NO317640B1 - Nye fosfonsyresubstituerte benzazepinon-N-edikksyrederivater, fremgangsmate for deres fremstilling, og legemidler inneholdende slike - Google Patents

Nye fosfonsyresubstituerte benzazepinon-N-edikksyrederivater, fremgangsmate for deres fremstilling, og legemidler inneholdende slike Download PDF

Info

Publication number: NO317640B1
Authority: NO; Norway
Prior art keywords: compounds; formula; biolabile; phosphonic acid; groups
Prior art date: 1997-11-12

Application number

NO19985262A

Other languages

English (en)

Norwegian (no)

Other versions

NO985262L (no

NO985262D0 (no

Inventor

Dirk Thormahlen

Harald Waldeck

Jorg Meil

Michael Wurl

Original Assignee

Solvay Pharm Gmbh

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.)

1997-11-12

Filing date

1998-11-11

Publication date

2004-11-29

1998-11-11 Application filed by Solvay Pharm Gmbh filed Critical Solvay Pharm Gmbh

1998-11-11 Publication of NO985262D0 publication Critical patent/NO985262D0/no

1999-05-14 Publication of NO985262L publication Critical patent/NO985262L/no

2004-11-29 Publication of NO317640B1 publication Critical patent/NO317640B1/no

Links

ABLZXFCXXLZCGV-UHFFFAOYSA-N phosphonic acid group Chemical group P(O)(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 title claims description 34
238000002360 preparation method Methods 0.000 title claims description 31
238000000034 method Methods 0.000 title claims description 30
239000003814 drug Substances 0.000 title claims description 6
229940079593 drug Drugs 0.000 title claims 2
AYQMNFRCBKOMIA-UHFFFAOYSA-N 1-benzazepin-2-one Chemical class O=C1C=CC=C2C=CC=CC2=N1 AYQMNFRCBKOMIA-UHFFFAOYSA-N 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims description 150
239000002253 acid Substances 0.000 claims description 41
150000007513 acids Chemical class 0.000 claims description 26
229910052739 hydrogen Inorganic materials 0.000 claims description 26
239000001257 hydrogen Substances 0.000 claims description 26
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
150000003839 salts Chemical class 0.000 claims description 17
125000006239 protecting group Chemical group 0.000 claims description 15
150000001732 carboxylic acid derivatives Chemical group 0.000 claims description 14
125000006244 carboxylic acid protecting group Chemical group 0.000 claims description 8
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
125000004185 ester group Chemical group 0.000 claims description 3
150000002431 hydrogen Chemical class 0.000 claims description 3
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 3
229940124531 pharmaceutical excipient Drugs 0.000 claims description 3
150000003008 phosphonic acid esters Chemical class 0.000 claims description 3
230000032050 esterification Effects 0.000 claims description 2
238000005886 esterification reaction Methods 0.000 claims description 2
125000001918 phosphonic acid ester group Chemical group 0.000 claims description 2
125000003262 carboxylic acid ester group Chemical class [H]C([H])([*:2])OC(=O)C([H])([H])[*:1] 0.000 claims 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 44
239000000243 solution Substances 0.000 description 43
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 40
239000000203 mixture Substances 0.000 description 37
238000012360 testing method Methods 0.000 description 32
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
-1 cyclopentylcarbonylamino residue Chemical group 0.000 description 27
125000000217 alkyl group Chemical group 0.000 description 25
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
239000000741 silica gel Substances 0.000 description 23
229910002027 silica gel Inorganic materials 0.000 description 23
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
239000003480 eluent Substances 0.000 description 22
239000002904 solvent Substances 0.000 description 22
102000003729 Neprilysin Human genes 0.000 description 21
108090000028 Neprilysin Proteins 0.000 description 21
238000006243 chemical reaction Methods 0.000 description 19
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 18
JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentanecarboxylic acid Chemical compound OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 0.000 description 18
239000000047 product Substances 0.000 description 18
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
239000012074 organic phase Substances 0.000 description 16
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 15
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
101800001288 Atrial natriuretic factor Proteins 0.000 description 14
101800001890 Atrial natriuretic peptide Proteins 0.000 description 14
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 14
238000004587 chromatography analysis Methods 0.000 description 14
239000002244 precipitate Substances 0.000 description 14
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102000002723 Atrial Natriuretic Factor Human genes 0.000 description 13
102000048186 Endothelin-converting enzyme 1 Human genes 0.000 description 13
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BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 13
NSQLIUXCMFBZME-MPVJKSABSA-N carperitide Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 NSQLIUXCMFBZME-MPVJKSABSA-N 0.000 description 13
239000012043 crude product Substances 0.000 description 13
230000000694 effects Effects 0.000 description 13
150000002148 esters Chemical class 0.000 description 13
229910052938 sodium sulfate Inorganic materials 0.000 description 13
235000011152 sodium sulphate Nutrition 0.000 description 13
241001465754 Metazoa Species 0.000 description 11
125000004432 carbon atom Chemical group C* 0.000 description 11
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 11
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
239000003054 catalyst Substances 0.000 description 10
230000002401 inhibitory effect Effects 0.000 description 10
239000007858 starting material Substances 0.000 description 10
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
241000700159 Rattus Species 0.000 description 9
239000002585 base Substances 0.000 description 9
238000001035 drying Methods 0.000 description 9
238000000746 purification Methods 0.000 description 9
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
108050009340 Endothelin Proteins 0.000 description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
230000036772 blood pressure Effects 0.000 description 8
230000002829 reductive effect Effects 0.000 description 8
102000002045 Endothelin Human genes 0.000 description 7
206010019280 Heart failures Diseases 0.000 description 7
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
238000001704 evaporation Methods 0.000 description 7
230000008020 evaporation Effects 0.000 description 7
230000005764 inhibitory process Effects 0.000 description 7
210000002700 urine Anatomy 0.000 description 7
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
229930040373 Paraformaldehyde Natural products 0.000 description 6
125000002947 alkylene group Chemical group 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
239000002775 capsule Substances 0.000 description 6
238000001816 cooling Methods 0.000 description 6
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
230000007717 exclusion Effects 0.000 description 6
238000011534 incubation Methods 0.000 description 6
238000001802 infusion Methods 0.000 description 6
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
229910052763 palladium Inorganic materials 0.000 description 6
229920002866 paraformaldehyde Polymers 0.000 description 6
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
239000000758 substrate Substances 0.000 description 6
XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 5
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 5
DLYDXCYTSDYGTJ-INIZCTEOSA-N benzyl 2-[(3s)-3-amino-2-oxo-4,5-dihydro-3h-1-benzazepin-1-yl]acetate Chemical compound C([C@@H](C1=O)N)CC2=CC=CC=C2N1CC(=O)OCC1=CC=CC=C1 DLYDXCYTSDYGTJ-INIZCTEOSA-N 0.000 description 5
230000037396 body weight Effects 0.000 description 5
229910052799 carbon Inorganic materials 0.000 description 5
230000015556 catabolic process Effects 0.000 description 5
238000009903 catalytic hydrogenation reaction Methods 0.000 description 5
239000002934 diuretic Substances 0.000 description 5
238000001727 in vivo Methods 0.000 description 5
229910052700 potassium Inorganic materials 0.000 description 5
239000011591 potassium Substances 0.000 description 5
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 4
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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 4
108010042237 Methionine Enkephalin Proteins 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
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239000003795 chemical substances by application Substances 0.000 description 4
239000013078 crystal Substances 0.000 description 4
229910052736 halogen Inorganic materials 0.000 description 4
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CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 4
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229910052708 sodium Inorganic materials 0.000 description 4
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JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
238000010626 work up procedure Methods 0.000 description 4
YFGBQHOOROIVKG-BHDDXSALSA-N (2R)-2-[[(2R)-2-[[2-[[2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C([C@H](C(=O)N[C@H](CCSC)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 YFGBQHOOROIVKG-BHDDXSALSA-N 0.000 description 3
HWGJRVLNZUAMDR-UHFFFAOYSA-N 1-[[hydroxy(3-phenylpropoxy)phosphoryl]methyl]cyclopentane-1-carboxylic acid Chemical compound C(C1=CC=CC=C1)CCOP(=O)(O)CC1(CCCC1)C(=O)O HWGJRVLNZUAMDR-UHFFFAOYSA-N 0.000 description 3
HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 3
JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 3
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QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
229910000510 noble metal Inorganic materials 0.000 description 1
238000010534 nucleophilic substitution reaction Methods 0.000 description 1
RQKYHDHLEMEVDR-UHFFFAOYSA-N oxo-bis(phenylmethoxy)phosphanium Chemical compound C=1C=CC=CC=1CO[P+](=O)OCC1=CC=CC=C1 RQKYHDHLEMEVDR-UHFFFAOYSA-N 0.000 description 1
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
239000012071 phase Substances 0.000 description 1
238000005191 phase separation Methods 0.000 description 1
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
150000003007 phosphonic acid derivatives Chemical class 0.000 description 1
150000003009 phosphonic acids Chemical class 0.000 description 1
239000001120 potassium sulphate Substances 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
230000004088 pulmonary circulation Effects 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
IYYIUOWKEMQYNV-UHFFFAOYSA-N sodium;ethoxy-oxido-oxophosphanium Chemical compound [Na+].CCO[P+]([O-])=O IYYIUOWKEMQYNV-UHFFFAOYSA-N 0.000 description 1
VYMZWGVJCJYPPZ-UHFFFAOYSA-N sodium;propan-2-yl hydrogen phosphite Chemical compound [Na+].CC(C)OP(O)[O-] VYMZWGVJCJYPPZ-UHFFFAOYSA-N 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
238000005728 strengthening Methods 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
230000035488 systolic blood pressure Effects 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000007885 tablet disintegrant Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
QTEDVVHLTMELTB-UHFFFAOYSA-N tert-butyl 2-(3-amino-2-oxo-4,5-dihydro-3h-1-benzazepin-1-yl)acetate Chemical compound C1CC(N)C(=O)N(CC(=O)OC(C)(C)C)C2=CC=CC=C21 QTEDVVHLTMELTB-UHFFFAOYSA-N 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-M toluenesulfonate group Chemical group C=1(C(=CC=CC1)S(=O)(=O)[O-])C LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
230000001960 triggered effect Effects 0.000 description 1
YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
210000003708 urethra Anatomy 0.000 description 1
210000003932 urinary bladder Anatomy 0.000 description 1
230000002227 vasoactive effect Effects 0.000 description 1
230000000304 vasodilatating effect Effects 0.000 description 1
BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
229960001600 xylazine Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- 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
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
- 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
- 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
- A61P9/12—Antihypertensives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Cardiology (AREA)
Bioinformatics & Cheminformatics (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Heart & Thoracic Surgery (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Molecular Biology (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Hospice & Palliative Care (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

NO19985262A 1997-11-12 1998-11-11 Nye fosfonsyresubstituerte benzazepinon-N-edikksyrederivater, fremgangsmate for deres fremstilling, og legemidler inneholdende slike NO317640B1 (no)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE19750002A DE19750002A1 (de)	1997-11-12	1997-11-12	Phosphonsäure-substituierte Benzazepinon-N-essigsäurederivate sowie Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel

Publications (3)

Publication Number	Publication Date
NO985262D0 NO985262D0 (no)	1998-11-11
NO985262L NO985262L (no)	1999-05-14
NO317640B1 true NO317640B1 (no)	2004-11-29

Family

ID=7848410

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19985262A NO317640B1 (no)	1997-11-12	1998-11-11	Nye fosfonsyresubstituerte benzazepinon-N-edikksyrederivater, fremgangsmate for deres fremstilling, og legemidler inneholdende slike

Country Status (27)

Country	Link
US (1)	US5952327A (fr)
EP (1)	EP0916679B1 (fr)
JP (1)	JP4162780B2 (fr)
KR (1)	KR19990045100A (fr)
CN (1)	CN1187361C (fr)
AR (1)	AR009911A1 (fr)
AT (1)	ATE228144T1 (fr)
AU (1)	AU746907B2 (fr)
BR (1)	BR9804582A (fr)
CA (1)	CA2253997C (fr)
CZ (1)	CZ296123B6 (fr)
DE (2)	DE19750002A1 (fr)
DK (1)	DK0916679T3 (fr)
DZ (1)	DZ2652A1 (fr)
ES (1)	ES2186961T3 (fr)
HU (1)	HU221177B1 (fr)
ID (1)	ID21393A (fr)
IL (1)	IL126984A (fr)
NO (1)	NO317640B1 (fr)
NZ (1)	NZ332744A (fr)
PL (1)	PL191436B1 (fr)
PT (1)	PT916679E (fr)
RU (1)	RU2211219C2 (fr)
SK (1)	SK283233B6 (fr)
TR (1)	TR199802289A2 (fr)
UA (1)	UA60304C2 (fr)
ZA (1)	ZA9810316B (fr)

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JP2004536063A (ja) *	2001-05-18	2004-12-02	ゾルファイ　ファーマスーティカルズ　ゲゼルシャフト　ミット　ベシュレンクテル　ハフツング	医薬の製造における組み合わせたｎｅｐ／ｍｐ−抑制活性を有する化合物の使用
DK1438316T3 (da) *	2001-10-19	2006-10-16	Ortho Mcneil Pharm Inc	Phosphonsyreforbindelser som inhibitorer af serinproteaser
RU2303041C2 (ru) *	2002-01-16	2007-07-20	Солвей Фармасьютикалс Б.В.	Твердые соли бензазепиновых соединений и их применение при получении фармацевтических соединений
CL2004000544A1 (es) *	2003-03-18	2005-01-28	Pharmacia Corp Sa Organizada B	Uso de una combinacion farmaceutica, de un antagonista del receptor de aldosterona y un inhibidor de endopeptidasa neutral, util para el tratamiento y prevencion de una condicion patologica relacionada con hipertension, disfuncion renal, insulinopati
US7452875B2 (en)	2003-09-26	2008-11-18	Solvay Pharmaceuticals Gmbh	Amidomethyl-substituted 1-(carboxyalkyl) cyclopentyl-carbonylamino-benzazepine-N-acetic acid compounds, process and intermediate products for their preparation and pharmaceutical compositions containing them
US7427611B2 (en) *	2003-09-26	2008-09-23	Solvay Pharmaceuticals Gmbh	Amidomethyl-substituted 1-(carboxyalkyl)-cyclopentyl-carbonylamino-benzazepine-N-acetic acid compounds, process and intermediate products for their preparation and pharmaceutical compositions containing them
SA04250283B1 (ar) *	2003-09-26	2008-05-26	سولفاي فارماسيتيكالز جي أم بي أتش	مشتقات من amidomethy1-substituted1-(carboxyalkyl)-cyclopentylcarbonylamino-benzazepine-N-acetic acid
US7262184B2 (en)	2003-09-26	2007-08-28	Solvay Pharmaceuticals Gmbh	Amidomethyl-substituted 1-(carboxyalkyl) cyclopentyl-carbonylamino-benzazepine-N-acetic acid compounds, process and intermediate products for their preparation and pharmaceutical compositions containing them
US7232813B2 (en) *	2004-01-12	2007-06-19	Solvay Pharmaceuticals B.V.	Neutral endopeptidase (NEP) and human soluble endopeptidase (hSEP) inhibitors for prophylaxis and treatment of neuro-degenerative disorders
PT1706121E (pt) *	2004-01-12	2008-12-04	Solvay Pharm Bv	Inibidores de endopeptidase neutra (nep) e endopeptidase humana solúvel (hsep) para profilaxia e tratamento de distúrbios neurodegenerativos
US20050267124A1 (en) *	2004-05-14	2005-12-01	Solvay Pharmaceuticals Gmbh	Pharmaceutical compositions comprising NEP-inhibitors, inhibitors of the endogenous producing system and PDEV inhibiitors
US20050267072A1 (en) *	2004-05-14	2005-12-01	Solvay Pharmaceuticals Gmbh	Pharmaceutical compositions containing dually acting inhibitors of neutral endopeptidase for the treatment of sexual dysfunction
US20050288272A1 (en) *	2004-06-23	2005-12-29	Solvay Pharmaceuticals Gmbh	Pharmaceutical compositions comprising NEP-inhibitors, inhibitors of the endogenous endothelin producing system and AT1 receptor antagonists
CN1972679B (zh) *	2004-06-23	2010-07-28	索尔瓦药物有限公司	包括nep-抑制剂、内源性内皮缩血管肽产生系统抑制剂和at1受体拮抗剂的药物组合物
RU2410118C2 (ru) *	2004-12-15	2011-01-27	Зольвай Фармасьютиклз Гмбх	ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ, ВКЛЮЧАЮЩИЕ ИНГИБИТОРЫ НЭП (НЕЙТРАЛЬНОЙ ЭНДОПЕПТИДАЗЫ), ИНГИБИТОРЫ ЭНДОГЕННОЙ ПРОДУЦИРУЮЩЕЙ ЭНДОТЕЛИН СИСТЕМЫ И ИНГИБИТОРЫ ГМГ (ГИДРОКСИМЕТИЛГЛУТАРИЛ)СоА РЕДУКТАЗЫ
US20060205625A1 (en) *	2005-02-18	2006-09-14	Solvay Pharmaceuticals Gmbh	Pharmaceutical compositions comprising NEP-inhibitors, inhibitors of the endogenous endothelin producing system and diuretics
ES2344800T3 (es) *	2005-02-18	2010-09-07	Solvay Pharmaceuticals Gmbh	Composiciones farmaceuticas que comprenden inhibidores de nep, inhibidores del sistema productor de endotelina endogena y diureticos.
PL1968990T3 (pl) *	2005-12-27	2015-06-30	Otsuka Pharma Co Ltd	Rozpuszczalny w wodzie związek benzoazepinowy i jego kompozycja farmaceutyczna
WO2007102171A2 (fr) *	2006-03-07	2007-09-13	Panacea Biotec Ltd	Nouveaux sels de l'acide 1h-1-benzazépine-1-acétique, préparation de ceux-ci et composition pharmaceutique comprenant ceux-ci
US8198341B2 (en)	2008-12-18	2012-06-12	Icl-Ip America Inc.	Method of making hydroxymethylphosphonate, polyurethane foam-forming compositions, polyurethane foam and articles made therefrom
CN107383093B (zh)	2012-10-17	2021-07-16	Icl-Ip美国有限公司	羟甲基膦酸酯、组合物、聚氨酯泡沫及制品
US9815256B2 (en)	2014-06-09	2017-11-14	Johns Manville	Foam boards including non-halogenated fire retardants
US9523195B2 (en)	2014-06-09	2016-12-20	Johns Manville	Wall insulation boards with non-halogenated fire retardant and insulated wall systems
US9528269B2 (en)	2014-06-09	2016-12-27	Johns Manville	Roofing systems and roofing boards with non-halogenated fire retardant
US9815966B2 (en)	2014-07-18	2017-11-14	Johns Manville	Spray foams containing non-halogenated fire retardants
CN107383084A (zh) *	2017-06-14	2017-11-24	浙江嘉华化工有限公司	一种0‑乙基磷酸钠的制备方法
PL424453A1 (pl)	2018-01-31	2019-08-12	Forty-Four Pharmaceuticals Spółka Z Ograniczoną Odpowiedzialnością	Sposoby zmniejszania szkodliwego działania niedoboru perfuzji narządów miąższowych przez inhibitory obojętnej endopeptydazy (NEP) i ludzkiej rozpuszczalnej endopeptydazy (hSEP)
PL424452A1 (pl)	2018-01-31	2019-08-12	Forty-Four Pharmaceuticals Spółka Z Ograniczoną Odpowiedzialnością	Inhibitory obojętnej endopeptydazy (NEP) i ludzkiej rozpuszczalnej endopeptydazy (hSEP) do profilaktyki i leczenia chorób oczu
CN115466754A (zh) *	2022-08-24	2022-12-13	中国人民解放军军事科学院防化研究院	一类P-手性α-羟(酯)基磷酸酯类化合物及其制备方法

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1997
- 1997-11-12 DE DE19750002A patent/DE19750002A1/de not_active Withdrawn
1998
- 1998-10-21 AR ARP980105254A patent/AR009911A1/es unknown
- 1998-11-02 HU HU9802517A patent/HU221177B1/hu not_active IP Right Cessation
- 1998-11-04 ES ES98120898T patent/ES2186961T3/es not_active Expired - Lifetime
- 1998-11-04 CZ CZ0356298A patent/CZ296123B6/cs not_active IP Right Cessation
- 1998-11-04 DE DE59806345T patent/DE59806345D1/de not_active Expired - Lifetime
- 1998-11-04 EP EP98120898A patent/EP0916679B1/fr not_active Expired - Lifetime
- 1998-11-04 PT PT98120898T patent/PT916679E/pt unknown
- 1998-11-04 DK DK98120898T patent/DK0916679T3/da active
- 1998-11-04 AT AT98120898T patent/ATE228144T1/de not_active IP Right Cessation
- 1998-11-05 SK SK1516-98A patent/SK283233B6/sk unknown
- 1998-11-07 KR KR1019980047652A patent/KR19990045100A/ko not_active Ceased
- 1998-11-10 IL IL12698498A patent/IL126984A/en not_active IP Right Cessation
- 1998-11-10 JP JP31913198A patent/JP4162780B2/ja not_active Expired - Fee Related
- 1998-11-10 CN CNB981241433A patent/CN1187361C/zh not_active Expired - Fee Related
- 1998-11-10 PL PL329635A patent/PL191436B1/pl not_active IP Right Cessation
- 1998-11-11 NZ NZ332744A patent/NZ332744A/en unknown
- 1998-11-11 RU RU98120256/04A patent/RU2211219C2/ru not_active IP Right Cessation
- 1998-11-11 DZ DZ980262A patent/DZ2652A1/fr active
- 1998-11-11 NO NO19985262A patent/NO317640B1/no not_active IP Right Cessation
- 1998-11-11 AU AU92344/98A patent/AU746907B2/en not_active Ceased
- 1998-11-11 BR BR9804582-2A patent/BR9804582A/pt not_active IP Right Cessation
- 1998-11-11 TR TR1998/02289A patent/TR199802289A2/xx unknown
- 1998-11-11 ZA ZA9810316A patent/ZA9810316B/xx unknown
- 1998-11-12 UA UA98116012A patent/UA60304C2/uk unknown
- 1998-11-12 CA CA002253997A patent/CA2253997C/fr not_active Expired - Fee Related
- 1998-11-12 ID IDP981485A patent/ID21393A/id unknown
- 1998-11-12 US US09/189,796 patent/US5952327A/en not_active Expired - Lifetime

Also Published As

Publication number	Publication date
AU9234498A (en)	2000-06-08
CA2253997C (fr)	2009-05-12
HK1019338A1 (en)	2000-02-03
CN1217334A (zh)	1999-05-26
IL126984A0 (en)	1999-09-22
DZ2652A1 (fr)	2003-03-15
EP0916679B1 (fr)	2002-11-20
HU221177B1 (en)	2002-08-28
DE19750002A1 (de)	1999-05-20
ZA9810316B (en)	1999-05-18
AR009911A1 (es)	2000-05-03
JPH11292886A (ja)	1999-10-26
SK283233B6 (sk)	2003-04-01
PL191436B1 (pl)	2006-05-31
BR9804582A (pt)	2000-05-09
IL126984A (en)	2001-07-24
TR199802289A3 (tr)	1999-06-21
CN1187361C (zh)	2005-02-02
ATE228144T1 (de)	2002-12-15
HU9802517D0 (en)	1998-12-28
NO985262L (no)	1999-05-14
KR19990045100A (ko)	1999-06-25
NO985262D0 (no)	1998-11-11
JP4162780B2 (ja)	2008-10-08
ES2186961T3 (es)	2003-05-16
EP0916679A1 (fr)	1999-05-19
ID21393A (id)	1999-06-03
DE59806345D1 (de)	2003-01-02
HUP9802517A3 (en)	2000-06-28
RU2211219C2 (ru)	2003-08-27
TR199802289A2 (xx)	1999-06-21
UA60304C2 (uk)	2003-10-15
CZ356298A3 (cs)	1999-06-16
SK151698A3 (en)	1999-05-07
CZ296123B6 (cs)	2006-01-11
NZ332744A (en)	2000-06-23
US5952327A (en)	1999-09-14
AU746907B2 (en)	2002-05-02
PL329635A1 (en)	1999-05-24
CA2253997A1 (fr)	1999-05-12
PT916679E (pt)	2003-03-31
DK0916679T3 (da)	2002-12-16
HUP9802517A2 (hu)	1999-09-28

Legal Events

Date	Code	Title	Description
2006-07-03	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
NO317640B1 (no)	2004-11-29	Nye fosfonsyresubstituerte benzazepinon-N-edikksyrederivater, fremgangsmate for deres fremstilling, og legemidler inneholdende slike
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