NO311523B1 - Antiallergiske imidazo[1,2-a](pyrrolo, tieno eller furano)- [2,3-d]azepinderivater - Google Patents

Antiallergiske imidazo[1,2-a](pyrrolo, tieno eller furano)- [2,3-d]azepinderivater Download PDF

Info

Publication number: NO311523B1
Authority: NO; Norway
Prior art keywords: formula; compound; acid; substituted; alkyl
Prior art date: 1992-12-04

Application number

NO19952199A

Other languages

English (en)

Norwegian (no)

Other versions

NO952199L (no

NO952199D0 (no

Inventor

Frans Eduard Janssens

Gaston Stanislas Marcell Diels

Joseph Elisabeth Leenaerts

Original Assignee

Janssen Pharmaceutica Nv

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.)

1992-12-04

Filing date

1995-06-02

Publication date

2001-12-03

1995-06-02 Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv

1995-06-02 Publication of NO952199D0 publication Critical patent/NO952199D0/no

1995-08-04 Publication of NO952199L publication Critical patent/NO952199L/no

2001-12-03 Publication of NO311523B1 publication Critical patent/NO311523B1/no

Links

150000001538 azepines Chemical class 0.000 title abstract description 4
230000003266 anti-allergic effect Effects 0.000 title description 8
150000001875 compounds Chemical class 0.000 claims abstract description 126
-1 hydroxyC1-4alkyl Chemical group 0.000 claims abstract description 32
238000000034 method Methods 0.000 claims abstract description 28
150000003839 salts Chemical class 0.000 claims abstract description 23
239000001257 hydrogen Substances 0.000 claims abstract description 21
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 21
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 16
238000002360 preparation method Methods 0.000 claims abstract description 14
ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims abstract description 9
125000003118 aryl group Chemical group 0.000 claims abstract description 7
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 6
150000002431 hydrogen Chemical group 0.000 claims abstract description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 5
125000001475 halogen functional group Chemical group 0.000 claims abstract description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 52
239000002253 acid Substances 0.000 claims description 27
238000006243 chemical reaction Methods 0.000 claims description 24
125000000217 alkyl group Chemical group 0.000 claims description 17
239000002904 solvent Substances 0.000 claims description 17
239000002585 base Substances 0.000 claims description 13
239000003153 chemical reaction reagent Substances 0.000 claims description 12
150000002576 ketones Chemical class 0.000 claims description 12
239000003054 catalyst Substances 0.000 claims description 10
239000012442 inert solvent Substances 0.000 claims description 9
239000004480 active ingredient Substances 0.000 claims description 6
239000003513 alkali Substances 0.000 claims description 5
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 5
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
125000003545 alkoxy group Chemical group 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
150000001336 alkenes Chemical class 0.000 claims description 2
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
125000004104 aryloxy group Chemical group 0.000 claims description 2
239000012458 free base Substances 0.000 claims description 2
125000000524 functional group Chemical group 0.000 claims description 2
125000002541 furyl group Chemical group 0.000 claims description 2
125000003386 piperidinyl group Chemical group 0.000 claims description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
125000001424 substituent group Chemical group 0.000 claims description 2
230000009466 transformation Effects 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
125000004949 alkyl amino carbonyl amino group Chemical group 0.000 claims 1
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims 1
239000003814 drug Substances 0.000 claims 1
150000002118 epoxides Chemical class 0.000 claims 1
239000000203 mixture Substances 0.000 abstract description 89
239000000543 intermediate Substances 0.000 abstract description 38
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 3
125000002485 formyl group Chemical group [H]C(*)=O 0.000 abstract 2
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 abstract 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 108
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 58
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
239000000243 solution Substances 0.000 description 29
239000003480 eluent Substances 0.000 description 24
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 20
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
239000000741 silica gel Substances 0.000 description 19
229910002027 silica gel Inorganic materials 0.000 description 19
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 16
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
238000002844 melting Methods 0.000 description 15
230000008018 melting Effects 0.000 description 15
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
239000012044 organic layer Substances 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
239000000460 chlorine Substances 0.000 description 11
238000004440 column chromatography Methods 0.000 description 11
238000003756 stirring Methods 0.000 description 10
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
229910000069 nitrogen hydride Inorganic materials 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 8
239000011521 glass Substances 0.000 description 8
239000002244 precipitate Substances 0.000 description 8
239000003826 tablet Substances 0.000 description 8
150000007513 acids Chemical class 0.000 description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
229910052757 nitrogen Inorganic materials 0.000 description 7
238000007363 ring formation reaction Methods 0.000 description 7
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
241000700159 Rattus Species 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 6
229910052784 alkaline earth metal Inorganic materials 0.000 description 6
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 6
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
229910000027 potassium carbonate Inorganic materials 0.000 description 6
239000000047 product Substances 0.000 description 6
238000010992 reflux Methods 0.000 description 6
238000007126 N-alkylation reaction Methods 0.000 description 5
238000006297 dehydration reaction Methods 0.000 description 5
230000000694 effects Effects 0.000 description 5
238000010438 heat treatment Methods 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
239000002202 Polyethylene glycol Substances 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
229910000147 aluminium phosphate Inorganic materials 0.000 description 4
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
150000004945 aromatic hydrocarbons Chemical class 0.000 description 4
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 4
239000002775 capsule Substances 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
239000012876 carrier material Substances 0.000 description 4
229960001701 chloroform Drugs 0.000 description 4
229920002055 compound 48/80 Polymers 0.000 description 4
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 4
150000002148 esters Chemical class 0.000 description 4
150000008282 halocarbons Chemical class 0.000 description 4
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
229940098779 methanesulfonic acid Drugs 0.000 description 4
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
239000003921 oil Substances 0.000 description 4
235000019198 oils Nutrition 0.000 description 4
229920001223 polyethylene glycol Polymers 0.000 description 4
150000003254 radicals Chemical class 0.000 description 4
239000000725 suspension Substances 0.000 description 4
HUCBCWSCTPKQIE-UHFFFAOYSA-N thieno[2,3-d]azepine Chemical compound C1=C[N]C=CC2=C1SC=C2 HUCBCWSCTPKQIE-UHFFFAOYSA-N 0.000 description 4
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
239000002841 Lewis acid Substances 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Natural products OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
239000000654 additive Substances 0.000 description 3
150000001298 alcohols Chemical class 0.000 description 3
238000001816 cooling Methods 0.000 description 3
HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical class OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 3
229930195733 hydrocarbon Natural products 0.000 description 3
238000005984 hydrogenation reaction Methods 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
235000014655 lactic acid Nutrition 0.000 description 3
231100000225 lethality Toxicity 0.000 description 3
150000007517 lewis acids Chemical class 0.000 description 3
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
231100000252 nontoxic Toxicity 0.000 description 3
230000003000 nontoxic effect Effects 0.000 description 3
150000007530 organic bases Chemical class 0.000 description 3
239000000843 powder Substances 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
239000007858 starting material Substances 0.000 description 3
229960005137 succinic acid Drugs 0.000 description 3
238000012360 testing method Methods 0.000 description 3
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
CUJPFPXNDSIBPG-UHFFFAOYSA-N 1,3-propanediyl Chemical group [CH2]C[CH2] CUJPFPXNDSIBPG-UHFFFAOYSA-N 0.000 description 2
QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 2
UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 2
SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
229910015900 BF3 Inorganic materials 0.000 description 2
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
239000004215 Carbon black (E152) Substances 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 2
229910021627 Tin(IV) chloride Inorganic materials 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
229910001516 alkali metal iodide Inorganic materials 0.000 description 2
150000001342 alkaline earth metals Chemical class 0.000 description 2
150000004703 alkoxides Chemical class 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
230000001387 anti-histamine Effects 0.000 description 2
239000000739 antihistaminic agent Substances 0.000 description 2
239000000010 aprotic solvent Substances 0.000 description 2
125000002785 azepinyl group Chemical group 0.000 description 2
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
230000037396 body weight Effects 0.000 description 2
238000009835 boiling Methods 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
150000001735 carboxylic acids Chemical class 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
239000011248 coating agent Substances 0.000 description 2
238000000576 coating method Methods 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
230000018044 dehydration Effects 0.000 description 2
239000006185 dispersion Substances 0.000 description 2
HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 2
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
230000002349 favourable effect Effects 0.000 description 2
239000008103 glucose Substances 0.000 description 2
235000011187 glycerol Nutrition 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
150000002367 halogens Chemical class 0.000 description 2
150000004678 hydrides Chemical class 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 2
239000011630 iodine Substances 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
239000008101 lactose Substances 0.000 description 2
239000007788 liquid Substances 0.000 description 2
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
239000002480 mineral oil Substances 0.000 description 2
235000010446 mineral oil Nutrition 0.000 description 2
230000001590 oxidative effect Effects 0.000 description 2
229910052763 palladium Inorganic materials 0.000 description 2
239000006187 pill Substances 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
229960003415 propylparaben Drugs 0.000 description 2
239000008213 purified water Substances 0.000 description 2
JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
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239000004094 surface-active agent Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
150000003626 triacylglycerols Chemical class 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
239000000080 wetting agent 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
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/14—Ortho-condensed systems
- 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

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Pulmonology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Immunology (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

NO19952199A 1992-12-04 1995-06-02 Antiallergiske imidazo[1,2-a](pyrrolo, tieno eller furano)- [2,3-d]azepinderivater NO311523B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP92203778		1992-12-04
PCT/EP1993/003321 WO1994013680A1 (fr)	1992-12-04	1993-11-25	DERIVES D'IMIDAZO[1-2-a](PYRROLO, THIENO OU FURANO)[2,3-d]AZEPINE A ACTION ANTIALLERGIQUE

Publications (3)

Publication Number	Publication Date
NO952199D0 NO952199D0 (no)	1995-06-02
NO952199L NO952199L (no)	1995-08-04
NO311523B1 true NO311523B1 (no)	2001-12-03

Family

ID=8211106

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19952199A NO311523B1 (no)	1992-12-04	1995-06-02	Antiallergiske imidazo[1,2-a](pyrrolo, tieno eller furano)- [2,3-d]azepinderivater

Country Status (16)

Country	Link
US (1)	US5629308A (fr)
EP (1)	EP0672047B1 (fr)
JP (1)	JP3503064B2 (fr)
KR (1)	KR100251295B1 (fr)
AT (1)	ATE239023T1 (fr)
AU (1)	AU676702B2 (fr)
CA (1)	CA2150805C (fr)
DE (1)	DE69332929T2 (fr)
ES (1)	ES2199224T3 (fr)
FI (1)	FI952723A7 (fr)
HU (1)	HU223466B1 (fr)
NO (1)	NO311523B1 (fr)
NZ (1)	NZ258552A (fr)
PL (1)	PL176235B1 (fr)
RU (1)	RU2134269C1 (fr)
WO (1)	WO1994013680A1 (fr)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2150806C (fr) *	1992-12-04	2006-01-31	Frans Eduard Janssens	Derives de la triazolobenzazepine ayant une action antiallergique
HU223465B1 (hu) *	1992-12-04	2004-07-28	Janssen Pharmaceutica N.V.	Allergia elleni triazolo(pirrolo, tieno vagy furán)-azepin-származékok, eljárás előállításukra és az ezeket tartalmazó gyógyszerkészítmények
FR2735474B1 (fr) *	1995-06-13	1997-08-08	Roussel Uclaf	Chlorhydrate de zilpaterol sous une forme cristallisee particuliere, son procede de preparation et les produits intermediaires mis en oeuvre
TW527186B (en)	1996-03-19	2003-04-11	Janssen Pharmaceutica Nv	Fused imidazole derivatives as multidrug resistance modulators
US6544979B1 (en)	1997-09-18	2003-04-08	Janssen Pharmaceuticals, N.V.	Fused imidazole derivatives for improving oral bioavailability of pharmaceutical agents
US7476662B2 (en)	2001-06-12	2009-01-13	Janssen Pharmaceutica N.V.	Substituted tetracyclic imidazole derivatives, processes for their preparation, pharmaceutical compositions comprising them and their use as a medicine
FR2872165B1 (fr) *	2004-06-24	2006-09-22	Sod Conseils Rech Applic	Nouveaux derives de pyrimido-benzimidazole
WO2011082269A2 (fr) *	2009-12-30	2011-07-07	Arqule, Inc.	Composés de benzo-pyrimido-tétrazolo-diazépine substituée
KR102431436B1 (ko)	2014-08-29	2022-08-10	테스 파마 에스.알.엘.	α-아미노-β-카복시뮤콘산 세미알데히드 데카복실라제의 억제제

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ZA755418B (en) *	1974-09-11	1977-06-29	Hoffmann La Roche	Diazepine derivatives
IL49161A (en) *	1975-08-07	1982-04-30	Sparamedica Ag	Imidazo(1,5-a)(1,4)-diazepine derivatives,their manufacture and pharmaceutical compositions containing them
FI880814A7 (fi) *	1987-03-10	1988-09-11	Hoffmann La Roche	Imidazodiazepin-derivat.
DE69110685T2 (de) *	1990-10-10	1995-11-09	Schering Corp	Substituierte imidazobenzazepine und imidazopyridoazepine.
IL101851A (en) *	1991-06-13	1996-05-14	Janssen Pharmaceutica Nv	10-(4-piperidinyl- and piperidinylidene)-imidazo [1,2-a] (pyrrolo thieno or furano) [2,3] azepine derivatives their preparation and pharmaceutical compositions containing them and certain novel intermediates therefor

1993
- 1993-11-25 ES ES94901887T patent/ES2199224T3/es not_active Expired - Lifetime
- 1993-11-25 HU HU9501620A patent/HU223466B1/hu not_active IP Right Cessation
- 1993-11-25 RU RU95114527A patent/RU2134269C1/ru not_active IP Right Cessation
- 1993-11-25 US US08/433,386 patent/US5629308A/en not_active Expired - Fee Related
- 1993-11-25 KR KR1019950702171A patent/KR100251295B1/ko not_active Expired - Fee Related
- 1993-11-25 NZ NZ258552A patent/NZ258552A/en unknown
- 1993-11-25 EP EP94901887A patent/EP0672047B1/fr not_active Expired - Lifetime
- 1993-11-25 CA CA002150805A patent/CA2150805C/fr not_active Expired - Fee Related
- 1993-11-25 JP JP51372194A patent/JP3503064B2/ja not_active Expired - Fee Related
- 1993-11-25 DE DE69332929T patent/DE69332929T2/de not_active Expired - Fee Related
- 1993-11-25 AT AT94901887T patent/ATE239023T1/de not_active IP Right Cessation
- 1993-11-25 AU AU56279/94A patent/AU676702B2/en not_active Ceased
- 1993-11-25 WO PCT/EP1993/003321 patent/WO1994013680A1/fr not_active Ceased
- 1993-11-25 PL PL93309254A patent/PL176235B1/pl not_active IP Right Cessation
1995
- 1995-06-02 FI FI952723A patent/FI952723A7/fi unknown
- 1995-06-02 NO NO19952199A patent/NO311523B1/no unknown

Also Published As

Publication number	Publication date
ES2199224T3 (es)	2004-02-16
PL309254A1 (en)	1995-10-02
DE69332929T2 (de)	2004-02-26
CA2150805C (fr)	2006-08-15
FI952723A0 (fi)	1995-06-02
HU223466B1 (hu)	2004-07-28
RU95114527A (ru)	1997-06-10
RU2134269C1 (ru)	1999-08-10
JPH08503953A (ja)	1996-04-30
NO952199L (no)	1995-08-04
JP3503064B2 (ja)	2004-03-02
US5629308A (en)	1997-05-13
DE69332929D1 (de)	2003-06-05
AU676702B2 (en)	1997-03-20
NZ258552A (en)	1996-07-26
NO952199D0 (no)	1995-06-02
ATE239023T1 (de)	2003-05-15
WO1994013680A1 (fr)	1994-06-23
HUT71807A (en)	1996-02-28
FI952723A7 (fi)	1995-06-02
HU9501620D0 (en)	1995-08-28
AU5627994A (en)	1994-07-04
EP0672047A1 (fr)	1995-09-20
KR100251295B1 (ko)	2000-05-01
EP0672047B1 (fr)	2003-05-02
CA2150805A1 (fr)	1994-06-23
PL176235B1 (pl)	1999-05-31

Publication	Publication Date	Title
EP0588858B1 (fr)	2003-09-17	DERIVES D'IMIDAZO 2,1-b] 3]BENZAZEPINE, COMPOSITIONS ET METHODE D'UTILISATION
IE58388B1 (en)	1993-09-08	1,2-benzisoxazol -3-yl and 1,2-benzisothiazol-3-yl derivatives
EP0675887B1 (fr)	2003-04-02	Derives de triazolobenzazepine anti-allergiques
EP0588859B1 (fr)	2003-08-13	Dérivés d'imidazo[1,2-a](pyrrolo, thieno ou furano)[3,2-d]azépine, compositions et méthodes d'utilisation
NO311523B1 (no)	2001-12-03	Antiallergiske imidazo[1,2-a](pyrrolo, tieno eller furano)- [2,3-d]azepinderivater
RU2133249C1 (ru)	1999-07-20	Производное имидазоазепина, фармацевтическая композиция, способ ее получения и способы получения производного имидазоазепина
EP0675889B1 (fr)	2000-07-05	Derives d'azepine triazolo(pyrrolo, thieno ou furano)
SI9500345A (sl)	1997-06-30	1,2-benzizoksazol-3-il derivati