LT3708B - N-(4-piperidinyl)(dihydrobenzofuran or dihydro-2h-benzopyran)carboxamide derivatives,processes for the preparation thereof and pharmaceutical compositions - Google Patents

N-(4-piperidinyl)(dihydrobenzofuran or dihydro-2h-benzopyran)carboxamide derivatives,processes for the preparation thereof and pharmaceutical compositions Download PDF

Info

Publication number: LT3708B
Authority: LT; Lithuania
Prior art keywords: formula; alkyl; hydrogen; radical; dihydro
Prior art date: 1990-03-06

Application number

LTIP846A

Other languages

English (en)

Lithuanian (lt)

Inventor

Georges Henri Paul Van Daele

Jean-Paul Rene Marie Bosmans

Michel Anna Jozef De Cleyn

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.)

1990-03-06

Filing date

1993-08-10

Publication date

1996-02-26

1993-08-10 Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv

1995-02-27 Publication of LTIP846A publication Critical patent/LTIP846A/xx

1996-02-26 Publication of LT3708B publication Critical patent/LT3708B/lt

Links

238000000034 method Methods 0.000 title claims abstract description 28
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 8
238000002360 preparation method Methods 0.000 title claims description 11
HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 title claims description 10
230000008569 process Effects 0.000 title claims description 4
150000001875 compounds Chemical class 0.000 claims abstract description 112
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 77
239000001257 hydrogen Substances 0.000 claims abstract description 76
125000003118 aryl group Chemical group 0.000 claims abstract description 50
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 28
150000003839 salts Chemical class 0.000 claims abstract description 23
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 16
239000004480 active ingredient Substances 0.000 claims abstract description 5
230000004936 stimulating effect Effects 0.000 claims abstract description 5
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 3
125000000217 alkyl group Chemical group 0.000 claims description 117
-1 alkyl radical Chemical class 0.000 claims description 86
239000000543 intermediate Substances 0.000 claims description 62
150000003254 radicals Chemical class 0.000 claims description 47
150000002431 hydrogen Chemical class 0.000 claims description 37
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 36
238000006243 chemical reaction Methods 0.000 claims description 36
229910052760 oxygen Inorganic materials 0.000 claims description 26
125000004093 cyano group Chemical group *C#N 0.000 claims description 25
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 25
125000003545 alkoxy group Chemical group 0.000 claims description 24
229910052736 halogen Inorganic materials 0.000 claims description 24
150000002367 halogens Chemical class 0.000 claims description 24
239000012442 inert solvent Substances 0.000 claims description 24
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 20
239000002253 acid Substances 0.000 claims description 20
125000000753 cycloalkyl group Chemical group 0.000 claims description 20
150000001412 amines Chemical class 0.000 claims description 19
125000001424 substituent group Chemical group 0.000 claims description 19
229910052757 nitrogen Inorganic materials 0.000 claims description 18
229910052717 sulfur Inorganic materials 0.000 claims description 17
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 14
125000000623 heterocyclic group Chemical group 0.000 claims description 14
239000001301 oxygen Substances 0.000 claims description 14
125000004432 carbon atom Chemical group C* 0.000 claims description 13
125000005843 halogen group Chemical group 0.000 claims description 12
125000005842 heteroatom Chemical group 0.000 claims description 12
125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
229910052799 carbon Inorganic materials 0.000 claims description 11
125000003386 piperidinyl group Chemical group 0.000 claims description 11
150000001204 N-oxides Chemical class 0.000 claims description 10
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
239000011593 sulfur Chemical group 0.000 claims description 10
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
239000003153 chemical reaction reagent Substances 0.000 claims description 9
150000002576 ketones Chemical class 0.000 claims description 9
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 9
125000003342 alkenyl group Chemical group 0.000 claims description 8
150000001408 amides Chemical class 0.000 claims description 8
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
210000001035 gastrointestinal tract Anatomy 0.000 claims description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
150000001299 aldehydes Chemical class 0.000 claims description 7
239000003513 alkali Substances 0.000 claims description 7
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
125000004434 sulfur atom Chemical group 0.000 claims description 7
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
125000003373 pyrazinyl group Chemical group 0.000 claims description 6
125000004076 pyridyl group Chemical group 0.000 claims description 6
230000002829 reductive effect Effects 0.000 claims description 6
125000003282 alkyl amino group Chemical group 0.000 claims description 5
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 5
125000000524 functional group Chemical group 0.000 claims description 4
125000001041 indolyl group Chemical group 0.000 claims description 4
125000004430 oxygen atom Chemical group O* 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
125000002619 bicyclic group Chemical group 0.000 claims description 3
231100000252 nontoxic Toxicity 0.000 claims description 3
230000003000 nontoxic effect Effects 0.000 claims description 3
JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 claims description 2
125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 2
TUCHYQZVQZXNBX-UHFFFAOYSA-N 4-amino-5-chloro-2,2-dimethyl-n-[1-(4-oxopentyl)piperidin-4-yl]-3h-1-benzofuran-7-carboxamide Chemical compound C1CN(CCCC(=O)C)CCC1NC(=O)C1=CC(Cl)=C(N)C2=C1OC(C)(C)C2 TUCHYQZVQZXNBX-UHFFFAOYSA-N 0.000 claims description 2
IAKAQFXZEFSADT-ZDUSSCGKSA-N 4-amino-5-chloro-n-[1-[[(2s)-oxolan-2-yl]methyl]piperidin-4-yl]-2,3-dihydro-1-benzofuran-7-carboxamide Chemical compound C1=C(Cl)C(N)=C2CCOC2=C1C(=O)NC(CC1)CCN1C[C@@H]1CCCO1 IAKAQFXZEFSADT-ZDUSSCGKSA-N 0.000 claims description 2
PENSADFYYNFWRP-UHFFFAOYSA-N 5-amino-6-chloro-n-[1-(oxolan-2-ylmethyl)piperidin-4-yl]-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound C1=2OCCCC=2C(N)=C(Cl)C=C1C(=O)NC(CC1)CCN1CC1CCCO1 PENSADFYYNFWRP-UHFFFAOYSA-N 0.000 claims description 2
XTPZUFSECASOGY-UHFFFAOYSA-N 5-amino-6-chloro-n-[1-[4-(3-ethyl-2-oxobenzimidazol-1-yl)butyl]piperidin-4-yl]-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound C1CCOC2=C1C(N)=C(Cl)C=C2C(=O)NC(CC1)CCN1CCCCN1C2=CC=CC=C2N(CC)C1=O XTPZUFSECASOGY-UHFFFAOYSA-N 0.000 claims description 2
PCBZRNYXXCIELG-WYFCWLEVSA-N COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 Chemical compound COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 PCBZRNYXXCIELG-WYFCWLEVSA-N 0.000 claims description 2
208000018522 Gastrointestinal disease Diseases 0.000 claims description 2
229910005965 SO 2 Inorganic materials 0.000 claims description 2
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 2
125000002837 carbocyclic group Chemical group 0.000 claims description 2
125000001309 chloro group Chemical group Cl* 0.000 claims description 2
239000012458 free base Substances 0.000 claims description 2
150000002496 iodine Chemical class 0.000 claims description 2
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 claims description 2
125000002950 monocyclic group Chemical group 0.000 claims description 2
125000004193 piperazinyl group Chemical group 0.000 claims description 2
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 2
150000003857 carboxamides Chemical class 0.000 claims 2
125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 claims 2
VNWYCQAUXWEBHU-UHFFFAOYSA-N 2h-chromene-8-carboxamide Chemical compound C1=CCOC2=C1C=CC=C2C(=O)N VNWYCQAUXWEBHU-UHFFFAOYSA-N 0.000 claims 1
241001465754 Metazoa Species 0.000 claims 1
125000004414 alkyl thio group Chemical group 0.000 claims 1
150000002118 epoxides Chemical class 0.000 claims 1
239000006260 foam Substances 0.000 claims 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical compound NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 claims 1
125000006850 spacer group Chemical group 0.000 claims 1
150000003053 piperidines Chemical class 0.000 abstract description 3
125000006619 (C1-C6) dialkylamino group Chemical group 0.000 abstract description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
125000000815 N-oxide group Chemical group 0.000 abstract 1
230000005176 gastrointestinal motility Effects 0.000 abstract 1
125000001475 halogen functional group Chemical group 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 87
239000000203 mixture Substances 0.000 description 61
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 60
239000000243 solution Substances 0.000 description 40
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
239000000460 chlorine Substances 0.000 description 32
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 31
239000011541 reaction mixture Substances 0.000 description 29
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
239000002244 precipitate Substances 0.000 description 25
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
239000002904 solvent Substances 0.000 description 24
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
239000000047 product Substances 0.000 description 21
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 20
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 20
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
238000004587 chromatography analysis Methods 0.000 description 19
239000000741 silica gel Substances 0.000 description 18
229910002027 silica gel Inorganic materials 0.000 description 18
SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 18
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 13
150000002148 esters Chemical class 0.000 description 13
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
239000002585 base Substances 0.000 description 12
150000002170 ethers Chemical class 0.000 description 12
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Natural products CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 11
239000003054 catalyst Substances 0.000 description 11
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
238000007126 N-alkylation reaction Methods 0.000 description 10
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
238000009835 boiling Methods 0.000 description 10
229960001701 chloroform Drugs 0.000 description 9
125000006239 protecting group Chemical group 0.000 description 9
239000007858 starting material Substances 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 8
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 8
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
150000001298 alcohols Chemical class 0.000 description 7
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
229910052794 bromium Inorganic materials 0.000 description 7
239000000284 extract Substances 0.000 description 7
229930195733 hydrocarbon Natural products 0.000 description 7
150000002430 hydrocarbons Chemical class 0.000 description 7
238000010992 reflux Methods 0.000 description 7
238000003756 stirring Methods 0.000 description 7
KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 description 6
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 6
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
230000002378 acidificating effect Effects 0.000 description 6
150000004945 aromatic hydrocarbons Chemical class 0.000 description 6
229910052801 chlorine Inorganic materials 0.000 description 6
229940052308 general anesthetics halogenated hydrocarbons Drugs 0.000 description 6
150000008282 halocarbons Chemical class 0.000 description 6
230000007062 hydrolysis Effects 0.000 description 6
238000006460 hydrolysis reaction Methods 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
239000011734 sodium Substances 0.000 description 6
239000000725 suspension Substances 0.000 description 6
239000003826 tablet Substances 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 5
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
229910052783 alkali metal Inorganic materials 0.000 description 5
238000005804 alkylation reaction Methods 0.000 description 5
239000000010 aprotic solvent Substances 0.000 description 5
230000008602 contraction Effects 0.000 description 5
150000004292 cyclic ethers Chemical class 0.000 description 5
USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 5
238000002156 mixing Methods 0.000 description 5
POSICDHOUBKJKP-UHFFFAOYSA-N prop-2-enoxybenzene Chemical compound C=CCOC1=CC=CC=C1 POSICDHOUBKJKP-UHFFFAOYSA-N 0.000 description 5
229920006395 saturated elastomer Polymers 0.000 description 5
239000012312 sodium hydride Substances 0.000 description 5
229910000104 sodium hydride Inorganic materials 0.000 description 5
238000012360 testing method Methods 0.000 description 5
239000004215 Carbon black (E152) Substances 0.000 description 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 4
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 4
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
230000029936 alkylation Effects 0.000 description 4
238000007112 amidation reaction Methods 0.000 description 4
239000012298 atmosphere Substances 0.000 description 4
210000001072 colon Anatomy 0.000 description 4
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 4
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
238000005658 halogenation reaction Methods 0.000 description 4
235000013675 iodine Nutrition 0.000 description 4
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
150000007530 organic bases Chemical class 0.000 description 4
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 4
229910000029 sodium carbonate Inorganic materials 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
IGERFAHWSHDDHX-UHFFFAOYSA-N 1,3-dioxanyl Chemical group [CH]1OCCCO1 IGERFAHWSHDDHX-UHFFFAOYSA-N 0.000 description 3
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
238000010934 O-alkylation reaction Methods 0.000 description 3
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
229910000564 Raney nickel Inorganic materials 0.000 description 3
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
150000001340 alkali metals Chemical class 0.000 description 3
230000009435 amidation Effects 0.000 description 3
229940053202 antiepileptics carboxamide derivative Drugs 0.000 description 3
239000002775 capsule Substances 0.000 description 3
230000000694 effects Effects 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
230000026030 halogenation Effects 0.000 description 3
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 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
150000004679 hydroxides Chemical class 0.000 description 3
239000011630 iodine Substances 0.000 description 3
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125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
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150000003624 transition metals Chemical class 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
FEONEKOZSGPOFN-UHFFFAOYSA-K tribromoiron Chemical compound Br[Fe](Br)Br FEONEKOZSGPOFN-UHFFFAOYSA-K 0.000 description 1
IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
239000000052 vinegar Substances 0.000 description 1
235000021419 vinegar Nutrition 0.000 description 1
230000008673 vomiting Effects 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1
GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/10—Laxatives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Nutrition Science (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pyrane Compounds (AREA)
Cosmetics (AREA)

LTIP846A 1990-03-06 1993-08-10 N-(4-piperidinyl)(dihydrobenzofuran or dihydro-2h-benzopyran)carboxamide derivatives,processes for the preparation thereof and pharmaceutical compositions LT3708B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB909005014A GB9005014D0 (en)	1990-03-06	1990-03-06	N.(4.piperidinyl)(dihydrobenzofuran or dihydro.2h.benzopyran)carboxamide derivatives

Publications (2)

Publication Number	Publication Date
LTIP846A LTIP846A (en)	1995-02-27
LT3708B true LT3708B (en)	1996-02-26

Family

ID=10672103

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
LTIP846A LT3708B (en)	1990-03-06	1993-08-10	N-(4-piperidinyl)(dihydrobenzofuran or dihydro-2h-benzopyran)carboxamide derivatives,processes for the preparation thereof and pharmaceutical compositions

Country Status (38)

Country	Link
US (2)	US5185335A (de)
EP (1)	EP0445862B1 (de)
JP (1)	JP2601566B2 (de)
KR (1)	KR0177521B1 (de)
CN (1)	CN1038936C (de)
AT (1)	ATE191912T1 (de)
AU (1)	AU636012B2 (de)
BG (1)	BG60381B1 (de)
CA (1)	CA2037575C (de)
CY (1)	CY2235B1 (de)
CZ (1)	CZ286617B6 (de)
DE (1)	DE69132119T2 (de)
DK (1)	DK0445862T3 (de)
ES (1)	ES2147175T3 (de)
FI (1)	FI101622B (de)
GB (1)	GB9005014D0 (de)
GR (1)	GR3033461T3 (de)
HR (1)	HRP930483B1 (de)
HU (2)	HU221627B1 (de)
IE (1)	IE910710A1 (de)
IL (1)	IL97018A (de)
LT (1)	LT3708B (de)
LV (1)	LV10085B (de)
MA (1)	MA22076A1 (de)
MY (1)	MY108831A (de)
NO (1)	NO177424C (de)
NZ (1)	NZ237189A (de)
PL (6)	PL168686B1 (de)
PT (1)	PT96937B (de)
RU (1)	RU2070884C1 (de)
SG (1)	SG47482A1 (de)
SI (1)	SI9110396B (de)
SK (2)	SK282406B6 (de)
TN (1)	TNSN91010A1 (de)
UA (1)	UA25969A1 (de)
YU (1)	YU48854B (de)
ZA (1)	ZA911611B (de)
ZW (1)	ZW2391A1 (de)

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US5595872A (en) *	1992-03-06	1997-01-21	Bristol-Myers Squibb Company	Nucleic acids encoding microsomal trigyceride transfer protein
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EP0664805A1 (de) *	1992-10-13	1995-08-02	Smithkline Beecham Plc	Heterozyklische karbonsäure-estern oder amide verwendbar als 5-ht4 rezeptor antagonisten
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GB9301660D0 (en) *	1993-01-28	1993-03-17	Smithkline Beecham Plc	Pharmaceuticals
US5739135A (en) *	1993-09-03	1998-04-14	Bristol-Myers Squibb Company	Inhibitors of microsomal triglyceride transfer protein and method
US5864039A (en) *	1994-03-30	1999-01-26	Yoshitomi Pharmaceutical Industries, Ltd.	Benzoic acid compounds and use thereof as medicaments
JPH0820586A (ja)	1994-07-05	1996-01-23	Sanwa Kagaku Kenkyusho Co Ltd	１−アザビシクロ［３．３．０］オクタン誘導体、その塩及び製法並びに用途
GB9418326D0 (en) *	1994-09-12	1994-11-02	Lilly Industries Ltd	Pharmaceutical compounds
JPH0873463A (ja)	1994-07-05	1996-03-19	Sanwa Kagaku Kenkyusho Co Ltd	ベンゾピランカルボキサミド誘導体、その塩及び製法並びに用途
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RU2154064C2 (ru) *	1994-09-27	2000-08-10	Жансен Фармасетика Н.В.	N-замещенные пиперидинилбензоаты, их n-оксидные формы, фармацевтически приемлемые соли присоединения кислот и стереохимически изомерные формы, способы их получения, фармацевтическая композиция на их основе и промежуточный продукт
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SE9902987D0 (sv)	1999-08-24	1999-08-24	Astra Pharma Prod	Novel compounds
CN1288730A (zh) *	1999-09-07	2001-03-28	麦克内尔-Ppc股份有限公司	轻泻组合物
GB0011838D0 (en) *	2000-05-17	2000-07-05	Astrazeneca Ab	Chemical compounds
GB0104050D0 (en)	2001-02-19	2001-04-04	Astrazeneca Ab	Chemical compounds
GB0107228D0 (en)	2001-03-22	2001-05-16	Astrazeneca Ab	Chemical compounds
SE0103818D0 (sv)	2001-11-15	2001-11-15	Astrazeneca Ab	Chemical compounds
US20050085510A1 (en) *	2002-01-16	2005-04-21	Telefonaktiebolaget Lm Ericsson (Publ)	Prucalopride-n-oxide
PT1489078E (pt) *	2002-03-28	2010-02-24	Mitsubishi Tanabe Pharma Corp	Derivados de benzofurano
AR040336A1 (es) *	2002-06-26	2005-03-30	Glaxo Group Ltd	Compuesto de piperidina, uso del mismo para la fabricacion de un medicamento, composicion farmaceutica que lo comprende y procedimiento para preparar dicho compuesto
SE0301369D0 (sv)	2003-05-09	2003-05-09	Astrazeneca Ab	Chemical compounds
DE10349113A1 (de) *	2003-10-17	2005-05-12	Boehringer Ingelheim Pharma	Verfahren zur Herstellung von Aminocrotonylverbindungen
US7652153B2 (en) *	2004-02-27	2010-01-26	Vertex Pharmaceuticals Incorporated	Caspase inhibitors and uses thereof
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CN102477002B (zh) *	2010-11-26	2015-04-15	苏州凯达生物医药技术有限公司	3-氨基-2,2-双甲基丙酰胺的制备方法
BR112013020641B1 (pt)	2011-02-25	2021-11-03	Yuhan Corporation	Composto, composição farmacêutica, processos para a preparação de composto e respectivo uso ou de seu sal farmaceuticamente aceitável
GB201103397D0 (de) *	2011-02-28	2011-04-13	Shire Movetis N V
KR101256908B1 (ko)	2011-04-28	2013-04-23	(주)에이치비메디컬스	주름제거용 충전체
CN102295594B (zh) *	2011-07-12	2016-01-20	上海医药工业研究院	4-n-取代-1-(3-甲氧基丙基)-4-哌啶胺类化合物及制备和应用
JP2014525927A (ja)	2011-08-18	2014-10-02	シャイアーアーゲー	治療法に使用される５−ｈｔ４受容体アゴニスト及びｐｄｅ４阻害剤の組合せ
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1990
- 1990-03-06 GB GB909005014A patent/GB9005014D0/en active Pending
1991
- 1991-02-04 US US07/650,328 patent/US5185335A/en not_active Expired - Lifetime
- 1991-02-21 NZ NZ237189A patent/NZ237189A/xx unknown
- 1991-02-22 SK SK460-91A patent/SK282406B6/sk not_active IP Right Cessation
- 1991-02-22 CZ CS1991460A patent/CZ286617B6/cs not_active IP Right Cessation
- 1991-02-22 DK DK91200382T patent/DK0445862T3/da active
- 1991-02-22 EP EP91200382A patent/EP0445862B1/de not_active Expired - Lifetime
- 1991-02-22 SK SK1623-98A patent/SK282407B6/sk not_active IP Right Cessation
- 1991-02-22 AT AT91200382T patent/ATE191912T1/de not_active IP Right Cessation
- 1991-02-22 ES ES91200382T patent/ES2147175T3/es not_active Expired - Lifetime
- 1991-02-22 DE DE69132119T patent/DE69132119T2/de not_active Expired - Lifetime
- 1991-02-22 SG SG1996002170A patent/SG47482A1/en unknown
- 1991-02-28 JP JP3058048A patent/JP2601566B2/ja not_active Expired - Lifetime
- 1991-03-02 KR KR1019910003440A patent/KR0177521B1/ko not_active Expired - Lifetime
- 1991-03-04 AU AU72079/91A patent/AU636012B2/en not_active Expired
- 1991-03-04 MY MYPI91000336A patent/MY108831A/en unknown
- 1991-03-04 IE IE071091A patent/IE910710A1/en not_active IP Right Cessation
- 1991-03-05 CA CA002037575A patent/CA2037575C/en not_active Expired - Lifetime
- 1991-03-05 BG BG93979A patent/BG60381B1/bg unknown
- 1991-03-05 RU SU914894778A patent/RU2070884C1/ru active
- 1991-03-05 PT PT96937A patent/PT96937B/pt not_active IP Right Cessation
- 1991-03-05 UA UA4894778A patent/UA25969A1/uk unknown
- 1991-03-05 FI FI911096A patent/FI101622B/fi active
- 1991-03-05 HU HU9100706A patent/HU221627B1/hu unknown
- 1991-03-05 ZA ZA911611A patent/ZA911611B/xx unknown
- 1991-03-05 NO NO910863A patent/NO177424C/no not_active IP Right Cessation
- 1991-03-05 ZW ZW23/91A patent/ZW2391A1/xx unknown
- 1991-03-06 PL PL91308053A patent/PL168686B1/pl unknown
- 1991-03-06 CN CN91101360A patent/CN1038936C/zh not_active Expired - Lifetime
- 1991-03-06 YU YU39691A patent/YU48854B/sh unknown
- 1991-03-06 PL PL91308054A patent/PL168693B1/pl unknown
- 1991-03-06 PL PL91289323A patent/PL168811B1/pl unknown
- 1991-03-06 PL PL91309550A patent/PL169238B1/pl unknown
- 1991-03-06 MA MA22349A patent/MA22076A1/fr unknown
- 1991-03-06 PL PL91308055A patent/PL168356B1/pl unknown
- 1991-03-06 TN TNTNSN91010A patent/TNSN91010A1/fr unknown
- 1991-03-06 PL PL91308052A patent/PL168384B1/pl unknown
- 1991-03-06 SI SI9110396A patent/SI9110396B/sl unknown
- 1991-10-24 IL IL9701891A patent/IL97018A/en not_active IP Right Cessation
1992
- 1992-11-17 US US07/977,314 patent/US5262418A/en not_active Expired - Lifetime
- 1992-11-27 LV LVP-92-232A patent/LV10085B/en unknown
1993
- 1993-03-23 HR HR930483A patent/HRP930483B1/xx not_active IP Right Cessation
- 1993-08-10 LT LTIP846A patent/LT3708B/lt not_active IP Right Cessation
1995
- 1995-06-16 HU HU95P/P00241P patent/HU211350A9/hu unknown
2000
- 2000-05-19 GR GR20000401151T patent/GR3033461T3/el not_active IP Right Cessation
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Also Published As

Publication number	Publication date
YU39691A (sh)	1994-06-10
AU7207991A (en)	1991-09-12
NO910863D0 (no)	1991-03-05
BG60381B1 (bg)	1995-01-31
FI911096A0 (fi)	1991-03-05
HU211350A9 (en)	1995-11-28
AU636012B2 (en)	1993-04-08
YU48854B (sh)	2002-06-19
IL97018A0 (en)	1992-03-29
NO910863L (no)	1991-09-09
BG93979A (bg)	1993-12-24
DK0445862T3 (da)	2000-09-04
HRP930483B1 (en)	2001-04-30
SI9110396B (sl)	2000-06-30
ZW2391A1 (en)	1992-09-07
MA22076A1 (fr)	1991-10-01
LV10085B (en)	1995-02-20
IE910710A1 (en)	1991-09-11
LV10085A (lv)	1994-05-10
ES2147175T3 (es)	2000-09-01
ZA911611B (en)	1992-11-25
PT96937A (pt)	1991-10-31
PL168811B1 (pl)	1996-04-30
LTIP846A (en)	1995-02-27
FI911096A7 (fi)	1991-09-07
CZ286617B6 (cs)	2000-05-17
PL169238B1 (pl)	1996-06-28
GB9005014D0 (en)	1990-05-02
CN1038936C (zh)	1998-07-01
NO177424B (no)	1995-06-06
KR0177521B1 (ko)	1999-03-20
FI101622B1 (fi)	1998-07-31
CA2037575C (en)	2003-09-16
RU2070884C1 (ru)	1996-12-27
PT96937B (pt)	1998-07-31
JP2601566B2 (ja)	1997-04-16
NO177424C (no)	1995-09-13
PL168686B1 (pl)	1996-03-29
US5185335A (en)	1993-02-09
HU221627B1 (hu)	2002-12-28
EP0445862A2 (de)	1991-09-11
SG47482A1 (en)	1998-04-17
ATE191912T1 (de)	2000-05-15
NZ237189A (en)	1992-11-25
DE69132119T2 (de)	2000-12-21
EP0445862B1 (de)	2000-04-19
DE69132119D1 (de)	2000-05-25
GR3033461T3 (en)	2000-09-29
PL168693B1 (pl)	1996-03-29
SK282407B6 (sk)	2002-01-07
HK1010727A1 (en)	1999-06-25
SI9110396A (en)	1997-12-31
IL97018A (en)	1995-11-27
HRP930483A2 (en)	1995-12-31
UA25969A1 (uk)	1999-02-26
HU910706D0 (en)	1991-09-30
PL289323A1 (en)	1992-03-09
FI101622B (fi)	1998-07-31
JPH04211685A (ja)	1992-08-03
EP0445862A3 (en)	1992-05-20
PL168356B1 (pl)	1996-02-29
TNSN91010A1 (fr)	1992-10-25
CS46091A3 (en)	1991-10-15
CY2235B1 (en)	2003-07-04
US5262418A (en)	1993-11-16
HUT60733A (en)	1992-10-28
SK282406B6 (sk)	2002-01-07
KR910016744A (ko)	1991-11-05
MY108831A (en)	1996-11-30
PL168384B1 (en)	1996-02-29
CA2037575A1 (en)	1991-09-07
CN1054598A (zh)	1991-09-18

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