compound CC1=CC=C(F)C=N1 LXAHHHIGZXPRKQ-UHFFFAOYSA-N 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
101710195187 Glutamate receptor ionotropic, NMDA 2B Proteins 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
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 1
239000004698 Polyethylene Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
108060000200 adenylate cyclase Proteins 0.000 description 1
102000030621 adenylate cyclase Human genes 0.000 description 1
230000001270 agonistic effect Effects 0.000 description 1
230000000202 analgesic effect Effects 0.000 description 1
230000000954 anitussive effect Effects 0.000 description 1
230000003042 antagnostic effect Effects 0.000 description 1
230000002921 anti-spasmodic effect Effects 0.000 description 1
125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
125000002102 aryl alkyloxo group Chemical group 0.000 description 1
238000003556 assay Methods 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
230000003139 buffering effect Effects 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000000969 carrier Substances 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
210000001638 cerebellum Anatomy 0.000 description 1
125000003636 chemical group Chemical class 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
239000000812 cholinergic antagonist Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
230000006726 chronic neurodegeneration Effects 0.000 description 1
238000006264 debenzylation reaction Methods 0.000 description 1
238000009826 distribution Methods 0.000 description 1
229960003638 dopamine Drugs 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
230000007831 electrophysiology Effects 0.000 description 1
238000002001 electrophysiology Methods 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
238000009472 formulation Methods 0.000 description 1
230000006870 function Effects 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
229930195712 glutamate Natural products 0.000 description 1
239000010931 gold Substances 0.000 description 1
229910052737 gold Inorganic materials 0.000 description 1
238000000265 homogenisation Methods 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
239000008101 lactose Substances 0.000 description 1
238000012417 linear regression Methods 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
108020004999 messenger RNA Proteins 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
210000004788 neurological cell Anatomy 0.000 description 1
230000000926 neurological effect Effects 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
229910000510 noble metal Inorganic materials 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
229920001515 polyalkylene glycol Polymers 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000000159 protein binding assay Methods 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
230000004044 response Effects 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
239000007787 solid Substances 0.000 description 1
241000894007 species Species 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
229940063673 spermidine Drugs 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
238000009736 wetting Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/16—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with acylated ring nitrogen atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/18—Aralkyl radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/18—Aralkyl radicals
- C07D217/20—Aralkyl radicals with oxygen atoms directly attached to the aromatic ring of said aralkyl radical, e.g. papaverine
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/10—Aza-phenanthrenes
- C07D221/12—Phenanthridines

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Neurology (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Neurosurgery (AREA)
Medicinal Chemistry (AREA)
Biomedical Technology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
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Psychology (AREA)
Pain & Pain Management (AREA)
Hospice & Palliative Care (AREA)
Anesthesiology (AREA)
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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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HR96101553.4A 1996-02-03 1997-01-31 Tetrahydroisoquinoline derivatives HRP970060A2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP96101553		1996-02-03

Publications (1)

Publication Number	Publication Date
HRP970060A2 true HRP970060A2 (en)	1998-04-30

Family

ID=8222462

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HR96101553.4A HRP970060A2 (en)	1996-02-03	1997-01-31	Tetrahydroisoquinoline derivatives

Country Status (29)

Country	Link
US (2)	US5952344A (cs)
JP (1)	JP3217290B2 (cs)
KR (1)	KR100229298B1 (cs)
CN (1)	CN1167762A (cs)
AR (1)	AR005613A1 (cs)
AU (1)	AU723586B2 (cs)
BR (1)	BR9700816A (cs)
CA (1)	CA2196392A1 (cs)
CO (1)	CO4761069A1 (cs)
CZ (1)	CZ29497A3 (cs)
DE (1)	DE19703985A1 (cs)
ES (1)	ES2124672B1 (cs)
FR (1)	FR2744447B1 (cs)
GB (1)	GB2309642A (cs)
HR (1)	HRP970060A2 (cs)
HU (1)	HUP9700273A1 (cs)
ID (1)	ID15866A (cs)
IL (1)	IL120100A (cs)
IT (1)	IT1289621B1 (cs)
MA (1)	MA24078A1 (cs)
NO (1)	NO970431L (cs)
NZ (1)	NZ314130A (cs)
PE (1)	PE35698A1 (cs)
PL (1)	PL318256A1 (cs)
SG (1)	SG55273A1 (cs)
TR (1)	TR199700071A2 (cs)
TW (1)	TW427978B (cs)
YU (1)	YU3997A (cs)
ZA (1)	ZA97672B (cs)

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US7375136B2 (en) *	2001-03-08	2008-05-20	Emory University	pH-dependent NMDA receptor antagonists
EA201070077A1 (ru) *	2007-06-29	2010-08-30	Эмори Юниверсити	Антагонисты nmda-рецепторов с нейропротективным действием
JP2012158527A (ja) *	2011-01-31	2012-08-23	Mitsubishi Gas Chemical Co Inc	うつ予防
WO2025124571A1 (zh) *	2023-12-14	2025-06-19	斯莱普泰(上海)生物医药科技有限公司	Nmda受体拮抗剂及其用途

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US3217007A (en) *		1965-11-09		Halo- and nitro-substituted phenethyl-z- methyl tetrahydroisoquinolsnes
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CH418336A (de) *	1962-02-23	1966-08-15	Hoffmann La Roche	Verfahren zur Herstellung von Octahydrophenanthridinverbindungen
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JPS5291868A (en) *	1976-01-26	1977-08-02	Takeda Chem Ind Ltd	Indenopyridine derivatives
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EP0226511B1 (fr) *	1985-12-13	1989-08-02	LABORATOIRE L. LAFON Société anonyme dite:	Dérivés de 5-phényl-1,4,5,6-tétrahydropyrimidine, procédé de préparation et utilisation en thérapeutique
DE68910999T2 (de) *	1988-02-19	1994-03-24	Smithkline Beecham Farma	1,2,3,4-Tetrahydroisoquinoline, Verfharen zu ihrer Herstellung und ihre Verwendung als Kappa-Rezeptor Agonisten.
US5011834A (en) *	1989-04-14	1991-04-30	State Of Oregon, Acting By And Through The Oregon State Board Of Higher Education, Acting For And On Behalf Of The Oregon Health Sciences University And The University Of Oregon	PCP receptor ligands and the use thereof
WO1991017156A1 (en) *	1990-05-10	1991-11-14	Pfizer Inc	Neuroprotective indolone and related derivatives
US5192751A (en) *	1992-07-24	1993-03-09	Eli Lilly And Company	Use of competitive NMDA receptor antagonists in the treatment of urinary incontinence
JPH0741481A (ja) *	1993-05-21	1995-02-10	Hokuriku Seiyaku Co Ltd	両性型三環系化合物
US5389638A (en) *	1993-09-10	1995-02-14	Abbott Laboratories	Tetrahydroisoquinolines as alpha-2 antagonists and biogenic amine uptake inhibitors
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1997
- 1997-01-20 TW TW086100559A patent/TW427978B/zh active
- 1997-01-22 PE PE1997000036A patent/PE35698A1/es not_active Application Discontinuation
- 1997-01-24 AU AU12335/97A patent/AU723586B2/en not_active Ceased
- 1997-01-27 ZA ZA9700672A patent/ZA97672B/xx unknown
- 1997-01-28 NZ NZ314130A patent/NZ314130A/en unknown
- 1997-01-28 IT IT97MI000153A patent/IT1289621B1/it active IP Right Grant
- 1997-01-29 SG SG1997000194A patent/SG55273A1/en unknown
- 1997-01-29 HU HU9700273A patent/HUP9700273A1/hu unknown
- 1997-01-29 IL IL12010097A patent/IL120100A/xx active IP Right Grant
- 1997-01-30 AR ARP970100377A patent/AR005613A1/es unknown
- 1997-01-30 BR BR9700816A patent/BR9700816A/pt active Search and Examination
- 1997-01-30 CA CA002196392A patent/CA2196392A1/en not_active Abandoned
- 1997-01-31 CN CN97102918A patent/CN1167762A/zh active Pending
- 1997-01-31 KR KR1019970003011A patent/KR100229298B1/ko not_active Expired - Fee Related
- 1997-01-31 ES ES009700190A patent/ES2124672B1/es not_active Expired - Fee Related
- 1997-01-31 HR HR96101553.4A patent/HRP970060A2/hr not_active Application Discontinuation
- 1997-01-31 NO NO970431A patent/NO970431L/no not_active Application Discontinuation
- 1997-01-31 GB GB9702049A patent/GB2309642A/en not_active Withdrawn
- 1997-01-31 CZ CZ97294A patent/CZ29497A3/cs unknown
- 1997-01-31 CO CO97004754A patent/CO4761069A1/es unknown
- 1997-01-31 FR FR9701081A patent/FR2744447B1/fr not_active Expired - Fee Related
- 1997-01-31 TR TR97/00071A patent/TR199700071A2/xx unknown
- 1997-02-03 DE DE19703985A patent/DE19703985A1/de not_active Withdrawn
- 1997-02-03 PL PL97318256A patent/PL318256A1/xx unknown
- 1997-02-03 MA MA24483A patent/MA24078A1/fr unknown
- 1997-02-03 JP JP02013297A patent/JP3217290B2/ja not_active Expired - Fee Related
- 1997-02-03 YU YU3997A patent/YU3997A/sh unknown
- 1997-02-03 ID IDP970316A patent/ID15866A/id unknown
1998
- 1998-01-19 US US09/008,724 patent/US5952344A/en not_active Expired - Fee Related
1999
- 1999-05-26 US US09/320,307 patent/US6071929A/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
JPH09221474A (ja)	1997-08-26
AU723586B2 (en)	2000-08-31
KR970061871A (ko)	1997-09-12
HUP9700273A1 (hu)	1999-08-30
MA24078A1 (fr)	1997-10-01
PE35698A1 (es)	1998-07-16
ZA97672B (en)	1997-08-04
ITMI970153A1 (it)	1998-07-28
ES2124672A1 (es)	1999-02-01
CO4761069A1 (es)	1999-04-27
ID15866A (id)	1997-08-14
FR2744447B1 (fr)	2000-09-29
AU1233597A (en)	1997-08-07
TR199700071A2 (tr)	1997-08-21
CA2196392A1 (en)	1997-08-04
GB9702049D0 (en)	1997-03-19
AR005613A1 (es)	1999-06-23
ES2124672B1 (es)	1999-11-16
US5952344A (en)	1999-09-14
CN1167762A (zh)	1997-12-17
FR2744447A1 (fr)	1997-08-08
TW427978B (en)	2001-04-01
IL120100A (en)	2001-01-28
KR100229298B1 (ko)	1999-11-01
NO970431D0 (no)	1997-01-31
JP3217290B2 (ja)	2001-10-09
US6071929A (en)	2000-06-06
CZ29497A3 (en)	1997-08-13
IL120100A0 (en)	1997-04-15
PL318256A1 (en)	1997-08-04
BR9700816A (pt)	1998-07-07
NO970431L (no)	1997-08-04
IT1289621B1 (it)	1998-10-15
YU3997A (sh)	1999-09-27
HU9700273D0 (en)	1997-03-28
SG55273A1 (en)	1998-12-21
DE19703985A1 (de)	1997-10-30
NZ314130A (en)	1998-04-27
GB2309642A (en)	1997-08-06

Legal Events

Date	Code	Title
1998-04-30	A1OB	Publication of a patent application
1998-10-14	AIPI	Request for the grant of a patent on the basis of a substantive examination of a patent application
2003-10-22	ODBI	Application refused

Publication	Publication Date	Title
Gasparini et al.	1999	2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist
Shimizu-Sasamata et al.	1996	YM90K: pharmacological characterization as a selective and potent alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptor antagonist.
ES2565515T3 (es)	2016-04-05	Derivados de 2-oxo-1-pirrolidinil imidazotiadiazol
EP0787493A1 (en)	1997-08-06	Tetrahydroisoquinoline derivatives
CA2831830A1 (en)	2012-10-26	2-oxo-1-imidazolidinyl imidazothiadiazole derivatives
AU2010340745B2 (en)	2014-11-20	Sulfone compounds as 5-HT6 receptor ligands
US5834482A (en)	1998-11-10	Heterocyclic chemistry
HRP970060A2 (en)	1998-04-30	Tetrahydroisoquinoline derivatives
EP0885004B1 (en)	2002-05-02	Use of 4-phenyl-3,6-dihydro-2h-pyridyl derivatives as nmda receptor subtype blockers
US6756398B1 (en)	2004-06-29	Positive modulators of nicotinic receptor agonists
US20210361631A1 (en)	2021-11-25	N-methyl-D-aspartic Acid Receptor Modulators
MXPA97000775A (en)	1998-01-01	Derivatives of tetrahidroisoquinol
HK1001764A (en)	1998-07-10	Tetrahydroisoquinoline derivatives
JP2017523245A (ja)	2017-08-17	Ｖｍａｔ阻害化合物
CA2242775A1 (en)	1997-07-24	1-arylphthalazine antagonists of excitatory amino acid receptors
ITTO960564A1 (it)	1998-01-02	Derivati diammidici dell'acido antranilico ad attivita' antigastrinica procedimento per la loro preparazione e loro uso farmaceutico.
Cannon et al.	1985	cis-and trans-4-n-Propyl-1, 2, 3, 4, 4a, 5, 6, 10b-octahydrobenzo (f) quinolines
KR100222238B1 (ko)	1999-10-01	스피로 교상 및 비교상 헤테로고리 화합물
Schwartz	1984	HoF