CA1185605A - Pyrrolo(2,3-d)carbazole derivatives and preparation thereof - Google Patents
Pyrrolo(2,3-d)carbazole derivatives and preparation thereofInfo
- Publication number
- CA1185605A CA1185605A CA000401623A CA401623A CA1185605A CA 1185605 A CA1185605 A CA 1185605A CA 000401623 A CA000401623 A CA 000401623A CA 401623 A CA401623 A CA 401623A CA 1185605 A CA1185605 A CA 1185605A
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- carboxylate
- pyrrolo
- formula
- pharmaceutically acceptable
- 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.)
- Expired
Links
- 238000002360 preparation method Methods 0.000 title abstract description 7
- WMRZNKQZSBJIHT-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]carbazole Chemical class C1=CC=C2NC3=CC=CC4=NC=CC34C2=C1 WMRZNKQZSBJIHT-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 49
- 150000003839 salts Chemical class 0.000 claims abstract description 37
- -1 alkyl pyrrolo-(2,3-d)carbazole-6-carboxylates Chemical class 0.000 claims abstract description 13
- 230000008707 rearrangement Effects 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 47
- 229910052739 hydrogen Inorganic materials 0.000 claims description 41
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
- 230000008569 process Effects 0.000 claims description 35
- 150000001299 aldehydes Chemical class 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 19
- ISZIQZCZKOFSBT-UHFFFAOYSA-N pyrrolo[2,3-g][1]benzazepine Chemical compound N1=CC=CC=C2C3=NC=CC3=CC=C21 ISZIQZCZKOFSBT-UHFFFAOYSA-N 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 239000000126 substance Substances 0.000 claims description 14
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 claims description 13
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical group CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 12
- AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical group CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 claims description 12
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical group CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 239000007859 condensation product Substances 0.000 claims description 7
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 claims description 6
- 239000002168 alkylating agent Substances 0.000 claims description 4
- 229940100198 alkylating agent Drugs 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 4
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 150000002373 hemiacetals Chemical class 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 2
- MBXNQZHITVCSLJ-UHFFFAOYSA-N methyl fluorosulfonate Chemical compound COS(F)(=O)=O MBXNQZHITVCSLJ-UHFFFAOYSA-N 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 2
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims 2
- HMAKRRPHAGABLO-UHFFFAOYSA-N ethyl 4,4-dimethyl-1,2,3,3a,5,7-hexahydropyrrolo[2,3-d]carbazole-6-carboxylate Chemical compound CC1(CC(=C2NC=3C=CC=CC3C23C1NCC3)C(=O)OCC)C HMAKRRPHAGABLO-UHFFFAOYSA-N 0.000 claims 2
- 125000001475 halogen functional group Chemical group 0.000 claims 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
- MQNNUHIVJAMYRY-UHFFFAOYSA-N methyl 2,3,3a,4,5,7-hexahydro-1h-pyrrolo[2,3-d]carbazole-6-carboxylate Chemical compound N1C2=CC=CC=C2C23C1=C(C(=O)OC)CCC3NCC2 MQNNUHIVJAMYRY-UHFFFAOYSA-N 0.000 claims 2
- IAZDKCRQVPIXDX-UHFFFAOYSA-N methyl 3-benzyl-1,2,3a,4,5,7-hexahydropyrrolo[2,3-d]carbazole-6-carboxylate Chemical compound C12CCC(C(=O)OC)=C3NC4=CC=CC=C4C32CCN1CC1=CC=CC=C1 IAZDKCRQVPIXDX-UHFFFAOYSA-N 0.000 claims 2
- MLICWKXTURAKBP-UHFFFAOYSA-N methyl 3-benzyl-4,4-dimethyl-2,3a,5,7-tetrahydro-1h-pyrrolo[2,3-d]carbazole-6-carboxylate Chemical compound C12C(C)(C)CC(C(=O)OC)=C3NC4=CC=CC=C4C32CCN1CC1=CC=CC=C1 MLICWKXTURAKBP-UHFFFAOYSA-N 0.000 claims 2
- QQHUOJRTNRPQQO-UHFFFAOYSA-N methyl 3-benzyl-4-methyl-1,2,3a,4,5,7-hexahydropyrrolo[2,3-d]carbazole-6-carboxylate Chemical compound C12C(C)CC(C(=O)OC)=C3NC4=CC=CC=C4C32CCN1CC1=CC=CC=C1 QQHUOJRTNRPQQO-UHFFFAOYSA-N 0.000 claims 2
- ISWBBYXHPXOQFP-UHFFFAOYSA-N methyl 3-ethyl-4,4-dimethyl-2,3a,5,7-tetrahydro-1h-pyrrolo[2,3-d]carbazole-6-carboxylate Chemical compound C1=CC=C2C34CCN(CC)C4C(C)(C)CC(C(=O)OC)=C3NC2=C1 ISWBBYXHPXOQFP-UHFFFAOYSA-N 0.000 claims 2
- DCSRKMKTHAOMBE-UHFFFAOYSA-N methyl 3-methyl-1,2,3a,4,5,7-hexahydropyrrolo[2,3-d]carbazole-6-carboxylate Chemical compound N1C2=CC=CC=C2C23C1=C(C(=O)OC)CCC3N(C)CC2 DCSRKMKTHAOMBE-UHFFFAOYSA-N 0.000 claims 2
- YLCULBMCNSJNKR-UHFFFAOYSA-N methyl 4,4-dimethyl-1,2,3,3a,5,7-hexahydropyrrolo[2,3-d]carbazole-6-carboxylate Chemical compound N1C2=CC=CC=C2C23C1=C(C(=O)OC)CC(C)(C)C3NCC2 YLCULBMCNSJNKR-UHFFFAOYSA-N 0.000 claims 2
- YSXJFRSCDTWZLJ-UHFFFAOYSA-N methyl 4-ethyl-2,3,3a,4,5,7-hexahydro-1h-pyrrolo[2,3-d]carbazole-6-carboxylate Chemical compound N1C2=CC=CC=C2C23C1=C(C(=O)OC)CC(CC)C3NCC2 YSXJFRSCDTWZLJ-UHFFFAOYSA-N 0.000 claims 2
- 150000001351 alkyl iodides Chemical class 0.000 claims 1
- KVFDZFBHBWTVID-UHFFFAOYSA-N cyclohexanecarbaldehyde Chemical group O=CC1CCCCC1 KVFDZFBHBWTVID-UHFFFAOYSA-N 0.000 claims 1
- CTOZCCZDPQNZFT-UHFFFAOYSA-N ethyl 1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate Chemical group CCOC(=O)C1CNCCC2=C1NC1=CC=CC=C21 CTOZCCZDPQNZFT-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- ZWJKWUGXCCUBFM-UHFFFAOYSA-N methyl 1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate Chemical group COC(=O)C1CNCCC2=C1NC1=CC=CC=C21 ZWJKWUGXCCUBFM-UHFFFAOYSA-N 0.000 claims 1
- LSVRCABJSZNPRN-UHFFFAOYSA-N methyl 3-benzyl-4-ethyl-1,2,3a,4,5,7-hexahydropyrrolo[2,3-d]carbazole-6-carboxylate Chemical compound C12C(CC)CC(C(=O)OC)=C3NC4=CC=CC=C4C32CCN1CC1=CC=CC=C1 LSVRCABJSZNPRN-UHFFFAOYSA-N 0.000 claims 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims 1
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 abstract description 12
- 230000015572 biosynthetic process Effects 0.000 abstract description 7
- 238000005804 alkylation reaction Methods 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 3
- 230000002425 cardiocirculatory effect Effects 0.000 abstract description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 69
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- 239000000047 product Substances 0.000 description 34
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
- 239000000243 solution Substances 0.000 description 22
- 238000001819 mass spectrum Methods 0.000 description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 239000000203 mixture Substances 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 239000000543 intermediate Substances 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 239000000377 silicon dioxide Substances 0.000 description 11
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 239000002585 base Substances 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 238000007792 addition Methods 0.000 description 8
- KDDCNSWPVMLDHI-UHFFFAOYSA-N azepino[3,2-b]indole Chemical compound C1=CC=CN=C2C3=CC=CC=C3N=C21 KDDCNSWPVMLDHI-UHFFFAOYSA-N 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 229910052681 coesite Inorganic materials 0.000 description 8
- 229910052906 cristobalite Inorganic materials 0.000 description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 8
- 235000012239 silicon dioxide Nutrition 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 229910052682 stishovite Inorganic materials 0.000 description 8
- 229910052905 tridymite Inorganic materials 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 150000001716 carbazoles Chemical class 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- GIGFIWJRTMBSRP-ACRUOGEOSA-N (-)-vincadifformine Chemical compound C1C(C(=O)OC)=C2NC3=CC=CC=C3[C@@]22CCN3CCC[C@]1(CC)[C@@H]23 GIGFIWJRTMBSRP-ACRUOGEOSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 230000029936 alkylation Effects 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000007921 spray Substances 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- 230000000875 corresponding effect Effects 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- CPNXQIOMUYAVKQ-ODHPHVRJSA-N methyl (1S,12S,14R,19R)-14-ethyl-14-hydroxy-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,9-tetraene-10-carboxylate Chemical compound N1C2=CC=CC=C2[C@@]2([C@@H]34)C1=C(C(=O)OC)C[C@H]3C[C@@](CC)(O)CN4CC2 CPNXQIOMUYAVKQ-ODHPHVRJSA-N 0.000 description 4
- DRYBMFJLYYEOBZ-UHFFFAOYSA-N methyl 1h-indole-5-carboxylate Chemical compound COC(=O)C1=CC=C2NC=CC2=C1 DRYBMFJLYYEOBZ-UHFFFAOYSA-N 0.000 description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- NAMSIRMSFVGAKD-UHFFFAOYSA-N vincadifformine Natural products CCC12CCCN3CCC4(C13)C(Nc1cc(OC)ccc41)=C(C2)C(=O)OC NAMSIRMSFVGAKD-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- GIGFIWJRTMBSRP-UHFFFAOYSA-N DL-Vincadifformin Natural products C1C(C(=O)OC)=C2NC3=CC=CC=C3C22CCN3CCCC1(CC)C23 GIGFIWJRTMBSRP-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 239000007832 Na2SO4 Substances 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 230000000496 anti-anoxic effect Effects 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 229960004132 diethyl ether Drugs 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 235000015320 potassium carbonate Nutrition 0.000 description 3
- 230000000506 psychotropic effect Effects 0.000 description 3
- QNMMYUBZGLXCCK-UHFFFAOYSA-N pyrrolo[3,2-a]carbazole Chemical class N1=C2C=CC=CC2=C2C1=C1C=CN=C1C=C2 QNMMYUBZGLXCCK-UHFFFAOYSA-N 0.000 description 3
- 150000003335 secondary amines Chemical class 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 210000002356 skeleton Anatomy 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 235000018734 Sambucus australis Nutrition 0.000 description 2
- 244000180577 Sambucus australis Species 0.000 description 2
- 230000009102 absorption Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 229930013930 alkaloid Natural products 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- YAAIPCQYJYPITK-NCXUSEDFSA-N aspidospermidine Chemical group C1=CC=C2[C@]3([C@@H]45)CCN5CCC[C@]4(CC)CC[C@H]3NC2=C1 YAAIPCQYJYPITK-NCXUSEDFSA-N 0.000 description 2
- 229940095076 benzaldehyde Drugs 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000006264 debenzylation reaction Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 150000002081 enamines Chemical class 0.000 description 2
- 238000006345 epimerization reaction Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000000004 hemodynamic effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229940116591 skeleton diagnostic radiopharmaceuticals Drugs 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000006257 total synthesis reaction Methods 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
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- YQBZNVRQCVYPFC-UHFFFAOYSA-N secodine Chemical compound CCC1=CN(CCc2c([nH]c3ccccc23)C(=C)C(=O)OC)CCC1 YQBZNVRQCVYPFC-UHFFFAOYSA-N 0.000 description 1
- 229910052814 silicon oxide Inorganic materials 0.000 description 1
- CMXPERZAMAQXSF-UHFFFAOYSA-M sodium;1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate;1,8-dihydroxyanthracene-9,10-dione Chemical compound [Na+].O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O.CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC CMXPERZAMAQXSF-UHFFFAOYSA-M 0.000 description 1
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- 238000012956 testing procedure Methods 0.000 description 1
- BKVIYDNLLOSFOA-UHFFFAOYSA-N thallium Chemical compound [Tl] BKVIYDNLLOSFOA-UHFFFAOYSA-N 0.000 description 1
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- 125000005270 trialkylamine group Chemical group 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
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- 229940124549 vasodilator Drugs 0.000 description 1
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- CXBGOBGJHGGWIE-IYJDUVQVSA-N vindoline Chemical compound CN([C@H]1[C@](O)([C@@H]2OC(C)=O)C(=O)OC)C3=CC(OC)=CC=C3[C@]11CCN3CC=C[C@]2(CC)[C@@H]13 CXBGOBGJHGGWIE-IYJDUVQVSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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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
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/260,415 US4362739A (en) | 1981-05-04 | 1981-05-04 | Pyrrolo(2,3-d)carbazole derivatives, compositions and use |
| US260,415 | 1981-05-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1185605A true CA1185605A (en) | 1985-04-16 |
Family
ID=22989067
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000401623A Expired CA1185605A (en) | 1981-05-04 | 1982-04-26 | Pyrrolo(2,3-d)carbazole derivatives and preparation thereof |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US4362739A (en, 2012) |
| EP (1) | EP0064317B1 (en, 2012) |
| JP (1) | JPS57206686A (en, 2012) |
| AT (1) | ATE18226T1 (en, 2012) |
| CA (1) | CA1185605A (en, 2012) |
| DE (1) | DE3269309D1 (en, 2012) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| LU84664A1 (fr) * | 1983-02-25 | 1984-11-08 | Onmichem S A | Alkyl-4-indolonaphtyridines et leur application therapeutique |
| JPS62502684A (ja) * | 1985-03-12 | 1987-10-15 | ザ・ユニバ−シテイ・オブ・バ−モント・アンド・ステイト・アグリカルチユラル・カレツジ | ビンブラスチン及びビンクリスチン型化合物の合成 |
| US4841045A (en) * | 1985-03-12 | 1989-06-20 | University Of Vermont & State Agricultural College | Synthesis of vinblastine and vincristine type compounds |
| LU85894A1 (fr) * | 1985-05-10 | 1986-12-05 | Omnichem Sa | Derives de 1,2,3,4,5,6-hexahydro-azepino (4,5-b) indole leur preparation,composes intermediaires,et leur application en therapeutique |
| GB9401921D0 (en) * | 1994-02-01 | 1994-03-30 | Wellcome Found | Heterocyclic compounds |
| US7595311B2 (en) * | 2002-05-24 | 2009-09-29 | Exelixis, Inc. | Azepinoindole derivatives as pharmaceutical agents |
| TWI329111B (en) * | 2002-05-24 | 2010-08-21 | X Ceptor Therapeutics Inc | Azepinoindole and pyridoindole derivatives as pharmaceutical agents |
| JP4679517B2 (ja) * | 2003-07-23 | 2011-04-27 | エグゼリクシス， インコーポレイテッド | 薬剤としてのアゼピン誘導体 |
| US20130178618A1 (en) | 2012-01-10 | 2013-07-11 | William Allen Boulanger | Novel pharmaceutical intermediates and methods for preparing the same |
| CN110437238B (zh) * | 2019-08-15 | 2020-10-23 | 广州大学 | 一种多环螺吲哚啉化合物及其制备方法和应用 |
| US12116372B1 (en) | 2023-12-14 | 2024-10-15 | William Allen Boulanger | Process for preparing methyl 3-bromo-2-(2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)propanoate |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3015661A (en) * | 1958-09-04 | 1962-01-02 | Georgian Vlasios | Decahydroisoquinoline derivatives |
| US4154943A (en) * | 1977-12-29 | 1979-05-15 | University Of Vermont | Preparation of vincadifformine |
-
1981
- 1981-05-04 US US06/260,415 patent/US4362739A/en not_active Expired - Fee Related
-
1982
- 1982-04-26 CA CA000401623A patent/CA1185605A/en not_active Expired
- 1982-04-26 JP JP57070157A patent/JPS57206686A/ja active Granted
- 1982-05-01 AT AT82200513T patent/ATE18226T1/de not_active IP Right Cessation
- 1982-05-01 DE DE8282200513T patent/DE3269309D1/de not_active Expired
- 1982-05-01 EP EP82200513A patent/EP0064317B1/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| US4362739A (en) | 1982-12-07 |
| EP0064317B1 (en) | 1986-02-26 |
| JPH0322390B2 (en, 2012) | 1991-03-26 |
| ATE18226T1 (de) | 1986-03-15 |
| EP0064317A3 (en) | 1983-04-27 |
| DE3269309D1 (en) | 1986-04-03 |
| JPS57206686A (en) | 1982-12-18 |
| EP0064317A2 (en) | 1982-11-10 |
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