ZA200602130B - Carbamoyl-type benzofuran derivatives - Google Patents
Carbamoyl-type benzofuran derivatives Download PDFInfo
- Publication number
- ZA200602130B ZA200602130B ZA200602130A ZA200602130A ZA200602130B ZA 200602130 B ZA200602130 B ZA 200602130B ZA 200602130 A ZA200602130 A ZA 200602130A ZA 200602130 A ZA200602130 A ZA 200602130A ZA 200602130 B ZA200602130 B ZA 200602130B
- Authority
- ZA
- South Africa
- Prior art keywords
- group
- lower alkyl
- substituted
- alkyl group
- optionally substituted
- Prior art date
Links
- 150000001907 coumarones Chemical class 0.000 title claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 322
- 150000001875 compounds Chemical class 0.000 claims description 182
- -1 piperidylcarbonyl group Chemical group 0.000 claims description 158
- 125000003277 amino group Chemical group 0.000 claims description 70
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 63
- 125000003545 alkoxy group Chemical group 0.000 claims description 62
- 125000005936 piperidyl group Chemical group 0.000 claims description 45
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 39
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 35
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 35
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 33
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 28
- 125000000623 heterocyclic group Chemical group 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- 125000002757 morpholinyl group Chemical group 0.000 claims description 26
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 25
- 125000002252 acyl group Chemical group 0.000 claims description 17
- 125000005843 halogen group Chemical group 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims description 13
- 125000006239 protecting group Chemical group 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 125000004193 piperazinyl group Chemical group 0.000 claims description 12
- 208000007536 Thrombosis Diseases 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 10
- 125000002947 alkylene group Chemical group 0.000 claims description 9
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 238000011282 treatment Methods 0.000 claims description 7
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 5
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 claims description 4
- 125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 claims description 3
- GTWXSZIQNTUNKR-UHFFFAOYSA-N benzofuran-5-carboxylic acid Natural products OC(=O)C1=CC=C2OC=CC2=C1 GTWXSZIQNTUNKR-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 125000004423 acyloxy group Chemical group 0.000 claims description 2
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 2
- 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 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 claims 2
- 239000011717 all-trans-retinol Substances 0.000 claims 1
- 235000019169 all-trans-retinol Nutrition 0.000 claims 1
- 125000001589 carboacyl group Chemical group 0.000 claims 1
- 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 109
- 238000006243 chemical reaction Methods 0.000 description 101
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 59
- 239000002904 solvent Substances 0.000 description 55
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 54
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 47
- 239000000243 solution Substances 0.000 description 46
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 30
- 239000000203 mixture Substances 0.000 description 30
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 238000001816 cooling Methods 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- 230000002829 reductive effect Effects 0.000 description 19
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 18
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 18
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 239000000460 chlorine Substances 0.000 description 15
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
- 235000017557 sodium bicarbonate Nutrition 0.000 description 15
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 14
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- 150000001408 amides Chemical class 0.000 description 13
- 238000001914 filtration Methods 0.000 description 13
- 239000002244 precipitate Substances 0.000 description 13
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 12
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 12
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 229910052938 sodium sulfate Inorganic materials 0.000 description 12
- 235000011152 sodium sulphate Nutrition 0.000 description 12
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
- 229910052751 metal Inorganic materials 0.000 description 11
- 239000002184 metal Substances 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- 230000008569 process Effects 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 10
- 150000002170 ethers Chemical class 0.000 description 10
- 239000012046 mixed solvent Substances 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 9
- 229910052783 alkali metal Inorganic materials 0.000 description 9
- 238000009835 boiling Methods 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
- 239000008096 xylene Substances 0.000 description 9
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 8
- 150000008041 alkali metal carbonates Chemical class 0.000 description 8
- 239000003146 anticoagulant agent Substances 0.000 description 8
- 229940127219 anticoagulant drug Drugs 0.000 description 8
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- 150000007529 inorganic bases Chemical class 0.000 description 8
- 150000002825 nitriles Chemical class 0.000 description 8
- 150000007530 organic bases Chemical class 0.000 description 8
- 150000001735 carboxylic acids Chemical class 0.000 description 7
- 239000012442 inert solvent Substances 0.000 description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 235000011181 potassium carbonates Nutrition 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 150000003973 alkyl amines Chemical class 0.000 description 5
- 238000007112 amidation reaction Methods 0.000 description 5
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 5
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 5
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical class C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 230000009435 amidation Effects 0.000 description 4
- 150000001555 benzenes Chemical group 0.000 description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 description 4
- 150000001733 carboxylic acid esters Chemical class 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 208000026106 cerebrovascular disease Diseases 0.000 description 4
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 4
- 230000014508 negative regulation of coagulation Effects 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 125000004430 oxygen atom Chemical group O* 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 239000002516 radical scavenger Substances 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 3
- FTTATHOUSOIFOQ-UHFFFAOYSA-N 1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]pyrazine Chemical compound C1NCCN2CCCC21 FTTATHOUSOIFOQ-UHFFFAOYSA-N 0.000 description 3
- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 3
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- ORTSXIXFVOZCBP-UHFFFAOYSA-N 3-amino-n-(5-chloropyridin-2-yl)-1-benzofuran-2-carboxamide Chemical compound O1C2=CC=CC=C2C(N)=C1C(=O)NC1=CC=C(Cl)C=N1 ORTSXIXFVOZCBP-UHFFFAOYSA-N 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- 208000032843 Hemorrhage Diseases 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 108090000190 Thrombin Proteins 0.000 description 3
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 3
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 3
- 150000008046 alkali metal hydrides Chemical class 0.000 description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 3
- 229940052651 anticholinergic tertiary amines Drugs 0.000 description 3
- 125000004532 benzofuran-3-yl group Chemical group O1C=C(C2=C1C=CC=C2)* 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 206010008118 cerebral infarction Diseases 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000015271 coagulation Effects 0.000 description 3
- 238000005345 coagulation Methods 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 230000022244 formylation Effects 0.000 description 3
- 238000006170 formylation reaction Methods 0.000 description 3
- 150000008282 halocarbons Chemical class 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 229910052987 metal hydride Inorganic materials 0.000 description 3
- 150000004681 metal hydrides Chemical class 0.000 description 3
- 150000002739 metals Chemical class 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 description 3
- 239000011736 potassium bicarbonate Substances 0.000 description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Surgery (AREA)
- Vascular Medicine (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2003334597 | 2003-09-26 |
Publications (1)
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ZA200602130B true ZA200602130B (en) | 2007-03-28 |
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Application Number | Title | Priority Date | Filing Date |
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ZA200602130A ZA200602130B (en) | 2003-09-26 | 2006-03-14 | Carbamoyl-type benzofuran derivatives |
Country Status (18)
Country | Link |
---|---|
US (1) | US7605158B2 (no) |
EP (1) | EP1666478A4 (no) |
JP (1) | JP4277022B2 (no) |
KR (1) | KR100763294B1 (no) |
CN (1) | CN100430392C (no) |
AR (1) | AR046027A1 (no) |
AU (1) | AU2004276127B2 (no) |
BR (1) | BRPI0414597A (no) |
CA (1) | CA2539471A1 (no) |
IL (1) | IL174187A0 (no) |
MX (1) | MXPA06003378A (no) |
MY (1) | MY139258A (no) |
NO (1) | NO20061831L (no) |
NZ (1) | NZ546159A (no) |
RU (1) | RU2319700C1 (no) |
TW (1) | TW200524915A (no) |
WO (1) | WO2005030759A1 (no) |
ZA (1) | ZA200602130B (no) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003082847A1 (fr) * | 2002-03-28 | 2003-10-09 | Tanabe Seiyaku Co., Ltd. | Derive de benzofurane |
US20070049748A1 (en) * | 2005-08-26 | 2007-03-01 | Uppala Venkata Bhaskara R | Preparation of ezetimibe |
US9647851B2 (en) | 2008-10-13 | 2017-05-09 | Ppc Broadband, Inc. | Ingress noise inhibiting network interface device and method for cable television networks |
US9505735B2 (en) * | 2012-06-21 | 2016-11-29 | Whitehead Institute For Biomedical Research | Compounds for treating infectious diseases |
BR112017009501A2 (pt) * | 2014-11-10 | 2018-02-06 | Glaxosmithkline Ip No 2 Ltd | método para tratar uma infecção por hcv, método para curar uma infecção por hcv, e, composição farmacêutica. |
WO2019087129A1 (en) * | 2017-11-03 | 2019-05-09 | Universite De Montreal | Compounds and use thereof in the expansion of stem cells and/or progenitor cells |
CN110407697A (zh) * | 2019-08-28 | 2019-11-05 | 上海毕得医药科技有限公司 | 一种4-甲酰基-3-羟基苯甲酸甲酯的合成方法 |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2168858A1 (en) | 1994-06-06 | 1995-12-14 | Shinichiro Ono | Novel fused-ring carboxylic acid compound or salt thereof, and medicinal use thereof |
WO1999032477A1 (en) * | 1997-12-19 | 1999-07-01 | Schering Aktiengesellschaft | Ortho-anthranilamide derivatives as anti-coagulants |
US6140351A (en) | 1997-12-19 | 2000-10-31 | Berlex Laboratories, Inc. | Ortho-anthranilamide derivatives as anti-coagulants |
EP0937711A1 (de) * | 1998-02-18 | 1999-08-25 | Roche Diagnostics GmbH | Neue Thiobenzamide, Verfahren zu ihrer Herstellung sowie diese enthaltende Arzneimittel |
AU2055500A (en) | 1998-12-23 | 2000-07-31 | Eli Lilly And Company | Aromatic amides |
CA2385592C (en) | 1999-09-17 | 2011-01-11 | Bing-Yan Zhu | Benzamides and related inhibitors of factor xa |
US6720317B1 (en) | 1999-09-17 | 2004-04-13 | Millennium Pharmaceuticals, Inc. | Inhibitors of factor Xa |
AU2001277731A1 (en) | 2000-08-09 | 2002-02-18 | Welfide Corporation | Fused bicyclic amide compounds and medicinal use thereof |
EP1373194B1 (en) | 2001-03-30 | 2007-08-01 | Millennium Pharmaceuticals, Inc. | BENZAMIDE INHIBITORS OF FACTOR Xa |
WO2003082847A1 (fr) | 2002-03-28 | 2003-10-09 | Tanabe Seiyaku Co., Ltd. | Derive de benzofurane |
JP2005104838A (ja) | 2003-01-09 | 2005-04-21 | Tanabe Seiyaku Co Ltd | 縮合フラン化合物 |
-
2004
- 2004-09-22 TW TW093128676A patent/TW200524915A/zh unknown
- 2004-09-24 AR ARP040103461A patent/AR046027A1/es unknown
- 2004-09-24 CA CA002539471A patent/CA2539471A1/en not_active Abandoned
- 2004-09-24 RU RU2006114056/04A patent/RU2319700C1/ru not_active IP Right Cessation
- 2004-09-24 MX MXPA06003378A patent/MXPA06003378A/es unknown
- 2004-09-24 JP JP2005514201A patent/JP4277022B2/ja not_active Expired - Fee Related
- 2004-09-24 NZ NZ546159A patent/NZ546159A/en unknown
- 2004-09-24 WO PCT/JP2004/013891 patent/WO2005030759A1/ja active Application Filing
- 2004-09-24 AU AU2004276127A patent/AU2004276127B2/en not_active Ceased
- 2004-09-24 CN CNB2004800279230A patent/CN100430392C/zh not_active Expired - Fee Related
- 2004-09-24 BR BRPI0414597-6A patent/BRPI0414597A/pt not_active IP Right Cessation
- 2004-09-24 EP EP04788050A patent/EP1666478A4/en not_active Withdrawn
- 2004-09-24 KR KR1020067005827A patent/KR100763294B1/ko not_active IP Right Cessation
- 2004-09-24 US US10/571,904 patent/US7605158B2/en not_active Expired - Fee Related
- 2004-09-25 MY MYPI20043940A patent/MY139258A/en unknown
-
2006
- 2006-03-08 IL IL174187A patent/IL174187A0/en unknown
- 2006-03-14 ZA ZA200602130A patent/ZA200602130B/en unknown
- 2006-04-25 NO NO20061831A patent/NO20061831L/no not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
MY139258A (en) | 2009-09-30 |
RU2319700C1 (ru) | 2008-03-20 |
WO2005030759A1 (ja) | 2005-04-07 |
CA2539471A1 (en) | 2005-04-07 |
CN100430392C (zh) | 2008-11-05 |
AU2004276127A1 (en) | 2005-04-07 |
KR100763294B1 (ko) | 2007-10-04 |
AU2004276127B2 (en) | 2008-02-07 |
JP4277022B2 (ja) | 2009-06-10 |
US20060247273A1 (en) | 2006-11-02 |
KR20060073963A (ko) | 2006-06-29 |
AR046027A1 (es) | 2005-11-23 |
TW200524915A (en) | 2005-08-01 |
IL174187A0 (en) | 2006-08-01 |
JPWO2005030759A1 (ja) | 2006-12-07 |
NO20061831L (no) | 2006-04-25 |
BRPI0414597A (pt) | 2006-11-07 |
US7605158B2 (en) | 2009-10-20 |
CN1856488A (zh) | 2006-11-01 |
EP1666478A1 (en) | 2006-06-07 |
NZ546159A (en) | 2009-06-26 |
MXPA06003378A (es) | 2006-06-08 |
EP1666478A4 (en) | 2008-12-03 |
RU2006114056A (ru) | 2007-11-10 |
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