NO310195B1 - Nye mellomprodukter og deres anvendelse for fremstilling av N,N'-broslåtte bisindolylmaleimider - Google Patents

Nye mellomprodukter og deres anvendelse for fremstilling av N,N'-broslåtte bisindolylmaleimider Download PDF

Info

Publication number: NO310195B1
Authority: NO; Norway
Prior art keywords: compound; reaction; formula; solution; added
Prior art date: 1995-11-20

Application number

NO19982105A

Other languages

English (en)

Norwegian (no)

Other versions

NO982105L (no

NO982105D0 (no

Inventor

Margaret Mary Faul

Christine Ann Krumrich

Jr Leonard Larry Winneroski

Original Assignee

Lilly Co Eli

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.)

1995-11-20

Filing date

1998-05-08

Publication date

2001-06-05

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=21725638&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=NO310195(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1998-05-08 Application filed by Lilly Co Eli filed Critical Lilly Co Eli

1998-05-08 Publication of NO982105L publication Critical patent/NO982105L/no

1998-05-08 Publication of NO982105D0 publication Critical patent/NO982105D0/no

2001-06-05 Publication of NO310195B1 publication Critical patent/NO310195B1/no

Links

229910052757 nitrogen Inorganic materials 0.000 title claims description 26
238000002360 preparation method Methods 0.000 title claims description 10
239000000543 intermediate Substances 0.000 title description 23
150000003924 bisindolylmaleimides Chemical class 0.000 title description 15
150000001875 compounds Chemical class 0.000 claims description 60
238000000034 method Methods 0.000 claims description 20
229910052794 bromium Inorganic materials 0.000 claims description 18
125000003277 amino group Chemical group 0.000 claims description 14
229910052740 iodine Inorganic materials 0.000 claims description 12
150000001412 amines Chemical class 0.000 claims description 9
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
230000008569 process Effects 0.000 claims description 8
DQYBRTASHMYDJG-UHFFFAOYSA-N Bisindolylmaleimide Chemical compound C1=CC=C2C(C=3C(=O)NC(C=3C=3C4=CC=CC=C4NC=3)=O)=CNC2=C1 DQYBRTASHMYDJG-UHFFFAOYSA-N 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
125000001246 bromo group Chemical group Br* 0.000 claims description 6
229920006395 saturated elastomer Polymers 0.000 claims description 6
239000001257 hydrogen Substances 0.000 claims description 5
229910052739 hydrogen Inorganic materials 0.000 claims description 5
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
239000002798 polar solvent Substances 0.000 claims description 4
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
239000011630 iodine Chemical group 0.000 claims description 3
125000002346 iodo group Chemical group I* 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
230000009466 transformation Effects 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 53
238000006243 chemical reaction Methods 0.000 description 50
239000000243 solution Substances 0.000 description 42
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
239000011541 reaction mixture Substances 0.000 description 34
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 32
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 23
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
239000012044 organic layer Substances 0.000 description 23
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 22
239000007787 solid Substances 0.000 description 21
239000000203 mixture Substances 0.000 description 20
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
235000019439 ethyl acetate Nutrition 0.000 description 18
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 16
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 16
238000004128 high performance liquid chromatography Methods 0.000 description 15
-1 t- butyl Chemical group 0.000 description 14
239000010410 layer Substances 0.000 description 13
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
239000003921 oil Substances 0.000 description 12
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 11
239000000047 product Substances 0.000 description 11
235000019270 ammonium chloride Nutrition 0.000 description 10
239000012535 impurity Substances 0.000 description 10
239000002002 slurry Substances 0.000 description 10
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
239000012047 saturated solution Substances 0.000 description 9
239000002904 solvent Substances 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
102000003923 Protein Kinase C Human genes 0.000 description 8
108090000315 Protein Kinase C Proteins 0.000 description 8
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 8
239000012267 brine Substances 0.000 description 8
150000004820 halides Chemical class 0.000 description 8
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
239000004480 active ingredient Substances 0.000 description 7
238000010992 reflux Methods 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
238000009472 formulation Methods 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
150000003839 salts Chemical class 0.000 description 6
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 5
108010044467 Isoenzymes Proteins 0.000 description 5
239000002585 base Substances 0.000 description 5
238000004519 manufacturing process Methods 0.000 description 5
239000003826 tablet Substances 0.000 description 5
231100000331 toxic Toxicity 0.000 description 5
230000002588 toxic effect Effects 0.000 description 5
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
229920002472 Starch Polymers 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
239000007903 gelatin capsule Substances 0.000 description 4
239000004615 ingredient Substances 0.000 description 4
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
238000000746 purification Methods 0.000 description 4
230000009257 reactivity Effects 0.000 description 4
230000004044 response Effects 0.000 description 4
235000019698 starch Nutrition 0.000 description 4
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 4
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
238000005481 NMR spectroscopy Methods 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
BEIIPJGHIJEDMT-SANMLTNESA-N [(3s)-3-(2-methylsulfonyloxyethoxy)-4-trityloxybutyl] methanesulfonate Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(OC[C@H](CCOS(C)(=O)=O)OCCOS(=O)(=O)C)C1=CC=CC=C1 BEIIPJGHIJEDMT-SANMLTNESA-N 0.000 description 3
238000003556 assay Methods 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
239000001913 cellulose Substances 0.000 description 3
235000010980 cellulose Nutrition 0.000 description 3
229920002678 cellulose Polymers 0.000 description 3
238000001816 cooling Methods 0.000 description 3
239000008367 deionised water Substances 0.000 description 3
229910021641 deionized water Inorganic materials 0.000 description 3
201000010099 disease Diseases 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
238000001914 filtration Methods 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
239000002480 mineral oil Substances 0.000 description 3
235000010446 mineral oil Nutrition 0.000 description 3
239000011734 sodium Substances 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
239000008107 starch Substances 0.000 description 3
GHCPFMUMJNJKLO-DEOSSOPVSA-N (3s)-3-(2-hydroxyethoxy)-4-trityloxybutan-1-ol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(OC[C@H](CCO)OCCO)C1=CC=CC=C1 GHCPFMUMJNJKLO-DEOSSOPVSA-N 0.000 description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 2
208000024172 Cardiovascular disease Diseases 0.000 description 2
229940126062 Compound A Drugs 0.000 description 2
FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 2
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 2
206010061218 Inflammation Diseases 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 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
241000124008 Mammalia Species 0.000 description 2
239000012359 Methanesulfonyl chloride Substances 0.000 description 2
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 2
102000001253 Protein Kinase Human genes 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
239000007983 Tris buffer Substances 0.000 description 2
UATOFRZSCHRPBG-UHFFFAOYSA-N acetamide;hydrate Chemical compound O.CC(N)=O UATOFRZSCHRPBG-UHFFFAOYSA-N 0.000 description 2
125000000217 alkyl group Chemical group 0.000 description 2
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
230000005587 bubbling Effects 0.000 description 2
239000006227 byproduct Substances 0.000 description 2
238000011088 calibration curve Methods 0.000 description 2
201000011510 cancer Diseases 0.000 description 2
239000002775 capsule Substances 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
208000015114 central nervous system disease Diseases 0.000 description 2
GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 2
206010012601 diabetes mellitus Diseases 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
230000000694 effects Effects 0.000 description 2
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
239000012467 final product Substances 0.000 description 2
239000012458 free base Substances 0.000 description 2
FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
125000004356 hydroxy functional group Chemical group O* 0.000 description 2
230000004054 inflammatory process Effects 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
208000028867 ischemia Diseases 0.000 description 2
238000000021 kinase assay Methods 0.000 description 2
AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
RMGJCSHZTFKPNO-UHFFFAOYSA-M magnesium;ethene;bromide Chemical compound [Mg+2].[Br-].[CH-]=C RMGJCSHZTFKPNO-UHFFFAOYSA-M 0.000 description 2
239000000463 material Substances 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
150000002739 metals Chemical class 0.000 description 2
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 2
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
239000012071 phase Substances 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
239000000843 powder Substances 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
108060006633 protein kinase Proteins 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
239000000725 suspension Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
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235000012222 talc Nutrition 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
HVLLSGMXQDNUAL-UHFFFAOYSA-N triphenyl phosphite Chemical compound C=1C=CC=CC=1OP(OC=1C=CC=CC=1)OC1=CC=CC=C1 HVLLSGMXQDNUAL-UHFFFAOYSA-N 0.000 description 2
JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 2
238000005303 weighing Methods 0.000 description 2
VPAHTUQECJIGCK-UHFFFAOYSA-N (2-methylphenyl)sulfonyl 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S(=O)(=O)OS(=O)(=O)C1=CC=CC=C1C VPAHTUQECJIGCK-UHFFFAOYSA-N 0.000 description 1
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
MSICOSWQOQACHW-FQEVSTJZSA-N (2s)-5-trityloxypentan-2-ol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(OCCC[C@@H](O)C)C1=CC=CC=C1 MSICOSWQOQACHW-FQEVSTJZSA-N 0.000 description 1
PDVFSPNIEOYOQL-UHFFFAOYSA-N (4-methylphenyl)sulfonyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OS(=O)(=O)C1=CC=C(C)C=C1 PDVFSPNIEOYOQL-UHFFFAOYSA-N 0.000 description 1
CTKINSOISVBQLD-GSVOUGTGSA-N (R)-Glycidol Chemical compound OC[C@@H]1CO1 CTKINSOISVBQLD-GSVOUGTGSA-N 0.000 description 1
CTKINSOISVBQLD-VKHMYHEASA-N (S)-Glycidol Chemical compound OC[C@H]1CO1 CTKINSOISVBQLD-VKHMYHEASA-N 0.000 description 1
LRHPLDYGYMQRHN-UHFFFAOYSA-N 1-butanol Substances CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
KDYRNYXQEPYCTD-UHFFFAOYSA-N 1-trityloxypent-4-en-2-ol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(OCC(O)CC=C)C1=CC=CC=C1 KDYRNYXQEPYCTD-UHFFFAOYSA-N 0.000 description 1
GHCPFMUMJNJKLO-UHFFFAOYSA-N 3-(2-hydroxyethoxy)-4-trityloxybutan-1-ol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(OCC(CCO)OCCO)C1=CC=CC=C1 GHCPFMUMJNJKLO-UHFFFAOYSA-N 0.000 description 1
XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
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 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
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- 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
- C07D487/08—Bridged systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
- A61P25/28—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]
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- 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

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Diabetes (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Hematology (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Obesity (AREA)
Hospice & Palliative Care (AREA)
Psychiatry (AREA)
Emergency Medicine (AREA)
Rheumatology (AREA)
Urology & Nephrology (AREA)
Pain & Pain Management (AREA)
Vascular Medicine (AREA)
Endocrinology (AREA)
Dermatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Plural Heterocyclic Compounds (AREA)
Pyrrole Compounds (AREA)

NO19982105A 1995-11-20 1998-05-08 Nye mellomprodukter og deres anvendelse for fremstilling av N,N'-broslåtte bisindolylmaleimider NO310195B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US734595P	1995-11-20	1995-11-20
PCT/US1996/018518 WO1997019080A1 (en)	1995-11-20	1996-11-18	Novel intermediates and their use to prepare n,n'-bridged bisindolylmaleimides

Publications (3)

Publication Number	Publication Date
NO982105L NO982105L (no)	1998-05-08
NO982105D0 NO982105D0 (no)	1998-05-08
NO310195B1 true NO310195B1 (no)	2001-06-05

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NO19982105A NO310195B1 (no)	1995-11-20	1998-05-08	Nye mellomprodukter og deres anvendelse for fremstilling av N,N'-broslåtte bisindolylmaleimider

Country Status (31)

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EP (1)	EP0776899B1 (pt)
JP (2)	JP4100708B2 (pt)
KR (1)	KR100342142B1 (pt)
CN (1)	CN1066734C (pt)
AR (2)	AR004719A1 (pt)
AT (1)	ATE191219T1 (pt)
AU (1)	AU701659B2 (pt)
BR (1)	BR9611709A (pt)
CA (1)	CA2237401C (pt)
CO (1)	CO4750824A1 (pt)
CZ (1)	CZ150398A3 (pt)
DE (1)	DE69607443T2 (pt)
DK (1)	DK0776899T3 (pt)
EA (1)	EA000639B1 (pt)
ES (1)	ES2145978T3 (pt)
GR (1)	GR3033729T3 (pt)
HU (1)	HU225716B1 (pt)
IL (1)	IL124415A (pt)
MX (1)	MX9803791A (pt)
MY (1)	MY118946A (pt)
NO (1)	NO310195B1 (pt)
NZ (1)	NZ323282A (pt)
PE (1)	PE17998A1 (pt)
PL (1)	PL184728B1 (pt)
PT (1)	PT776899E (pt)
TR (1)	TR199800876T2 (pt)
TW (1)	TW371661B (pt)
UA (1)	UA56145C2 (pt)
WO (1)	WO1997019080A1 (pt)
YU (1)	YU49316B (pt)
ZA (1)	ZA969645B (pt)

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Publication number	Priority date	Publication date	Assignee	Title
EP1070068B2 (en) *	1998-03-13	2007-01-17	The University Of British Columbia	Granulatimide derivatives for use in cancer treatment
CA2245029A1 (en)	1998-03-13	1999-09-13	University Of British Columbia	Granulatimide compounds as g2 checkpoint inhibitors
US6127401A (en) *	1998-06-05	2000-10-03	Cephalon, Inc.	Bridged indenopyrrolocarbazoles
US6300106B1 (en)	2000-11-22	2001-10-09	Ppg Industries Ohio, Inc.	Method of preparing 3-[2-{(Methylsulfonyl)oxy}-ethoxy ]-4-(triphenylmethoxy)-1-butanol, methane sulfonate
EP2181999A1 (en)	2008-11-03	2010-05-05	Zentiva, A.S.	Method of manufacturing ruboxistarin
KR20240170825A (ko) *	2022-03-31	2024-12-04	포엠 테라퓨틱스 인크.	키나제 억제제로서 n-데스메틸 루복시스타우린
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1996
- 1996-11-18 TR TR1998/00876T patent/TR199800876T2/xx unknown
- 1996-11-18 AU AU77388/96A patent/AU701659B2/en not_active Ceased
- 1996-11-18 HU HU9901975A patent/HU225716B1/hu not_active IP Right Cessation
- 1996-11-18 DE DE69607443T patent/DE69607443T2/de not_active Expired - Fee Related
- 1996-11-18 PE PE1996000828A patent/PE17998A1/es not_active Application Discontinuation
- 1996-11-18 CA CA002237401A patent/CA2237401C/en not_active Expired - Fee Related
- 1996-11-18 PT PT96308317T patent/PT776899E/pt unknown
- 1996-11-18 CZ CZ981503A patent/CZ150398A3/cs unknown
- 1996-11-18 AT AT96308317T patent/ATE191219T1/de not_active IP Right Cessation
- 1996-11-18 TW TW085114104A patent/TW371661B/zh active
- 1996-11-18 YU YU61096A patent/YU49316B/sh unknown
- 1996-11-18 WO PCT/US1996/018518 patent/WO1997019080A1/en not_active Application Discontinuation
- 1996-11-18 IL IL12441596A patent/IL124415A/xx not_active IP Right Cessation
- 1996-11-18 UA UA98052516A patent/UA56145C2/uk unknown
- 1996-11-18 KR KR1019980703626A patent/KR100342142B1/ko not_active IP Right Cessation
- 1996-11-18 EA EA199800368A patent/EA000639B1/ru not_active IP Right Cessation
- 1996-11-18 PL PL96326753A patent/PL184728B1/pl not_active IP Right Cessation
- 1996-11-18 ES ES96308317T patent/ES2145978T3/es not_active Expired - Lifetime
- 1996-11-18 CN CN96199575A patent/CN1066734C/zh not_active Expired - Fee Related
- 1996-11-18 BR BR9611709A patent/BR9611709A/pt not_active IP Right Cessation
- 1996-11-18 DK DK96308317T patent/DK0776899T3/da active
- 1996-11-18 NZ NZ323282A patent/NZ323282A/xx unknown
- 1996-11-18 ZA ZA9609645A patent/ZA969645B/xx unknown
- 1996-11-18 JP JP51983897A patent/JP4100708B2/ja not_active Expired - Fee Related
- 1996-11-18 EP EP96308317A patent/EP0776899B1/en not_active Expired - Lifetime
- 1996-11-19 CO CO96060836A patent/CO4750824A1/es unknown
- 1996-11-19 MY MYPI96004798A patent/MY118946A/en unknown
- 1996-11-20 AR ARP960105257A patent/AR004719A1/es unknown
- 1996-11-20 AR ARP960105256A patent/AR004718A1/es unknown
1998
- 1998-05-08 NO NO19982105A patent/NO310195B1/no not_active IP Right Cessation
- 1998-05-13 MX MX9803791A patent/MX9803791A/es unknown
2000
- 2000-06-20 GR GR20000401423T patent/GR3033729T3/el not_active IP Right Cessation
2007
- 2007-12-28 JP JP2007338808A patent/JP2008138006A/ja not_active Ceased

Also Published As

Publication number	Publication date
DE69607443D1 (de)	2000-05-04
ATE191219T1 (de)	2000-04-15
PL184728B1 (pl)	2002-12-31
PT776899E (pt)	2000-08-31
EP0776899B1 (en)	2000-03-29
NO982105L (no)	1998-05-08
JP4100708B2 (ja)	2008-06-11
HUP9901975A3 (en)	2000-01-28
CN1207740A (zh)	1999-02-10
DE69607443T2 (de)	2000-08-10
MX9803791A (es)	1998-09-30
BR9611709A (pt)	1999-02-23
HU225716B1 (en)	2007-07-30
AU701659B2 (en)	1999-02-04
CO4750824A1 (es)	1999-03-31
IL124415A0 (en)	1998-12-06
JP2008138006A (ja)	2008-06-19
ZA969645B (en)	1998-05-18
CN1066734C (zh)	2001-06-06
DK0776899T3 (da)	2000-07-10
AU7738896A (en)	1997-06-11
JP2000500496A (ja)	2000-01-18
EA000639B1 (ru)	1999-12-29
EP0776899A1 (en)	1997-06-04
MY118946A (en)	2005-02-28
KR100342142B1 (ko)	2002-08-22
NO982105D0 (no)	1998-05-08
YU61096A (sh)	1999-03-04
GR3033729T3 (en)	2000-10-31
AR004718A1 (es)	1999-03-10
PE17998A1 (es)	1998-04-20
HUP9901975A2 (hu)	1999-11-29
CZ150398A3 (cs)	1998-12-16
WO1997019080A1 (en)	1997-05-29
PL326753A1 (en)	1998-10-26
AR004719A1 (es)	1999-03-10
IL124415A (en)	2003-11-23
CA2237401C (en)	2003-10-21
UA56145C2 (uk)	2003-05-15
TW371661B (en)	1999-10-11
TR199800876T2 (xx)	1998-08-21
EA199800368A1 (ru)	1998-12-24
NZ323282A (en)	1999-01-28
ES2145978T3 (es)	2000-07-16
CA2237401A1 (en)	1997-05-29
YU49316B (sh)	2005-06-10
KR19990067600A (ko)	1999-08-25

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