LT3675B - Indenoindole copounds ii, process for preraring them and pharmaceutical composition containing them - Google Patents

Indenoindole copounds ii, process for preraring them and pharmaceutical composition containing them Download PDF

Info

Publication number: LT3675B
Authority: LT; Lithuania
Prior art keywords: tetrahydro; indole; cis; formula; thii
Prior art date: 1989-06-22

Application number

LTIP912A

Other languages

English (en)

Lithuanian (lt)

Inventor

Malcolm Sainsbury

Howard G Shertzer

Original Assignee

Univ Bath

Univ Cincinnati

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.)

1989-06-22

Filing date

1993-08-30

Publication date

1996-01-25

1993-08-30 Application filed by Univ Bath, Univ Cincinnati filed Critical Univ Bath

1995-03-27 Publication of LTIP912A publication Critical patent/LTIP912A/xx

1996-01-25 Publication of LT3675B publication Critical patent/LT3675B/lt

Links

238000000034 method Methods 0.000 title claims abstract description 24
230000008569 process Effects 0.000 title claims description 9
239000008194 pharmaceutical composition Substances 0.000 title claims description 3
RXXXUIOZOITBII-UHFFFAOYSA-N indeno[1,2-g]indole Chemical compound C1=C2C=CC=CC2=C2C1=C1N=CC=C1C=C2 RXXXUIOZOITBII-UHFFFAOYSA-N 0.000 title description 15
150000001875 compounds Chemical class 0.000 claims abstract description 98
125000000217 alkyl group Chemical group 0.000 claims abstract description 44
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 43
239000001257 hydrogen Substances 0.000 claims abstract description 41
125000003282 alkyl amino group Chemical group 0.000 claims abstract description 20
150000002431 hydrogen Chemical class 0.000 claims abstract description 19
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 16
125000003545 alkoxy group Chemical group 0.000 claims abstract description 16
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 15
150000003839 salts Chemical class 0.000 claims abstract description 12
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 claims abstract description 11
229910052736 halogen Inorganic materials 0.000 claims abstract description 8
150000002367 halogens Chemical class 0.000 claims abstract description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 6
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 319
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 162
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 159
239000000203 mixture Substances 0.000 claims description 78
-1 indenoindole compound Chemical class 0.000 claims description 23
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 20
238000006243 chemical reaction Methods 0.000 claims description 16
230000009467 reduction Effects 0.000 claims description 13
238000002360 preparation method Methods 0.000 claims description 11
150000003254 radicals Chemical class 0.000 claims description 11
238000007126 N-alkylation reaction Methods 0.000 claims description 10
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
239000000126 substance Substances 0.000 claims description 9
201000010099 disease Diseases 0.000 claims description 8
239000002253 acid Substances 0.000 claims description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
239000003638 chemical reducing agent Substances 0.000 claims description 6
150000002475 indoles Chemical class 0.000 claims description 6
150000004031 phenylhydrazines Chemical class 0.000 claims description 6
230000000302 ischemic effect Effects 0.000 claims description 5
230000000087 stabilizing effect Effects 0.000 claims description 5
201000001320 Atherosclerosis Diseases 0.000 claims description 4
208000018737 Parkinson disease Diseases 0.000 claims description 4
230000000172 allergic effect Effects 0.000 claims description 4
208000010668 atopic eczema Diseases 0.000 claims description 4
230000004054 inflammatory process Effects 0.000 claims description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 4
150000002828 nitro derivatives Chemical class 0.000 claims description 4
206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
208000005189 Embolism Diseases 0.000 claims description 3
241000282414 Homo sapiens Species 0.000 claims description 3
208000007536 Thrombosis Diseases 0.000 claims description 3
230000032683 aging Effects 0.000 claims description 3
230000000259 anti-tumor effect Effects 0.000 claims description 3
208000006673 asthma Diseases 0.000 claims description 3
125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 3
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 3
239000003018 immunosuppressive agent Substances 0.000 claims description 3
UMJJFEIKYGFCAT-UHFFFAOYSA-N indan-2-one Chemical class C1=CC=C2CC(=O)CC2=C1 UMJJFEIKYGFCAT-UHFFFAOYSA-N 0.000 claims description 3
208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 3
230000003647 oxidation Effects 0.000 claims description 3
238000007254 oxidation reaction Methods 0.000 claims description 3
HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 claims description 3
229940067157 phenylhydrazine Drugs 0.000 claims description 3
230000005855 radiation Effects 0.000 claims description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
208000024827 Alzheimer disease Diseases 0.000 claims description 2
206010028980 Neoplasm Diseases 0.000 claims description 2
230000020335 dealkylation Effects 0.000 claims description 2
238000006900 dealkylation reaction Methods 0.000 claims description 2
239000003814 drug Substances 0.000 claims description 2
230000004968 inflammatory condition Effects 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
230000002265 prevention Effects 0.000 claims description 2
125000001424 substituent group Chemical group 0.000 claims 3
230000003902 lesion Effects 0.000 claims 2
KWRSKZMCJVFUGU-UHFFFAOYSA-N 1h-inden-1-ol Chemical compound C1=CC=C2C(O)C=CC2=C1 KWRSKZMCJVFUGU-UHFFFAOYSA-N 0.000 claims 1
208000005623 Carcinogenesis Diseases 0.000 claims 1
206010014523 Embolism and thrombosis Diseases 0.000 claims 1
239000002246 antineoplastic agent Substances 0.000 claims 1
230000036952 cancer formation Effects 0.000 claims 1
231100000504 carcinogenesis Toxicity 0.000 claims 1
239000003701 inert diluent Substances 0.000 claims 1
229910021653 sulphate ion Inorganic materials 0.000 claims 1
239000003963 antioxidant agent Substances 0.000 abstract description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 180
239000000243 solution Substances 0.000 description 126
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 125
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 96
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 80
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 76
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 62
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 60
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239000007787 solid Substances 0.000 description 54
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239000002904 solvent Substances 0.000 description 50
239000011541 reaction mixture Substances 0.000 description 48
235000019439 ethyl acetate Nutrition 0.000 description 47
239000003208 petroleum Substances 0.000 description 43
239000000047 product Substances 0.000 description 43
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 42
239000011734 sodium Substances 0.000 description 32
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 31
238000004587 chromatography analysis Methods 0.000 description 30
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
229960000583 acetic acid Drugs 0.000 description 22
239000000284 extract Substances 0.000 description 21
239000007788 liquid Substances 0.000 description 20
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 18
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 17
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
239000012074 organic phase Substances 0.000 description 16
239000012362 glacial acetic acid Substances 0.000 description 15
239000000377 silicon dioxide Substances 0.000 description 15
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 14
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
239000012267 brine Substances 0.000 description 12
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
239000000725 suspension Substances 0.000 description 12
235000006708 antioxidants Nutrition 0.000 description 11
239000008346 aqueous phase Substances 0.000 description 11
239000013078 crystal Substances 0.000 description 11
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 10
239000000706 filtrate Substances 0.000 description 10
238000001914 filtration Methods 0.000 description 10
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238000006722 reduction reaction Methods 0.000 description 10
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229910002027 silica gel Inorganic materials 0.000 description 10
238000003756 stirring Methods 0.000 description 10
GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
239000004480 active ingredient Substances 0.000 description 9
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 9
230000003859 lipid peroxidation Effects 0.000 description 9
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 8
229910000029 sodium carbonate Inorganic materials 0.000 description 8
239000007858 starting material Substances 0.000 description 8
AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 8
239000003925 fat Substances 0.000 description 7
239000010410 layer Substances 0.000 description 7
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239000011780 sodium chloride Substances 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
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QNXSIUBBGPHDDE-UHFFFAOYSA-N indan-1-one Chemical class C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 description 4
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DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
125000004437 phosphorous atom Chemical group 0.000 description 1
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
229920000137 polyphosphoric acid Polymers 0.000 description 1
239000004323 potassium nitrate Substances 0.000 description 1
235000010333 potassium nitrate Nutrition 0.000 description 1
239000008057 potassium phosphate buffer Substances 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
238000010926 purge Methods 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
239000000376 reactant Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000027756 respiratory electron transport chain Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
238000002390 rotary evaporation Methods 0.000 description 1
235000019204 saccharin Nutrition 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
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
239000004576 sand Substances 0.000 description 1
230000009758 senescence Effects 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
239000002002 slurry Substances 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 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
229940095064 tartrate Drugs 0.000 description 1
NTGDNGLXKNRQDL-CQSZACIVSA-N tert-butyl N-methyl-N-[4-[(4R)-4-methyl-2-oxo-1,3,4,5-tetrahydro-1,5-benzodiazepin-6-yl]phenyl]carbamate Chemical group C[C@@H]1CC(=O)NC2=C(N1)C(=CC=C2)C1=CC=C(C=C1)N(C)C(=O)OC(C)(C)C NTGDNGLXKNRQDL-CQSZACIVSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
235000010215 titanium dioxide Nutrition 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
230000005740 tumor formation Effects 0.000 description 1
230000035899 viability Effects 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
239000011652 vitamin K3 Substances 0.000 description 1
235000012711 vitamin K3 Nutrition 0.000 description 1
229940041603 vitamin k 3 Drugs 0.000 description 1
239000001993 wax Substances 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/58—[b]- or [c]-condensed
- C07D209/70—[b]- or [c]-condensed containing carbocyclic rings other than six-membered
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/94—[b, c]- or [b, d]-condensed containing carbocyclic rings other than six-membered
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory 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
- 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
- A61P25/28—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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Immunology (AREA)
Pulmonology (AREA)
Biochemistry (AREA)
Pain & Pain Management (AREA)
Vascular Medicine (AREA)
Hematology (AREA)
Diabetes (AREA)
Toxicology (AREA)
Psychology (AREA)
Urology & Nephrology (AREA)
Rheumatology (AREA)
Hospice & Palliative Care (AREA)
Psychiatry (AREA)
Indole Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

LTIP912A 1989-06-22 1993-08-30 Indenoindole copounds ii, process for preraring them and pharmaceutical composition containing them LT3675B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
SE8902274A SE8902274D0 (sv)	1989-06-22	1989-06-22	Indenoidole compounds ii

Publications (2)

Publication Number	Publication Date
LTIP912A LTIP912A (en)	1995-03-27
LT3675B true LT3675B (en)	1996-01-25

Family

ID=20376370

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
LTIP912A LT3675B (en)	1989-06-22	1993-08-30	Indenoindole copounds ii, process for preraring them and pharmaceutical composition containing them

Country Status (34)

Country	Link
EP (1)	EP0409410B1 (de)
JP (1)	JP3064411B2 (de)
KR (1)	KR920702679A (de)
CN (1)	CN1033029C (de)
AT (1)	ATE135688T1 (de)
BG (1)	BG60317B2 (de)
CA (1)	CA2060897A1 (de)
DD (1)	DD297960A5 (de)
DE (1)	DE69025998T2 (de)
DK (1)	DK0409410T3 (de)
DZ (1)	DZ1428A1 (de)
ES (1)	ES2084660T3 (de)
FI (1)	FI100800B (de)
GR (1)	GR3019779T3 (de)
HR (1)	HRP920903B1 (de)
HU (1)	HUT59097A (de)
IE (1)	IE74682B1 (de)
IL (1)	IL94830A (de)
IS (1)	IS3590A7 (de)
LT (1)	LT3675B (de)
LV (1)	LV10253B (de)
MX (1)	MX21244A (de)
MY (1)	MY107311A (de)
NO (1)	NO177932C (de)
NZ (1)	NZ234175A (de)
PL (1)	PL167761B1 (de)
PT (1)	PT94468B (de)
RO (1)	RO111573B1 (de)
RU (1)	RU2104270C1 (de)
SE (1)	SE8902274D0 (de)
SI (1)	SI9011223B (de)
WO (1)	WO1990015799A1 (de)
YU (1)	YU122390A (de)
ZA (1)	ZA904827B (de)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
HU9301104D0 (en) *	1990-10-16	1993-07-28	Univ Bath	Method for producing tetrahydro-indeno-indole derivatves and pharmaceutical preparatives containing it
JPH0656669A (ja) *	1992-06-11	1994-03-01	Asahi Breweries Ltd	活性酸素消去作用を持つプテリン誘導体製剤
SE9302431D0 (sv) *	1993-07-16	1993-07-16	Ab Astra	Use of indenoindole compounds
CA2128283A1 (fr) *	1993-07-20	1995-01-21	Paul Caubere	(thia)cycloalkyl¬b\|indoles, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
US6288099B1 (en)	1998-12-04	2001-09-11	American Home Products Corporation	Substituted benzofuranoindoles and indenoindoles as novel potassium channel openers
JP2002531569A (ja) *	1998-12-04	2002-09-24	ワイス	新規なカリウムチャンネル開放物質としての置換ベンゾフラノインドール及びインデノインドール
FR2826009B1 (fr) *	2001-06-13	2003-08-15	Servier Lab	Nouveaux derives d'indenoindolones, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
CA2612442A1 (en)	2005-07-14	2007-01-18	Irm Llc	Heterotetracyclic compounds as tpo mimetics
DE102006047231B4 (de) *	2006-10-04	2009-02-12	Hemmerling, Hans-Jörg, Dr.	Substituierte Indeno[1,2-b]indolderivate als neue Hemmstoffe der Protein Kinase CK2 und ihre Verwendung als Tumor Therapeutika, Cytostatika und Diagnostika
EP2722042B1 (de) *	2011-06-16	2019-05-29	Korea Research Institute of Chemical Technology	Indanonderivate, pharmazeutisch zulässige salze oder optische isomere davon, verfahren zu ihrer herstellung und pharmazeutische zusammensetzungen damit als wirkstoff zur verhinderung oder behandlung von virenerkrankungen
PT3882244T (pt)	2012-12-14	2025-04-04	Univ Leuven Kath	Composto, sal farmaceuticamente aceitável ou isómero ótico do mesmo, método para a sua preparação e composição farmacêutica para prevenção ou tratamento de doenças virais que contenha o mesmo como ingrediente ativo
KR102894005B1 (ko)	2020-04-20	2025-12-03	노파르티스 아게	항바이러스 1,3-다이-옥소-인덴 화합물
CN115916763B (zh)	2020-04-20	2025-06-03	诺华股份有限公司	抗病毒素1,3-二氧代茚化合物

1989
- 1989-06-22 SE SE8902274A patent/SE8902274D0/xx unknown
1990
- 1990-06-13 IS IS3590A patent/IS3590A7/is unknown
- 1990-06-20 HU HU904825A patent/HUT59097A/hu unknown
- 1990-06-20 CA CA002060897A patent/CA2060897A1/en not_active Abandoned
- 1990-06-20 JP JP2508940A patent/JP3064411B2/ja not_active Expired - Fee Related
- 1990-06-20 MX MX21244A patent/MX21244A/es unknown
- 1990-06-20 PL PL90285752A patent/PL167761B1/pl unknown
- 1990-06-20 RU SU5010937A patent/RU2104270C1/ru active
- 1990-06-20 AT AT90306718T patent/ATE135688T1/de active
- 1990-06-20 DZ DZ900114A patent/DZ1428A1/fr active
- 1990-06-20 EP EP90306718A patent/EP0409410B1/de not_active Expired - Lifetime
- 1990-06-20 WO PCT/GB1990/000949 patent/WO1990015799A1/en not_active Ceased
- 1990-06-20 RO RO149127A patent/RO111573B1/ro unknown
- 1990-06-20 DK DK90306718.9T patent/DK0409410T3/da active
- 1990-06-20 ES ES90306718T patent/ES2084660T3/es not_active Expired - Lifetime
- 1990-06-20 DE DE69025998T patent/DE69025998T2/de not_active Expired - Fee Related
- 1990-06-20 IE IE224790A patent/IE74682B1/en not_active IP Right Cessation
- 1990-06-21 IL IL9483090A patent/IL94830A/en not_active IP Right Cessation
- 1990-06-21 ZA ZA904827A patent/ZA904827B/xx unknown
- 1990-06-21 NZ NZ234175A patent/NZ234175A/xx unknown
- 1990-06-21 MY MYPI90001050A patent/MY107311A/en unknown
- 1990-06-21 DD DD90341939A patent/DD297960A5/de not_active IP Right Cessation
- 1990-06-22 YU YU122390A patent/YU122390A/sh unknown
- 1990-06-22 CN CN90104933A patent/CN1033029C/zh not_active Expired - Fee Related
- 1990-06-22 SI SI9011223A patent/SI9011223B/sl unknown
- 1990-06-22 PT PT94468A patent/PT94468B/pt not_active IP Right Cessation
1991
- 1991-12-19 FI FI915999A patent/FI100800B/fi active
- 1991-12-20 NO NO915049A patent/NO177932C/no unknown
- 1991-12-20 BG BG095667A patent/BG60317B2/bg unknown
- 1991-12-23 KR KR1019910701951A patent/KR920702679A/ko not_active Ceased
1992
- 1992-10-02 HR HRP-1223/90A patent/HRP920903B1/xx not_active IP Right Cessation
1993
- 1993-06-14 LV LVP-93-568A patent/LV10253B/xx unknown
- 1993-08-30 LT LTIP912A patent/LT3675B/lt not_active IP Right Cessation
1996
- 1996-04-29 GR GR960401159T patent/GR3019779T3/el unknown

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
A.G. ANASTASSIOU ET AL.: "Generation and thermal reorganization of a linearly-fused N-methyldibenzoazocinyl anion", J. CHEM. SOC., CHEM. COMMUN., 1981, pages 647 - 648

Also Published As

Publication number	Publication date
MX21244A (es)	1994-03-31
BG60317B2 (bg)	1994-07-25
IE902247A1 (en)	1991-01-16
CN1033029C (zh)	1996-10-16
PL285752A1 (en)	1991-03-11
ES2084660T3 (es)	1996-05-16
NO915049D0 (no)	1991-12-20
HRP920903B1 (en)	1998-06-30
CN1051554A (zh)	1991-05-22
HRP920903A2 (hr)	1994-04-30
SI9011223B (sl)	1998-08-31
HUT59097A (en)	1992-04-28
NO915049L (no)	1992-02-21
IL94830A0 (en)	1991-04-15
SE8902274D0 (sv)	1989-06-22
NO177932B (no)	1995-09-11
EP0409410A1 (de)	1991-01-23
PT94468B (pt)	1997-12-31
DE69025998T2 (de)	1996-08-08
DE69025998D1 (de)	1996-04-25
LTIP912A (en)	1995-03-27
HU904825D0 (en)	1992-03-30
YU122390A (sh)	1992-09-07
IE74682B1 (en)	1997-07-30
WO1990015799A1 (en)	1990-12-27
MY107311A (en)	1995-11-30
IS3590A7 (is)	1990-12-23
EP0409410B1 (de)	1996-03-20
FI100800B (fi)	1998-02-27
DD297960A5 (de)	1992-01-30
RU2104270C1 (ru)	1998-02-10
ZA904827B (en)	1991-04-24
JP3064411B2 (ja)	2000-07-12
CA2060897A1 (en)	1990-12-23
GR3019779T3 (en)	1996-07-31
DZ1428A1 (fr)	2004-09-13
NZ234175A (en)	1992-12-23
JPH04505923A (ja)	1992-10-15
KR920702679A (ko)	1992-10-06
LV10253B (en)	1995-04-20
LV10253A (lv)	1994-10-20
SI9011223A (en)	1997-10-31
FI915999A0 (fi)	1991-12-19
DK0409410T3 (da)	1996-04-29
IL94830A (en)	1996-07-23
IE902247L (en)	1990-12-22
PT94468A (pt)	1991-02-08
PL167761B1 (pl)	1995-10-31
AU5836990A (en)	1991-01-08
AU644084B2 (en)	1993-12-02
RO111573B1 (ro)	1996-11-29
NO177932C (no)	1995-12-20
ATE135688T1 (de)	1996-04-15

Legal Events

Date	Code	Title	Description
1999-04-26	MM9A	Lapsed patents	Effective date: 19980830

Publication	Publication Date	Title
US20020128480A1 (en)	2002-09-12	Sulfonamide-containing indole compounds
RU2104270C1 (ru)	1998-02-10	Тетрагидроинденоиндольные соединения, способы их получения, фармацевтическая композиция, обладающая антиоксидантной активностью, противоокислительная композиция и способ стабилизации соединений, восприимчивых к окислению
EP0148167B1 (de)	1989-05-31	Quinolinderivate, Verfahren zu ihrer Herstellung und sie enthaltende pharmazeutische Mittel
US5185360A (en)	1993-02-09	Dihydroindenoindole compounds and methods for using the same
US5516788A (en)	1996-05-14	Tetrahydroindenoindole compounds useful in the treatment of conditions associated with free radical formation
AP339A (en)	1994-05-02	Indenoindoles compounds.
AU644084C (en)	1995-01-05	Indenoindole compounds II
CN102617465A (zh)	2012-08-01	他克林-咖啡酸杂联体,其制备方法及其药物组合物
EP1474390B1 (de)	2009-07-22	Indolderivate substituiert mit langkettigen alcoholen und sie enthaltende arzneimittel
JPH11504616A (ja)	1999-04-27	ジベンズ［ｃｄ，ｆ］インドール誘導体
CN108440278A (zh)	2018-08-24	一种二羧基查尔酮类化合物及其在制备抗炎药物中的应用
FR2800071A1 (fr)	2001-04-27	Tetrahydropyridines, procede pour leur preparation et compositions pharmaceutiques les contenant