DD284003A5 - Verfahren zur herstellung von alkoxy-4(1h)-pyridon-derivaten und deren verwendung - Google Patents

Verfahren zur herstellung von alkoxy-4(1h)-pyridon-derivaten und deren verwendung Download PDF

Info

Publication number: DD284003A5
Authority: DD; German Democratic Republic
Prior art keywords: group; general formula; atoms; pyridone; radical
Prior art date: 1988-08-06

Application number

DD89331409A

Other languages

German (de)

English (en)

Inventor

Julian Aranda

Johannes Hartenstein

Reinhard Reck

Christoph Schaechtele

Claus Rudolph

Hartmut Osswald

Guenter Weinheimer

Original Assignee

��@��k��

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.)

1988-08-06

Filing date

1989-08-02

Publication date

1990-10-31

1989-08-02 Application filed by ��@��k�� filed Critical ��@��k��

1990-10-31 Publication of DD284003A5 publication Critical patent/DD284003A5/de

Links

238000000034 method Methods 0.000 title claims abstract description 22
238000002360 preparation method Methods 0.000 title description 11
150000001875 compounds Chemical class 0.000 claims abstract description 37
206010020751 Hypersensitivity Diseases 0.000 claims abstract description 5
206010028980 Neoplasm Diseases 0.000 claims abstract description 5
230000007815 allergy Effects 0.000 claims abstract description 5
210000003169 central nervous system Anatomy 0.000 claims abstract description 5
230000004054 inflammatory process Effects 0.000 claims abstract description 5
206010003210 Arteriosclerosis Diseases 0.000 claims abstract description 4
206010020772 Hypertension Diseases 0.000 claims abstract description 4
208000007536 Thrombosis Diseases 0.000 claims abstract description 4
208000011775 arteriosclerosis disease Diseases 0.000 claims abstract description 4
230000003412 degenerative effect Effects 0.000 claims abstract description 4
230000002265 prevention Effects 0.000 claims abstract description 4
125000004432 carbon atom Chemical group C* 0.000 claims description 53
-1 benzyloxy-substituted phenyl Chemical group 0.000 claims description 52
239000001257 hydrogen Substances 0.000 claims description 27
229910052739 hydrogen Inorganic materials 0.000 claims description 27
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
125000000217 alkyl group Chemical group 0.000 claims description 22
239000002904 solvent Substances 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 19
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
150000003839 salts Chemical class 0.000 claims description 15
229920006395 saturated elastomer Polymers 0.000 claims description 15
150000002431 hydrogen Chemical class 0.000 claims description 11
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
125000003884 phenylalkyl group Chemical group 0.000 claims description 10
125000003545 alkoxy group Chemical group 0.000 claims description 9
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 9
229910052736 halogen Inorganic materials 0.000 claims description 9
150000002367 halogens Chemical class 0.000 claims description 9
125000004093 cyano group Chemical group *C#N 0.000 claims description 8
125000004663 dialkyl amino group Chemical group 0.000 claims description 8
125000000623 heterocyclic group Chemical group 0.000 claims description 8
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 5
125000005843 halogen group Chemical group 0.000 claims description 5
125000004417 unsaturated alkyl group Chemical group 0.000 claims description 5
PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical compound [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 claims description 4
201000011510 cancer Diseases 0.000 claims description 4
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
208000024172 Cardiovascular disease Diseases 0.000 claims description 3
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
125000004103 aminoalkyl group Chemical group 0.000 claims description 3
125000005392 carboxamide group Chemical group NC(=O)* 0.000 claims description 3
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
RQCAREAVVCFQHW-UHFFFAOYSA-N 1-cyano-n-hydroxyformamide Chemical compound ONC(=O)C#N RQCAREAVVCFQHW-UHFFFAOYSA-N 0.000 claims description 2
125000003277 amino group Chemical group 0.000 claims description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
239000003814 drug Substances 0.000 claims description 2
239000001301 oxygen Substances 0.000 claims description 2
229910052760 oxygen Inorganic materials 0.000 claims description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims 2
125000004429 atom Chemical group 0.000 claims 2
125000003917 carbamoyl group Chemical class [H]N([H])C(*)=O 0.000 claims 2
BGOMWUVCJOVFPQ-UHFFFAOYSA-N (1-phenylpiperidin-2-yl)methanamine Chemical compound NCC1CCCCN1C1=CC=CC=C1 BGOMWUVCJOVFPQ-UHFFFAOYSA-N 0.000 claims 1
MRBFGEHILMYPTF-UHFFFAOYSA-N 1-(2-Pyrimidyl)piperazine Chemical group C1CNCCN1C1=NC=CC=N1 MRBFGEHILMYPTF-UHFFFAOYSA-N 0.000 claims 1
LKUAPSRIYZLAAO-UHFFFAOYSA-N 1-(2-phenylethyl)piperazine Chemical compound C1CNCCN1CCC1=CC=CC=C1 LKUAPSRIYZLAAO-UHFFFAOYSA-N 0.000 claims 1
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims 1
IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical compound C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 claims 1
125000005250 alkyl acrylate group Chemical group 0.000 claims 1
125000001204 arachidyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
125000005518 carboxamido group Chemical group 0.000 claims 1
125000004803 chlorobenzyl group Chemical group 0.000 claims 1
125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
238000009795 derivation Methods 0.000 claims 1
125000006289 hydroxybenzyl group Chemical group 0.000 claims 1
125000004464 hydroxyphenyl group Chemical group 0.000 claims 1
CUILPNURFADTPE-UHFFFAOYSA-N hypobromous acid Chemical compound BrO CUILPNURFADTPE-UHFFFAOYSA-N 0.000 claims 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
UHHVABRWHRKEPJ-UHFFFAOYSA-N methyl 2-piperazin-1-ylacetate Chemical compound COC(=O)CN1CCNCC1 UHHVABRWHRKEPJ-UHFFFAOYSA-N 0.000 claims 1
125000006178 methyl benzyl group Chemical group 0.000 claims 1
125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
125000005064 octadecenyl group Chemical group C(=CCCCCCCCCCCCCCCCC)* 0.000 claims 1
YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 claims 1
125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
201000010099 disease Diseases 0.000 abstract description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 2
210000004204 blood vessel Anatomy 0.000 abstract 1
239000008194 pharmaceutical composition Substances 0.000 abstract 1
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 174
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 103
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 87
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 56
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 35
239000000243 solution Substances 0.000 description 30
UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical class OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 29
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 24
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
238000006243 chemical reaction Methods 0.000 description 19
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
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
239000000203 mixture Substances 0.000 description 16
239000000047 product Substances 0.000 description 16
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
239000013078 crystal Substances 0.000 description 15
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 12
239000000126 substance Substances 0.000 description 12
238000004440 column chromatography Methods 0.000 description 11
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 10
239000002253 acid Substances 0.000 description 9
238000001816 cooling Methods 0.000 description 9
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
238000003756 stirring Methods 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
102000003923 Protein Kinase C Human genes 0.000 description 8
108090000315 Protein Kinase C Proteins 0.000 description 8
230000000694 effects Effects 0.000 description 8
210000003038 endothelium Anatomy 0.000 description 8
KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 8
238000000746 purification Methods 0.000 description 8
239000011734 sodium Substances 0.000 description 8
239000007787 solid Substances 0.000 description 8
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 7
239000012074 organic phase Substances 0.000 description 7
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
230000001419 dependent effect Effects 0.000 description 6
150000003254 radicals Chemical class 0.000 description 6
102000004190 Enzymes Human genes 0.000 description 5
108090000790 Enzymes Proteins 0.000 description 5
239000002585 base Substances 0.000 description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
BEJNERDRQOWKJM-UHFFFAOYSA-N kojic acid Chemical compound OCC1=CC(=O)C(O)=CO1 BEJNERDRQOWKJM-UHFFFAOYSA-N 0.000 description 5
229960004705 kojic acid Drugs 0.000 description 5
WZNJWVWKTVETCG-UHFFFAOYSA-N kojic acid Natural products OC(=O)C(N)CN1C=CC(=O)C(O)=C1 WZNJWVWKTVETCG-UHFFFAOYSA-N 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
238000001953 recrystallisation Methods 0.000 description 5
SWHWWDQVLJPUDV-UHFFFAOYSA-N 2-(hydroxymethyl)-5-octadecoxypyran-4-one Chemical compound CCCCCCCCCCCCCCCCCCOC1=COC(CO)=CC1=O SWHWWDQVLJPUDV-UHFFFAOYSA-N 0.000 description 4
DMCVVFIWYIKAEJ-UHFFFAOYSA-N 4-phenylpiperidine-4-carbonitrile Chemical compound C=1C=CC=CC=1C1(C#N)CCNCC1 DMCVVFIWYIKAEJ-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
239000007789 gas Substances 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
125000006239 protecting group Chemical group 0.000 description 4
238000012360 testing method Methods 0.000 description 4
125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 3
239000007868 Raney catalyst Substances 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
229960000583 acetic acid Drugs 0.000 description 3
230000033228 biological regulation Effects 0.000 description 3
238000009835 boiling Methods 0.000 description 3
239000011575 calcium Substances 0.000 description 3
239000007795 chemical reaction product Substances 0.000 description 3
239000000066 endothelium dependent relaxing factor Substances 0.000 description 3
150000002170 ethers Chemical class 0.000 description 3
238000001914 filtration Methods 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
150000003904 phospholipids Chemical class 0.000 description 3
229910000033 sodium borohydride Inorganic materials 0.000 description 3
239000012279 sodium borohydride Substances 0.000 description 3
230000002792 vascular Effects 0.000 description 3
SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
CPZDBLWATZDEIV-UHFFFAOYSA-N 2-(bromomethyl)-5-octadecoxy-1-(1-phenylethyl)pyridin-4-one;hydrobromide Chemical compound Br.BrCC1=CC(=O)C(OCCCCCCCCCCCCCCCCCC)=CN1C(C)C1=CC=CC=C1 CPZDBLWATZDEIV-UHFFFAOYSA-N 0.000 description 2
WIYRTPDOMZELHK-UHFFFAOYSA-N 2-(hydroxymethyl)-5-(2-octyldecoxy)pyran-4-one Chemical compound CCCCCCCCC(CCCCCCCC)COC1=COC(CO)=CC1=O WIYRTPDOMZELHK-UHFFFAOYSA-N 0.000 description 2
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
108010033040 Histones Proteins 0.000 description 2
229910019142 PO4 Inorganic materials 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
239000000654 additive Substances 0.000 description 2
210000000709 aorta Anatomy 0.000 description 2
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
210000004556 brain Anatomy 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
238000010828 elution Methods 0.000 description 2
235000011087 fumaric acid Nutrition 0.000 description 2
QBKSWRVVCFFDOT-UHFFFAOYSA-N gossypol Chemical compound CC(C)C1=C(O)C(O)=C(C=O)C2=C(O)C(C=3C(O)=C4C(C=O)=C(O)C(O)=C(C4=CC=3C)C(C)C)=C(C)C=C21 QBKSWRVVCFFDOT-UHFFFAOYSA-N 0.000 description 2
229920006158 high molecular weight polymer Polymers 0.000 description 2
229910000042 hydrogen bromide Inorganic materials 0.000 description 2
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
229910000041 hydrogen chloride Inorganic materials 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
238000010348 incorporation Methods 0.000 description 2
CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
239000007924 injection Substances 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
230000003834 intracellular effect Effects 0.000 description 2
239000007788 liquid Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
229960002748 norepinephrine Drugs 0.000 description 2
SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
235000006408 oxalic acid Nutrition 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
239000010452 phosphate Substances 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
230000002062 proliferating effect Effects 0.000 description 2
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
239000011347 resin Substances 0.000 description 2
229920005989 resin Polymers 0.000 description 2
230000003248 secreting effect Effects 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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OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
229960004373 acetylcholine Drugs 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
125000003368 amide group Chemical group 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
MLIREBYILWEBDM-UHFFFAOYSA-N anhydrous cyanoacetic acid Natural products OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
125000005997 bromomethyl group Chemical group 0.000 description 1
239000000872 buffer Substances 0.000 description 1
244000309464 bull Species 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
UBAZGMLMVVQSCD-UHFFFAOYSA-N carbon dioxide;molecular oxygen Chemical compound O=O.O=C=O UBAZGMLMVVQSCD-UHFFFAOYSA-N 0.000 description 1
150000003857 carboxamides Chemical class 0.000 description 1
150000001733 carboxylic acid esters Chemical class 0.000 description 1
125000002843 carboxylic acid group Chemical group 0.000 description 1
239000000969 carrier Substances 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
239000002738 chelating agent Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000007979 citrate buffer Substances 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
239000008139 complexing agent Substances 0.000 description 1
230000008602 contraction Effects 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
238000006114 decarboxylation reaction Methods 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
OCXGTPDKNBIOTF-UHFFFAOYSA-N dibromo(triphenyl)-$l^{5}-phosphane Chemical compound C=1C=CC=CC=1P(Br)(C=1C=CC=CC=1)(Br)C1=CC=CC=C1 OCXGTPDKNBIOTF-UHFFFAOYSA-N 0.000 description 1
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
230000003511 endothelial effect Effects 0.000 description 1
210000003743 erythrocyte Anatomy 0.000 description 1
210000003617 erythrocyte membrane Anatomy 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
239000012458 free base Substances 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
150000002238 fumaric acids Chemical class 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
229930000755 gossypol Natural products 0.000 description 1
229950005277 gossypol Drugs 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
229960000905 indomethacin Drugs 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
239000008101 lactose Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
150000002691 malonic acids Chemical class 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
239000012528 membrane Substances 0.000 description 1
229910052987 metal hydride Inorganic materials 0.000 description 1
150000004681 metal hydrides Chemical class 0.000 description 1
LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N methanesulfonic acid Substances CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 1
229960000907 methylthioninium chloride Drugs 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
HCZKYJDFEPMADG-UHFFFAOYSA-N nordihydroguaiaretic acid Chemical compound C=1C=C(O)C(O)=CC=1CC(C)C(C)CC1=CC=C(O)C(O)=C1 HCZKYJDFEPMADG-UHFFFAOYSA-N 0.000 description 1
238000010534 nucleophilic substitution reaction Methods 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000002913 oxalic acids Chemical class 0.000 description 1
229940097886 phosphorus 32 Drugs 0.000 description 1
102000020233 phosphotransferase Human genes 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
150000004885 piperazines Chemical class 0.000 description 1
239000003880 polar aprotic solvent Substances 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
229940080818 propionamide Drugs 0.000 description 1
108060006633 protein kinase Proteins 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
150000003870 salicylic acids Chemical class 0.000 description 1
230000007017 scission Effects 0.000 description 1
238000005245 sintering Methods 0.000 description 1
ZNJHFNUEQDVFCJ-UHFFFAOYSA-M sodium;2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid;hydroxide Chemical compound [OH-].[Na+].OCCN1CCN(CCS(O)(=O)=O)CC1 ZNJHFNUEQDVFCJ-UHFFFAOYSA-M 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
235000011044 succinic acid Nutrition 0.000 description 1
150000003444 succinic acids Chemical class 0.000 description 1
239000000725 suspension Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
AYEKOFBPNLCAJY-UHFFFAOYSA-O thiamine pyrophosphate Chemical compound CC1=C(CCOP(O)(=O)OP(O)(O)=O)SC=[N+]1CC1=CN=C(C)N=C1N AYEKOFBPNLCAJY-UHFFFAOYSA-O 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
230000001960 triggered effect Effects 0.000 description 1
208000019553 vascular disease Diseases 0.000 description 1
235000019871 vegetable fat Nutrition 0.000 description 1
239000001993 wax Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/69—Two or more oxygen atoms

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
Engineering & Computer Science (AREA)
Medicinal Chemistry (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Pulmonology (AREA)
Immunology (AREA)
Diabetes (AREA)
Hematology (AREA)
Pyridine Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)

DD89331409A 1988-08-06 1989-08-02 Verfahren zur herstellung von alkoxy-4(1h)-pyridon-derivaten und deren verwendung DD284003A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE3826846A DE3826846A1 (de)	1988-08-06	1988-08-06	Alkoxy-4(1h)-pyridon-derivate, verfahren zu deren herstellung und deren verwendung als arzneimittel

Publications (1)

Publication Number	Publication Date
DD284003A5 true DD284003A5 (de)	1990-10-31

Family

ID=6360419

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD89331409A DD284003A5 (de)	1988-08-06	1989-08-02	Verfahren zur herstellung von alkoxy-4(1h)-pyridon-derivaten und deren verwendung

Country Status (18)

Country	Link
US (2)	US5185352A (da)
EP (2)	EP0427765B1 (da)
JP (1)	JP2878361B2 (da)
KR (1)	KR920006779B1 (da)
CN (1)	CN1040193A (da)
AT (1)	ATE188469T1 (da)
AU (1)	AU627766B2 (da)
CA (1)	CA1340608C (da)
DD (1)	DD284003A5 (da)
DE (2)	DE3826846A1 (da)
DK (1)	DK174097B1 (da)
ES (1)	ES2144391T3 (da)
GR (1)	GR3033072T3 (da)
HU (1)	HUT56545A (da)
NO (1)	NO177785C (da)
PT (1)	PT91351B (da)
WO (1)	WO1990001477A1 (da)
ZA (1)	ZA895969B (da)

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US4822786A (en) *	1986-07-01	1989-04-18	Kaken Pharmaceutical Co., Ltd.	Cephalosporin compounds, and antibacterial agents
DE3826846A1 (de) *	1988-08-06	1990-02-08	Goedecke Ag	Alkoxy-4(1h)-pyridon-derivate, verfahren zu deren herstellung und deren verwendung als arzneimittel
FR2687674B1 (fr) *	1992-02-07	1995-05-19	Roussel Uclaf	Nouveaux derives de la pyridone, leur procede de preparation, les nouveaux intermediaires obtenus, leur application a titre de medicaments et les compositions pharmaceutiques les renfermant.
US5674883A (en) *	1992-02-07	1997-10-07	Roussel Uclaf	Derivatives of pyridone, their preparation process, the new intermediates obtained, their use as medicaments and the pharmaceutical compositions containing them
DE4243321A1 (de) *	1992-12-21	1994-06-23	Goedecke Ag	Aminosäurederivate von Heterocyclen als PKC-Inhibitoren
US6046219A (en) *	1995-01-20	2000-04-04	Cornell Research Foundation, Inc.	Method for the treatment of conditions mediated by collagen formation together with cell proliferation by application of inhibitors of protein hydroxylation
US5849587A (en) *	1995-06-09	1998-12-15	Cornell Research Foundation, Inc.	Method of inhibiting viral replication in eukaryotic cells and of inducing apoptosis of virally-infected cells
GB2321455A (en)	1997-01-24	1998-07-29	Norsk Hydro As	Lipophilic derivatives of biologically active compounds
JP2002531511A (ja) *	1998-12-07	2002-09-24	エコスマートテクノロジーズ，インコーポレーテッド	シグナル伝達調節物質と天然植物精油を用いた癌治療薬配合物および方法
US6750342B1 (en)	1999-05-19	2004-06-15	Pharmacia Corporation	Substituted polycyclic aryl and heteroaryl pyrimidinones useful for selective inhibition of the coagulation cascade
US6867217B1 (en)	1999-05-19	2005-03-15	Pharmacia Corporation	Substituted polycyclic aryl and heteroaryl pyridones useful for selective inhibition of the coagulation cascade
US6716838B1 (en)	1999-05-19	2004-04-06	Pharmacia Corporation	Substituted polycyclic aryl and heteroaryl uracils as anticoagulative agents
US7015230B1 (en)	1999-05-19	2006-03-21	Pharmacia Corporation	Substituted polycyclic aryl and heteroaryl uracils useful for selective inhibition of the coagulation cascade
US6653316B1 (en)	1999-05-19	2003-11-25	Pharmacia Corporation	Substituted polycyclic aryl and heteroaryl pyrimidinones useful for selective inhibition of the coagulation cascade
US6664255B1 (en)	1999-05-19	2003-12-16	Pharmacia Corporation	Substituted polycyclic aryl and heteroaryl pyrazinones useful for selective inhibition of the coagulation cascade
US6906068B1 (en)	1999-05-19	2005-06-14	Pharmacia Corporation	Substituted polycyclic aryl and heteroaryl 1,2,4 - triazinones useful as anticoagulants
US6660885B2 (en)	2000-03-13	2003-12-09	Pharmacia Corporation	Polycyclic aryl and heteroaryl substituted benzenes useful for selective inhibition of the coagulation cascade
US6693121B2 (en)	2000-04-05	2004-02-17	Pharmacia Corporation	Polycyclic aryl and heteroaryl substituted 4-pyridones useful for selective inhibition of the coagulation cascade
PT1268463E (pt)	2000-04-05	2005-05-31	Pharmacia Corp	4-pironas substituidas com arilo e heteroarilo policiclicos uteis para a inibicao selectiva da cascata de coagulacao
US7015223B1 (en)	2000-11-20	2006-03-21	Pharmacia Corporation	Substituted polycyclic aryl and heteroaryl 1,2,4-triazinones useful for selective inhibition of the coagulation cascade
US7119094B1 (en)	2000-11-20	2006-10-10	Warner-Lambert Company	Substituted polycyclic aryl and heteroarpyl pyrazinones useful for selective inhibition of the coagulation cascade
WO2002042272A2 (en)	2000-11-20	2002-05-30	Pharmacia Corporation	Substituted polycyclic aryl and heteroaryl pyridines useful for selective inhibition of the coagulation cascade
JP2005519866A (ja)	2001-10-03	2005-07-07	ファルマシア・コーポレーション	凝固カスケードの選択阻害に有用な６員複素環式化合物
EP1432687A2 (en)	2001-10-03	2004-06-30	Pharmacia Corporation	Substituted 5-membered polycyclic compounds useful for selective inhibition of the coagulation cascade
WO2008116301A1 (en) *	2007-03-28	2008-10-02	Apotex Technologies Inc.	Fluorinated derivatives of deferiprone
CN102014904B (zh)	2008-04-25	2013-02-06	阿普泰克斯科技公司	具有适口味道的去铁酮液体配制品
AR076540A1 (es)	2009-05-01	2011-06-22	Eurand Inc	Composiciones de comprimidos de desintegracion oral que comprenden combinaciones de analgesicos no- opioides y opioides, forma de dosificacion. metodo de preparacion. metodo para tratar dolor
AU2010268666B2 (en)	2009-07-03	2014-07-24	Apotex Inc.	Fluorinated derivatives of 3-Hydroxypyridin-4-ones
JP6358639B2 (ja) *	2015-04-24	2018-07-18	塩野義製薬株式会社	６員複素環誘導体およびそれらを含有する医薬組成物
JP6692113B2 (ja) *	2016-10-21	2020-05-13	塩野義製薬株式会社	６員複素環誘導体を含有する医薬組成物

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CA554715A (en) *		1958-03-18	Boesch Roger	Ethers and thioethers and processes for their preparation
US2965641A (en) *	1959-07-06	1960-12-20	Searle & Co	Derivatives of 1-(2-aminoethyl)-5-alkoxy-4-pyridones
CA978958A (en) *	1971-10-04	1975-12-02	Haydn W.R. Williams	Substituted pyranones and -pyridones and process of manufacture
JPS59110674A (ja) *	1982-12-16	1984-06-26	Ss Pharmaceut Co Ltd	ピリジン誘導体及びその製造法
JPS59110675A (ja) *	1982-12-16	1984-06-26	Ss Pharmaceut Co Ltd	ピリジン誘導体及びその製造方法
GB8308055D0 (en) *	1983-03-24	1983-05-05	Hider R C	Pharmaceutical compositions
US4822786A (en) *	1986-07-01	1989-04-18	Kaken Pharmaceutical Co., Ltd.	Cephalosporin compounds, and antibacterial agents
DE3826846A1 (de) *	1988-08-06	1990-02-08	Goedecke Ag	Alkoxy-4(1h)-pyridon-derivate, verfahren zu deren herstellung und deren verwendung als arzneimittel

1988
- 1988-08-06 DE DE3826846A patent/DE3826846A1/de not_active Ceased
1989
- 1989-08-02 DD DD89331409A patent/DD284003A5/de not_active IP Right Cessation
- 1989-08-02 PT PT91351A patent/PT91351B/pt not_active IP Right Cessation
- 1989-08-04 HU HU894581A patent/HUT56545A/hu unknown
- 1989-08-04 EP EP89908987A patent/EP0427765B1/de not_active Expired - Lifetime
- 1989-08-04 AT AT89908987T patent/ATE188469T1/de not_active IP Right Cessation
- 1989-08-04 AU AU40489/89A patent/AU627766B2/en not_active Ceased
- 1989-08-04 KR KR1019900700696A patent/KR920006779B1/ko not_active Expired
- 1989-08-04 DE DE58909865T patent/DE58909865D1/de not_active Expired - Fee Related
- 1989-08-04 JP JP1508466A patent/JP2878361B2/ja not_active Expired - Fee Related
- 1989-08-04 EP EP89114477A patent/EP0354495A1/de active Pending
- 1989-08-04 WO PCT/EP1989/000927 patent/WO1990001477A1/de not_active Ceased
- 1989-08-04 ES ES89908987T patent/ES2144391T3/es not_active Expired - Lifetime
- 1989-08-04 CA CA000607563A patent/CA1340608C/en not_active Expired - Fee Related
- 1989-08-04 ZA ZA895969A patent/ZA895969B/xx unknown
- 1989-08-04 US US07/640,407 patent/US5185352A/en not_active Expired - Lifetime
- 1989-08-05 CN CN89105574A patent/CN1040193A/zh active Pending
1991
- 1991-01-23 DK DK199100113A patent/DK174097B1/da not_active IP Right Cessation
- 1991-02-05 NO NO910444A patent/NO177785C/no unknown
1992
- 1992-10-07 US US07/957,937 patent/US5322844A/en not_active Expired - Fee Related
2000
- 2000-03-27 GR GR20000400761T patent/GR3033072T3/el not_active IP Right Cessation

Also Published As

Publication number	Publication date
GR3033072T3 (en)	2000-08-31
US5322844A (en)	1994-06-21
ATE188469T1 (de)	2000-01-15
ES2144391T3 (es)	2000-06-16
CN1040193A (zh)	1990-03-07
ZA895969B (en)	1990-05-30
JPH04500958A (ja)	1992-02-20
NO910444L (no)	1991-02-05
KR900701755A (ko)	1990-12-04
NO177785B (no)	1995-08-14
HUT56545A (en)	1991-09-30
EP0427765B1 (de)	2000-01-05
NO177785C (no)	1995-11-22
EP0427765A1 (de)	1991-05-22
PT91351B (pt)	1997-01-31
EP0354495A1 (de)	1990-02-14
JP2878361B2 (ja)	1999-04-05
DK11391D0 (da)	1991-01-23
PT91351A (pt)	1990-03-08
DE58909865D1 (de)	2000-02-10
AU4048989A (en)	1990-03-05
DE3826846A1 (de)	1990-02-08
DK11391A (da)	1991-01-23
CA1340608C (en)	1999-06-22
WO1990001477A1 (de)	1990-02-22
US5185352A (en)	1993-02-09
HU894581D0 (en)	1991-07-29
AU627766B2 (en)	1992-09-03
KR920006779B1 (ko)	1992-08-17
DK174097B1 (da)	2002-06-10
NO910444D0 (no)	1991-02-05

Legal Events

Date	Code	Title	Description
1999-12-09	ENJ	Ceased due to non-payment of renewal fee

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DE69722360T2 (de)	2003-11-27	Piperazin-derivate und verfahren zu ihrer herstellung
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JPH06228112A (ja)	1994-08-16	（１ｈ，４ｈ）キノキサリン誘導体
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DE69203401T2 (de)	1996-03-07	2-Aminopyrimidin-4-Carboxamidderivate, deren Herstellung und deren Verwendung als Heilmittel.