KR890003425B1 - 3-아미노-[1]벤즈아제핀-2-온-1-알카노산의 제조방법 - Google Patents
3-아미노-[1]벤즈아제핀-2-온-1-알카노산의 제조방법 Download PDFInfo
- Publication number
- KR890003425B1 KR890003425B1 KR8203588A KR820003588A KR890003425B1 KR 890003425 B1 KR890003425 B1 KR 890003425B1 KR 8203588 A KR8203588 A KR 8203588A KR 820003588 A KR820003588 A KR 820003588A KR 890003425 B1 KR890003425 B1 KR 890003425B1
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- amino
- alkoxy
- hydrogen
- compound
- 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
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- 239000002253 acid Substances 0.000 title claims description 32
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 150000007513 acids Chemical class 0.000 title description 3
- -1 3-phthalidoxy Chemical group 0.000 claims description 175
- 150000001875 compounds Chemical class 0.000 claims description 155
- 125000003545 alkoxy group Chemical group 0.000 claims description 103
- 125000000217 alkyl group Chemical group 0.000 claims description 95
- 229910052739 hydrogen Inorganic materials 0.000 claims description 92
- 239000001257 hydrogen Substances 0.000 claims description 92
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 75
- 238000002844 melting Methods 0.000 claims description 74
- 230000008018 melting Effects 0.000 claims description 74
- 150000003839 salts Chemical class 0.000 claims description 62
- 238000000034 method Methods 0.000 claims description 54
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 53
- 125000003118 aryl group Chemical group 0.000 claims description 42
- 150000002431 hydrogen Chemical class 0.000 claims description 39
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 37
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 32
- 125000003282 alkyl amino group Chemical group 0.000 claims description 28
- 125000004043 oxo group Chemical group O=* 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 24
- 150000002367 halogens Chemical class 0.000 claims description 23
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 22
- 125000004423 acyloxy group Chemical group 0.000 claims description 20
- 230000008569 process Effects 0.000 claims description 20
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000006239 protecting group Chemical group 0.000 claims description 17
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 239000003638 chemical reducing agent Substances 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 7
- 238000009833 condensation Methods 0.000 claims description 6
- 230000005494 condensation Effects 0.000 claims description 6
- 125000002837 carbocyclic group Chemical group 0.000 claims description 4
- 238000005932 reductive alkylation reaction Methods 0.000 claims description 4
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 2
- CREXVNNSNOKDHW-UHFFFAOYSA-N azaniumylideneazanide Chemical group N[N] CREXVNNSNOKDHW-UHFFFAOYSA-N 0.000 claims description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 230000002152 alkylating effect Effects 0.000 claims 2
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 claims 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical class N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 1
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims 1
- 238000006266 etherification reaction Methods 0.000 claims 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 198
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 177
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 165
- 239000000243 solution Substances 0.000 description 161
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 141
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 121
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 117
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 103
- 230000002829 reductive effect Effects 0.000 description 87
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 81
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 78
- 239000002904 solvent Substances 0.000 description 78
- 235000019441 ethanol Nutrition 0.000 description 77
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 76
- 239000000203 mixture Chemical class 0.000 description 70
- 239000003054 catalyst Substances 0.000 description 65
- 229940093499 ethyl acetate Drugs 0.000 description 59
- 235000019439 ethyl acetate Nutrition 0.000 description 59
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 55
- 239000011541 reaction mixture Substances 0.000 description 54
- 229910052757 nitrogen Inorganic materials 0.000 description 43
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- 239000007787 solid Substances 0.000 description 36
- 238000003756 stirring Methods 0.000 description 34
- 239000000725 suspension Substances 0.000 description 34
- 238000006243 chemical reaction Methods 0.000 description 31
- 239000007858 starting material Substances 0.000 description 30
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 28
- 229960000583 acetic acid Drugs 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 26
- 235000019341 magnesium sulphate Nutrition 0.000 description 26
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 239000000047 product Substances 0.000 description 23
- 235000011054 acetic acid Nutrition 0.000 description 22
- 238000002360 preparation method Methods 0.000 description 22
- 230000036772 blood pressure Effects 0.000 description 21
- 239000000463 material Substances 0.000 description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- 150000003254 radicals Chemical class 0.000 description 19
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 239000007864 aqueous solution Substances 0.000 description 18
- 238000000746 purification Methods 0.000 description 18
- 102400000344 Angiotensin-1 Human genes 0.000 description 17
- 101800000734 Angiotensin-1 Proteins 0.000 description 17
- ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 17
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 17
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 17
- 229910052938 sodium sulfate Inorganic materials 0.000 description 17
- 235000011152 sodium sulphate Nutrition 0.000 description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- 239000000706 filtrate Substances 0.000 description 16
- 238000006722 reduction reaction Methods 0.000 description 16
- 238000005804 alkylation reaction Methods 0.000 description 15
- 239000002585 base Substances 0.000 description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 15
- 238000004128 high performance liquid chromatography Methods 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 14
- 230000009467 reduction Effects 0.000 description 14
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 13
- 230000005764 inhibitory process Effects 0.000 description 13
- 239000011734 sodium Substances 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- 238000001914 filtration Methods 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- 229910052708 sodium Inorganic materials 0.000 description 12
- 229910052717 sulfur Inorganic materials 0.000 description 12
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 11
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 11
- 241000700159 Rattus Species 0.000 description 11
- 235000011114 ammonium hydroxide Nutrition 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 11
- 239000007789 gas Substances 0.000 description 11
- 239000012074 organic phase Substances 0.000 description 11
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 11
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- 150000001298 alcohols Chemical class 0.000 description 9
- 238000005984 hydrogenation reaction Methods 0.000 description 9
- 206010020772 Hypertension Diseases 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- 150000001408 amides Chemical class 0.000 description 8
- 239000002775 capsule Substances 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 210000001072 colon Anatomy 0.000 description 8
- STPXIOGYOLJXMZ-UHFFFAOYSA-N ethyl 2-oxo-4-phenylbutanoate Chemical compound CCOC(=O)C(=O)CCC1=CC=CC=C1 STPXIOGYOLJXMZ-UHFFFAOYSA-N 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
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- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 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 7
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 7
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 7
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 7
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 7
- 241000124008 Mammalia Species 0.000 description 7
- DXZDEAJXVCLRLE-UHFFFAOYSA-N azepin-2-one Chemical compound O=C1C=CC=CC=N1 DXZDEAJXVCLRLE-UHFFFAOYSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000009835 boiling Methods 0.000 description 7
- 125000004185 ester group Chemical group 0.000 description 7
- 235000019253 formic acid Nutrition 0.000 description 7
- 239000008101 lactose Substances 0.000 description 7
- 229910052751 metal Inorganic materials 0.000 description 7
- 239000002184 metal Substances 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 239000000908 ammonium hydroxide Substances 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 238000000354 decomposition reaction Methods 0.000 description 6
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 150000007522 mineralic acids Chemical class 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 230000003287 optical effect Effects 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 239000000376 reactant Substances 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 238000001179 sorption measurement Methods 0.000 description 6
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 5
- 238000005917 acylation reaction Methods 0.000 description 5
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 125000003277 amino group Chemical group 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 230000009286 beneficial effect Effects 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
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- 238000009472 formulation Methods 0.000 description 5
- 239000012362 glacial acetic acid Substances 0.000 description 5
- 238000007327 hydrogenolysis reaction Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 229910052987 metal hydride Inorganic materials 0.000 description 5
- 150000004681 metal hydrides Chemical class 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 5
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 5
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 5
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- CLRHEGMAWYPMJF-UHFFFAOYSA-N ethyl 2-oxo-3-phenylpropanoate Chemical compound CCOC(=O)C(=O)CC1=CC=CC=C1 CLRHEGMAWYPMJF-UHFFFAOYSA-N 0.000 description 1
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- FTQWRYSLUYAIRQ-UHFFFAOYSA-N n-[(octadecanoylamino)methyl]octadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(=O)NCNC(=O)CCCCCCCCCCCCCCCCC FTQWRYSLUYAIRQ-UHFFFAOYSA-N 0.000 description 1
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- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
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- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- LJFSZDRPNLUQMV-UHFFFAOYSA-N oxolane-2,3-dione Chemical compound O=C1CCOC1=O LJFSZDRPNLUQMV-UHFFFAOYSA-N 0.000 description 1
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
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- 230000004962 physiological condition Effects 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
- 239000001205 polyphosphate Substances 0.000 description 1
- 235000011176 polyphosphates Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
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- 235000011164 potassium chloride Nutrition 0.000 description 1
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M potassium chloride Inorganic materials [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- ZLMJMSJWJFRBEC-OUBTZVSYSA-N potassium-40 Chemical compound [40K] ZLMJMSJWJFRBEC-OUBTZVSYSA-N 0.000 description 1
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- 239000000651 prodrug Substances 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000012048 reactive intermediate Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000009938 salting Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 210000003752 saphenous vein Anatomy 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
- 150000003334 secondary amides Chemical class 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 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
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229950000244 sulfanilic acid Drugs 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- NOILBTUWXJCEER-UHFFFAOYSA-N tert-butyl 2-(3-amino-2-oxo-4,5-dihydro-3h-1-benzazepin-1-yl)propanoate Chemical compound C1CC(N)C(=O)N(C(C)C(=O)OC(C)(C)C)C2=CC=CC=C21 NOILBTUWXJCEER-UHFFFAOYSA-N 0.000 description 1
- RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical group CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical class CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/022—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2
- C07K5/0222—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2 with the first amino acid being heterocyclic, e.g. Pro, Trp
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06086—Dipeptides with the first amino acid being basic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR8906486A KR900001190B1 (ko) | 1981-08-11 | 1989-05-13 | 3-아미노-[1]벤즈아제핀-2-온-1-알카노산의 제조방법 |
| KR1019890006489A KR900001195B1 (ko) | 1982-08-10 | 1989-05-13 | 3-아미노-[1]벤즈아제핀-2-온-1-알카노산의 제조방법 |
| KR1019890006488A KR900001192B1 (ko) | 1982-08-10 | 1989-05-13 | 3-아미노-[1]벤즈아제핀-2-온-1-알카노산의 제조방법 |
| KR1019890006487A KR900001191B1 (ko) | 1981-08-11 | 1989-05-13 | 3-아미노-[1]벤즈아제핀-2-온-1-알카노산의 제조방법 |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US29190781A | 1981-08-11 | 1981-08-11 | |
| US291,907 | 1981-08-11 | ||
| US31986381A | 1981-11-09 | 1981-11-09 | |
| US319,863 | 1981-11-09 |
Related Child Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019890006487A Division KR900001191B1 (ko) | 1981-08-11 | 1989-05-13 | 3-아미노-[1]벤즈아제핀-2-온-1-알카노산의 제조방법 |
| KR8906486A Division KR900001190B1 (ko) | 1981-08-11 | 1989-05-13 | 3-아미노-[1]벤즈아제핀-2-온-1-알카노산의 제조방법 |
| KR1019890006488A Division KR900001192B1 (ko) | 1982-08-10 | 1989-05-13 | 3-아미노-[1]벤즈아제핀-2-온-1-알카노산의 제조방법 |
| KR1019890006489A Division KR900001195B1 (ko) | 1982-08-10 | 1989-05-13 | 3-아미노-[1]벤즈아제핀-2-온-1-알카노산의 제조방법 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR840001139A KR840001139A (ko) | 1984-03-28 |
| KR890003425B1 true KR890003425B1 (ko) | 1989-09-20 |
Family
ID=26967047
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR8203588A Expired KR890003425B1 (ko) | 1981-08-11 | 1982-08-10 | 3-아미노-[1]벤즈아제핀-2-온-1-알카노산의 제조방법 |
| KR8906486A Expired KR900001190B1 (ko) | 1981-08-11 | 1989-05-13 | 3-아미노-[1]벤즈아제핀-2-온-1-알카노산의 제조방법 |
| KR1019890006487A Expired KR900001191B1 (ko) | 1981-08-11 | 1989-05-13 | 3-아미노-[1]벤즈아제핀-2-온-1-알카노산의 제조방법 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR8906486A Expired KR900001190B1 (ko) | 1981-08-11 | 1989-05-13 | 3-아미노-[1]벤즈아제핀-2-온-1-알카노산의 제조방법 |
| KR1019890006487A Expired KR900001191B1 (ko) | 1981-08-11 | 1989-05-13 | 3-아미노-[1]벤즈아제핀-2-온-1-알카노산의 제조방법 |
Country Status (22)
| Country | Link |
|---|---|
| EP (1) | EP0072352B1 (enExample) |
| KR (3) | KR890003425B1 (enExample) |
| AR (3) | AR240806A1 (enExample) |
| AT (1) | ATE18397T1 (enExample) |
| AU (1) | AU561395B2 (enExample) |
| CA (1) | CA1196636A (enExample) |
| CY (1) | CY1403A (enExample) |
| DD (1) | DD202546A5 (enExample) |
| DE (1) | DE3269625D1 (enExample) |
| DK (1) | DK157881C (enExample) |
| ES (6) | ES8502974A1 (enExample) |
| FI (1) | FI76074C (enExample) |
| GB (1) | GB2103614B (enExample) |
| GR (1) | GR77256B (enExample) |
| HK (1) | HK93387A (enExample) |
| HU (1) | HU189628B (enExample) |
| IE (1) | IE53668B1 (enExample) |
| IL (1) | IL66501A (enExample) |
| NL (1) | NL930112I2 (enExample) |
| NO (1) | NO161558C (enExample) |
| NZ (1) | NZ201555A (enExample) |
| PT (1) | PT75395B (enExample) |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3242599A1 (de) * | 1982-11-18 | 1984-05-24 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neue benzazepinderivate, ihre herstellung und ihre verwendung als arzneimittel |
| US4473575A (en) * | 1982-07-19 | 1984-09-25 | Ciba-Geigy Corporation | 3-Amino-(1)-benzazepin-2-one-1-alkanoic acids |
| EP0107095B1 (en) * | 1982-09-30 | 1987-09-09 | Merck & Co. Inc. | 1-n-alkylcarboxy-benzofused lactams useful as antihypertensive agents |
| US4575503A (en) * | 1983-02-10 | 1986-03-11 | Ciba-Geigy Corporation | 3-Amino-[1]-benzazepin-2-one-1-alkanoic acids |
| US4564612A (en) * | 1983-04-22 | 1986-01-14 | Takeda Chemical Industries, Ltd. | Condensed, seven-membered ring compounds and their use |
| US4539150A (en) * | 1983-06-29 | 1985-09-03 | Mitsui Toatsu Chemicals, Inc. | Benzothiazepine derivatives and their methods of preparation |
| JPS608284A (ja) * | 1983-06-29 | 1985-01-17 | Mitsui Toatsu Chem Inc | ベンゾチアゼピン誘導体およびその製造法 |
| US4638000A (en) * | 1983-08-12 | 1987-01-20 | Takeda Chemical Industries, Ltd. | Condensed seven-membered ring compounds, their production and use |
| IL72523A (en) * | 1983-08-12 | 1988-06-30 | Takeda Chemical Industries Ltd | 3-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine derivatives,their production and pharmaceutical compositions containing them |
| AU570710B2 (en) * | 1983-08-12 | 1988-03-24 | Takeda Chemical Industries Ltd. | 4-oxo-2, 3, 4, 5-tetrahydro-1, 5-benzoxazepine derivatives |
| EP0166357A3 (en) * | 1984-06-26 | 1988-10-26 | Merck & Co. Inc. | Benzofused lactams and pharmaceutical compositions containing them |
| CA1266647A (en) * | 1984-06-26 | 1990-03-13 | William H. Parsons | Benzofused lactams useful as antihypertensive agents and as cholecystokinin antagonists |
| EP0166354B1 (en) * | 1984-06-26 | 1992-08-05 | Merck & Co. Inc. | Benzofused lactam compounds and pharmaceutical compositions containing them |
| US4785089A (en) * | 1985-06-13 | 1988-11-15 | Ciba-Geigy Corporation | Novel sulfonic acid esters and their preparation |
| DE3704661A1 (de) * | 1987-02-14 | 1988-08-25 | Hoechst Ag | Annelierte azepinon- und azocinon-derivate, verfahren zu ihrer herstellung, diese enthaltende mittel und ihre verwendung, sowie zwischenprodukte bei ihrer herstellung |
| EP0322779A3 (en) * | 1987-12-29 | 1991-05-08 | Yoshitomi Pharmaceutical Industries, Ltd. | Benzolactam compounds and pharmaceutical uses thereof |
| TW197945B (enExample) * | 1990-11-27 | 1993-01-11 | Hoechst Ag | |
| GB9100028D0 (en) * | 1991-01-02 | 1991-02-20 | Ici Plc | Compounds |
| GB9212308D0 (en) * | 1992-06-10 | 1992-07-22 | Ici Plc | Therapeutic compositions |
| US5504080A (en) * | 1992-10-28 | 1996-04-02 | Bristol-Myers Squibb Co. | Benzo-fused lactams |
| CA2151384A1 (en) * | 1992-12-11 | 1994-06-23 | Peter Buhlmayer | Benzazepinone derivatives |
| GB9310075D0 (en) * | 1993-05-17 | 1993-06-30 | Fujisawa Pharmaceutical Co | New mercapto-amide derivatives,processes for the preparation thereof and pharmaceutical composition comprising the same |
| GB9311948D0 (en) * | 1993-06-10 | 1993-07-28 | Zeneca Ltd | Substituted nitrogen heterocycles |
| US5801168A (en) * | 1994-06-09 | 1998-09-01 | Zeneca Limited | Substituted nitrogen heterocycles |
| US5597922A (en) * | 1994-07-29 | 1997-01-28 | State Of Oregon, Acting By And Through The Oregon State Board Of Higher Education, Acting For And On Behalf Of The Oregon Health Sciences University And The University Of Oregon | Glycine receptor antagonist pharmacophore |
| JP2003514022A (ja) * | 1999-11-18 | 2003-04-15 | アンテックスファーマ・インコーポレーテッド | 置換された１−ベンズアゼピンとその誘導体 |
| ATE517870T1 (de) | 2000-12-27 | 2011-08-15 | Merck Patent Gmbh | Verfahren zur herstellung von alpha- aminosubstituierten carbonsäureamiden |
| CN1585744A (zh) | 2001-03-27 | 2005-02-23 | 兰贝克赛实验室有限公司 | 贝那普利的制备方法 |
| EP1443919A4 (en) | 2001-11-16 | 2006-03-22 | Bristol Myers Squibb Co | DOUBLE INHIBITORS OF THE FATTY ACID BINDING PROTEIN OF THE ADIPOCYTES AND THE FATTY ACID BINDING PROTEIN OF KERATINOCYTES |
| EP1525189A1 (en) * | 2002-07-26 | 2005-04-27 | Ciba Specialty Chemicals Holding Inc. | Crystalline polymorphic and amorphous forms of benazepril hydrochloride |
| KR100710548B1 (ko) * | 2002-12-26 | 2007-04-24 | 에스케이 주식회사 | (ｓ)-3-아미노-2,3,4,5-테트라히드로-2-옥소-1Ｈ-1-벤자제핀-1-아세트산 및 이의 에스테르 화합물의 제조방법 |
| US7459474B2 (en) | 2003-06-11 | 2008-12-02 | Bristol-Myers Squibb Company | Modulators of the glucocorticoid receptor and method |
| US8080579B2 (en) | 2005-10-03 | 2011-12-20 | The Regents Of The University Of Michigan | Compositions and methods for treatment of inflammatory bowel disease |
| US7592461B2 (en) | 2005-12-21 | 2009-09-22 | Bristol-Myers Squibb Company | Indane modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof |
| EP2089355A2 (en) | 2006-11-01 | 2009-08-19 | Brystol-Myers Squibb Company | Modulators of glucocorticoid receptor, ap-1, and/or nf- kappa b activity and use thereof |
| WO2008057857A1 (en) | 2006-11-01 | 2008-05-15 | Bristol-Myers Squibb Company | MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-ϰB ACTIVITY AND USE THEREOF |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| CN103601792B (zh) | 2007-06-04 | 2016-06-29 | 协同医药品公司 | 有效用于胃肠功能紊乱、炎症、癌症和其他疾病治疗的鸟苷酸环化酶激动剂 |
| US7828840B2 (en) | 2007-11-15 | 2010-11-09 | Med Institute, Inc. | Medical devices and methods for local delivery of angiotensin II type 2 receptor antagonists |
| AU2009256157B2 (en) | 2008-06-04 | 2014-12-18 | Bausch Health Ireland Limited | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| CN102149710A (zh) | 2008-06-24 | 2011-08-10 | 百时美施贵宝公司 | 糖皮质激素受体、AP-1和/或NF-κB 活性的环戊噻吩调节剂及其用途 |
| ES2624828T3 (es) | 2008-07-16 | 2017-07-17 | Synergy Pharmaceuticals Inc. | Agonistas de la guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| WO2014151206A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| US9486494B2 (en) | 2013-03-15 | 2016-11-08 | Synergy Pharmaceuticals, Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| EP4424697A3 (en) | 2013-06-05 | 2024-12-25 | Bausch Health Ireland Limited | Ultra-pure agonists of guanylate cyclase c, method of making and using same |
| US9593113B2 (en) | 2013-08-22 | 2017-03-14 | Bristol-Myers Squibb Company | Imide and acylurea derivatives as modulators of the glucocorticoid receptor |
| CN113292495B (zh) * | 2021-06-18 | 2022-09-13 | 迪嘉药业集团有限公司 | 一种 (s)-氨基化合物的合成方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3395150A (en) * | 1965-02-26 | 1968-07-30 | Squibb & Sons Inc | Benzothiazepine carboxamides and derivatives thereof |
| GB1305278A (enExample) * | 1970-03-12 | 1973-01-31 |
-
1982
- 1982-08-05 AT AT82810329T patent/ATE18397T1/de active
- 1982-08-05 EP EP82810329A patent/EP0072352B1/de not_active Expired
- 1982-08-05 CY CY140382A patent/CY1403A/en unknown
- 1982-08-05 DE DE8282810329T patent/DE3269625D1/de not_active Expired
- 1982-08-05 GB GB08222564A patent/GB2103614B/en not_active Expired
- 1982-08-09 GR GR68996A patent/GR77256B/el unknown
- 1982-08-09 CA CA000409019A patent/CA1196636A/en not_active Expired
- 1982-08-09 ES ES514856A patent/ES8502974A1/es not_active Expired
- 1982-08-09 PT PT75395A patent/PT75395B/pt unknown
- 1982-08-09 IL IL66501A patent/IL66501A/xx not_active IP Right Cessation
- 1982-08-09 FI FI822770A patent/FI76074C/fi not_active IP Right Cessation
- 1982-08-10 NO NO822722A patent/NO161558C/no not_active IP Right Cessation
- 1982-08-10 AU AU87014/82A patent/AU561395B2/en not_active Expired
- 1982-08-10 DD DD82242400A patent/DD202546A5/de not_active IP Right Cessation
- 1982-08-10 DK DK358682A patent/DK157881C/da active
- 1982-08-10 HU HU822585A patent/HU189628B/hu unknown
- 1982-08-10 NZ NZ201555A patent/NZ201555A/en unknown
- 1982-08-10 KR KR8203588A patent/KR890003425B1/ko not_active Expired
- 1982-08-10 IE IE1929/82A patent/IE53668B1/en not_active IP Right Cessation
- 1982-08-11 AR AR290295A patent/AR240806A1/es active
-
1983
- 1983-10-28 ES ES526888A patent/ES8504728A1/es not_active Expired
- 1983-10-28 ES ES526887A patent/ES8606285A1/es not_active Expired
- 1983-10-28 ES ES526889A patent/ES8604523A1/es not_active Expired
- 1983-10-28 ES ES526886A patent/ES526886A0/es active Granted
-
1984
- 1984-02-28 AR AR84295865A patent/AR241222A1/es active
- 1984-02-28 AR AR295866A patent/AR240807A1/es active
- 1984-03-15 ES ES530658A patent/ES530658A0/es active Granted
-
1987
- 1987-12-10 HK HK933/87A patent/HK93387A/xx not_active IP Right Cessation
-
1989
- 1989-05-13 KR KR8906486A patent/KR900001190B1/ko not_active Expired
- 1989-05-13 KR KR1019890006487A patent/KR900001191B1/ko not_active Expired
-
1993
- 1993-06-29 NL NL930112C patent/NL930112I2/nl unknown
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