DD279877A5 - Verfahren zur herstellung annelierter azepinon- und azocinon-derivate - Google Patents

Verfahren zur herstellung annelierter azepinon- und azocinon-derivate Download PDF

Info

Publication number: DD279877A5
Authority: DD; German Democratic Republic
Prior art keywords: formula; hydrogen; compound; alkyl; compounds
Prior art date: 1987-02-14

Application number

DD88312878A

Other languages

German (de)

English (en)

Inventor

Hansjoerg Urbach

Rainer Henning

Bernward Schoelkens

Reinhard Becker

Original Assignee

��@��k��

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.)

1987-02-14

Filing date

1988-02-12

Publication date

1990-06-20

1988-02-12 Application filed by ��@��k�� filed Critical ��@��k��

1990-06-20 Publication of DD279877A5 publication Critical patent/DD279877A5/de

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DXZDEAJXVCLRLE-UHFFFAOYSA-N azepin-2-one Chemical compound O=C1C=CC=CC=N1 DXZDEAJXVCLRLE-UHFFFAOYSA-N 0.000 title description 4
MXYHHRIZRNXYAN-UHFFFAOYSA-N (3z,5z,7z)-1h-azocin-2-one Chemical class O=C\1N\C=C/C=C\C=C/1 MXYHHRIZRNXYAN-UHFFFAOYSA-N 0.000 title description 3
238000004519 manufacturing process Methods 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 180
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 74
239000001257 hydrogen Substances 0.000 claims abstract description 74
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 48
238000000034 method Methods 0.000 claims abstract description 29
150000002431 hydrogen Chemical class 0.000 claims abstract description 16
238000002360 preparation method Methods 0.000 claims abstract description 14
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 11
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 10
125000003118 aryl group Chemical group 0.000 claims abstract description 7
239000008177 pharmaceutical agent Substances 0.000 claims abstract description 3
-1 hydroxy, mercapto Chemical group 0.000 claims description 27
238000006243 chemical reaction Methods 0.000 claims description 20
150000003839 salts Chemical class 0.000 claims description 16
239000000460 chlorine Substances 0.000 claims description 14
XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 claims description 11
229910052760 oxygen Inorganic materials 0.000 claims description 11
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
239000001301 oxygen Substances 0.000 claims description 10
230000002829 reductive effect Effects 0.000 claims description 9
150000001412 amines Chemical class 0.000 claims description 8
108090000765 processed proteins & peptides Proteins 0.000 claims description 8
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
239000003638 chemical reducing agent Substances 0.000 claims description 7
229910052801 chlorine Inorganic materials 0.000 claims description 7
229910052736 halogen Inorganic materials 0.000 claims description 7
150000002367 halogens Chemical class 0.000 claims description 7
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
125000006239 protecting group Chemical group 0.000 claims description 6
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
XXRGLCKZBCIEKO-DLMDZQPMSA-N azocine Chemical compound C/1=C/C=C\N=C/C=C\1 XXRGLCKZBCIEKO-DLMDZQPMSA-N 0.000 claims description 5
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 5
125000004043 oxo group Chemical group O=* 0.000 claims description 5
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 3
238000006683 Mannich reaction Methods 0.000 claims description 3
238000006957 Michael reaction Methods 0.000 claims description 3
125000004432 carbon atom Chemical group C* 0.000 claims description 3
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
239000002934 diuretic Substances 0.000 claims description 3
125000004185 ester group Chemical group 0.000 claims description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
229910052731 fluorine Inorganic materials 0.000 claims description 3
239000011737 fluorine Substances 0.000 claims description 3
125000001153 fluoro group Chemical group F* 0.000 claims description 3
125000000524 functional group Chemical group 0.000 claims description 3
229910052740 iodine Inorganic materials 0.000 claims description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
125000006536 (C1-C2)alkoxy group Chemical group 0.000 claims description 2
125000004442 acylamino group Chemical group 0.000 claims description 2
230000015572 biosynthetic process Effects 0.000 claims description 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
230000001882 diuretic effect Effects 0.000 claims description 2
125000002883 imidazolyl group Chemical group 0.000 claims description 2
125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 1
125000006528 (C2-C6) alkyl group Chemical group 0.000 claims 1
125000003545 alkoxy group Chemical group 0.000 claims 1
125000000217 alkyl group Chemical group 0.000 abstract description 8
125000000753 cycloalkyl group Chemical group 0.000 abstract description 6
239000004480 active ingredient Substances 0.000 abstract description 3
238000011282 treatment Methods 0.000 abstract description 3
206010020772 Hypertension Diseases 0.000 abstract description 2
208000019622 heart disease Diseases 0.000 abstract description 2
125000003342 alkenyl group Chemical group 0.000 abstract 3
125000003710 aryl alkyl group Chemical group 0.000 abstract 2
125000000547 substituted alkyl group Chemical group 0.000 abstract 2
125000000392 cycloalkenyl group Chemical group 0.000 abstract 1
125000001316 cycloalkyl alkyl group Chemical group 0.000 abstract 1
125000001041 indolyl group Chemical group 0.000 abstract 1
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 abstract 1
125000003107 substituted aryl group Chemical group 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 17
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
239000000203 mixture Substances 0.000 description 15
238000005160 1H NMR spectroscopy Methods 0.000 description 14
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
239000002253 acid Substances 0.000 description 13
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
239000003054 catalyst Substances 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
239000012071 phase Substances 0.000 description 8
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
238000005481 NMR spectroscopy Methods 0.000 description 7
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
229910000041 hydrogen chloride Inorganic materials 0.000 description 7
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
239000002798 polar solvent Substances 0.000 description 7
239000002904 solvent Substances 0.000 description 7
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
238000001816 cooling Methods 0.000 description 6
230000032050 esterification Effects 0.000 description 6
238000005886 esterification reaction Methods 0.000 description 6
150000003254 radicals Chemical class 0.000 description 6
239000000741 silica gel Substances 0.000 description 6
229910002027 silica gel Inorganic materials 0.000 description 6
239000012312 sodium hydride Substances 0.000 description 6
229910000104 sodium hydride Inorganic materials 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
239000002585 base Substances 0.000 description 5
238000009835 boiling Methods 0.000 description 5
238000001035 drying Methods 0.000 description 5
229910052751 metal Inorganic materials 0.000 description 5
239000002184 metal Substances 0.000 description 5
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
239000007868 Raney catalyst Substances 0.000 description 4
229910000564 Raney nickel Inorganic materials 0.000 description 4
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-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
229960000583 acetic acid Drugs 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
229910052794 bromium Inorganic materials 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
238000004440 column chromatography Methods 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
239000012467 final product Substances 0.000 description 4
150000004678 hydrides Chemical class 0.000 description 4
230000007062 hydrolysis Effects 0.000 description 4
238000006460 hydrolysis reaction Methods 0.000 description 4
239000012454 non-polar solvent Substances 0.000 description 4
238000007363 ring formation reaction Methods 0.000 description 4
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 3
241000251730 Chondrichthyes Species 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 3
108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 3
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
230000001476 alcoholic effect Effects 0.000 description 3
125000003277 amino group Chemical group 0.000 description 3
150000001540 azides Chemical class 0.000 description 3
150000001735 carboxylic acids Chemical class 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
239000012362 glacial acetic acid Substances 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
150000002500 ions Chemical class 0.000 description 3
150000003951 lactams Chemical class 0.000 description 3
229910052763 palladium Inorganic materials 0.000 description 3
229910052697 platinum Inorganic materials 0.000 description 3
239000000047 product Substances 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
238000006884 silylation reaction Methods 0.000 description 3
239000000725 suspension Substances 0.000 description 3
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
SACVBVWZMSAEIX-UHFFFAOYSA-N 4-(2-aminocyclopentyl)butanoic acid Chemical compound NC1CCCC1CCCC(O)=O SACVBVWZMSAEIX-UHFFFAOYSA-N 0.000 description 2
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
102400000344 Angiotensin-1 Human genes 0.000 description 2
101800000734 Angiotensin-1 Proteins 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
125000005907 alkyl ester group Chemical group 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
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 2
150000008064 anhydrides Chemical class 0.000 description 2
125000004429 atom Chemical group 0.000 description 2
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
239000000969 carrier Substances 0.000 description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
239000003814 drug Substances 0.000 description 2
230000000694 effects Effects 0.000 description 2
239000008103 glucose Substances 0.000 description 2
230000026030 halogenation Effects 0.000 description 2
238000005658 halogenation reaction Methods 0.000 description 2
230000001077 hypotensive effect Effects 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
150000007529 inorganic bases Chemical class 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
150000002923 oximes Chemical class 0.000 description 2
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 2
239000008194 pharmaceutical composition Substances 0.000 description 2
102000004196 processed proteins & peptides Human genes 0.000 description 2
238000010992 reflux Methods 0.000 description 2
238000002390 rotary evaporation Methods 0.000 description 2
239000011734 sodium Substances 0.000 description 2
239000001632 sodium acetate Substances 0.000 description 2
235000017281 sodium acetate Nutrition 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
238000003756 stirring Methods 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
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 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
OIGMGICPZXNGPI-SECBINFHSA-N (2r)-4-phenyl-2-(trifluoromethylsulfonyloxy)butanoic acid Chemical compound FC(F)(F)S(=O)(=O)O[C@@H](C(=O)O)CCC1=CC=CC=C1 OIGMGICPZXNGPI-SECBINFHSA-N 0.000 description 1
CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox 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](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 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 1
125000005862 (C1-C6)alkanoyl group Chemical group 0.000 description 1
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
125000006763 (C3-C9) cycloalkyl group Chemical group 0.000 description 1
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
LLUBVCCZUMPBMI-UHFFFAOYSA-N 1-[[ethyl(methyl)phosphoryl]oxy-methylphosphoryl]ethane Chemical compound CCP(C)(=O)OP(C)(=O)CC LLUBVCCZUMPBMI-UHFFFAOYSA-N 0.000 description 1
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235000011009 potassium phosphates Nutrition 0.000 description 1
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238000001953 recrystallisation Methods 0.000 description 1
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230000007017 scission Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
239000000243 solution Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
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150000003460 sulfonic acids Chemical class 0.000 description 1
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150000003509 tertiary alcohols Chemical class 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
150000003568 thioethers Chemical class 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
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Classifications

- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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
- A61P9/12—Antihypertensives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

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)
General Chemical & Material Sciences (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Ophthalmology & Optometry (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Heart & Thoracic Surgery (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Cardiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Plural Heterocyclic Compounds (AREA)
Indole Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

DD88312878A 1987-02-14 1988-02-12 Verfahren zur herstellung annelierter azepinon- und azocinon-derivate DD279877A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE19873704661 DE3704661A1 (de)	1987-02-14	1987-02-14	Annelierte azepinon- und azocinon-derivate, verfahren zu ihrer herstellung, diese enthaltende mittel und ihre verwendung, sowie zwischenprodukte bei ihrer herstellung

Publications (1)

Publication Number	Publication Date
DD279877A5 true DD279877A5 (de)	1990-06-20

Family

ID=6320980

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD88312878A DD279877A5 (de)	1987-02-14	1988-02-12	Verfahren zur herstellung annelierter azepinon- und azocinon-derivate

Country Status (26)

Country	Link
US (1)	US4857520A (fr)
EP (1)	EP0279350B1 (fr)
JP (1)	JP2638034B2 (fr)
KR (1)	KR960011376B1 (fr)
AR (1)	AR246957A1 (fr)
AT (1)	ATE97913T1 (fr)
AU (1)	AU610124B2 (fr)
CA (1)	CA1313371C (fr)
CZ (1)	CZ280148B6 (fr)
DD (1)	DD279877A5 (fr)
DE (2)	DE3704661A1 (fr)
DK (1)	DK172553B1 (fr)
ES (1)	ES2061531T3 (fr)
FI (1)	FI86849C (fr)
HU (2)	HU208425B (fr)
IE (1)	IE62354B1 (fr)
IL (1)	IL85406A (fr)
JO (1)	JO1524B1 (fr)
MA (1)	MA21181A1 (fr)
MX (1)	MX174166B (fr)
NO (1)	NO176763C (fr)
NZ (1)	NZ223500A (fr)
PH (1)	PH25186A (fr)
PT (1)	PT86748B (fr)
TN (1)	TNSN88010A1 (fr)
ZA (1)	ZA88991B (fr)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
TW483763B (en) *	1994-09-02	2002-04-21	Astra Ab	Pharmaceutical composition comprising of ramipril and dihydropyridine compound
US5587375A (en) *	1995-02-17	1996-12-24	Bristol-Myers Squibb Company	Azepinone compounds useful in the inhibition of ACE and NEP
SE9903028D0 (sv) *	1999-08-27	1999-08-27	Astra Ab	New use
BR0013704A (pt) *	1999-08-30	2002-05-07	Aventis Pharma Gmbh	Uso de inibidores do sistema renina-angiotensina na prevenção de casos cardiovasculares

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3354146A (en) *		1967-11-21		Process for the production of cyclo- pentano omega-oenantholactam
US4141893A (en) *	1976-11-02	1979-02-27	Eli Lilly And Company	Decahydrocyclopent[c]azepines
GB2103614B (en) *	1981-08-11	1984-11-21	Ciba Geigy Ag	Benzazepin-2-ones
DE3373469D1 (en) *	1982-09-30	1987-10-15	Merck & Co Inc	1-n-alkylcarboxy-benzofused lactams useful as antihypertensive agents
US4470988A (en) *	1983-02-10	1984-09-11	Ciba-Geigy Corporation	Benzazocinone and benzazoninone derivatives, and their pharmaceutical use
DE3426720A1 (de) *	1984-07-20	1986-01-23	Hoechst Ag, 6230 Frankfurt	Benzthiazepinon- und benzthiazocinon-derivate, verfahren zu ihrer herstellung, diese enthaltende mittel und ihre verwendung, sowie zwischenprodukte bei ihrer herstellung

1987
- 1987-02-14 DE DE19873704661 patent/DE3704661A1/de not_active Withdrawn
1988
- 1988-02-11 JO JO19881524A patent/JO1524B1/en active
- 1988-02-11 AR AR88310062A patent/AR246957A1/es active
- 1988-02-11 AT AT88101975T patent/ATE97913T1/de not_active IP Right Cessation
- 1988-02-11 DE DE88101975T patent/DE3885914D1/de not_active Expired - Lifetime
- 1988-02-11 FI FI880632A patent/FI86849C/fi not_active IP Right Cessation
- 1988-02-11 EP EP88101975A patent/EP0279350B1/fr not_active Expired - Lifetime
- 1988-02-11 ES ES88101975T patent/ES2061531T3/es not_active Expired - Lifetime
- 1988-02-11 PT PT86748A patent/PT86748B/pt not_active IP Right Cessation
- 1988-02-12 NO NO880628A patent/NO176763C/no not_active IP Right Cessation
- 1988-02-12 IE IE39088A patent/IE62354B1/en not_active IP Right Cessation
- 1988-02-12 HU HU8621A patent/HU208425B/hu not_active IP Right Cessation
- 1988-02-12 JP JP63029043A patent/JP2638034B2/ja not_active Expired - Lifetime
- 1988-02-12 ZA ZA880991A patent/ZA88991B/xx unknown
- 1988-02-12 IL IL85406A patent/IL85406A/xx not_active IP Right Cessation
- 1988-02-12 CZ CS88892A patent/CZ280148B6/cs not_active IP Right Cessation
- 1988-02-12 MA MA21418A patent/MA21181A1/fr unknown
- 1988-02-12 CA CA000558818A patent/CA1313371C/fr not_active Expired - Fee Related
- 1988-02-12 TN TNTNSN88010A patent/TNSN88010A1/fr unknown
- 1988-02-12 HU HU88689A patent/HU203727B/hu not_active IP Right Cessation
- 1988-02-12 PH PH36490A patent/PH25186A/en unknown
- 1988-02-12 AU AU11672/88A patent/AU610124B2/en not_active Ceased
- 1988-02-12 US US07/155,595 patent/US4857520A/en not_active Expired - Lifetime
- 1988-02-12 MX MX010408A patent/MX174166B/es unknown
- 1988-02-12 DD DD88312878A patent/DD279877A5/de not_active IP Right Cessation
- 1988-02-12 NZ NZ223500A patent/NZ223500A/en unknown
- 1988-02-12 DK DK198800724A patent/DK172553B1/da not_active IP Right Cessation
- 1988-02-13 KR KR1019880001437A patent/KR960011376B1/ko not_active Expired - Fee Related

Also Published As

Publication number	Publication date
EP0279350A3 (en)	1990-09-05
DE3704661A1 (de)	1988-08-25
NZ223500A (en)	1990-11-27
AU1167288A (en)	1988-08-18
AR246957A1 (es)	1994-10-31
HUT50785A (en)	1990-03-28
JPS63203665A (ja)	1988-08-23
NO176763B (no)	1995-02-13
CZ89288A3 (en)	1994-12-15
FI880632A0 (fi)	1988-02-11
CA1313371C (fr)	1993-02-02
JP2638034B2 (ja)	1997-08-06
KR880009939A (ko)	1988-10-06
DK72488A (da)	1988-08-15
ATE97913T1 (de)	1993-12-15
MX174166B (es)	1994-04-26
US4857520A (en)	1989-08-15
PT86748B (pt)	1992-04-30
EP0279350B1 (fr)	1993-12-01
HU208425B (en)	1993-10-28
FI86849B (fi)	1992-07-15
DK72488D0 (da)	1988-02-12
EP0279350A2 (fr)	1988-08-24
CZ280148B6 (cs)	1995-11-15
FI86849C (fi)	1992-10-26
IE880390L (en)	1988-08-14
HU203727B (en)	1991-09-30
PH25186A (en)	1991-03-27
KR960011376B1 (ko)	1996-08-22
DE3885914D1 (de)	1994-01-13
DK172553B1 (da)	1999-01-11
AU610124B2 (en)	1991-05-16
ZA88991B (en)	1988-08-10
NO880628L (no)	1988-08-15
NO880628D0 (no)	1988-02-12
HUT48602A (en)	1989-06-28
ES2061531T3 (es)	1994-12-16
PT86748A (pt)	1988-03-01
MX10408A (es)	1993-07-01
JO1524B1 (en)	1989-01-25
MA21181A1 (fr)	1988-10-01
IL85406A (en)	1992-06-21
NO176763C (no)	1995-05-24
IE62354B1 (en)	1995-01-25
FI880632A7 (fi)	1988-08-15
TNSN88010A1 (fr)	1990-07-10
IL85406A0 (en)	1988-07-31

Legal Events

Date	Code	Title	Description
1998-10-08	ENJ	Ceased due to non-payment of renewal fee

Publication	Publication Date	Title
EP0150263B1 (fr)	1990-06-20	Dérivés de l'acide cis, endo-2-azabicyclo-[3.3.0]-octane-3-carboxylique, procédé pour leur préparation, médicaments les contenant et leur application
EP0131226B1 (fr)	1990-05-30	Dérivés de l'acide 2-azabicyclo(3.1.0)hexane-3-carboxylique, procédé pour leur préparation, agents les contenant et leur utilisation; dérivés de 2-azabicylco(3.1.0)hexane comme intermédiaires et procédé pour leur préparation
EP0089637B1 (fr)	1986-10-15	Dérivés d'amino acides bicycliques, procédé pour leur préparation, agents les contenant et leur utilisation, ainsi que des amino acides bicycliques comme produits intermédiaires et procédé pour leur préparation
EP0111873B1 (fr)	1987-10-07	Dérivés de l'acide cis, endo-aza-2 bicyclo(5.3.0)décane-carboxylique-3, procédé pour leur préparation, compositions les contenant et leur application
EP0084164B1 (fr)	1987-01-28	Dérivés d'amino-acides bicycliques, procédé pour leur préparation, agents les contenant et leur utilisation ainsi que des amino-acides bicycliques comme intermédiaires et procédé pour leur préparation
EP0109020B1 (fr)	1987-09-23	Dérivés d'amino-acides tricycliques, leur procédé de préparation, les composés les contenant, leur emploi, et les amino-acides bicycliques comme intermédiaires et leur procédé de préparation
EP0090341B1 (fr)	1987-07-29	Dérivés des acides spiro(4,(3+n))-2-aza-alcan-3-carboxyliques, leur procédé de préparation, les agents les contenant et leur emploi
DE3211676A1 (de)	1983-10-06	Neue derivate von cycloalka (c) pyrrol-carbonsaeuren, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung sowie neue cycloalka (c) pyrrol-carbonsaeuren als zwischenstufen und verfahren zu deren herstellung
EP0105102A1 (fr)	1984-04-11	Dérivés d'acides 2-aza-bicyclo(2,2,2)-octane-3-carboxyliques, leur procédé de préparation, les médicaments les contenant et leur application, ainsi que l'acide 2-aza-bicyclo(2,2,2)-octane-3-carboxylique comme intermédiaire et le procédé pour sa préparation
DE3303112A1 (de)	1984-08-09	Verfahren zur racemattrennung optisch aktiver bicyclischer imino-(alpha)-carbonsaeuren
EP0116276B1 (fr)	1989-01-11	Dérivés d'amino-acides spirocycliques, leur procédé de préparation, les agents les contenant et leur emploi de même que les amino-acides spirocycliques comme intermédiaires et leur procédé de préparation
EP0119161A2 (fr)	1984-09-19	Dérivés de benzazocinone et benzazoninon, leur procédé de préparation, préparations pharmaceutiques contenant ces composés, et leur application thérapeutique
DE3300316A1 (de)	1984-07-12	Disubstituierte prolinderivate, verfahren zu ihrer herstellung und ihre verwendung
EP0115345B1 (fr)	1988-01-07	Procédé de dédoublement d'esters d'acides imino-alpha-carboxyliques bicycliques optiquement actifs et utilisation des composés ainsi productibles pour la synthèse de carboxyalkyldipeptides
DD279877A5 (de)	1990-06-20	Verfahren zur herstellung annelierter azepinon- und azocinon-derivate
EP0113880A2 (fr)	1984-07-25	Derivés de 2-azabicyclo(2.2.1)heptane, leur procédé de préparation, les composés les contentant et leur emploi, de même que les dérivés de 2-azabicyclo(2.2.1)heptane comme intermédiaires et leur procédé de préparation
EP0203450B1 (fr)	1992-04-01	Dérivés d'amino-acides bicycliques, leur procédé de préparation, les agents les contenant et leur emploi
DE3426720A1 (de)	1986-01-23	Benzthiazepinon- und benzthiazocinon-derivate, verfahren zu ihrer herstellung, diese enthaltende mittel und ihre verwendung, sowie zwischenprodukte bei ihrer herstellung
EP0170775B2 (fr)	1994-10-12	Dérivés d'amino-acides bicycliques, procédé pour leur préparation, agents les contenant et leur utilisation ainsi que d'amino-acides bicycliques comme intermédiaires et procédé pour leur préparation
DE3151690A1 (de)	1983-07-07	"neue derivate bicyclischer aminosaeuren, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung sowie neue bicyclische aminosaeuren als zwischenstufen und verfahren zu deren herstellung"
DE3708484A1 (de)	1987-09-24	Neue 3-(3-cycloalkylpropyl)amino-1-benzazepin-2-on-1-alkansaeuren
DE3537460A1 (de)	1987-04-23	Neue derivate bicyclischer aminosaeuren, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung
DD263052A5 (de)	1988-12-21	Verfahren zur herstellung von neuen verbindungen
DE1104950B (de)	1961-04-20	Verfahren zur Herstellung des analgetisch wirksamen ª-Oxybuttersaeurecyclohexylamids
DE3303139A1 (de)	1984-08-09	Verfahren zur herstellung von carboxyalkyldipeptiden