FR2478639A1 - Nouveaux derives de l'indolizino (8,7-b) indole et intermediaires, leur procede de preparation et leur utilisation en therapeutique - Google Patents
Nouveaux derives de l'indolizino (8,7-b) indole et intermediaires, leur procede de preparation et leur utilisation en therapeutique Download PDFInfo
- Publication number
- FR2478639A1 FR2478639A1 FR8006222A FR8006222A FR2478639A1 FR 2478639 A1 FR2478639 A1 FR 2478639A1 FR 8006222 A FR8006222 A FR 8006222A FR 8006222 A FR8006222 A FR 8006222A FR 2478639 A1 FR2478639 A1 FR 2478639A1
- Authority
- FR
- France
- Prior art keywords
- sep
- cis
- indolizino
- indole
- derivative
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 230000002490 cerebral effect Effects 0.000 title claims abstract description 7
- 230000001706 oxygenating effect Effects 0.000 title claims description 4
- NOPZVYXDJGZFKI-UHFFFAOYSA-N 1H-indolizino[1,2-g]indole Chemical compound C1=CC=CC2=C3C=CC(C=CN4)=C4C3=CN21 NOPZVYXDJGZFKI-UHFFFAOYSA-N 0.000 title claims 5
- 230000003110 anti-inflammatory effect Effects 0.000 title abstract 2
- 230000001105 regulatory effect Effects 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 10
- 239000002253 acid Substances 0.000 claims abstract description 9
- YAMNPRZWDUBVQI-UHFFFAOYSA-N 11h-indolizino[8,7-b]indole Chemical class N1C2=CC=CC=C2C2=C1C1=CC=CN1C=C2 YAMNPRZWDUBVQI-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 6
- 150000002367 halogens Chemical class 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- 125000002252 acyl group Chemical group 0.000 claims abstract description 5
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 33
- 150000002148 esters Chemical class 0.000 claims description 25
- 150000001875 compounds Chemical class 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 17
- NEUAIKNYTYQIMN-UHFFFAOYSA-N 1h-indolizino[8,7-b]indole Chemical compound C1=CC=CC2=C3C=CN4C=CCC4=C3N=C21 NEUAIKNYTYQIMN-UHFFFAOYSA-N 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 238000003786 synthesis reaction Methods 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 150000002431 hydrogen Chemical group 0.000 claims 3
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims 2
- 150000007513 acids Chemical class 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 239000000543 intermediate Substances 0.000 claims 2
- ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 claims 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims 1
- 229910052782 aluminium Inorganic materials 0.000 claims 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims 1
- SIAPCJWMELPYOE-UHFFFAOYSA-N lithium hydride Chemical compound [LiH] SIAPCJWMELPYOE-UHFFFAOYSA-N 0.000 claims 1
- 229910000103 lithium hydride Inorganic materials 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229940121363 anti-inflammatory agent Drugs 0.000 abstract 1
- 239000002260 anti-inflammatory agent Substances 0.000 abstract 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 abstract 1
- 238000002474 experimental method Methods 0.000 description 71
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 49
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
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- 239000000243 solution Substances 0.000 description 38
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- 239000013078 crystal Substances 0.000 description 26
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- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
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- 241001465754 Metazoa Species 0.000 description 7
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- 238000006243 chemical reaction Methods 0.000 description 7
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
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- 241000283973 Oryctolagus cuniculus Species 0.000 description 6
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- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
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- 239000006196 drop Substances 0.000 description 1
- 238000006345 epimerization reaction Methods 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- ICLWTJIMXVISSR-UHFFFAOYSA-N gallamine Chemical compound CCN(CC)CCOC1=CC=CC(OCCN(CC)CC)=C1OCCN(CC)CC ICLWTJIMXVISSR-UHFFFAOYSA-N 0.000 description 1
- 229960003054 gallamine Drugs 0.000 description 1
- 239000007789 gas Substances 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
- 239000008103 glucose Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 125000001145 hydrido group Chemical group *[H] 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 208000021822 hypotensive Diseases 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- MHCFAGZWMAWTNR-UHFFFAOYSA-M lithium perchlorate Chemical compound [Li+].[O-]Cl(=O)(=O)=O MHCFAGZWMAWTNR-UHFFFAOYSA-M 0.000 description 1
- 229910001486 lithium perchlorate Inorganic materials 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- RHMQNXNXUZLEIY-UHFFFAOYSA-N methanol;2-propan-2-yloxypropane Chemical compound OC.CC(C)OC(C)C RHMQNXNXUZLEIY-UHFFFAOYSA-N 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 230000004089 microcirculation Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001936 parietal effect Effects 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 229940072033 potash Drugs 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000011182 sodium carbonates Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- 230000003422 vasoregulatory effect Effects 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 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
- C07D471/12—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 three hetero rings
- C07D471/14—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8006222A FR2478639A1 (fr) | 1980-03-20 | 1980-03-20 | Nouveaux derives de l'indolizino (8,7-b) indole et intermediaires, leur procede de preparation et leur utilisation en therapeutique |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8006222A FR2478639A1 (fr) | 1980-03-20 | 1980-03-20 | Nouveaux derives de l'indolizino (8,7-b) indole et intermediaires, leur procede de preparation et leur utilisation en therapeutique |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| FR2478639A1 true FR2478639A1 (fr) | 1981-09-25 |
| FR2478639B1 FR2478639B1 (enExample) | 1983-11-10 |
Family
ID=9239887
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FR8006222A Granted FR2478639A1 (fr) | 1980-03-20 | 1980-03-20 | Nouveaux derives de l'indolizino (8,7-b) indole et intermediaires, leur procede de preparation et leur utilisation en therapeutique |
Country Status (1)
| Country | Link |
|---|---|
| FR (1) | FR2478639A1 (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0089926A3 (de) * | 1982-03-24 | 1984-05-16 | Ciba-Geigy Ag | Pharmazeutische Präparate enthaltend stickstoffhaltige Tetracyclen sowie neue Verbindungen dieser Art |
| WO2001081305A3 (en) * | 2000-04-19 | 2002-05-02 | Hoffmann La Roche | Methylation of indole compounds using dimethy carbonate |
| US7592350B2 (en) | 2002-04-03 | 2009-09-22 | Orion Corporation | Polycyclic compounds as potent alpha2-adrenoceptor antagonists |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4428877A (en) | 1978-07-12 | 1984-01-31 | Richter Gedeon Vegyeszeti Gyar Rt. | Cis-10-bromo-E-homoeburnanes |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1003645A (en) * | 1962-10-09 | 1965-09-08 | Koninklijke Pharma Fab Nv | Indolo-indolizine compounds |
| FR1418030A (fr) * | 1963-03-21 | 1965-11-19 | Mead Johnson & Co | Composés chimiques hétérocycliques nouveaux du type 1, 2, 3, 5, 6, 11b-hexahydro [3, 2, g] indolizinyl-2-méthyl-3, 4, 5-triméthoxybenzoate et composés intermédiaires permettant la mise en oeuvre de leur procédé de préparation |
| BE746698A (fr) * | 1970-02-27 | 1970-08-27 | American Home Prod | Derives de l'indolazonine et de l'indolazecine |
| GB1499546A (en) * | 1974-05-07 | 1978-02-01 | Richter Gedeon Vegyeszet | Indolo-quinolizidine derivatives and a process for the preparation thereof |
-
1980
- 1980-03-20 FR FR8006222A patent/FR2478639A1/fr active Granted
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1003645A (en) * | 1962-10-09 | 1965-09-08 | Koninklijke Pharma Fab Nv | Indolo-indolizine compounds |
| FR1418030A (fr) * | 1963-03-21 | 1965-11-19 | Mead Johnson & Co | Composés chimiques hétérocycliques nouveaux du type 1, 2, 3, 5, 6, 11b-hexahydro [3, 2, g] indolizinyl-2-méthyl-3, 4, 5-triméthoxybenzoate et composés intermédiaires permettant la mise en oeuvre de leur procédé de préparation |
| BE746698A (fr) * | 1970-02-27 | 1970-08-27 | American Home Prod | Derives de l'indolazonine et de l'indolazecine |
| GB1499546A (en) * | 1974-05-07 | 1978-02-01 | Richter Gedeon Vegyeszet | Indolo-quinolizidine derivatives and a process for the preparation thereof |
Non-Patent Citations (1)
| Title |
|---|
| EXBK/72 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0089926A3 (de) * | 1982-03-24 | 1984-05-16 | Ciba-Geigy Ag | Pharmazeutische Präparate enthaltend stickstoffhaltige Tetracyclen sowie neue Verbindungen dieser Art |
| WO2001081305A3 (en) * | 2000-04-19 | 2002-05-02 | Hoffmann La Roche | Methylation of indole compounds using dimethy carbonate |
| US7592350B2 (en) | 2002-04-03 | 2009-09-22 | Orion Corporation | Polycyclic compounds as potent alpha2-adrenoceptor antagonists |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2478639B1 (enExample) | 1983-11-10 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| ST | Notification of lapse |