FI113178B - Menetelmä valmistaa terapeuttisesti arvokas 5,6-dihydro-4H-tiatsolo[5,4-d]-, -oksatsolo[4,5-d]- tai - imidatso[4,5-d][1]-bentsatsepiini-6-fenyylikarbonyylijohdannainen - Google Patents

Menetelmä valmistaa terapeuttisesti arvokas 5,6-dihydro-4H-tiatsolo[5,4-d]-, -oksatsolo[4,5-d]- tai - imidatso[4,5-d][1]-bentsatsepiini-6-fenyylikarbonyylijohdannainen Download PDF

Info

Publication number: FI113178B
Authority: FI; Finland
Prior art keywords: group; carbonyl; derivative; formula; benzazepine
Prior art date: 1993-07-21

Application number

FI960260A

Other languages

English (en)

Finnish (fi)

Swedish (sv)

Other versions

FI960260A0 (fi

FI960260A7 (fi

Inventor

Akira Matsuhisa

Nobuaki Taniguchi

Akihiro Tanaka

Ken-Ichiro Sakamoto

Hiroyuki Koshio

Takeyuki Yatsu

Atsuki Yamazaki

Original Assignee

Yamanouchi Pharma Co Ltd

Priority date (The priority date 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 date listed.)

1993-07-21

Filing date

1996-01-19

Publication date

2004-03-15

1996-01-19 Application filed by Yamanouchi Pharma Co Ltd filed Critical Yamanouchi Pharma Co Ltd

1996-01-19 Publication of FI960260A0 publication Critical patent/FI960260A0/fi

1996-01-19 Publication of FI960260A7 publication Critical patent/FI960260A7/fi

2004-03-15 Application granted granted Critical

2004-03-15 Publication of FI113178B publication Critical patent/FI113178B/fi

Links

238000000034 method Methods 0.000 title claims description 58
230000008569 process Effects 0.000 title claims description 10
238000002360 preparation method Methods 0.000 title claims description 7
-1 4-Aminophenylcarbonyl Chemical group 0.000 claims description 121
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 89
125000006239 protecting group Chemical group 0.000 claims description 34
150000003839 salts Chemical class 0.000 claims description 31
125000000217 alkyl group Chemical group 0.000 claims description 26
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 18
239000007858 starting material Substances 0.000 claims description 18
125000001424 substituent group Chemical group 0.000 claims description 14
125000003277 amino group Chemical group 0.000 claims description 13
DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical compound N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 claims description 9
125000004432 carbon atom Chemical group C* 0.000 claims description 9
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
125000002252 acyl group Chemical group 0.000 claims description 8
125000003545 alkoxy group Chemical group 0.000 claims description 8
125000003282 alkyl amino group Chemical group 0.000 claims description 7
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 6
125000002883 imidazolyl group Chemical group 0.000 claims description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
150000001409 amidines Chemical class 0.000 claims description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
125000000753 cycloalkyl group Chemical group 0.000 claims description 4
229910052736 halogen Inorganic materials 0.000 claims description 4
125000005843 halogen group Chemical group 0.000 claims description 4
150000002367 halogens Chemical class 0.000 claims description 4
229910052739 hydrogen Inorganic materials 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
150000002357 guanidines Chemical class 0.000 claims description 3
239000001257 hydrogen Substances 0.000 claims description 3
125000004043 oxo group Chemical group O=* 0.000 claims description 3
150000003672 ureas Chemical class 0.000 claims description 3
GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 claims description 2
150000001408 amides Chemical class 0.000 claims description 2
150000001558 benzoic acid derivatives Chemical class 0.000 claims description 2
235000013877 carbamide Nutrition 0.000 claims description 2
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 2
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
125000004076 pyridyl group Chemical group 0.000 claims description 2
150000003556 thioamides Chemical class 0.000 claims description 2
150000003585 thioureas Chemical class 0.000 claims description 2
150000001538 azepines Chemical class 0.000 claims 1
125000001475 halogen functional group Chemical group 0.000 claims 1
KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 abstract description 24
101800001144 Arg-vasopressin Proteins 0.000 abstract description 16
102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 abstract description 16
229940116211 Vasopressin antagonist Drugs 0.000 abstract description 6
239000003038 vasopressin antagonist Substances 0.000 abstract description 6
150000008038 benzoazepines Chemical class 0.000 abstract description 5
239000005711 Benzoic acid Substances 0.000 abstract description 3
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 abstract description 3
230000015572 biosynthetic process Effects 0.000 abstract description 3
235000010233 benzoic acid Nutrition 0.000 abstract description 2
GTKIGDZXPDCIKR-UHFFFAOYSA-N 2-phenylbenzamide Chemical compound NC(=O)C1=CC=CC=C1C1=CC=CC=C1 GTKIGDZXPDCIKR-UHFFFAOYSA-N 0.000 abstract 1
238000003786 synthesis reaction Methods 0.000 abstract 1
239000000243 solution Substances 0.000 description 162
150000001875 compounds Chemical class 0.000 description 100
238000006243 chemical reaction Methods 0.000 description 94
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 90
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 90
239000000126 substance Substances 0.000 description 88
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 77
239000002904 solvent Substances 0.000 description 64
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 57
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 56
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 55
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 52
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 52
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 44
229920006395 saturated elastomer Polymers 0.000 description 40
238000005481 NMR spectroscopy Methods 0.000 description 39
238000010992 reflux Methods 0.000 description 36
238000001914 filtration Methods 0.000 description 35
238000002844 melting Methods 0.000 description 34
230000008018 melting Effects 0.000 description 34
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 34
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
239000013078 crystal Substances 0.000 description 33
235000019441 ethanol Nutrition 0.000 description 31
238000003756 stirring Methods 0.000 description 31
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
239000012044 organic layer Substances 0.000 description 30
238000004821 distillation Methods 0.000 description 29
229910000030 sodium bicarbonate Inorganic materials 0.000 description 26
235000017557 sodium bicarbonate Nutrition 0.000 description 26
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 25
239000007787 solid Substances 0.000 description 23
239000000203 mixture Substances 0.000 description 22
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
ZVSKZLHKADLHSD-UHFFFAOYSA-N benzanilide Chemical compound C=1C=CC=CC=1C(=O)NC1=CC=CC=C1 ZVSKZLHKADLHSD-UHFFFAOYSA-N 0.000 description 21
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
239000000706 filtrate Substances 0.000 description 19
238000000921 elemental analysis Methods 0.000 description 18
239000000460 chlorine Substances 0.000 description 17
QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 17
229910000027 potassium carbonate Inorganic materials 0.000 description 17
235000011181 potassium carbonates Nutrition 0.000 description 17
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
102000004136 Vasopressin Receptors Human genes 0.000 description 16
108090000643 Vasopressin Receptors Proteins 0.000 description 16
239000002198 insoluble material Substances 0.000 description 16
238000005160 1H NMR spectroscopy Methods 0.000 description 15
230000008485 antagonism Effects 0.000 description 15
238000012360 testing method Methods 0.000 description 15
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
230000000694 effects Effects 0.000 description 14
239000010410 layer Substances 0.000 description 14
238000010898 silica gel chromatography Methods 0.000 description 14
239000002253 acid Substances 0.000 description 13
239000003795 chemical substances by application Substances 0.000 description 13
ZXTHWIZHGLNEPG-UHFFFAOYSA-N 2-phenyl-4,5-dihydro-1,3-oxazole Chemical compound O1CCN=C1C1=CC=CC=C1 ZXTHWIZHGLNEPG-UHFFFAOYSA-N 0.000 description 12
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 12
239000011780 sodium chloride Substances 0.000 description 12
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 11
HTEBRZSDKWSGNQ-UHFFFAOYSA-N n-[4-(5-oxo-3,4-dihydro-2h-1-benzazepine-1-carbonyl)phenyl]-2-phenylbenzamide Chemical compound C=1C=C(C(=O)N2C3=CC=CC=C3C(=O)CCC2)C=CC=1NC(=O)C1=CC=CC=C1C1=CC=CC=C1 HTEBRZSDKWSGNQ-UHFFFAOYSA-N 0.000 description 11
238000007112 amidation reaction Methods 0.000 description 10
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
125000003118 aryl group Chemical group 0.000 description 9
238000001816 cooling Methods 0.000 description 9
239000007924 injection Substances 0.000 description 9
238000002347 injection Methods 0.000 description 9
239000012528 membrane Substances 0.000 description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 9
229910021590 Copper(II) bromide Inorganic materials 0.000 description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
229910052786 argon Inorganic materials 0.000 description 8
WCQOBLXWLRDEQA-UHFFFAOYSA-N ethanimidamide;hydrochloride Chemical compound Cl.CC(N)=N WCQOBLXWLRDEQA-UHFFFAOYSA-N 0.000 description 8
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 8
239000012046 mixed solvent Substances 0.000 description 8
238000005191 phase separation Methods 0.000 description 8
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
241000700159 Rattus Species 0.000 description 7
239000007864 aqueous solution Substances 0.000 description 7
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
229910052794 bromium Inorganic materials 0.000 description 7
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 7
238000010438 heat treatment Methods 0.000 description 7
230000002401 inhibitory effect Effects 0.000 description 7
238000001953 recrystallisation Methods 0.000 description 7
239000003826 tablet Substances 0.000 description 7
238000011282 treatment Methods 0.000 description 7
210000002700 urine Anatomy 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 6
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 6
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
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 6
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235000011054 acetic acid Nutrition 0.000 description 6
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
239000008101 lactose Substances 0.000 description 6
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
239000000843 powder Substances 0.000 description 6
230000002035 prolonged effect Effects 0.000 description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 5
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 5
125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 5
238000010511 deprotection reaction Methods 0.000 description 5
239000012153 distilled water Substances 0.000 description 5
150000002148 esters Chemical class 0.000 description 5
238000009472 formulation Methods 0.000 description 5
125000000524 functional group Chemical group 0.000 description 5
230000002140 halogenating effect Effects 0.000 description 5
239000001863 hydroxypropyl cellulose Substances 0.000 description 5
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 5
230000005764 inhibitory process Effects 0.000 description 5
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
230000003389 potentiating effect Effects 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
239000000047 product Substances 0.000 description 5
239000000725 suspension Substances 0.000 description 5
ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 4
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 4
JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 4
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
150000008065 acid anhydrides Chemical class 0.000 description 4
230000009435 amidation Effects 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
239000002585 base Substances 0.000 description 4
230000036772 blood pressure Effects 0.000 description 4
ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
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235000014655 lactic acid Nutrition 0.000 description 4
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WRNXUQJJCIZICJ-UHFFFAOYSA-N mozavaptan Chemical compound C12=CC=CC=C2C(N(C)C)CCCN1C(=O)C(C=C1)=CC=C1NC(=O)C1=CC=CC=C1C WRNXUQJJCIZICJ-UHFFFAOYSA-N 0.000 description 4
KSNUCNRMDYJBKT-UHFFFAOYSA-N n-[3-[4-[4-(2-oxo-3,4-dihydroquinolin-1-yl)piperidine-1-carbonyl]phenoxy]propyl]acetamide Chemical compound C1=CC(OCCCNC(=O)C)=CC=C1C(=O)N1CCC(N2C3=CC=CC=C3CCC2=O)CC1 KSNUCNRMDYJBKT-UHFFFAOYSA-N 0.000 description 4
238000007363 ring formation reaction Methods 0.000 description 4
229910000029 sodium carbonate Inorganic materials 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
229910052727 yttrium Inorganic materials 0.000 description 4
NKRKBYFBKLDCFB-UHFFFAOYSA-N 1,2,3,4-tetrahydro-1-benzazepin-5-one Chemical compound O=C1CCCNC2=CC=CC=C12 NKRKBYFBKLDCFB-UHFFFAOYSA-N 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
VWFZSVSAZLYSFX-UHFFFAOYSA-N 1-(4-aminobenzoyl)-3,4-dihydro-2h-1-benzazepin-5-one Chemical compound C1=CC(N)=CC=C1C(=O)N1C2=CC=CC=C2C(=O)CCC1 VWFZSVSAZLYSFX-UHFFFAOYSA-N 0.000 description 3
KUCBNTWUKOGPPC-UHFFFAOYSA-N 1-(4-nitrobenzoyl)-3,4-dihydro-2h-1-benzazepin-5-one Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(=O)N1C2=CC=CC=C2C(=O)CCC1 KUCBNTWUKOGPPC-UHFFFAOYSA-N 0.000 description 3
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 3
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208000004880 Polyuria Diseases 0.000 description 3
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238000010306 acid treatment Methods 0.000 description 3
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239000000314 lubricant Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
235000001055 magnesium Nutrition 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
NSBNSZAXNUGWDJ-UHFFFAOYSA-O monopyridin-1-ium tribromide Chemical compound Br[Br-]Br.C1=CC=[NH+]C=C1 NSBNSZAXNUGWDJ-UHFFFAOYSA-O 0.000 description 1
239000004570 mortar (masonry) Substances 0.000 description 1
JVRMUFJCFLXSMJ-UHFFFAOYSA-N n,2-diphenylbenzamide Chemical compound C=1C=CC=C(C=2C=CC=CC=2)C=1C(=O)NC1=CC=CC=C1 JVRMUFJCFLXSMJ-UHFFFAOYSA-N 0.000 description 1
URFXEEAKFUIOAL-UHFFFAOYSA-N n-[4-(2-methyl-4,5-dihydro-[1,3]oxazolo[4,5-d][1]benzazepine-6-carbonyl)phenyl]-2-phenylbenzamide Chemical compound C12=CC=CC=C2C=2OC(C)=NC=2CCN1C(=O)C(C=C1)=CC=C1NC(=O)C1=CC=CC=C1C1=CC=CC=C1 URFXEEAKFUIOAL-UHFFFAOYSA-N 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
201000008383 nephritis Diseases 0.000 description 1
208000009928 nephrosis Diseases 0.000 description 1
231100001027 nephrosis Toxicity 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
KPADFPAILITQBG-UHFFFAOYSA-N non-4-ene Chemical compound CCCCC=CCCC KPADFPAILITQBG-UHFFFAOYSA-N 0.000 description 1
239000012457 nonaqueous media Substances 0.000 description 1
125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
229960003104 ornithine Drugs 0.000 description 1
150000002916 oxazoles Chemical class 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
150000002989 phenols Chemical class 0.000 description 1
125000005544 phthalimido group Chemical group 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
229920000053 polysorbate 80 Polymers 0.000 description 1
229940068968 polysorbate 80 Drugs 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
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
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000003180 prostaglandins Chemical class 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000008213 purified water Substances 0.000 description 1
BBFCIBZLAVOLCF-UHFFFAOYSA-N pyridin-1-ium;bromide Chemical compound Br.C1=CC=NC=C1 BBFCIBZLAVOLCF-UHFFFAOYSA-N 0.000 description 1
230000005855 radiation Effects 0.000 description 1
239000000376 reactant Substances 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
230000008085 renal dysfunction Effects 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
230000000580 secretagogue effect Effects 0.000 description 1
230000035807 sensation Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
229910052710 silicon Inorganic materials 0.000 description 1
239000010703 silicon Substances 0.000 description 1
150000003385 sodium Chemical class 0.000 description 1
239000008279 sol Substances 0.000 description 1
208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
235000013616 tea Nutrition 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
230000001331 thermoregulatory effect Effects 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
239000010936 titanium Substances 0.000 description 1
229910052719 titanium Inorganic materials 0.000 description 1
OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000036325 urinary excretion Effects 0.000 description 1
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000024883 vasodilation Effects 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- 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
- A61P9/08—Vasodilators for multiple indications
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Diabetes (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Public Health (AREA)
Hematology (AREA)
Gastroenterology & Hepatology (AREA)
Cardiology (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Obesity (AREA)
Heart & Thoracic Surgery (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Output Control And Ontrol Of Special Type Engine (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

FI960260A 1993-07-21 1996-01-19 Menetelmä valmistaa terapeuttisesti arvokas 5,6-dihydro-4H-tiatsolo[5,4-d]-, -oksatsolo[4,5-d]- tai - imidatso[4,5-d][1]-bentsatsepiini-6-fenyylikarbonyylijohdannainen FI113178B (fi)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
JP18043593		1993-07-21
JP18043593		1993-07-21
PCT/JP1994/001183 WO1995003305A1 (fr)	1993-07-21	1994-07-19	Derive de benzazepine de fusion et composition pharmaceutique renfermant ce derive
JP9401183		1994-07-19

Publications (3)

Publication Number	Publication Date
FI960260A0 FI960260A0 (fi)	1996-01-19
FI960260A7 FI960260A7 (fi)	1996-01-19
FI113178B true FI113178B (fi)	2004-03-15

Family

ID=16083198

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
FI960260A FI113178B (fi)	1993-07-21	1996-01-19	Menetelmä valmistaa terapeuttisesti arvokas 5,6-dihydro-4H-tiatsolo[5,4-d]-, -oksatsolo[4,5-d]- tai - imidatso[4,5-d][1]-bentsatsepiini-6-fenyylikarbonyylijohdannainen

Country Status (18)

Country	Link
US (2)	US5723606A (fr)
EP (2)	EP1097920B1 (fr)
KR (1)	KR100304331B1 (fr)
CN (1)	CN1040210C (fr)
AT (2)	ATE277003T1 (fr)
AU (2)	AU683483B2 (fr)
CA (1)	CA2167673C (fr)
DE (2)	DE69434032T2 (fr)
ES (2)	ES2198418T3 (fr)
FI (1)	FI113178B (fr)
HU (1)	HUT74582A (fr)
NO (1)	NO306303B1 (fr)
NZ (1)	NZ268671A (fr)
PL (1)	PL177738B1 (fr)
RU (1)	RU2129123C1 (fr)
TW (1)	TW279163B (fr)
UA (1)	UA64690C2 (fr)
WO (1)	WO1995003305A1 (fr)

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CA2319649A1 (fr) *	1998-01-28	1999-08-05	Mitsunori Waki	Mesures prophylactiques ou remedes contre les troubles de la vision
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US7015212B1 (en)	1999-05-12	2006-03-21	The United States Of America As Represented By The Department Of Health And Human Services	Thiazepine inhibitors of HIV-1 integrase
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WO2001054698A1 (fr) *	2000-01-26	2001-08-02	Warner-Lambert Company	Procede permettant d'empecher ou de traiter des occlusions intestinales postoperatoires
US20030103983A1 (en) *	2002-05-09	2003-06-05	Pressler Milton Lethan	Ace inhibitor-vasopressin antagonist combinations
JP2003521496A (ja) *	2000-01-26	2003-07-15	ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー	Ａｃｅ阻害剤−バソプレッシンアンタゴニストの組み合わせ
US20030008860A1 (en) *	2002-05-09	2003-01-09	Bakker-Arkema Rebecca Guggemos	Treatment of congestive heart failure
ATE367815T1 (de) *	2000-10-04	2007-08-15	Astellas Pharma Inc	Verwendung von einem vasopressin-antagonisten wie conivaptan zur herstellung eines medikaments für die behandlung der pulmonalen hypertension
AU779929B2 (en) *	2000-10-04	2005-02-17	Warner-Lambert Company	Treatment of pulmonary hypertension
US7056910B2 (en) *	2000-11-28	2006-06-06	Astellas Pharma Inc.	1,4,5.6-tetrahydroimidazo[4,5-d]diazepine derivatives or salts thereof
EP1632494A1 (fr) *	2004-08-24	2006-03-08	Ferring B.V.	Antagonistes de la v1a vasopressine
AU2006336504C9 (en) *	2005-12-28	2015-05-14	Vertex Pharmaceuticals Incorporated	1-(benzo [D] [1,3] dioxol-5-yl) -N- (phenyl) cyclopropane- carboxamide derivatives and related compounds as modulators of ATP-Binding Cassette transporters for the treatment of Cystic Fibrosis
US7671221B2 (en) *	2005-12-28	2010-03-02	Vertex Pharmaceuticals Incorporated	Modulators of ATP-Binding Cassette transporters
US20080221084A1 (en) *	2006-10-30	2008-09-11	Otsuka Pharmaceutical Co., Ltd.	Method for reducing infarction using vasopressin antagonist compounds, and compositions and combinations therefor
US20090069295A1 (en) *	2007-09-09	2009-03-12	Protia, Llc	Deuterium-enriched conivaptan
US20110052643A1 (en) *	2008-01-07	2011-03-03	Synta Pharmaceuticals Corp.	Compounds for inflammation and immune-related uses
WO2009102761A1 (fr) *	2008-02-12	2009-08-20	Bristol-Myers Squibb Company	1,2,3-triazoles en tant qu'inhibiteurs de 11-bêta-hydroxysteroïde déshydrogénase type i
JP2011525915A (ja) *	2008-06-26	2011-09-29	アムジエン・インコーポレーテツド	キナーゼ阻害薬としてのアルキニルアルコール類
SG10201406839VA (en)	2009-10-26	2014-12-30	Otsuka Pharma Co Ltd	Benzazepine compound
WO2014062888A1 (fr)	2012-10-18	2014-04-24	University Of South Florida	Compositions et procédés de traitement d'accident vasculaire cérébral
CN103497195B (zh) *	2013-10-21	2016-01-27	北京科莱博医药开发有限责任公司	盐酸考尼伐坦新晶型及其制备方法
CN105310978A (zh) *	2014-08-04	2016-02-10	李峰	一种含有活性成分盐酸考尼伐坦的药物组合物及其制剂
CN105884778A (zh) *	2014-09-24	2016-08-24	李峰	一种化合物和制备方法
CN105153168A (zh) *	2015-09-29	2015-12-16	上海天慈国际药业有限公司	N-[4-(2-甲基-4,5-二氢-3H-咪唑并[4,5-d][1]苯并氮杂卓-6-甲酰基)苯基]-2-苯基苯甲酰胺盐酸盐的制备方法
CN106317060B (zh) *	2016-08-22	2019-02-15	山东罗欣药业集团恒欣药业有限公司	一种盐酸考尼伐坦的制备方法
WO2019036024A1 (fr)	2017-08-17	2019-02-21	Bristol-Myers Squibb Company	Dérivés de 2-(1,1'-biphényl)-1h-benzo[d]imidazole et composés apparentés en tant qu'agonistes d'apéline et d'apj pour le traitement de maladies cardiovasculaires
TW201938171A (zh)	2017-12-15	2019-10-01	匈牙利商羅特格登公司	作為血管升壓素Ｖ１ａ受體拮抗劑之三環化合物
HU231206B1 (hu)	2017-12-15	2021-10-28	Richter Gedeon Nyrt.	Triazolobenzazepinek
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TW202246273A (zh) *	2021-03-05	2022-12-01	大陸商上海濟煜醫藥科技有限公司	新型苯并氮雜卓并環衍生物
KR102801544B1 (ko)	2023-07-27	2025-04-25	김주형	논슬립 기능을 구비한 자외선 차단 안면 보호커버
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1994
- 1994-07-19 EP EP00204704A patent/EP1097920B1/fr not_active Expired - Lifetime
- 1994-07-19 KR KR1019960700265A patent/KR100304331B1/ko not_active Expired - Fee Related
- 1994-07-19 ES ES94921117T patent/ES2198418T3/es not_active Expired - Lifetime
- 1994-07-19 ES ES00204704T patent/ES2228405T3/es not_active Expired - Lifetime
- 1994-07-19 WO PCT/JP1994/001183 patent/WO1995003305A1/fr not_active Ceased
- 1994-07-19 PL PL94312654A patent/PL177738B1/pl not_active IP Right Cessation
- 1994-07-19 HU HU9600102A patent/HUT74582A/hu unknown
- 1994-07-19 AT AT00204704T patent/ATE277003T1/de not_active IP Right Cessation
- 1994-07-19 RU RU96105390/04A patent/RU2129123C1/ru not_active IP Right Cessation
- 1994-07-19 AT AT94921117T patent/ATE239726T1/de not_active IP Right Cessation
- 1994-07-19 AU AU71957/94A patent/AU683483B2/en not_active Ceased
- 1994-07-19 CN CN94192831A patent/CN1040210C/zh not_active Expired - Fee Related
- 1994-07-19 DE DE69434032T patent/DE69434032T2/de not_active Expired - Lifetime
- 1994-07-19 NZ NZ268671A patent/NZ268671A/en not_active IP Right Cessation
- 1994-07-19 US US08/586,686 patent/US5723606A/en not_active Expired - Lifetime
- 1994-07-19 UA UA96010145A patent/UA64690C2/uk unknown
- 1994-07-19 DE DE69432632T patent/DE69432632T2/de not_active Expired - Lifetime
- 1994-07-19 CA CA002167673A patent/CA2167673C/fr not_active Expired - Lifetime
- 1994-07-19 EP EP94921117A patent/EP0709386B1/fr not_active Expired - Lifetime
- 1994-07-20 TW TW083106656A patent/TW279163B/zh not_active IP Right Cessation
1996
- 1996-01-19 FI FI960260A patent/FI113178B/fi active
- 1996-01-19 NO NO960231A patent/NO306303B1/no not_active IP Right Cessation
1997
- 1997-10-02 AU AU39906/97A patent/AU3990697A/en not_active Abandoned
- 1997-11-18 US US08/972,271 patent/US5856564A/en not_active Expired - Lifetime

Also Published As

Publication number	Publication date
EP1097920B1 (fr)	2004-09-22
UA64690C2 (en)	2004-03-15
RU2129123C1 (ru)	1999-04-20
FI960260A0 (fi)	1996-01-19
DE69434032T2 (de)	2005-09-22
AU3990697A (en)	1997-12-18
CN1040210C (zh)	1998-10-14
EP0709386A4 (fr)	1997-06-25
PL177738B1 (pl)	2000-01-31
CN1127508A (zh)	1996-07-24
NO960231D0 (no)	1996-01-19
NZ268671A (en)	1997-09-22
US5723606A (en)	1998-03-03
AU7195794A (en)	1995-02-20
KR100304331B1 (ko)	2001-11-22
ATE277003T1 (de)	2004-10-15
KR960703917A (ko)	1996-08-31
EP1097920A1 (fr)	2001-05-09
FI960260A7 (fi)	1996-01-19
TW279163B (fr)	1996-06-21
ATE239726T1 (de)	2003-05-15
EP0709386A1 (fr)	1996-05-01
WO1995003305A1 (fr)	1995-02-02
NO960231L (no)	1996-03-21
EP0709386B1 (fr)	2003-05-07
NO306303B1 (no)	1999-10-18
ES2198418T3 (es)	2004-02-01
HU9600102D0 (en)	1996-03-28
HUT74582A (en)	1997-01-28
ES2228405T3 (es)	2005-04-16
CA2167673A1 (fr)	1995-02-02
DE69432632T2 (de)	2004-02-19
DE69434032D1 (de)	2004-10-28
US5856564A (en)	1999-01-05
AU683483B2 (en)	1997-11-13
CA2167673C (fr)	2004-09-21
DE69432632D1 (de)	2003-06-12
PL312654A1 (en)	1996-04-29

Legal Events

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2006-03-22

PC

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Owner name: ASTELLAS PHARMA INC.

Free format text: ASTELLAS PHARMA INC.

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