DE69634045T2 - Antithrombotische diamine - Google Patents
Antithrombotische diamine Download PDFInfo
- Publication number
- DE69634045T2 DE69634045T2 DE69634045T DE69634045T DE69634045T2 DE 69634045 T2 DE69634045 T2 DE 69634045T2 DE 69634045 T DE69634045 T DE 69634045T DE 69634045 T DE69634045 T DE 69634045T DE 69634045 T2 DE69634045 T2 DE 69634045T2
- Authority
- DE
- Germany
- Prior art keywords
- pyrrolidinyl
- benzo
- compound
- phenyl
- ethoxy
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Fee Related
Links
- 150000004985 diamines Chemical class 0.000 title abstract description 7
- 239000003146 anticoagulant agent Substances 0.000 title description 19
- 230000002785 anti-thrombosis Effects 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 491
- 238000002360 preparation method Methods 0.000 claims abstract description 140
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 230000009424 thromboembolic effect Effects 0.000 claims abstract description 9
- -1 methylene, carbonyl Chemical group 0.000 claims description 256
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 120
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 87
- 125000005605 benzo group Chemical group 0.000 claims description 82
- 150000003839 salts Chemical class 0.000 claims description 82
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 79
- 108090000190 Thrombin Proteins 0.000 claims description 55
- 229960004072 thrombin Drugs 0.000 claims description 55
- 239000001257 hydrogen Substances 0.000 claims description 54
- 229910052739 hydrogen Inorganic materials 0.000 claims description 54
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 46
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 43
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 38
- 239000002253 acid Substances 0.000 claims description 36
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 34
- 238000011282 treatment Methods 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- 150000002431 hydrogen Chemical class 0.000 claims description 27
- 229910052760 oxygen Inorganic materials 0.000 claims description 26
- 229910052717 sulfur Inorganic materials 0.000 claims description 24
- 230000002401 inhibitory effect Effects 0.000 claims description 22
- 150000002367 halogens Chemical class 0.000 claims description 21
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 21
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 19
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 16
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 9
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 6
- 125000001246 bromo group Chemical group Br* 0.000 claims description 5
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- MIGQQNQBSBENQE-UHFFFAOYSA-N 3-[[3-methoxy-4-(pyrrolidin-1-ylmethyl)phenyl]methyl]-2-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-1-benzothiophen-6-ol Chemical compound C=1C=C(CN2CCCC2)C(OC)=CC=1CC(C1=CC=C(O)C=C1S1)=C1C(C=C1)=CC=C1OCCN1CCCC1 MIGQQNQBSBENQE-UHFFFAOYSA-N 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- SLDXQJUMTBHRQO-UHFFFAOYSA-N 3-[[3-methyl-4-(pyrrolidin-1-ylmethyl)phenyl]methyl]-2-[6-(2-pyrrolidin-1-ylethoxy)pyridin-3-yl]-1-benzothiophen-6-ol Chemical compound C=1C=C(CN2CCCC2)C(C)=CC=1CC(C1=CC=C(O)C=C1S1)=C1C(C=N1)=CC=C1OCCN1CCCC1 SLDXQJUMTBHRQO-UHFFFAOYSA-N 0.000 claims 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 322
- 239000000543 intermediate Substances 0.000 abstract description 22
- 230000008569 process Effects 0.000 abstract description 21
- 229940122388 Thrombin inhibitor Drugs 0.000 abstract description 11
- 239000003868 thrombin inhibitor Substances 0.000 abstract description 11
- 239000003795 chemical substances by application Substances 0.000 abstract description 6
- 239000003130 blood coagulation factor inhibitor Substances 0.000 abstract 1
- 238000000434 field desorption mass spectrometry Methods 0.000 description 278
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 254
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 252
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 208
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 170
- 239000000203 mixture Substances 0.000 description 134
- 238000004458 analytical method Methods 0.000 description 131
- 239000000243 solution Substances 0.000 description 130
- 235000019439 ethyl acetate Nutrition 0.000 description 125
- 238000005481 NMR spectroscopy Methods 0.000 description 113
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 91
- 239000007787 solid Substances 0.000 description 74
- 238000006243 chemical reaction Methods 0.000 description 73
- 229910004298 SiO 2 Inorganic materials 0.000 description 69
- 239000003921 oil Substances 0.000 description 68
- 235000019198 oils Nutrition 0.000 description 68
- 239000012458 free base Substances 0.000 description 67
- 238000004587 chromatography analysis Methods 0.000 description 60
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 59
- 239000000460 chlorine Substances 0.000 description 59
- 239000012074 organic phase Substances 0.000 description 59
- 150000002576 ketones Chemical class 0.000 description 57
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 51
- 229920006395 saturated elastomer Polymers 0.000 description 50
- 238000003818 flash chromatography Methods 0.000 description 48
- 239000006260 foam Substances 0.000 description 46
- 230000002829 reductive effect Effects 0.000 description 43
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 37
- 239000011541 reaction mixture Substances 0.000 description 37
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 35
- 239000011734 sodium Substances 0.000 description 34
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
- 238000012360 testing method Methods 0.000 description 33
- 125000001424 substituent group Chemical group 0.000 description 31
- 239000012267 brine Substances 0.000 description 30
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 30
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 29
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 28
- 239000008346 aqueous phase Substances 0.000 description 28
- 239000012071 phase Substances 0.000 description 27
- 210000002381 plasma Anatomy 0.000 description 27
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 26
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical group C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 25
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 24
- 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 24
- 238000000746 purification Methods 0.000 description 24
- 238000003756 stirring Methods 0.000 description 24
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 22
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 22
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- 239000000047 product Substances 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 239000000741 silica gel Substances 0.000 description 21
- 229910002027 silica gel Inorganic materials 0.000 description 21
- 239000002002 slurry Substances 0.000 description 21
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 20
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
- 230000005494 condensation Effects 0.000 description 20
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 19
- 238000010992 reflux Methods 0.000 description 19
- 239000002904 solvent Substances 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 238000009472 formulation Methods 0.000 description 18
- 150000003254 radicals Chemical class 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
- 239000007858 starting material Substances 0.000 description 16
- 238000006467 substitution reaction Methods 0.000 description 16
- 210000004369 blood Anatomy 0.000 description 15
- 239000008280 blood Substances 0.000 description 15
- 239000003153 chemical reaction reagent Substances 0.000 description 15
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 14
- 208000007536 Thrombosis Diseases 0.000 description 14
- 239000004327 boric acid Substances 0.000 description 13
- 230000015271 coagulation Effects 0.000 description 13
- 238000005345 coagulation Methods 0.000 description 13
- 239000000523 sample Substances 0.000 description 13
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 12
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 12
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 239000012043 crude product Substances 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 230000009467 reduction Effects 0.000 description 12
- 229960000187 tissue plasminogen activator Drugs 0.000 description 12
- QZZPYILWKWAQRM-UHFFFAOYSA-N 1-[2-[4-(6-methoxy-1-benzothiophen-2-yl)phenoxy]ethyl]pyrrolidine Chemical compound S1C2=CC(OC)=CC=C2C=C1C(C=C1)=CC=C1OCCN1CCCC1 QZZPYILWKWAQRM-UHFFFAOYSA-N 0.000 description 11
- ZEXIVBYDDCIOKA-UHFFFAOYSA-N 1-benzothiophen-2-ol Chemical class C1=CC=C2SC(O)=CC2=C1 ZEXIVBYDDCIOKA-UHFFFAOYSA-N 0.000 description 11
- 241000124008 Mammalia Species 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 229940127219 anticoagulant drug Drugs 0.000 description 11
- 229910052786 argon Inorganic materials 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 11
- FSNGFFWICFYWQC-UHFFFAOYSA-N 1-(2-chloroethyl)pyrrolidine;hydron;chloride Chemical compound Cl.ClCCN1CCCC1 FSNGFFWICFYWQC-UHFFFAOYSA-N 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- 108010023197 Streptokinase Proteins 0.000 description 10
- 230000029936 alkylation Effects 0.000 description 10
- 238000005804 alkylation reaction Methods 0.000 description 10
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 10
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 10
- 238000009833 condensation Methods 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 10
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- 0 *c1c(-c2cnc(*)cc2)[n]c2c1cc(*)c(*=C)c2 Chemical compound *c1c(-c2cnc(*)cc2)[n]c2c1cc(*)c(*=C)c2 0.000 description 9
- 229910003827 NRaRb Inorganic materials 0.000 description 9
- 239000013543 active substance Substances 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- XBRDBODLCHKXHI-UHFFFAOYSA-N epolamine Chemical compound OCCN1CCCC1 XBRDBODLCHKXHI-UHFFFAOYSA-N 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 239000003527 fibrinolytic agent Substances 0.000 description 9
- 125000001072 heteroaryl group Chemical group 0.000 description 9
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- GKAJJEOXDGDXKG-UHFFFAOYSA-N n,n-dimethyl-6-phenylmethoxy-1-benzothiophen-2-amine Chemical compound C1=C2SC(N(C)C)=CC2=CC=C1OCC1=CC=CC=C1 GKAJJEOXDGDXKG-UHFFFAOYSA-N 0.000 description 9
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 9
- ADKCFCOXELVRJV-UHFFFAOYSA-N 2-(4-methoxyphenyl)-1-benzothiophene Chemical compound C1=CC(OC)=CC=C1C1=CC2=CC=CC=C2S1 ADKCFCOXELVRJV-UHFFFAOYSA-N 0.000 description 8
- LDCQRJXSIHDEKI-UHFFFAOYSA-N 2-methoxy-1-benzothiophene Chemical compound C1=CC=C2SC(OC)=CC2=C1 LDCQRJXSIHDEKI-UHFFFAOYSA-N 0.000 description 8
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- 239000005909 Kieselgur Substances 0.000 description 8
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 8
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- 150000001499 aryl bromides Chemical class 0.000 description 8
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- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 8
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- CREADFHAHZTKKQ-UHFFFAOYSA-N (3-bromo-4-methoxyphenyl)-[2-(4-methoxyphenyl)-1-benzothiophen-3-yl]methanone Chemical compound C1=CC(OC)=CC=C1C1=C(C(=O)C=2C=C(Br)C(OC)=CC=2)C2=CC=CC=C2S1 CREADFHAHZTKKQ-UHFFFAOYSA-N 0.000 description 7
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- 230000000740 bleeding effect Effects 0.000 description 6
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- 150000002900 organolithium compounds Chemical class 0.000 description 6
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- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
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- 229910052709 silver Inorganic materials 0.000 description 1
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- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
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- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
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- 229910001220 stainless steel Inorganic materials 0.000 description 1
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- 239000008117 stearic acid Substances 0.000 description 1
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- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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- PUGUQINMNYINPK-UHFFFAOYSA-N tert-butyl 4-(2-chloroacetyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(C(=O)CCl)CC1 PUGUQINMNYINPK-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- AFCAKJKUYFLYFK-UHFFFAOYSA-N tetrabutyltin Chemical compound CCCC[Sn](CCCC)(CCCC)CCCC AFCAKJKUYFLYFK-UHFFFAOYSA-N 0.000 description 1
- RWWNQEOPUOCKGR-UHFFFAOYSA-N tetraethyltin Chemical compound CC[Sn](CC)(CC)CC RWWNQEOPUOCKGR-UHFFFAOYSA-N 0.000 description 1
- OIQCWAIEHVRCCG-UHFFFAOYSA-N tetrapropylstannane Chemical compound CCC[Sn](CCC)(CCC)CCC OIQCWAIEHVRCCG-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- VOVUARRWDCVURC-UHFFFAOYSA-N thiirane Chemical compound C1CS1 VOVUARRWDCVURC-UHFFFAOYSA-N 0.000 description 1
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- 238000012546 transfer Methods 0.000 description 1
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- 238000006478 transmetalation reaction Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
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- 239000003981 vehicle Substances 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes 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 carbon atoms of the hetero ring
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
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- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
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- A61K31/42—Oxazoles
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
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- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- 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
- C07D233/56—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D333/56—Radicals substituted by oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D333/58—Radicals substituted by nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes 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 carbon atoms of the hetero ring
- C07D333/64—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
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- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes 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 carbon atoms of the hetero ring
- C07D333/66—Nitrogen atoms not forming part of a nitro radical
-
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US712095P | 1995-10-31 | 1995-10-31 | |
| US7120P | 1995-10-31 | ||
| US2825296P | 1996-10-09 | 1996-10-09 | |
| US28252P | 1996-10-09 | ||
| PCT/US1996/017995 WO1997025033A1 (en) | 1995-10-31 | 1996-10-30 | Antithrombotic diamines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69634045D1 DE69634045D1 (de) | 2005-01-20 |
| DE69634045T2 true DE69634045T2 (de) | 2005-05-19 |
Family
ID=26676549
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69634045T Expired - Fee Related DE69634045T2 (de) | 1995-10-31 | 1996-10-30 | Antithrombotische diamine |
Country Status (9)
| Country | Link |
|---|---|
| US (3) | US6025382A (enExample) |
| EP (1) | EP0863755B1 (enExample) |
| JP (1) | JP2002500618A (enExample) |
| AT (1) | ATE284690T1 (enExample) |
| AU (1) | AU7725596A (enExample) |
| CA (1) | CA2236007A1 (enExample) |
| DE (1) | DE69634045T2 (enExample) |
| ES (1) | ES2233982T3 (enExample) |
| WO (1) | WO1997025033A1 (enExample) |
Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2217373A1 (en) * | 1996-10-10 | 1998-04-10 | Michael John Martin | Benzo¬b|thiophene compounds, intermediates, formulations, and methods |
| WO1998048797A1 (en) | 1997-04-30 | 1998-11-05 | Eli Lilly And Company | Antithrombotic agents |
| AU7170898A (en) | 1997-04-30 | 1998-11-24 | Eli Lilly And Company | Antithrombotic agents |
| AU7470098A (en) | 1997-04-30 | 1998-11-24 | Eli Lilly And Company | Antithrombotic agents |
| AU7274098A (en) | 1997-04-30 | 1998-11-24 | Eli Lilly And Company | Antithrombotic agents |
| CA2287982A1 (en) | 1997-04-30 | 1998-11-05 | Michael Enrico Richett | Antithrombotic agents |
| CA2287984A1 (en) | 1997-05-01 | 1998-11-05 | Gerald Floyd Smith | Antithrombotic agents |
| US7008950B1 (en) | 1997-06-05 | 2006-03-07 | Takeda Chemical Industries, Ltd. | Benzofurans as suppressors of neurodegeneration |
| US6017914A (en) * | 1997-09-03 | 2000-01-25 | Eli Lilly And Company | Benzo[b]thiophene compounds, intermediates, formulations, and methods |
| US6284756B1 (en) | 1998-04-30 | 2001-09-04 | Eli Lilly And Company | Antithrombotic agents |
| US6166069A (en) * | 1998-05-12 | 2000-12-26 | American Home Products Corporation | Phenyl oxo-acetic acids useful in the treatment of insulin resistance and hyperglycemia |
| PT997460E (pt) * | 1998-10-28 | 2003-03-31 | Lilly Co Eli | Compostos benzotiofenos como agentes antitromboticos e seus intermediarios |
| ES2213984T3 (es) | 1998-10-30 | 2004-09-01 | Eli Lilly And Company | Derivados de azaindol y su uso como agentes antitrombicos. |
| DE60008430T2 (de) * | 1999-11-19 | 2004-12-23 | Eli Lilly And Co., Indianapolis | Verbindungen mit antithrombotischer wirkung |
| ES2236536T3 (es) | 2001-05-22 | 2005-07-16 | Eli Lilly And Company | Derivados tetrahidroquinolino para la inhibicion de enfermedades asociadas con la privacion de estrogenos o con una respuesta fisiologica aberrante a estrogenos endogenos. |
| DE60210283T2 (de) | 2001-05-22 | 2006-11-09 | Eli Lilly And Co., Indianapolis | 2-substituierte 1,2,3,4-tetrahydrochinoline und derivate davon, zusammensetzungen und verfahren |
| US7482366B2 (en) | 2001-12-21 | 2009-01-27 | X-Ceptor Therapeutics, Inc. | Modulators of LXR |
| EP1465869B1 (en) | 2001-12-21 | 2013-05-15 | Exelixis Patent Company LLC | Modulators of lxr |
| ES2326593T3 (es) * | 2002-07-22 | 2009-10-15 | Eli Lilly And Company | Moduladores de receptores de estrogeno selectivos que contienen un grupo fenilsulfonilo. |
| US7296361B2 (en) * | 2003-07-31 | 2007-11-20 | University Of Pittsburgh | Measuring device and method of measuring |
| EP2514756B1 (en) | 2003-08-01 | 2014-12-17 | Mitsubishi Tanabe Pharma Corporation | Novel compounds having inhibitory activity against sodium-dependant glucose transporter |
| US8785403B2 (en) | 2003-08-01 | 2014-07-22 | Mitsubishi Tanabe Pharma Corporation | Glucopyranoside compound |
| NZ556686A (en) | 2005-02-14 | 2010-01-29 | Bionomics Ltd | Novel tubulin polymerisation inhibitors |
| GB0507577D0 (en) | 2005-04-14 | 2005-05-18 | Novartis Ag | Organic compounds |
| UY30730A1 (es) | 2006-12-04 | 2008-07-03 | Mitsubishi Tanabe Pharma Corp | Forma cristalina del hemihidrato de 1-(b (beta)-d-glucopiranosil) -4-metil-3-[5-(4-fluorofenil) -2-tienilmetil]benceno |
| HUE035130T2 (en) | 2007-09-10 | 2018-05-02 | Janssen Pharmaceutica Nv | A method for preparing compounds useful as SGLT inhibitors |
| CL2008003653A1 (es) | 2008-01-17 | 2010-03-05 | Mitsubishi Tanabe Pharma Corp | Uso de un inhibidor de sglt derivado de glucopiranosilo y un inhibidor de dppiv seleccionado para tratar la diabetes; y composicion farmaceutica. |
| US9056850B2 (en) | 2008-10-17 | 2015-06-16 | Janssen Pharmaceutica N.V. | Process for the preparation of compounds useful as inhibitors of SGLT |
| US20110009347A1 (en) | 2009-07-08 | 2011-01-13 | Yin Liang | Combination therapy for the treatment of diabetes |
| EP2488515B1 (en) | 2009-10-14 | 2017-01-04 | Janssen Pharmaceutica NV | Process for the preparation of compounds useful as inhibitors of sglt2 |
| TWI599360B (zh) | 2010-05-11 | 2017-09-21 | 健生藥品公司 | 醫藥調配物 |
| RS55056B1 (sr) | 2011-04-13 | 2016-12-30 | Janssen Pharmaceutica Nv | Proces za pripremu jedinjenja koja su korisna kao inhibitori sglt2 |
| TWI542596B (zh) | 2011-05-09 | 2016-07-21 | 健生藥品公司 | (2s,3r,4r,5s,6r)-2-(3-((5-(4-氟苯基)噻吩-2-基)甲基)-4-甲基苯基)-6-(羥甲基)四氫-2h-哌喃-3,4,5-三醇之l-脯胺酸及檸檬酸共晶體 |
| EP2791143B1 (en) | 2011-12-15 | 2016-02-24 | Bayer Intellectual Property GmbH | Substituted benzothienyl-pyrrolotriazines and uses thereof in the treatment of cancer |
| CA2865021C (en) | 2012-02-23 | 2020-06-30 | Bayer Intellectual Property Gmbh | Substituted benzothienyl-pyrrolotriazines and uses thereof |
| KR20170118687A (ko) | 2015-02-19 | 2017-10-25 | 제이엔씨 주식회사 | 벤조티오펜을 가지는 액정성 화합물, 액정 조성물 및 액정 표시 소자 |
| US20170071970A1 (en) | 2015-09-15 | 2017-03-16 | Janssen Pharmaceutica Nv | Co-therapy comprising canagliflozin and phentermine for the treatment of obesity and obesity related disorders |
| EA202092442A3 (ru) | 2016-06-07 | 2021-08-31 | Джакобио Фармасьютикалс Ко., Лтд. | Новые гетероциклические производные, применимые в качестве ингибиторов shp2 |
| KR102317480B1 (ko) | 2017-03-23 | 2021-10-25 | 자코바이오 파마슈티칼스 컴퍼니 리미티드 | Shp2 억제제로서 유용한 신규한 헤테로환형 유도체 |
| WO2020063760A1 (en) | 2018-09-26 | 2020-04-02 | Jacobio Pharmaceuticals Co., Ltd. | Novel heterocyclic derivatives useful as shp2 inhibitors |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3274213A (en) * | 1961-09-05 | 1966-09-20 | Upjohn Co | Alkoxy-substituted 2-phenyl-1-(tertiary-aminoalkoxy)phenyl-3, 4-dihydronaphthalenes |
| US3293263A (en) * | 1963-12-09 | 1966-12-20 | Upjohn Co | Diphenylbenzocycloalkenes |
| GB1456323A (en) * | 1974-06-06 | 1976-11-24 | Labaz | Benzothiophenes process for preparing them and pharmaceutical compositions containing the same |
| US4001426A (en) * | 1974-10-17 | 1977-01-04 | Smithkline Corporation | Substituted benzofurans and benzothiophenes |
| US4133814A (en) * | 1975-10-28 | 1979-01-09 | Eli Lilly And Company | 2-Phenyl-3-aroylbenzothiophenes useful as antifertility agents |
| KR920703558A (ko) | 1990-11-15 | 1992-12-18 | 원본미기재 | 메타-치환 페닐알라닌 유도체 |
| JP3157882B2 (ja) * | 1991-11-15 | 2001-04-16 | 帝国臓器製薬株式会社 | 新規なベンゾチオフエン誘導体 |
| US5371091A (en) * | 1992-08-31 | 1994-12-06 | Bristol-Myers Squibb Company | Heteroaromatic amine thrombin inhibitors |
| US6756388B1 (en) * | 1993-10-12 | 2004-06-29 | Pfizer Inc. | Benzothiophenes and related compounds as estrogen agonists |
| US5441965A (en) * | 1993-12-21 | 1995-08-15 | Eli Lilly And Company | Methods of inhibiting thrombin |
| US5510357A (en) * | 1995-02-28 | 1996-04-23 | Eli Lilly And Company | Benzothiophene compounds as anti-estrogenic agents |
| US5523309A (en) * | 1995-03-10 | 1996-06-04 | Eli Lilly And Company | Benzofuran pharmaceutical compounds |
| CA2218756A1 (en) | 1996-10-25 | 1998-04-25 | Kristin Sue Marron | Substituted benzo¢b!thiophene compounds having activity as selective estrogen receptor modulators |
| US5929090A (en) | 1997-09-12 | 1999-07-27 | Eli Lilly And Company | 2-aryl-3-aminoaryloxynaphthy1 compounds, intermediates, compositions and methods |
-
1996
- 1996-10-30 ES ES96940354T patent/ES2233982T3/es not_active Expired - Lifetime
- 1996-10-30 AU AU77255/96A patent/AU7725596A/en not_active Abandoned
- 1996-10-30 WO PCT/US1996/017995 patent/WO1997025033A1/en not_active Ceased
- 1996-10-30 JP JP52518397A patent/JP2002500618A/ja not_active Withdrawn
- 1996-10-30 DE DE69634045T patent/DE69634045T2/de not_active Expired - Fee Related
- 1996-10-30 CA CA002236007A patent/CA2236007A1/en not_active Abandoned
- 1996-10-30 EP EP96940354A patent/EP0863755B1/en not_active Expired - Lifetime
- 1996-10-30 AT AT96940354T patent/ATE284690T1/de not_active IP Right Cessation
-
1997
- 1997-04-30 US US08/846,647 patent/US6025382A/en not_active Expired - Fee Related
-
1999
- 1999-05-14 US US09/312,593 patent/US6251921B1/en not_active Expired - Fee Related
- 1999-08-05 US US09/369,416 patent/US6265575B1/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ATE284690T1 (de) | 2005-01-15 |
| US6025382A (en) | 2000-02-15 |
| AU7725596A (en) | 1997-08-01 |
| CA2236007A1 (en) | 1997-07-17 |
| WO1997025033A1 (en) | 1997-07-17 |
| EP0863755A1 (en) | 1998-09-16 |
| JP2002500618A (ja) | 2002-01-08 |
| DE69634045D1 (de) | 2005-01-20 |
| ES2233982T3 (es) | 2005-06-16 |
| US6251921B1 (en) | 2001-06-26 |
| US6265575B1 (en) | 2001-07-24 |
| EP0863755B1 (en) | 2004-12-15 |
| EP0863755A4 (en) | 1999-01-20 |
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