NO326051B1 - 5-leddete heterocykler, medikament og anvendelse derav, samt farmasoytisk preparat. - Google Patents
5-leddete heterocykler, medikament og anvendelse derav, samt farmasoytisk preparat. Download PDFInfo
- Publication number
- NO326051B1 NO326051B1 NO20034524A NO20034524A NO326051B1 NO 326051 B1 NO326051 B1 NO 326051B1 NO 20034524 A NO20034524 A NO 20034524A NO 20034524 A NO20034524 A NO 20034524A NO 326051 B1 NO326051 B1 NO 326051B1
- Authority
- NO
- Norway
- Prior art keywords
- thiazol
- methyl
- butyl
- imidazol
- biphenyl
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims description 24
- 229940079593 drug Drugs 0.000 title claims description 22
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 title description 31
- 150000001875 compounds Chemical class 0.000 claims description 369
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 212
- -1 4-methyl-1,4-diazepan-1-yl Chemical group 0.000 claims description 174
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 claims description 164
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 78
- 150000003839 salts Chemical class 0.000 claims description 76
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 69
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 53
- 229910052757 nitrogen Inorganic materials 0.000 claims description 44
- 238000002360 preparation method Methods 0.000 claims description 34
- 229950000688 phenothiazine Drugs 0.000 claims description 33
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 claims description 30
- 102000010909 Monoamine Oxidase Human genes 0.000 claims description 23
- 108010062431 Monoamine oxidase Proteins 0.000 claims description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 23
- 230000003859 lipid peroxidation Effects 0.000 claims description 20
- 208000024827 Alzheimer disease Diseases 0.000 claims description 18
- 230000000694 effects Effects 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- 108010052164 Sodium Channels Proteins 0.000 claims description 14
- 102000018674 Sodium Channels Human genes 0.000 claims description 14
- 208000002193 Pain Diseases 0.000 claims description 13
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 13
- 208000018737 Parkinson disease Diseases 0.000 claims description 12
- 208000035475 disorder Diseases 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 11
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 11
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 10
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 10
- 208000019695 Migraine disease Diseases 0.000 claims description 9
- 206010027599 migraine Diseases 0.000 claims description 9
- 201000000980 schizophrenia Diseases 0.000 claims description 8
- 208000023105 Huntington disease Diseases 0.000 claims description 7
- 208000028017 Psychotic disease Diseases 0.000 claims description 7
- 206010039966 Senile dementia Diseases 0.000 claims description 7
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 7
- 208000004296 neuralgia Diseases 0.000 claims description 7
- 208000021722 neuropathic pain Diseases 0.000 claims description 7
- 125000006308 propyl amino group Chemical group 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 5
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000006309 butyl amino group Chemical group 0.000 claims description 5
- 230000000674 effect on sodium Effects 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 4
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 4
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 239000004305 biphenyl Substances 0.000 claims description 2
- NTVCMEJZWNSEFW-ICSRJNTNSA-N 4-(diaminomethylideneamino)-n-[[(2s)-1-[(2s)-3-hydroxy-2-(naphthalen-2-ylsulfonylamino)propanoyl]pyrrolidin-2-yl]methyl]butanamide Chemical compound NC(N)=NCCCC(=O)NC[C@@H]1CCCN1C(=O)[C@H](CO)NS(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 NTVCMEJZWNSEFW-ICSRJNTNSA-N 0.000 claims 1
- LSBDFXRDZJMBSC-UHFFFAOYSA-N Amide-Phenylacetic acid Natural products NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 claims 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims 1
- SITAAQMFOKQDJV-UHFFFAOYSA-N n-[[4-(10h-phenothiazin-2-yl)-1,3-thiazol-2-yl]methyl]butan-1-amine Chemical compound S1C(CNCCCC)=NC(C=2C=C3NC4=CC=CC=C4SC3=CC=2)=C1 SITAAQMFOKQDJV-UHFFFAOYSA-N 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 135
- 239000000543 intermediate Substances 0.000 description 133
- 230000008018 melting Effects 0.000 description 133
- 238000002844 melting Methods 0.000 description 133
- 125000000217 alkyl group Chemical group 0.000 description 117
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 114
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 108
- 239000000047 product Substances 0.000 description 87
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 81
- 239000007787 solid Substances 0.000 description 73
- 238000000034 method Methods 0.000 description 66
- 239000000203 mixture Substances 0.000 description 66
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 61
- 239000002904 solvent Substances 0.000 description 58
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 57
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 56
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 54
- 125000004433 nitrogen atom Chemical group N* 0.000 description 51
- 238000010586 diagram Methods 0.000 description 50
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 47
- 239000000243 solution Substances 0.000 description 47
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
- 125000003545 alkoxy group Chemical group 0.000 description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 40
- 239000002253 acid Substances 0.000 description 40
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 38
- 125000005842 heteroatom Chemical group 0.000 description 37
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 33
- 239000012074 organic phase Substances 0.000 description 32
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
- 238000003786 synthesis reaction Methods 0.000 description 30
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 28
- 235000019341 magnesium sulphate Nutrition 0.000 description 28
- 150000007513 acids Chemical class 0.000 description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 26
- 150000001412 amines Chemical group 0.000 description 25
- 125000003118 aryl group Chemical group 0.000 description 25
- 238000006243 chemical reaction Methods 0.000 description 25
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 24
- 125000003342 alkenyl group Chemical group 0.000 description 24
- 239000002585 base Substances 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 239000012429 reaction media Substances 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 125000000304 alkynyl group Chemical group 0.000 description 21
- 125000003710 aryl alkyl group Chemical group 0.000 description 21
- 230000015572 biosynthetic process Effects 0.000 description 21
- 125000004966 cyanoalkyl group Chemical group 0.000 description 21
- 125000001424 substituent group Chemical group 0.000 description 21
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
- 229910052736 halogen Inorganic materials 0.000 description 20
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 20
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 19
- 150000002367 halogens Chemical group 0.000 description 19
- 239000000843 powder Substances 0.000 description 19
- 238000010992 reflux Methods 0.000 description 19
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 18
- 125000006239 protecting group Chemical group 0.000 description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
- 230000002401 inhibitory effect Effects 0.000 description 17
- 125000004434 sulfur atom Chemical group 0.000 description 17
- 125000003341 7 membered heterocyclic group Chemical group 0.000 description 16
- 125000005282 allenyl group Chemical group 0.000 description 16
- 238000010511 deprotection reaction Methods 0.000 description 16
- 125000005843 halogen group Chemical group 0.000 description 16
- 229910052760 oxygen Inorganic materials 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
- 125000000753 cycloalkyl group Chemical group 0.000 description 15
- 239000003480 eluent Substances 0.000 description 15
- 238000001914 filtration Methods 0.000 description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 15
- 239000000377 silicon dioxide Substances 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 238000001704 evaporation Methods 0.000 description 14
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 14
- 239000003921 oil Substances 0.000 description 14
- 235000019198 oils Nutrition 0.000 description 14
- 230000008020 evaporation Effects 0.000 description 13
- 239000005457 ice water Substances 0.000 description 13
- 125000004430 oxygen atom Chemical group O* 0.000 description 13
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 150000003857 carboxamides Chemical class 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 11
- 125000004432 carbon atom Chemical group C* 0.000 description 11
- 239000000460 chlorine Substances 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 11
- 229910052739 hydrogen Inorganic materials 0.000 description 11
- CYEBJEDOHLIWNP-UHFFFAOYSA-N methanethioamide Chemical compound NC=S CYEBJEDOHLIWNP-UHFFFAOYSA-N 0.000 description 11
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 10
- 210000003710 cerebral cortex Anatomy 0.000 description 10
- 125000004093 cyano group Chemical group *C#N 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- 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 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 9
- 229960000583 acetic acid Drugs 0.000 description 9
- 238000002425 crystallisation Methods 0.000 description 9
- 230000008025 crystallization Effects 0.000 description 9
- 238000001035 drying Methods 0.000 description 9
- 125000001188 haloalkyl group Chemical group 0.000 description 9
- 125000002883 imidazolyl group Chemical group 0.000 description 9
- 239000008188 pellet Substances 0.000 description 9
- 239000011347 resin Substances 0.000 description 9
- 229920005989 resin Polymers 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 8
- 235000001014 amino acid Nutrition 0.000 description 8
- 150000001413 amino acids Chemical class 0.000 description 8
- 238000005893 bromination reaction Methods 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 239000012047 saturated solution Substances 0.000 description 8
- 150000003557 thiazoles Chemical class 0.000 description 8
- 125000004414 alkyl thio group Chemical group 0.000 description 7
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 7
- 239000012300 argon atmosphere Substances 0.000 description 7
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 description 7
- 238000009739 binding Methods 0.000 description 7
- 230000031709 bromination Effects 0.000 description 7
- 229910052794 bromium Inorganic materials 0.000 description 7
- AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 150000002460 imidazoles Chemical class 0.000 description 7
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 6
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 6
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 6
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 6
- 239000007983 Tris buffer Substances 0.000 description 6
- 125000005129 aryl carbonyl group Chemical group 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
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- 238000005859 coupling reaction Methods 0.000 description 6
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 6
- 125000001072 heteroaryl group Chemical group 0.000 description 6
- ZXRCAYWYTOIRQS-UHFFFAOYSA-N hydron;phenol;chloride Chemical compound Cl.OC1=CC=CC=C1 ZXRCAYWYTOIRQS-UHFFFAOYSA-N 0.000 description 6
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 6
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 6
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 6
- 230000007170 pathology Effects 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 125000004076 pyridyl group Chemical group 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 6
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 5
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 5
- 102200084471 c.4C>T Human genes 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 239000006071 cream Substances 0.000 description 5
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 5
- 229940118019 malondialdehyde Drugs 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 150000002916 oxazoles Chemical class 0.000 description 5
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- UYPXQSLSPUBZQW-UHFFFAOYSA-N 2-bromo-1-(3,5-ditert-butyl-4-hydroxyphenyl)ethanone Chemical compound CC(C)(C)C1=CC(C(=O)CBr)=CC(C(C)(C)C)=C1O UYPXQSLSPUBZQW-UHFFFAOYSA-N 0.000 description 4
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 4
- 239000005695 Ammonium acetate Substances 0.000 description 4
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- 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
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/06—Antimigraine agents
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- A—HUMAN NECESSITIES
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- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
- C07D233/44—Nitrogen atoms not forming part of a nitro radical
- C07D233/50—Nitrogen atoms not forming part of a nitro radical with carbocyclic radicals directly attached to said nitrogen atoms
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- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
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- C—CHEMISTRY; METALLURGY
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- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/28—Radicals substituted by nitrogen atoms
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- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D277/34—Oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Anesthesiology (AREA)
- Rheumatology (AREA)
- Hospice & Palliative Care (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0104943A FR2823208B1 (fr) | 2001-04-10 | 2001-04-10 | Derives d'heterocycles a 5 chainons, leur preparation et leur application a titre de medicaments |
FR0201811 | 2002-02-14 | ||
PCT/FR2002/001218 WO2002083656A2 (fr) | 2001-04-10 | 2002-04-09 | Derives d'heterocycles a 5 chainons et leur utilisation en tant qu'inhibiteurs de la mao et/ou peroxydation lipidique, leur preparation et leur application comme medicaments |
Publications (3)
Publication Number | Publication Date |
---|---|
NO20034524D0 NO20034524D0 (no) | 2003-10-09 |
NO20034524L NO20034524L (no) | 2003-10-29 |
NO326051B1 true NO326051B1 (no) | 2008-09-08 |
Family
ID=26212970
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20034524A NO326051B1 (no) | 2001-04-10 | 2003-10-09 | 5-leddete heterocykler, medikament og anvendelse derav, samt farmasoytisk preparat. |
Country Status (23)
Country | Link |
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EP (1) | EP1379514B1 (ja) |
JP (1) | JP4422964B2 (ja) |
KR (1) | KR100865809B1 (ja) |
CN (1) | CN1284777C (ja) |
AR (1) | AR036329A1 (ja) |
AU (1) | AU2002307980B2 (ja) |
BR (2) | BR0208703A (ja) |
CA (1) | CA2443403C (ja) |
CZ (1) | CZ304550B6 (ja) |
DE (1) | DE60232959D1 (ja) |
ES (1) | ES2328467T3 (ja) |
HK (1) | HK1070055A1 (ja) |
HU (1) | HU228192B1 (ja) |
IL (2) | IL158121A0 (ja) |
IS (1) | IS2724B (ja) |
MX (1) | MXPA03009194A (ja) |
MY (1) | MY142094A (ja) |
NO (1) | NO326051B1 (ja) |
NZ (1) | NZ528645A (ja) |
PL (1) | PL211939B1 (ja) |
RU (1) | RU2288224C2 (ja) |
TW (1) | TWI248438B (ja) |
WO (1) | WO2002083656A2 (ja) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7291641B2 (en) * | 1999-10-11 | 2007-11-06 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Derivatives of heterocycles with 5 members, their preparation and their use as medicaments |
TWI292316B (en) | 1999-10-11 | 2008-01-11 | Sod Conseils Rech Applic | Pharmaceutical composition of thiazole derivatives intended to inhibit mao and/or lipidic peroxidation and/or to act as modulators of sodium channels and the use thereof |
US7163952B2 (en) | 2001-12-03 | 2007-01-16 | Japan Tobacco Inc. | Azole compound and medicinal use thereof |
MXPA05010945A (es) * | 2003-04-09 | 2005-11-25 | Japan Tobacco Inc | Compuesto pentaciclico heteroaromatico y uso medicinal del mismo. |
EP1470818B1 (en) * | 2003-04-25 | 2006-07-26 | Neuro3D | Use of piperazine phenothiazine derivatives in the manufacture of a medicament with neuroprotector and/or neurotrophic effects on cns and/or pns |
FR2888116A1 (fr) | 2005-07-08 | 2007-01-12 | Sod Conseils Rech Applic | Derives de thiazoles pour traiter les dyskinesies |
EP1806819A1 (en) * | 2006-01-05 | 2007-07-11 | Constructions Electroniques + Telecommunications, en abrégé "C.E.+T" | Backup power system |
TW200848417A (en) * | 2007-02-22 | 2008-12-16 | Organon Nv | Indole derivatives |
PE20141682A1 (es) * | 2011-10-26 | 2014-11-14 | Pfizer Ltd | Derivados de (4-fenilimidazol-2-il) etilamina utiles como moduladores de canal de sodio |
CN113831360A (zh) * | 2021-09-10 | 2021-12-24 | 中钢集团南京新材料研究院有限公司 | 酰胺邻位导向硼化合成1-咔唑-硼酸频哪醇酯的方法 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
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US5326770A (en) | 1992-07-17 | 1994-07-05 | The Du Pont Merck Pharmaceutical Company | Monoamine oxidase-B (MAO-B) inhibitory 5-substituted 2,4-thiazolidinediones useful in treating memory disorders of mammals |
CN1088062C (zh) * | 1994-11-23 | 2002-07-24 | 纽罗根公司 | 某些4-氨基甲基-2-取代的咪唑衍生物2-氨基甲基-4-取代的咪唑衍生物新的一族多巴胺受体亚型特异性配体 |
WO1997013768A1 (fr) * | 1995-10-11 | 1997-04-17 | Synthelabo | Composes derives d'oxazolidin-2-one, leur procede de preparation et leur application en therapeutique |
JP2001505585A (ja) * | 1996-12-16 | 2001-04-24 | 藤沢薬品工業株式会社 | 新規アミド化合物およびそれらの一酸化窒素シンターゼ阻害剤としての用途 |
FR2764889B1 (fr) * | 1997-06-20 | 2000-09-01 | Sod Conseils Rech Applic | Nouveaux derives du 2-(iminomethyl)amino-phenyle, leur preparation, leur application a titre de medicaments et les compositions pharmaceutiques les contenant |
PL339673A1 (en) * | 1997-10-06 | 2001-01-02 | Lilly Co Eli | Novel compounds suitable for use as neuroprotective agents |
IL140197A0 (en) * | 1998-06-12 | 2002-02-10 | Sod Conseils Rech Applic | β-CARBOLINE COMPOUNDS |
DE60044395D1 (de) * | 1999-03-26 | 2010-06-24 | Euro Celtique Sa | Arylsubstituierte pyrazole, imidazole, oxazole, thiazole und pyrrole, sowie deren verwendung |
TWI292316B (en) * | 1999-10-11 | 2008-01-11 | Sod Conseils Rech Applic | Pharmaceutical composition of thiazole derivatives intended to inhibit mao and/or lipidic peroxidation and/or to act as modulators of sodium channels and the use thereof |
-
2002
- 2002-03-26 TW TW091105848A patent/TWI248438B/zh not_active IP Right Cessation
- 2002-04-05 MY MYPI20021232A patent/MY142094A/en unknown
- 2002-04-09 BR BRPI0208703-0A patent/BR0208703A/pt not_active IP Right Cessation
- 2002-04-09 DE DE60232959T patent/DE60232959D1/de not_active Expired - Lifetime
- 2002-04-09 KR KR1020037013243A patent/KR100865809B1/ko not_active IP Right Cessation
- 2002-04-09 AU AU2002307980A patent/AU2002307980B2/en not_active Ceased
- 2002-04-09 EP EP02761921A patent/EP1379514B1/fr not_active Expired - Lifetime
- 2002-04-09 CN CNB02807937XA patent/CN1284777C/zh not_active Expired - Fee Related
- 2002-04-09 WO PCT/FR2002/001218 patent/WO2002083656A2/fr active IP Right Grant
- 2002-04-09 CA CA2443403A patent/CA2443403C/fr not_active Expired - Fee Related
- 2002-04-09 JP JP2002581412A patent/JP4422964B2/ja not_active Expired - Fee Related
- 2002-04-09 NZ NZ528645A patent/NZ528645A/en not_active IP Right Cessation
- 2002-04-09 PL PL372297A patent/PL211939B1/pl unknown
- 2002-04-09 HU HU0303799A patent/HU228192B1/hu not_active IP Right Cessation
- 2002-04-09 RU RU2003132471/04A patent/RU2288224C2/ru not_active IP Right Cessation
- 2002-04-09 CZ CZ2003-3054A patent/CZ304550B6/cs not_active IP Right Cessation
- 2002-04-09 IL IL15812102A patent/IL158121A0/xx unknown
- 2002-04-09 BR BRPI0208703-0A patent/BRPI0208703B1/pt unknown
- 2002-04-09 ES ES02761921T patent/ES2328467T3/es not_active Expired - Lifetime
- 2002-04-09 MX MXPA03009194A patent/MXPA03009194A/es active IP Right Grant
- 2002-04-10 AR ARP020101330A patent/AR036329A1/es active IP Right Grant
-
2003
- 2003-09-25 IL IL158121A patent/IL158121A/en not_active IP Right Cessation
- 2003-10-08 IS IS6979A patent/IS2724B/is unknown
- 2003-10-09 NO NO20034524A patent/NO326051B1/no not_active IP Right Cessation
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2005
- 2005-03-18 HK HK05102380A patent/HK1070055A1/xx not_active IP Right Cessation
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