BRPI0009558B1 - composto derivado bicíclico heteroaromático ou um sal farmaceuticamente aceitável do mesmo, seu uso, e composição farmacêutica - Google Patents
composto derivado bicíclico heteroaromático ou um sal farmaceuticamente aceitável do mesmo, seu uso, e composição farmacêutica Download PDFInfo
- Publication number
- BRPI0009558B1 BRPI0009558B1 BRPI0009558A BR0009558A BRPI0009558B1 BR PI0009558 B1 BRPI0009558 B1 BR PI0009558B1 BR PI0009558 A BRPI0009558 A BR PI0009558A BR 0009558 A BR0009558 A BR 0009558A BR PI0009558 B1 BRPI0009558 B1 BR PI0009558B1
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- BR
- Brazil
- Prior art keywords
- amino
- silica gel
- ethyl
- dichloromethane
- pyrimidine
- Prior art date
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- -1 heteroaromatic bicyclic derivative compound Chemical class 0.000 title claims abstract description 48
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 11
- 150000003839 salts Chemical class 0.000 title claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 101
- 125000003118 aryl group Chemical group 0.000 claims abstract description 51
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 49
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 34
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 24
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 22
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 21
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 20
- 125000001424 substituent group Chemical group 0.000 claims abstract description 20
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 17
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 16
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims abstract description 16
- 125000005129 aryl carbonyl group Chemical group 0.000 claims abstract description 15
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 6
- 230000035558 fertility Effects 0.000 claims abstract description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 20
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 9
- 125000005199 aryl carbonyloxy group Chemical group 0.000 claims description 9
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 9
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 8
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 7
- 125000001769 aryl amino group Chemical group 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 6
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 6
- 125000004658 aryl carbonyl amino group Chemical group 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 101100516572 Caenorhabditis elegans nhr-8 gene Proteins 0.000 claims description 3
- 125000005429 oxyalkyl group Chemical group 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims 1
- 102000005962 receptors Human genes 0.000 abstract description 14
- 108020003175 receptors Proteins 0.000 abstract description 14
- 230000000694 effects Effects 0.000 abstract description 9
- 238000002560 therapeutic procedure Methods 0.000 abstract description 2
- 230000004913 activation Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 516
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 186
- 239000000741 silica gel Substances 0.000 description 184
- 229910002027 silica gel Inorganic materials 0.000 description 184
- 238000000034 method Methods 0.000 description 130
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 120
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 102
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 88
- 238000006243 chemical reaction Methods 0.000 description 78
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 78
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 74
- 238000007363 ring formation reaction Methods 0.000 description 69
- 239000003480 eluent Substances 0.000 description 61
- YPOXGDJGKBXRFP-UHFFFAOYSA-N pyrimidine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC=N1 YPOXGDJGKBXRFP-UHFFFAOYSA-N 0.000 description 58
- 239000000047 product Substances 0.000 description 45
- PVBRSNZAOAJRKO-UHFFFAOYSA-N ethyl 2-sulfanylacetate Chemical compound CCOC(=O)CS PVBRSNZAOAJRKO-UHFFFAOYSA-N 0.000 description 44
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 41
- 229910019213 POCl3 Inorganic materials 0.000 description 39
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 38
- 235000019439 ethyl acetate Nutrition 0.000 description 37
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- 125000004432 carbon atom Chemical group C* 0.000 description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- 239000011541 reaction mixture Substances 0.000 description 28
- 239000000243 solution Substances 0.000 description 26
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 25
- 239000002253 acid Substances 0.000 description 25
- 150000001408 amides Chemical class 0.000 description 23
- 239000000203 mixture Substances 0.000 description 22
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 20
- 210000004027 cell Anatomy 0.000 description 19
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 19
- 150000002576 ketones Chemical class 0.000 description 17
- BHPYMZQTCPRLNR-UHFFFAOYSA-N 2-cyanoethanethioamide Chemical compound NC(=S)CC#N BHPYMZQTCPRLNR-UHFFFAOYSA-N 0.000 description 16
- WMPDAIZRQDCGFH-UHFFFAOYSA-N 3-methoxybenzaldehyde Chemical compound COC1=CC=CC(C=O)=C1 WMPDAIZRQDCGFH-UHFFFAOYSA-N 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 238000005882 aldol condensation reaction Methods 0.000 description 16
- 239000000460 chlorine Substances 0.000 description 16
- 230000032050 esterification Effects 0.000 description 16
- 238000005886 esterification reaction Methods 0.000 description 16
- 238000012360 testing method Methods 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- 238000004587 chromatography analysis Methods 0.000 description 15
- VEUUMBGHMNQHGO-UHFFFAOYSA-N ethyl chloroacetate Chemical compound CCOC(=O)CCl VEUUMBGHMNQHGO-UHFFFAOYSA-N 0.000 description 15
- NNBBQNFHCVVQHZ-UHFFFAOYSA-N methyl carbamimidothioate;sulfuric acid Chemical compound CSC(N)=N.OS(O)(=O)=O NNBBQNFHCVVQHZ-UHFFFAOYSA-N 0.000 description 15
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
- 238000010898 silica gel chromatography Methods 0.000 description 11
- 108010011942 LH Receptors Proteins 0.000 description 10
- 230000027455 binding Effects 0.000 description 10
- 238000009739 binding Methods 0.000 description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 102000023108 LH Receptors Human genes 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 9
- WYJOVVXUZNRJQY-UHFFFAOYSA-N 2-Acetylthiophene Chemical compound CC(=O)C1=CC=CS1 WYJOVVXUZNRJQY-UHFFFAOYSA-N 0.000 description 8
- IAVREABSGIHHMO-UHFFFAOYSA-N 3-hydroxybenzaldehyde Chemical compound OC1=CC=CC(C=O)=C1 IAVREABSGIHHMO-UHFFFAOYSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 8
- 102000011022 Chorionic Gonadotropin Human genes 0.000 description 8
- 108010062540 Chorionic Gonadotropin Proteins 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 229940084986 human chorionic gonadotropin Drugs 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- HKSQZEGSMBFHGC-UHFFFAOYSA-N pyrimidine-4-carboxamide Chemical compound NC(=O)C1=CC=NC=N1 HKSQZEGSMBFHGC-UHFFFAOYSA-N 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 229910052717 sulfur Inorganic materials 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 7
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 7
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 7
- 102000006771 Gonadotropins Human genes 0.000 description 7
- 108010086677 Gonadotropins Proteins 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 230000014509 gene expression Effects 0.000 description 7
- 239000002622 gonadotropin Substances 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- 230000016087 ovulation Effects 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 229960003604 testosterone Drugs 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- AZVSIHIBYRHSLB-UHFFFAOYSA-N 3-furaldehyde Chemical compound O=CC=1C=COC=1 AZVSIHIBYRHSLB-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-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
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 239000000556 agonist Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 229940028334 follicle stimulating hormone Drugs 0.000 description 6
- 229940094892 gonadotropins Drugs 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- SIOXPEMLGUPBBT-UHFFFAOYSA-M picolinate Chemical compound [O-]C(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-M 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- ZFCHNZDUMIOWFV-UHFFFAOYSA-M pyrimidine-2-carboxylate Chemical compound [O-]C(=O)C1=NC=CC=N1 ZFCHNZDUMIOWFV-UHFFFAOYSA-M 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 230000000638 stimulation Effects 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- RBIGKSZIQCTIJF-UHFFFAOYSA-N 3-formylthiophene Chemical compound O=CC=1C=CSC=1 RBIGKSZIQCTIJF-UHFFFAOYSA-N 0.000 description 5
- GSKZNNQWJVVTRT-UHFFFAOYSA-N 5-amino-2-methylsulfanyl-4-phenylthieno[2,3-d]pyrimidine-6-carboxylic acid Chemical compound C=12C(N)=C(C(O)=O)SC2=NC(SC)=NC=1C1=CC=CC=C1 GSKZNNQWJVVTRT-UHFFFAOYSA-N 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 210000002332 leydig cell Anatomy 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 4
- 108700008625 Reporter Genes Proteins 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- GTRLQRHWPXEBLF-UHFFFAOYSA-N benzyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=CC=C1 GTRLQRHWPXEBLF-UHFFFAOYSA-N 0.000 description 4
- 238000009833 condensation Methods 0.000 description 4
- 230000005494 condensation Effects 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 210000003101 oviduct Anatomy 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- BIJRUEBMNUUNIJ-UHFFFAOYSA-N pyridine-4-carboximidamide Chemical compound NC(=N)C1=CC=NC=C1 BIJRUEBMNUUNIJ-UHFFFAOYSA-N 0.000 description 4
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- QSELGEUCFNFITD-UHFFFAOYSA-N thiophene-2-carboximidamide Chemical compound NC(=N)C1=CC=CS1 QSELGEUCFNFITD-UHFFFAOYSA-N 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- XSAYZAUNJMRRIR-UHFFFAOYSA-N 2-acetylnaphthalene Chemical compound C1=CC=CC2=CC(C(=O)C)=CC=C21 XSAYZAUNJMRRIR-UHFFFAOYSA-N 0.000 description 3
- MLIREBYILWEBDM-UHFFFAOYSA-M 2-cyanoacetate Chemical compound [O-]C(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-M 0.000 description 3
- LIUCHRXQRHVSJI-UHFFFAOYSA-N 3-(2-hydroxyethoxy)benzaldehyde Chemical compound OCCOC1=CC=CC(C=O)=C1 LIUCHRXQRHVSJI-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 3
- 235000013601 eggs Nutrition 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- SDDKIZNHOCEXTF-UHFFFAOYSA-N methyl carbamimidothioate Chemical compound CSC(N)=N SDDKIZNHOCEXTF-UHFFFAOYSA-N 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- APVPOHHVBBYQAV-UHFFFAOYSA-N n-(4-aminophenyl)sulfonyloctadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(=O)NS(=O)(=O)C1=CC=C(N)C=C1 APVPOHHVBBYQAV-UHFFFAOYSA-N 0.000 description 3
- 125000004430 oxygen atom Chemical group O* 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 239000000018 receptor agonist Substances 0.000 description 3
- 229940044601 receptor agonist Drugs 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 125000001544 thienyl group Chemical group 0.000 description 3
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- HJLINEXLRZJOQU-UHFFFAOYSA-N pentyl carbamimidothioate Chemical compound CCCCCSC(N)=N HJLINEXLRZJOQU-UHFFFAOYSA-N 0.000 description 1
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- IUBKMGVNAYWGSL-UHFFFAOYSA-N pyrimidin-2-yl hydrogen carbonate Chemical compound OC(=O)OC1=NC=CC=N1 IUBKMGVNAYWGSL-UHFFFAOYSA-N 0.000 description 1
- ZFCHNZDUMIOWFV-UHFFFAOYSA-N pyrimidine-2-carboxylic acid Chemical compound OC(=O)C1=NC=CC=N1 ZFCHNZDUMIOWFV-UHFFFAOYSA-N 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000027272 reproductive process Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
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- 229940124597 therapeutic agent Drugs 0.000 description 1
- QXKDYVQSQQPDSE-UHFFFAOYSA-N thieno[3,2-d]pyrimidine-6-carboxylic acid Chemical compound C1=NC=C2SC(C(=O)O)=CC2=N1 QXKDYVQSQQPDSE-UHFFFAOYSA-N 0.000 description 1
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- 150000003556 thioamides Chemical class 0.000 description 1
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- KBPHJBAIARWVSC-XQIHNALSSA-N trans-lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C KBPHJBAIARWVSC-XQIHNALSSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/16—Masculine contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/18—Feminine contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Endocrinology (AREA)
- Public Health (AREA)
- Reproductive Health (AREA)
- Diabetes (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP99201152 | 1999-04-08 | ||
| PCT/EP2000/002865 WO2000061586A1 (en) | 1999-04-08 | 2000-04-03 | Bicyclic heteroaromatic compounds useful as lh agonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| BR0009558A BR0009558A (pt) | 2002-02-19 |
| BRPI0009558B1 true BRPI0009558B1 (pt) | 2016-10-25 |
Family
ID=8240094
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0009558A BRPI0009558B1 (pt) | 1999-04-08 | 2000-04-03 | composto derivado bicíclico heteroaromático ou um sal farmaceuticamente aceitável do mesmo, seu uso, e composição farmacêutica |
Country Status (30)
| Country | Link |
|---|---|
| US (2) | US6569863B1 (enExample) |
| EP (1) | EP1171443B1 (enExample) |
| JP (1) | JP4854856B2 (enExample) |
| KR (1) | KR100691546B1 (enExample) |
| CN (1) | CN1177848C (enExample) |
| AR (1) | AR028474A1 (enExample) |
| AT (1) | ATE299507T1 (enExample) |
| AU (1) | AU772258B2 (enExample) |
| BR (1) | BRPI0009558B1 (enExample) |
| CA (1) | CA2368834C (enExample) |
| CO (1) | CO5160348A1 (enExample) |
| CZ (1) | CZ300832B6 (enExample) |
| DE (1) | DE60021262T2 (enExample) |
| DK (1) | DK1171443T3 (enExample) |
| ES (1) | ES2245304T3 (enExample) |
| HK (1) | HK1041266B (enExample) |
| HU (1) | HU229002B1 (enExample) |
| ID (1) | ID30502A (enExample) |
| IL (2) | IL145483A0 (enExample) |
| MX (1) | MXPA01010144A (enExample) |
| NO (1) | NO328826B1 (enExample) |
| NZ (1) | NZ514445A (enExample) |
| PE (1) | PE20010030A1 (enExample) |
| PL (1) | PL219316B1 (enExample) |
| PT (1) | PT1171443E (enExample) |
| RU (1) | RU2248979C2 (enExample) |
| TR (1) | TR200102839T2 (enExample) |
| TW (1) | TW564247B (enExample) |
| WO (1) | WO2000061586A1 (enExample) |
| ZA (1) | ZA200107917B (enExample) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4977940B2 (ja) | 2000-09-22 | 2012-07-18 | エム・エス・ディー・オス・ベー・フェー | 二環式ヘテロ芳香族化合物 |
| GB0100622D0 (en) | 2001-01-10 | 2001-02-21 | Vernalis Res Ltd | Chemical compounds V111 |
| DE10108481A1 (de) | 2001-02-22 | 2002-10-24 | Bayer Ag | Pyridylpyrimidine |
| EP1427734B1 (en) * | 2001-09-04 | 2005-11-09 | Akzo Nobel N.V. | GLYCINE-SUBSTITUTED THIENO[2,3-d]PYRIMIDINES WITH COMBINED LH AND FSH AGONISTIC ACTIVITY |
| TWI228508B (en) * | 2001-09-04 | 2005-03-01 | Akzo Nobel Nv | Thieno[2,3-d]pyrimidines with combined LH and FSH agonistic activity |
| UY27834A1 (es) | 2002-06-06 | 2003-12-31 | Boehringer Ingelheim Pharma | Compuestos de amidas de acido 3-amino-tieno(2,3-b) piiridino-2-carboxilico sustituido y procedimientos para prepararlos y sus usos. |
| US6974870B2 (en) | 2002-06-06 | 2005-12-13 | Boehringer Ingelheim Phamaceuticals, Inc. | Substituted 3-amino-thieno [2,3-b]pyridine-2-carboxylic acid amide compounds and processes for preparing and their uses |
| WO2004092173A2 (en) | 2003-04-09 | 2004-10-28 | Biogen Idec Ma Inc. | A2a adenosine receptor antagonists |
| US7674791B2 (en) | 2003-04-09 | 2010-03-09 | Biogen Idec Ma Inc. | Triazolopyrazines and methods of making and using the same |
| US7285550B2 (en) | 2003-04-09 | 2007-10-23 | Biogen Idec Ma Inc. | Triazolotriazines and pyrazolotriazines and methods of making and using the same |
| JPWO2005019225A1 (ja) * | 2003-08-21 | 2007-11-01 | 杏林製薬株式会社 | Ｎｋ１受容体拮抗作用を有する化合物の製造方法及びその製造中間体 |
| US7550485B2 (en) * | 2003-10-14 | 2009-06-23 | Wyeth | Substituted N-heterocycle derivatives and methods of their use |
| WO2005039506A2 (en) * | 2003-10-24 | 2005-05-06 | Exelixis, Inc. | P70s6 kinase modulators and method of use |
| US7781478B2 (en) | 2004-07-14 | 2010-08-24 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| NZ553329A (en) * | 2004-07-22 | 2010-09-30 | Ptc Therapeutics Inc | Thienopyridines for treating hepatitis C |
| CA2630920A1 (en) * | 2005-11-22 | 2007-05-31 | University Of South Florida | Inhibition of cell proliferation |
| AR059898A1 (es) | 2006-03-15 | 2008-05-07 | Janssen Pharmaceutica Nv | Derivados de 3-ciano-piridona 1,4-disustituida y su uso como moduladores alostericos de los receptores mglur2 |
| AU2007254165A1 (en) * | 2006-05-17 | 2007-11-29 | Forschungsverbund Berlin E.V. | Pyrimidine low molecular weight ligands for modulating hormone receptors |
| EP2029608A1 (en) | 2006-06-06 | 2009-03-04 | Boehringer Ingelheim International GmbH | Substituted 3-amino-thieno[2,3-b] pyridine-2-carboxamide compounds, their preparation and use |
| RU2444524C2 (ru) * | 2006-08-21 | 2012-03-10 | Дженентек, Инк. | Азабензотиофенильные соединения и способы применения |
| TW200900065A (en) | 2007-03-07 | 2009-01-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives |
| TW200845978A (en) | 2007-03-07 | 2008-12-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives |
| KR20100065191A (ko) | 2007-09-14 | 2010-06-15 | 오르토-맥닐-얀센 파마슈티칼스 인코포레이티드 | １,３-이치환된 ４-(아릴-ｘ-페닐)-１ｈ-피리딘-２-온 |
| MX2010002536A (es) | 2007-09-14 | 2010-08-10 | Ortho Mcneil Janssen Pharm | 4-fenil-3,4,5,6-tetrahidro-2h, 1'h-[1,4]bipiridinil-2'-onas 1',3'-disubstituidas. |
| EP2205565B1 (en) * | 2007-09-14 | 2013-04-17 | Janssen Pharmaceuticals, Inc. | 1,3-disubstituted-4-phenyl-1 h-pyridin-2-ones |
| CN103497201A (zh) * | 2007-10-18 | 2014-01-08 | 贝林格尔.英格海姆国际有限公司 | 二氢噻吩并[3,2-d]嘧啶的制备中使用的中间体及其制备 |
| EP2220083B1 (en) | 2007-11-14 | 2017-07-19 | Janssen Pharmaceuticals, Inc. | Imidazo[1,2-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| MX2011002042A (es) | 2008-09-02 | 2011-06-20 | Ortho Mcneil Janssen Pharm | Derivados de 3-azabiciclo[3.1.o]hexilo como moduladores de los receptores del glutamato metabotropico. |
| AU2009304293B2 (en) | 2008-10-16 | 2012-04-26 | Addex Pharma S.A. | Indole and benzomorpholine derivatives as modulators of metabotropic glutamate receptors |
| CN102232074B (zh) | 2008-11-28 | 2014-12-03 | 奥梅-杨森制药有限公司 | 作为代谢性谷氨酸盐受体调节剂的吲哚和苯并噁嗪衍生物 |
| EA020672B1 (ru) | 2009-05-12 | 2014-12-30 | Янссен Фармасьютикалс, Инк. | Производные 1,2,4-триазоло[4,3-a]пиридина и их применение для лечения или предупреждения неврологических и психиатрических расстройств |
| MY153913A (en) | 2009-05-12 | 2015-04-15 | Janssen Pharmaceuticals Inc | 7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| SG176018A1 (en) | 2009-05-12 | 2011-12-29 | Janssen Pharmaceuticals Inc | 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| CA2815002C (en) | 2010-11-08 | 2019-10-22 | Janssen Pharmaceuticals, Inc. | 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| ES2552455T3 (es) | 2010-11-08 | 2015-11-30 | Janssen Pharmaceuticals, Inc. | Derivados de 1,2,4-triazolo[4,3-a]piridina y su uso como moduladores alostéricos positivos de receptores mGluR2 |
| US9012448B2 (en) | 2010-11-08 | 2015-04-21 | Janssen Pharmaceuticals, Inc. | 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of MGLUR2 receptors |
| RU2014103185A (ru) | 2011-07-18 | 2015-08-27 | Артс Байолоджикс А/С | Биологически активное соединение на основе лютеинизирующего гормона (lh) с пролонгированным действием |
| MX355088B (es) | 2011-11-23 | 2018-04-04 | Cancer Research Tech Ltd | Inhibidores de tienopirimidina de proteina cinasa c atipica. |
| JO3368B1 (ar) | 2013-06-04 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 6، 7- ثاني هيدرو بيرازولو [5،1-a] بيرازين- 4 (5 يد)- اون واستخدامها بصفة منظمات تفارغية سلبية لمستقبلات ميجلور 2 |
| JO3367B1 (ar) | 2013-09-06 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 2،1، 4- ثلاثي زولو [3،4-a] بيريدين واستخدامها بصفة منظمات تفارغية موجبة لمستقبلات ميجلور 2 |
| UA121965C2 (uk) | 2014-01-21 | 2020-08-25 | Янссен Фармацевтика Нв | Комбінації, які містять позитивні алостеричні модулятори або ортостеричні агоністи метаботропного глутаматергічного рецептора 2 підтипу, та їх застосування |
| KR102502485B1 (ko) | 2014-01-21 | 2023-02-21 | 얀센 파마슈티카 엔.브이. | 대사 조절형 글루탐산 작동성 수용체 제2아형의 양성 알로스테릭 조절제 또는 오르토스테릭 작동제를 포함하는 조합 및 그 용도 |
| CN107602585A (zh) * | 2017-10-23 | 2018-01-19 | 遵义医学院 | 噻吩并吡啶双杂环化合物的制备工艺 |
| BR102019022529A2 (pt) * | 2019-10-25 | 2021-05-04 | Anhanguera Educacional Ltda. | Processo para obtenção de composições farmacêuticas antitumorais através de butadienos push-pull, compostos e seus usos |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993013664A2 (en) * | 1992-01-11 | 1993-07-22 | Schering Agrochemicals Limited | Biheterocyclic fungicidal compounds |
| TW449600B (en) | 1994-04-19 | 2001-08-11 | Takeda Chemical Industries Ltd | Condensed-ring thiophene derivatives, their production and use |
| JP3854648B2 (ja) * | 1994-04-19 | 2006-12-06 | 武田薬品工業株式会社 | 縮合チオフェン誘導体、その製造法及び用途 |
| HUT77348A (hu) * | 1994-11-08 | 1998-03-30 | Takeda Chemical Industries, Ltd. | Tienopiridin- és tienopirimidinszármazékok, eljárás előállításukra és az ezeket tartalmazó gyógyszerkészítmények |
| EP0862573A1 (en) * | 1995-10-19 | 1998-09-09 | Takeda Chemical Industries, Ltd. | Thienopyridine derivatives as gonadotropin releasing hormone antagonists |
| JPH09169767A (ja) * | 1995-10-19 | 1997-06-30 | Takeda Chem Ind Ltd | 複素環化合物、その製造法および用途 |
| JPH09169766A (ja) * | 1995-10-19 | 1997-06-30 | Takeda Chem Ind Ltd | チエノピリジン誘導体，その製造法および用途 |
| EP0900222A1 (en) * | 1996-04-26 | 1999-03-10 | Takeda Chemical Industries, Ltd. | Thienopyridine derivatives, their production and use |
-
2000
- 2000-03-23 TW TW089105361A patent/TW564247B/zh not_active IP Right Cessation
- 2000-04-03 BR BRPI0009558A patent/BRPI0009558B1/pt not_active IP Right Cessation
- 2000-04-03 ES ES00917026T patent/ES2245304T3/es not_active Expired - Lifetime
- 2000-04-03 MX MXPA01010144A patent/MXPA01010144A/es active IP Right Grant
- 2000-04-03 CZ CZ20013605A patent/CZ300832B6/cs not_active IP Right Cessation
- 2000-04-03 KR KR1020017012792A patent/KR100691546B1/ko not_active Expired - Fee Related
- 2000-04-03 ID IDW00200102449A patent/ID30502A/id unknown
- 2000-04-03 EP EP00917026A patent/EP1171443B1/en not_active Expired - Lifetime
- 2000-04-03 TR TR2001/02839T patent/TR200102839T2/xx unknown
- 2000-04-03 DK DK00917026T patent/DK1171443T3/da active
- 2000-04-03 CA CA002368834A patent/CA2368834C/en not_active Expired - Fee Related
- 2000-04-03 US US09/937,416 patent/US6569863B1/en not_active Expired - Lifetime
- 2000-04-03 NZ NZ514445A patent/NZ514445A/en not_active IP Right Cessation
- 2000-04-03 JP JP2000610857A patent/JP4854856B2/ja not_active Expired - Fee Related
- 2000-04-03 HK HK02103025.1A patent/HK1041266B/en not_active IP Right Cessation
- 2000-04-03 IL IL14548300A patent/IL145483A0/xx active IP Right Grant
- 2000-04-03 HU HU0200653A patent/HU229002B1/hu not_active IP Right Cessation
- 2000-04-03 PT PT00917026T patent/PT1171443E/pt unknown
- 2000-04-03 AT AT00917026T patent/ATE299507T1/de active
- 2000-04-03 WO PCT/EP2000/002865 patent/WO2000061586A1/en not_active Ceased
- 2000-04-03 RU RU2001130051/04A patent/RU2248979C2/ru not_active IP Right Cessation
- 2000-04-03 PL PL350964A patent/PL219316B1/pl unknown
- 2000-04-03 AU AU38166/00A patent/AU772258B2/en not_active Ceased
- 2000-04-03 CN CNB008069077A patent/CN1177848C/zh not_active Expired - Fee Related
- 2000-04-03 DE DE60021262T patent/DE60021262T2/de not_active Expired - Lifetime
- 2000-04-06 PE PE2000000312A patent/PE20010030A1/es not_active Application Discontinuation
- 2000-04-06 AR ARP000101578A patent/AR028474A1/es not_active Application Discontinuation
- 2000-04-07 CO CO00025852A patent/CO5160348A1/es unknown
-
2001
- 2001-09-16 IL IL145483A patent/IL145483A/en not_active IP Right Cessation
- 2001-09-26 ZA ZA200107917A patent/ZA200107917B/xx unknown
- 2001-10-04 NO NO20014824A patent/NO328826B1/no not_active IP Right Cessation
-
2003
- 2003-04-11 US US10/411,960 patent/US6841553B2/en not_active Expired - Lifetime
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Legal Events
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| B06A | Patent application procedure suspended [chapter 6.1 patent gazette] | ||
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Free format text: ALTERADA DE INT.CL: C07D 495/04, A61K 31/505, C07D 487/04, A61K 31/44 Ipc: C07D 495/04 (2009.01), C07D 487/04 (2009.01), A61K |
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| B24J | Lapse because of non-payment of annual fees (definitively: art 78 iv lpi, resolution 113/2013 art. 12) |
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