SK126893A3 - Derivatives of perhydroisoindole and preparation thereof - Google Patents

Derivatives of perhydroisoindole and preparation thereof Download PDF

Info

Publication number: SK126893A3
Authority: SK; Slovakia
Prior art keywords: group; atom; diphenyl; derivative; hydroxy
Prior art date: 1991-05-17

Application number

SK1268-93A

Other languages

English (en)

Slovak (sk)

Inventor

Daniel Achard

Serge Grisoni

Stephen Hanessian

Claude Moutonnier

Jean-Francois Peyronel

Michel Tabart

Alain Truchon

Original Assignee

Rhone Poulenc Rorer Sa

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.)

1991-05-17

Filing date

1992-05-15

Publication date

1994-11-09

1992-05-15 Application filed by Rhone Poulenc Rorer Sa filed Critical Rhone Poulenc Rorer Sa

1994-11-09 Publication of SK126893A3 publication Critical patent/SK126893A3/sk

Links

ODSNARDHJFFSRH-UHFFFAOYSA-N 2,3,3a,4,5,6,7,7a-octahydro-1h-isoindole Chemical class C1CCCC2CNCC21 ODSNARDHJFFSRH-UHFFFAOYSA-N 0.000 title claims abstract description 20
238000002360 preparation method Methods 0.000 title claims abstract description 12
239000000203 mixture Substances 0.000 claims abstract description 61
-1 phenyl radicals Chemical class 0.000 claims abstract description 54
125000005843 halogen group Chemical group 0.000 claims abstract description 28
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 26
150000003839 salts Chemical class 0.000 claims abstract description 23
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 38
229910052757 nitrogen Inorganic materials 0.000 claims description 29
238000000034 method Methods 0.000 claims description 25
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
125000006239 protecting group Chemical group 0.000 claims description 18
125000000217 alkyl group Chemical group 0.000 claims description 17
229910052739 hydrogen Inorganic materials 0.000 claims description 15
229920006395 saturated elastomer Polymers 0.000 claims description 15
150000001875 compounds Chemical class 0.000 claims description 14
239000001257 hydrogen Substances 0.000 claims description 11
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
229910052801 chlorine Inorganic materials 0.000 claims description 8
125000001309 chloro group Chemical group Cl* 0.000 claims description 8
229910052731 fluorine Inorganic materials 0.000 claims description 8
125000003282 alkyl amino group Chemical group 0.000 claims description 7
125000004663 dialkyl amino group Chemical group 0.000 claims description 7
125000001153 fluoro group Chemical group F* 0.000 claims description 7
150000002475 indoles Chemical class 0.000 claims description 7
125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
125000000623 heterocyclic group Chemical group 0.000 claims description 6
125000003545 alkoxy group Chemical group 0.000 claims description 5
125000003277 amino group Chemical group 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 5
125000004043 oxo group Chemical group O=* 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 5
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
239000003795 chemical substances by application Substances 0.000 claims description 4
125000005842 heteroatom Chemical group 0.000 claims description 4
125000000904 isoindolyl group Chemical class C=1(NC=C2C=CC=CC12)* 0.000 claims description 4
125000004430 oxygen atom Chemical group O* 0.000 claims description 4
229910052717 sulfur Inorganic materials 0.000 claims description 4
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 3
KZKIDTOJVJYNRY-UHFFFAOYSA-N 4,4-difluoro-7,7-diphenyl-2,3,3a,5,6,7a-hexahydro-1h-isoindole Chemical compound C12CNCC2C(F)(F)CCC1(C=1C=CC=CC=1)C1=CC=CC=C1 KZKIDTOJVJYNRY-UHFFFAOYSA-N 0.000 claims description 2
OHCPKHFAXXEUQK-UHFFFAOYSA-N 4-fluoro-7,7-diphenyl-1,2,3,3a,4,5,6,7a-octahydroisoindole Chemical compound C12CNCC2C(F)CCC1(C=1C=CC=CC=1)C1=CC=CC=C1 OHCPKHFAXXEUQK-UHFFFAOYSA-N 0.000 claims description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
125000002252 acyl group Chemical group 0.000 claims description 2
125000004442 acylamino group Chemical group 0.000 claims description 2
125000004423 acyloxy group Chemical group 0.000 claims description 2
125000004103 aminoalkyl group Chemical group 0.000 claims description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
125000001624 naphthyl group Chemical group 0.000 claims description 2
229910052760 oxygen Inorganic materials 0.000 claims description 2
239000001301 oxygen Substances 0.000 claims description 2
239000011593 sulfur Chemical group 0.000 claims description 2
125000004434 sulfur atom Chemical group 0.000 claims description 2
230000002140 halogenating effect Effects 0.000 claims 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims 1
125000004414 alkyl thio group Chemical group 0.000 claims 1
125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
125000002911 monocyclic heterocycle group Chemical group 0.000 claims 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 claims 1
229940099990 ogen Drugs 0.000 claims 1
125000004585 polycyclic heterocycle group Chemical group 0.000 claims 1
102100024304 Protachykinin-1 Human genes 0.000 abstract description 9
101800003906 Substance P Proteins 0.000 abstract description 9
QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 abstract description 7
239000000543 intermediate Substances 0.000 abstract description 4
239000005557 antagonist Substances 0.000 abstract description 2
TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical group [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 abstract 1
WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 abstract 1
150000003254 radicals Chemical class 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 168
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 69
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 52
239000011541 reaction mixture Substances 0.000 description 49
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 38
239000013078 crystal Substances 0.000 description 37
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
239000007787 solid Substances 0.000 description 27
229910052943 magnesium sulfate Inorganic materials 0.000 description 26
235000019341 magnesium sulphate Nutrition 0.000 description 26
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 21
239000000047 product Substances 0.000 description 20
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
239000000741 silica gel Substances 0.000 description 18
229910002027 silica gel Inorganic materials 0.000 description 18
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
239000002904 solvent Substances 0.000 description 17
239000002253 acid Substances 0.000 description 16
238000003756 stirring Methods 0.000 description 16
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 15
238000010992 reflux Methods 0.000 description 15
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 14
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
238000006243 chemical reaction Methods 0.000 description 14
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
238000002329 infrared spectrum Methods 0.000 description 13
150000002518 isoindoles Chemical class 0.000 description 13
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
125000003118 aryl group Chemical group 0.000 description 11
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 11
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
239000011780 sodium chloride Substances 0.000 description 9
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 8
239000012074 organic phase Substances 0.000 description 8
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 7
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 7
150000002148 esters Chemical class 0.000 description 7
239000003960 organic solvent Substances 0.000 description 7
235000017557 sodium bicarbonate Nutrition 0.000 description 7
229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
238000010511 deprotection reaction Methods 0.000 description 6
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
238000000926 separation method Methods 0.000 description 6
HMFUXNHJEIQIPM-JQPLGUQCSA-N (3ar,4r,7ar)-4-fluoro-7,7-diphenyl-1,2,3,3a,4,5,6,7a-octahydroisoindole;hydrochloride Chemical compound Cl.C([C@H]([C@H]1CNC[C@H]11)F)CC1(C=1C=CC=CC=1)C1=CC=CC=C1 HMFUXNHJEIQIPM-JQPLGUQCSA-N 0.000 description 5
DQSBXVQJLSMPKA-UHFFFAOYSA-N 2-[2-(dimethylamino)phenyl]acetic acid Chemical compound CN(C)C1=CC=CC=C1CC(O)=O DQSBXVQJLSMPKA-UHFFFAOYSA-N 0.000 description 5
230000002411 adverse Effects 0.000 description 5
238000002425 crystallisation Methods 0.000 description 5
230000008025 crystallization Effects 0.000 description 5
239000012153 distilled water Substances 0.000 description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
239000000725 suspension Substances 0.000 description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
230000002378 acidificating effect Effects 0.000 description 4
150000001408 amides Chemical class 0.000 description 4
230000000694 effects Effects 0.000 description 4
IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 4
239000006260 foam Substances 0.000 description 4
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 4
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 4
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
NUSLQDOXLCYVTQ-ZETCQYMHSA-N (2s)-2-(2-methoxyphenyl)propanoic acid Chemical compound COC1=CC=CC=C1[C@H](C)C(O)=O NUSLQDOXLCYVTQ-ZETCQYMHSA-N 0.000 description 3
CIJLMNDNUOEELM-CJRXIRLBSA-N (3ar,7ar)-7,7-diphenyl-2,3,3a,5,6,7a-hexahydro-1h-isoindol-4-one;hydrochloride Chemical compound Cl.O=C([C@H]1CNC[C@H]11)CCC1(C=1C=CC=CC=1)C1=CC=CC=C1 CIJLMNDNUOEELM-CJRXIRLBSA-N 0.000 description 3
AWWGCTHFNOCGCA-SCLBCKFNSA-N (4s,5s)-3-[2-(2-methoxyphenyl)acetyl]-4-methyl-5-phenyl-1,3-oxazolidin-2-one Chemical compound COC1=CC=CC=C1CC(=O)N1C(=O)O[C@@H](C=2C=CC=CC=2)[C@@H]1C AWWGCTHFNOCGCA-SCLBCKFNSA-N 0.000 description 3
ANYKQHZQCLOANE-UHFFFAOYSA-N 2-[2-[3-(dimethylamino)propoxy]phenyl]acetic acid Chemical compound CN(C)CCCOC1=CC=CC=C1CC(O)=O ANYKQHZQCLOANE-UHFFFAOYSA-N 0.000 description 3
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 3
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
CIJLMNDNUOEELM-UHFFFAOYSA-N 7,7-diphenyl-2,3,3a,5,6,7a-hexahydro-1h-isoindol-4-one;hydrochloride Chemical compound Cl.C12CNCC2C(=O)CCC1(C=1C=CC=CC=1)C1=CC=CC=C1 CIJLMNDNUOEELM-UHFFFAOYSA-N 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
150000001409 amidines Chemical class 0.000 description 3
150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
239000002585 base Substances 0.000 description 3
239000004305 biphenyl Substances 0.000 description 3
125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000001816 cooling Methods 0.000 description 3
238000000354 decomposition reaction Methods 0.000 description 3
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 3
235000019253 formic acid Nutrition 0.000 description 3
230000026030 halogenation Effects 0.000 description 3
238000005658 halogenation reaction Methods 0.000 description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
150000002825 nitriles Chemical class 0.000 description 3
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
239000012279 sodium borohydride Substances 0.000 description 3
229910000033 sodium borohydride Inorganic materials 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
VMOVDDAZVSSFIT-BHDDXSALSA-N tert-butyl (3ar,4r,7ar)-4-fluoro-7,7-diphenyl-3,3a,4,5,6,7a-hexahydro-1h-isoindole-2-carboxylate Chemical compound C=1C=CC=CC=1C1([C@H]2[C@@H]([C@@H](CC1)F)CN(C2)C(=O)OC(C)(C)C)C1=CC=CC=C1 VMOVDDAZVSSFIT-BHDDXSALSA-N 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
XIFVRDPCHMNRJU-JQPLGUQCSA-N (3ar,4r,7ar)-4-chloro-7,7-diphenyl-1,2,3,3a,4,5,6,7a-octahydroisoindole;hydrochloride Chemical compound Cl.C([C@H]([C@H]1CNC[C@H]11)Cl)CC1(C=1C=CC=CC=1)C1=CC=CC=C1 XIFVRDPCHMNRJU-JQPLGUQCSA-N 0.000 description 2
USEOOBRASMLWTF-JQPLGUQCSA-N (3ar,4r,7ar)-7,7-diphenyl-1,2,3,3a,4,5,6,7a-octahydroisoindol-4-ol;hydrochloride Chemical compound Cl.C([C@H]([C@H]1CNC[C@H]11)O)CC1(C=1C=CC=CC=1)C1=CC=CC=C1 USEOOBRASMLWTF-JQPLGUQCSA-N 0.000 description 2
XIFVRDPCHMNRJU-FQTISCLSSA-N (3ar,4s,7ar)-4-chloro-7,7-diphenyl-1,2,3,3a,4,5,6,7a-octahydroisoindole;hydrochloride Chemical compound Cl.C([C@@H]([C@H]1CNC[C@H]11)Cl)CC1(C=1C=CC=CC=1)C1=CC=CC=C1 XIFVRDPCHMNRJU-FQTISCLSSA-N 0.000 description 2
YDTCAOIRGWQXAI-LOSJGSFVSA-N (3ar,7ar)-2-benzyl-7,7-diphenyl-1,3,3a,5,6,7a-hexahydroisoindol-4-one Chemical compound C([C@H]1C(CCC([C@H]1C1)=O)(C=2C=CC=CC=2)C=2C=CC=CC=2)N1CC1=CC=CC=C1 YDTCAOIRGWQXAI-LOSJGSFVSA-N 0.000 description 2
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
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AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
125000006242 amine protecting group Chemical group 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
230000036592 analgesia Effects 0.000 description 1
230000002921 anti-spasmodic effect Effects 0.000 description 1
229940054051 antipsychotic indole derivative Drugs 0.000 description 1
239000003849 aromatic solvent Substances 0.000 description 1
238000003556 assay Methods 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
WURBFLDFSFBTLW-UHFFFAOYSA-N benzil Chemical group C=1C=CC=CC=1C(=O)C(=O)C1=CC=CC=C1 WURBFLDFSFBTLW-UHFFFAOYSA-N 0.000 description 1
HQKFEUBRVQNYME-UHFFFAOYSA-N benzyl 2-(2-hydroxyphenyl)acetate Chemical compound OC1=CC=CC=C1CC(=O)OCC1=CC=CC=C1 HQKFEUBRVQNYME-UHFFFAOYSA-N 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
238000009835 boiling Methods 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
210000000748 cardiovascular system Anatomy 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
239000000812 cholinergic antagonist Substances 0.000 description 1
150000001860 citric acid derivatives Chemical class 0.000 description 1
239000004927 clay Substances 0.000 description 1
OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 1
229960004126 codeine Drugs 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
239000006071 cream Substances 0.000 description 1
125000004093 cyano group Chemical group *C#N 0.000 description 1
238000006352 cycloaddition reaction Methods 0.000 description 1
JHIVVAPYMSGYDF-PTQBSOBMSA-N cyclohexanone Chemical class O=[13C]1CCCCC1 JHIVVAPYMSGYDF-PTQBSOBMSA-N 0.000 description 1
238000010908 decantation Methods 0.000 description 1
125000003963 dichloro group Chemical group Cl* 0.000 description 1
229940113088 dimethylacetamide Drugs 0.000 description 1
ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000002526 effect on cardiovascular system Effects 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000012025 fluorinating agent Substances 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
238000001033 granulometry Methods 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
150000002431 hydrogen Chemical class 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
125000001841 imino group Chemical group [H]N=* 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical class OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
125000005956 isoquinolyl group Chemical group 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
210000001616 monocyte Anatomy 0.000 description 1
229960005181 morphine Drugs 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
NGZYRKGJWYJGRS-UHFFFAOYSA-N n-methylpyrrolidin-3-amine Chemical compound CNC1CCNC1 NGZYRKGJWYJGRS-UHFFFAOYSA-N 0.000 description 1
125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
150000002823 nitrates Chemical class 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
229960001027 opium Drugs 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
150000002924 oxiranes Chemical class 0.000 description 1
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
230000008506 pathogenesis Effects 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
235000019271 petrolatum Nutrition 0.000 description 1
229940066842 petrolatum Drugs 0.000 description 1
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
125000005544 phthalimido group Chemical group 0.000 description 1
238000000053 physical method Methods 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
125000003367 polycyclic group Chemical group 0.000 description 1
239000011698 potassium fluoride Substances 0.000 description 1
235000003270 potassium fluoride Nutrition 0.000 description 1
239000000843 powder Substances 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
230000028327 secretion Effects 0.000 description 1
LMDVZDMBPZVAIV-UHFFFAOYSA-N selenium hexafluoride Chemical compound F[Se](F)(F)(F)(F)F LMDVZDMBPZVAIV-UHFFFAOYSA-N 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
241000894007 species Species 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
VMOVDDAZVSSFIT-BDTNDASRSA-N tert-butyl (3ar,4s,7ar)-4-fluoro-7,7-diphenyl-3,3a,4,5,6,7a-hexahydro-1h-isoindole-2-carboxylate Chemical compound C=1C=CC=CC=1C1([C@H]2[C@@H]([C@H](CC1)F)CN(C2)C(=O)OC(C)(C)C)C1=CC=CC=C1 VMOVDDAZVSSFIT-BDTNDASRSA-N 0.000 description 1
FLXNNFRBWJTNAX-ZPHWTRHBSA-N tert-butyl (3ar,4s,7ar)-4-hydroxy-7,7-diphenyl-1,2,3,3a,4,5,6,7a-octahydroisoindole-1-carboxylate Chemical compound C=1C=CC=CC=1C1([C@H]2[C@@H]([C@H](CC1)O)CNC2C(=O)OC(C)(C)C)C1=CC=CC=C1 FLXNNFRBWJTNAX-ZPHWTRHBSA-N 0.000 description 1
GRZXYQUMNHMMSP-LEWJYISDSA-N tert-butyl (3ar,7ar)-7-oxo-4,4-diphenyl-1,3,3a,5,6,7a-hexahydroisoindole-2-carboxylate Chemical compound C=1C=CC=CC=1C1([C@H]2[C@@H](C(CC1)=O)CN(C2)C(=O)OC(C)(C)C)C1=CC=CC=C1 GRZXYQUMNHMMSP-LEWJYISDSA-N 0.000 description 1
MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 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
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
125000005505 thiomorpholino group Chemical group 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
125000004665 trialkylsilyl group Chemical group 0.000 description 1
125000001425 triazolyl 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
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Indole Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
Luminescent Compositions (AREA)

SK1268-93A 1991-05-17 1992-05-15 Derivatives of perhydroisoindole and preparation thereof SK126893A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
FR9106036A FR2676443B1 (fr)	1991-05-17	1991-05-17	Nouveaux derives de perhydroisoindole et leur preparation.
PCT/FR1992/000430 WO1992020654A1 (fr)	1991-05-17	1992-05-15	Nouveaux derives de perhydroisoindole et leur preparation

Publications (1)

Publication Number	Publication Date
SK126893A3 true SK126893A3 (en)	1994-11-09

Family

ID=9412908

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1268-93A SK126893A3 (en)	1991-05-17	1992-05-15	Derivatives of perhydroisoindole and preparation thereof

Country Status (23)

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US (1)	US5508433A (zh)
EP (2)	EP0514274A1 (zh)
JP (1)	JPH06507628A (zh)
AT (1)	ATE116295T1 (zh)
AU (1)	AU1884092A (zh)
CA (1)	CA2109297A1 (zh)
CZ (1)	CZ244893A3 (zh)
DE (1)	DE69201058T2 (zh)
DK (1)	DK0586471T3 (zh)
ES (1)	ES2066620T3 (zh)
FI (1)	FI935072A (zh)
FR (1)	FR2676443B1 (zh)
HU (1)	HUT68913A (zh)
IE (1)	IE921579A1 (zh)
IL (1)	IL101867A0 (zh)
MX (1)	MX9202288A (zh)
NO (1)	NO933976L (zh)
NZ (1)	NZ242773A (zh)
SK (1)	SK126893A3 (zh)
TW (1)	TW226991B (zh)
WO (1)	WO1992020654A1 (zh)
YU (1)	YU51692A (zh)
ZA (1)	ZA923541B (zh)

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AU502760B2 (en) *	1977-02-28	1979-08-09	Science Union Et Cie, Societe Francaise De Recherche Medicale	Azabicycloalkanes and their preparation
EP0058567B1 (en) *	1981-02-17	1984-07-25	Warner-Lambert Company	Substituted acyl derivatives of octahydro-1h-isoindole-1-carboxylic acids and esters
US4439229A (en) *	1981-06-29	1984-03-27	Rohm And Haas Company	Substituted phthalimides herbicides
JPH0278659A (ja) *	1988-09-12	1990-03-19	Shionogi & Co Ltd	アザビシクロアルカン類化合物
FR2654725B1 (fr) *	1989-11-23	1992-02-14	Rhone Poulenc Sante	Nouveaux derives de l'isoindolone, leur preparation et les compositions pharmaceutiques qui les contiennent.

1991
- 1991-05-17 FR FR9106036A patent/FR2676443B1/fr not_active Expired - Lifetime
1992
- 1992-05-12 CZ CS932448A patent/CZ244893A3/cs unknown
- 1992-05-14 IL IL101867A patent/IL101867A0/xx unknown
- 1992-05-15 ES ES92911071T patent/ES2066620T3/es not_active Expired - Lifetime
- 1992-05-15 EP EP92401330A patent/EP0514274A1/fr active Pending
- 1992-05-15 TW TW081103793A patent/TW226991B/zh active
- 1992-05-15 DE DE69201058T patent/DE69201058T2/de not_active Expired - Fee Related
- 1992-05-15 HU HU9303250A patent/HUT68913A/hu unknown
- 1992-05-15 WO PCT/FR1992/000430 patent/WO1992020654A1/fr not_active Application Discontinuation
- 1992-05-15 CA CA002109297A patent/CA2109297A1/fr not_active Abandoned
- 1992-05-15 EP EP92911071A patent/EP0586471B1/fr not_active Expired - Lifetime
- 1992-05-15 AT AT92911071T patent/ATE116295T1/de not_active IP Right Cessation
- 1992-05-15 DK DK92911071.6T patent/DK0586471T3/da active
- 1992-05-15 AU AU18840/92A patent/AU1884092A/en not_active Abandoned
- 1992-05-15 YU YU51692A patent/YU51692A/sh unknown
- 1992-05-15 JP JP4510463A patent/JPH06507628A/ja active Pending
- 1992-05-15 SK SK1268-93A patent/SK126893A3/sk unknown
- 1992-05-15 MX MX9202288A patent/MX9202288A/es unknown
- 1992-05-15 ZA ZA923541A patent/ZA923541B/xx unknown
- 1992-05-15 US US08/146,142 patent/US5508433A/en not_active Expired - Fee Related
- 1992-05-15 NZ NZ242773A patent/NZ242773A/xx unknown
- 1992-07-01 IE IE157992A patent/IE921579A1/en not_active Application Discontinuation
1993
- 1993-11-03 NO NO933976A patent/NO933976L/no unknown
- 1993-11-16 FI FI935072A patent/FI935072A/fi not_active Application Discontinuation

Also Published As

Publication number	Publication date
ES2066620T3 (es)	1995-03-01
MX9202288A (es)	1992-11-01
ZA923541B (en)	1993-01-27
DE69201058D1 (de)	1995-02-09
FI935072A0 (fi)	1993-11-16
CA2109297A1 (fr)	1992-11-18
FI935072A (fi)	1993-11-16
ATE116295T1 (de)	1995-01-15
DK0586471T3 (da)	1995-06-06
WO1992020654A1 (fr)	1992-11-26
JPH06507628A (ja)	1994-09-01
IL101867A0 (en)	1992-12-30
IE921579A1 (en)	1992-11-18
YU51692A (sh)	1994-06-10
EP0586471B1 (fr)	1994-12-28
FR2676443A1 (fr)	1992-11-20
NO933976D0 (no)	1993-11-03
HU9303250D0 (en)	1994-03-28
EP0586471A1 (fr)	1994-03-16
CZ244893A3 (en)	1994-04-13
FR2676443B1 (fr)	1993-08-06
EP0514274A1 (fr)	1992-11-19
NZ242773A (en)	1994-06-27
NO933976L (no)	1993-11-03
TW226991B (zh)	1994-07-21
US5508433A (en)	1996-04-16
AU1884092A (en)	1992-12-30
HUT68913A (en)	1995-08-28
DE69201058T2 (de)	1995-05-11

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