DD283772A5 - Verfahren zur herstellung von enantiomeren glutaramid-verbindungen, die diuretisch wirken - Google Patents

Verfahren zur herstellung von enantiomeren glutaramid-verbindungen, die diuretisch wirken Download PDF

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Publication number: DD283772A5
Authority: DD; German Democratic Republic
Prior art keywords: formula; ethyl; compound; benzyl; och
Prior art date: 1988-05-19

Application number

DD89328675A

Other languages

German (de)

English (en)

Inventor

John Ch Danilewicz

Michael T Williams

Original Assignee

��@��Kk��

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.)

1988-05-19

Filing date

1989-05-17

Publication date

1990-10-24

1989-05-17 Application filed by ��@��Kk�� filed Critical ��@��Kk��

1990-10-24 Publication of DD283772A5 publication Critical patent/DD283772A5/de

Links

RCCYSVYHULFYHE-UHFFFAOYSA-N pentanediamide Chemical class NC(=O)CCCC(N)=O RCCYSVYHULFYHE-UHFFFAOYSA-N 0.000 title abstract description 5
238000004519 manufacturing process Methods 0.000 title description 2
238000000034 method Methods 0.000 claims abstract description 19
125000004185 ester group Chemical group 0.000 claims abstract description 11
238000002360 preparation method Methods 0.000 claims abstract description 4
-1 1- (2,4,6-trimethylbenzoyloxy) ethyl pivaloyloxymethyl phenethyl phenpropyl 1- (benzoyloxy) ethyl 1- (2,4-dimethylbenzoyloxy) ethyl Chemical group 0.000 claims description 59
150000001875 compounds Chemical class 0.000 claims description 27
150000003839 salts Chemical class 0.000 claims description 13
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 11
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 9
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 5
238000005859 coupling reaction Methods 0.000 claims description 4
125000001424 substituent group Chemical group 0.000 claims description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
230000008878 coupling Effects 0.000 claims description 2
238000010168 coupling process Methods 0.000 claims description 2
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims 1
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 1
125000006244 carboxylic acid protecting group Chemical group 0.000 claims 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
238000005984 hydrogenation reaction Methods 0.000 claims 1
230000007062 hydrolysis Effects 0.000 claims 1
238000006460 hydrolysis reaction Methods 0.000 claims 1
239000002934 diuretic Substances 0.000 abstract description 6
102000003729 Neprilysin Human genes 0.000 abstract description 5
108090000028 Neprilysin Proteins 0.000 abstract description 5
230000000694 effects Effects 0.000 abstract description 5
230000001882 diuretic effect Effects 0.000 abstract description 2
230000001452 natriuretic effect Effects 0.000 abstract description 2
230000005764 inhibitory process Effects 0.000 abstract 1
239000000543 intermediate Substances 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 48
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 45
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
239000000243 solution Substances 0.000 description 36
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
239000000377 silicon dioxide Substances 0.000 description 22
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
239000000047 product Substances 0.000 description 15
239000000203 mixture Substances 0.000 description 14
238000004458 analytical method Methods 0.000 description 12
239000003921 oil Substances 0.000 description 12
238000003756 stirring Methods 0.000 description 10
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
229960000583 acetic acid Drugs 0.000 description 9
125000003118 aryl group Chemical group 0.000 description 9
KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical class CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 description 8
XMKLTEGSALONPH-UHFFFAOYSA-N 1,2,4,5-tetrazinane-3,6-dione Chemical compound O=C1NNC(=O)NN1 XMKLTEGSALONPH-UHFFFAOYSA-N 0.000 description 7
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 7
150000005690 diesters Chemical class 0.000 description 7
238000001035 drying Methods 0.000 description 7
150000002148 esters Chemical class 0.000 description 7
229920006395 saturated elastomer Polymers 0.000 description 7
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
229910052799 carbon Inorganic materials 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
229960002179 ephedrine Drugs 0.000 description 6
125000000623 heterocyclic group Chemical group 0.000 description 6
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 5
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 5
239000013078 crystal Substances 0.000 description 5
125000004122 cyclic group Chemical group 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
229910052739 hydrogen Inorganic materials 0.000 description 5
239000000463 material Substances 0.000 description 5
239000012044 organic layer Substances 0.000 description 5
239000012071 phase Substances 0.000 description 5
238000000926 separation method Methods 0.000 description 5
102000002723 Atrial Natriuretic Factor Human genes 0.000 description 4
101800001288 Atrial natriuretic factor Proteins 0.000 description 4
101800001890 Atrial natriuretic peptide Proteins 0.000 description 4
KWGRBVOPPLSCSI-WPRPVWTQSA-N L-Ephedrine Natural products CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 4
238000005481 NMR spectroscopy Methods 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
239000008346 aqueous phase Substances 0.000 description 4
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 4
238000009903 catalytic hydrogenation reaction Methods 0.000 description 4
238000001914 filtration Methods 0.000 description 4
PEHSSTUGJUBZBI-UHFFFAOYSA-N indan-5-ol Chemical compound OC1=CC=C2CCCC2=C1 PEHSSTUGJUBZBI-UHFFFAOYSA-N 0.000 description 4
239000002904 solvent Substances 0.000 description 4
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
239000002253 acid Substances 0.000 description 3
230000004071 biological effect Effects 0.000 description 3
239000012230 colorless oil Substances 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
239000000284 extract Substances 0.000 description 3
238000001640 fractional crystallisation Methods 0.000 description 3
239000012362 glacial acetic acid Substances 0.000 description 3
DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 3
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
230000003389 potentiating effect Effects 0.000 description 3
235000019260 propionic acid Nutrition 0.000 description 3
229960003908 pseudoephedrine Drugs 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
239000011347 resin Substances 0.000 description 3
229920005989 resin Polymers 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
239000007787 solid Substances 0.000 description 3
PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
206010019280 Heart failures Diseases 0.000 description 2
206010020772 Hypertension Diseases 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
125000003545 alkoxy group Chemical group 0.000 description 2
125000000217 alkyl group Chemical group 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
125000004104 aryloxy group Chemical group 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
238000001816 cooling Methods 0.000 description 2
125000000753 cycloalkyl group Chemical group 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
208000035475 disorder Diseases 0.000 description 2
238000010828 elution Methods 0.000 description 2
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
230000012495 positive regulation of renal sodium excretion Effects 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
238000005406 washing Methods 0.000 description 2
239000011701 zinc Substances 0.000 description 2
229910052725 zinc Inorganic materials 0.000 description 2
JUCGVCVPNPBJIG-IUCAKERBSA-N (1s,2s)-2-amino-1-phenylpropane-1,3-diol Chemical compound OC[C@H](N)[C@@H](O)C1=CC=CC=C1 JUCGVCVPNPBJIG-IUCAKERBSA-N 0.000 description 1
125000006727 (C1-C6) alkenyl group Chemical group 0.000 description 1
125000006728 (C1-C6) alkynyl group Chemical group 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
PLMSUUQZBONVAA-JTQLQIEISA-N 1-[(2s)-2-carboxy-3-(2-methoxyethoxy)propyl]cyclopentane-1-carboxylic acid Chemical compound COCCOC[C@@H](C(O)=O)CC1(C(O)=O)CCCC1 PLMSUUQZBONVAA-JTQLQIEISA-N 0.000 description 1
HYBVWCCIEBYQJZ-UHFFFAOYSA-N 1-[2-(2-methoxyethoxymethyl)-3-[(2-methylpropan-2-yl)oxy]-3-oxopropyl]cyclopentane-1-carboxylic acid Chemical compound COCCOCC(C(=O)OC(C)(C)C)CC1(C(O)=O)CCCC1 HYBVWCCIEBYQJZ-UHFFFAOYSA-N 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
DRNGLYHKYPNTEA-UHFFFAOYSA-N 4-azaniumylcyclohexane-1-carboxylate Chemical compound NC1CCC(C(O)=O)CC1 DRNGLYHKYPNTEA-UHFFFAOYSA-N 0.000 description 1
125000001054 5 membered carbocyclic group Chemical group 0.000 description 1
125000004008 6 membered carbocyclic group Chemical group 0.000 description 1
125000001960 7 membered carbocyclic group Chemical group 0.000 description 1
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 1
206010002383 Angina Pectoris Diseases 0.000 description 1
208000024172 Cardiovascular disease Diseases 0.000 description 1
101150065749 Churc1 gene Proteins 0.000 description 1
206010012289 Dementia Diseases 0.000 description 1
206010012735 Diarrhoea Diseases 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
208000018522 Gastrointestinal disease Diseases 0.000 description 1
208000010412 Glaucoma Diseases 0.000 description 1
206010020590 Hypercalciuria Diseases 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
STVVMTBJNDTZBF-VIFPVBQESA-N L-phenylalaninol Chemical compound OC[C@@H](N)CC1=CC=CC=C1 STVVMTBJNDTZBF-VIFPVBQESA-N 0.000 description 1
208000027530 Meniere disease Diseases 0.000 description 1
241001529936 Murinae Species 0.000 description 1
125000003047 N-acetyl group Chemical group 0.000 description 1
208000008589 Obesity Diseases 0.000 description 1
206010030113 Oedema Diseases 0.000 description 1
208000002193 Pain Diseases 0.000 description 1
206010036618 Premenstrual syndrome Diseases 0.000 description 1
102100038239 Protein Churchill Human genes 0.000 description 1
208000001647 Renal Insufficiency Diseases 0.000 description 1
JVVXZOOGOGPDRZ-SLFFLAALSA-N [(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methanamine Chemical compound NC[C@]1(C)CCC[C@]2(C)C3=CC=C(C(C)C)C=C3CC[C@H]21 JVVXZOOGOGPDRZ-SLFFLAALSA-N 0.000 description 1
XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 description 1
WDJHALXBUFZDSR-UHFFFAOYSA-N acetoacetic acid Chemical compound CC(=O)CC(O)=O WDJHALXBUFZDSR-UHFFFAOYSA-N 0.000 description 1
238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
239000006286 aqueous extract Substances 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
238000011914 asymmetric synthesis Methods 0.000 description 1
239000003876 biosurfactant Substances 0.000 description 1
239000012267 brine Substances 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
238000006243 chemical reaction Methods 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentane carboxylic acid Natural products OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
230000007071 enzymatic hydrolysis Effects 0.000 description 1
238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
206010015037 epilepsy Diseases 0.000 description 1
239000012259 ether extract Substances 0.000 description 1
UPVSMFHQPMRMLP-UHFFFAOYSA-N ethyl 4-aminocyclohexane-1-carboxylate;hydrochloride Chemical compound Cl.CCOC(=O)C1CCC(N)CC1 UPVSMFHQPMRMLP-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
230000027119 gastric acid secretion Effects 0.000 description 1
239000008187 granular material Substances 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
125000005844 heterocyclyloxy group Chemical group 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
208000002551 irritable bowel syndrome Diseases 0.000 description 1
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical class CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
201000006370 kidney failure Diseases 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
235000020824 obesity Nutrition 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
239000000813 peptide hormone Substances 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
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235000012239 silicon dioxide Nutrition 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
230000000304 vasodilatating effect Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/40—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- 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
- A61P7/10—Antioedematous agents; Diuretics
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/16—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
- C07C233/17—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/18—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (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)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Diabetes (AREA)
Hematology (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Steroid Compounds (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Detergent Compositions (AREA)
Hydrogenated Pyridines (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Cosmetics (AREA)

DD89328675A 1988-05-19 1989-05-17 Verfahren zur herstellung von enantiomeren glutaramid-verbindungen, die diuretisch wirken DD283772A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB888811873A GB8811873D0 (en)	1988-05-19	1988-05-19	Therapeutic agents

Publications (1)

Publication Number	Publication Date
DD283772A5 true DD283772A5 (de)	1990-10-24

Family

ID=10637176

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD89328675A DD283772A5 (de)	1988-05-19	1989-05-17	Verfahren zur herstellung von enantiomeren glutaramid-verbindungen, die diuretisch wirken

Country Status (29)

Country	Link
EP (1)	EP0342850B1 (cs)
JP (1)	JPH072699B2 (cs)
KR (1)	KR920000561B1 (cs)
CN (1)	CN1015361B (cs)
AT (1)	ATE76399T1 (cs)
AU (1)	AU602813B2 (cs)
CA (1)	CA1331197C (cs)
CS (1)	CS274502B2 (cs)
DD (1)	DD283772A5 (cs)
DE (1)	DE68901582D1 (cs)
DK (1)	DK172032B1 (cs)
EG (1)	EG19007A (cs)
ES (1)	ES2037418T3 (cs)
FI (1)	FI93541C (cs)
GB (1)	GB8811873D0 (cs)
GR (1)	GR3004968T3 (cs)
HU (1)	HU205067B (cs)
IE (1)	IE60724B1 (cs)
IL (1)	IL90267A (cs)
MX (1)	MX16067A (cs)
MY (1)	MY104735A (cs)
NO (1)	NO173647C (cs)
NZ (1)	NZ229186A (cs)
PH (1)	PH26740A (cs)
PL (1)	PL154813B1 (cs)
PT (1)	PT90584B (cs)
SU (1)	SU1766251A3 (cs)
YU (1)	YU47973B (cs)
ZA (1)	ZA893696B (cs)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB8812597D0 (en) *	1988-05-27	1988-06-29	Pfizer Ltd	Therapeutic agents
GB8820844D0 (en) *	1988-09-05	1988-10-05	Pfizer Ltd	Therapeutic agents
GB9000725D0 (en) *	1990-01-12	1990-03-14	Pfizer Ltd	Therapeutic agents
DK0644176T3 (da) *	1993-09-22	1996-02-26	Pfizer Ltd	Hydrogenering
US7468390B2 (en)	2002-01-17	2008-12-23	Novartis Ag	Methods of treatment and pharmaceutical composition
AR057882A1 (es)	2005-11-09	2007-12-26	Novartis Ag	Compuestos de accion doble de bloqueadores del receptor de angiotensina e inhibidores de endopeptidasa neutra
US8993631B2 (en) *	2010-11-16	2015-03-31	Novartis Ag	Method of treating contrast-induced nephropathy
SI2887961T1 (sl)	2012-08-24	2021-08-31	Novartis Ag	Zaviralci NEP za zdravljenje bolezni, značilnih po atrialni širitvi ali preoblikovanju
WO2017033128A1 (en)	2015-08-25	2017-03-02	Novartis Ag	Biphenyl-substitued 4-amino-butyric acid derivatives and their use in the synthesis of nep inhibitors
WO2017072636A1 (en)	2015-10-29	2017-05-04	Cadila Healthcare Limited	Pharmaceutical synergistic combination

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
KR880007441A (ko) *	1986-12-11	1988-08-27	알렌 제이.스피겔	스피로-치환된 글루타르아미드 이뇨제

1988
- 1988-05-19 GB GB888811873A patent/GB8811873D0/en active Pending
1989
- 1989-05-09 DE DE8989304698T patent/DE68901582D1/de not_active Expired - Lifetime
- 1989-05-09 EP EP89304698A patent/EP0342850B1/en not_active Expired - Lifetime
- 1989-05-09 AT AT89304698T patent/ATE76399T1/de not_active IP Right Cessation
- 1989-05-09 ES ES198989304698T patent/ES2037418T3/es not_active Expired - Lifetime
- 1989-05-11 IL IL90267A patent/IL90267A/xx not_active IP Right Cessation
- 1989-05-16 MY MYPI89000654A patent/MY104735A/en unknown
- 1989-05-17 PL PL1989279491A patent/PL154813B1/pl unknown
- 1989-05-17 HU HU892460A patent/HU205067B/hu not_active IP Right Cessation
- 1989-05-17 SU SU4614002A patent/SU1766251A3/ru active
- 1989-05-17 CA CA000599911A patent/CA1331197C/en not_active Expired - Fee Related
- 1989-05-17 CS CS296589A patent/CS274502B2/cs not_active IP Right Cessation
- 1989-05-17 ZA ZA893696A patent/ZA893696B/xx unknown
- 1989-05-17 PT PT90584A patent/PT90584B/pt not_active IP Right Cessation
- 1989-05-17 DD DD89328675A patent/DD283772A5/de not_active IP Right Cessation
- 1989-05-17 MX MX1606789A patent/MX16067A/es unknown
- 1989-05-18 FI FI892386A patent/FI93541C/fi not_active IP Right Cessation
- 1989-05-18 AU AU34904/89A patent/AU602813B2/en not_active Ceased
- 1989-05-18 NZ NZ229186A patent/NZ229186A/xx unknown
- 1989-05-18 IE IE161389A patent/IE60724B1/en not_active IP Right Cessation
- 1989-05-18 JP JP1125479A patent/JPH072699B2/ja not_active Expired - Fee Related
- 1989-05-18 NO NO892002A patent/NO173647C/no not_active IP Right Cessation
- 1989-05-18 YU YU102289A patent/YU47973B/sh unknown
- 1989-05-18 DK DK240889A patent/DK172032B1/da not_active IP Right Cessation
- 1989-05-19 KR KR1019890006691A patent/KR920000561B1/ko not_active Expired
- 1989-05-19 CN CN89103437A patent/CN1015361B/zh not_active Expired
- 1989-05-21 EG EG25089A patent/EG19007A/xx active
- 1989-06-12 PH PH38643A patent/PH26740A/en unknown
1992
- 1992-06-18 GR GR920401302T patent/GR3004968T3/el unknown

Also Published As

Publication number	Publication date
CS296589A2 (en)	1990-09-12
CN1015361B (zh)	1992-02-05
DK172032B1 (da)	1997-09-22
EP0342850B1 (en)	1992-05-20
GR3004968T3 (cs)	1993-04-28
EP0342850A1 (en)	1989-11-23
NZ229186A (en)	1990-10-26
YU102289A (en)	1991-06-30
PL154813B1 (en)	1991-09-30
CS274502B2 (en)	1991-04-11
JPH0222256A (ja)	1990-01-25
AU602813B2 (en)	1990-10-25
KR900017993A (ko)	1990-12-20
HUT53596A (en)	1990-11-28
NO892002L (no)	1989-11-20
ZA893696B (en)	1990-12-28
NO892002D0 (no)	1989-05-18
NO173647B (no)	1993-10-04
IL90267A (en)	1993-08-18
JPH072699B2 (ja)	1995-01-18
NO173647C (no)	1994-01-12
MY104735A (en)	1994-05-31
AU3490489A (en)	1989-11-23
MX16067A (es)	1993-10-01
IL90267A0 (en)	1989-12-15
PT90584A (pt)	1989-11-30
FI892386A0 (fi)	1989-05-18
FI892386L (fi)	1989-11-20
SU1766251A3 (ru)	1992-09-30
IE891613L (en)	1989-11-19
EG19007A (en)	1994-11-30
PL279491A1 (en)	1989-11-27
PT90584B (pt)	1994-09-30
ATE76399T1 (de)	1992-06-15
GB8811873D0 (en)	1988-06-22
YU47973B (sh)	1996-08-13
CA1331197C (en)	1994-08-02
IE60724B1 (en)	1994-08-10
DE68901582D1 (de)	1992-06-25
KR920000561B1 (ko)	1992-01-16
DK240889D0 (da)	1989-05-18
FI93541B (fi)	1995-01-13
PH26740A (en)	1992-09-28
CN1037704A (zh)	1989-12-06
DK240889A (da)	1989-11-20
ES2037418T3 (es)	1993-06-16
HU205067B (en)	1992-03-30
FI93541C (fi)	1995-04-25

Legal Events

Date	Code	Title	Description
1995-08-31	ENJ	Ceased due to non-payment of renewal fee

Publication	Publication Date	Title
WO1995005358A1 (de)	1995-02-23	Verwendung von phenolen und phenolderivaten als arzneimittel mit fibrinogensenkender wirkung
EP0342850B1 (en)	1992-05-20	Enantiomeric glutaramide diuretic agents
DD283807A5 (de)	1990-10-24	Verfahren zur herstellung von cycloalkyl-substituierten glutaramid-derivaten
DE3811120A1 (de)	1989-10-12	Neopentylesterderivate, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel
DE68912811T2 (de)	1994-06-16	Amide von Cyclomethylen-1,2 bicarbonsäure mit therapeutischer Wirkung, Verfahren zu deren Herstellung sowie diese enthaltende pharmazeutische Zusammensetzungen.
DE2745222A1 (de)	1978-04-20	Alkanolaminderivate
DE68906572T2 (de)	1993-08-26	Peptide mit inhibitorischer wirkung auf enzymatische systeme, verfahren zu deren herstellung und diese enthaltende pharmazeutische zusammensetzungen.
CH653996A5 (de)	1986-01-31	Tryptaminderivate und verfahren zu deren herstellung.
DE3872100T2 (de)	1993-01-28	Verfahren zur herstellung von phenylaethanolaminotetralinen.
EP0385423B1 (de)	1995-02-08	Verfahren zur Herstellung der optischen Isomeren von 1,4-Dihydro-5-isopropoxy-2-methyl-4-(2-trifluormethylphenyl)-1,6-naphthyridin-3-carbonsäure-ethyl-ester und 1,4-Dihydro-5-isopropoxy-2-methyl-4-(2-trifluormethylphenyl)-1,6-naphthyridin-3-carbonsäure- 2-(N-methyl-N-phenylmethylamino)ethyl ester
CH619468A5 (cs)	1980-09-30
EP0511558B1 (de)	1996-10-23	Racemat-Spaltverfahren und diastereomere Assoziate
DE69303333T2 (de)	1996-11-21	Substituierte Benzoate-Derivate
DE3874166T2 (de)	1993-03-25	Verfahren zum herstellen und isolieren von estern der (r)-2-hydroxyphenylbuttersaeure.
DE3121189A1 (de)	1982-02-25	"n-substituierte mercaptoacylpropionamide"
EP0416583B1 (de)	1992-12-23	Verfahren zur Herstellung von Crotonobetainhydrochlorid
AT350517B (de)	1979-06-11	Verfahren zur herstellung von neuen alkylthio- cyclopentanderivaten
DE69423030T2 (de)	2000-09-28	Verfahren zu stereospezifistischer Herstellung von 1,3-Dioxan-4,6-dion Derivaten, Vorläufer von tetramischen Säuren Derivaten mit Chiralstelle
EP0154886A2 (de)	1985-09-18	Carboxyalkyldipeptidderivate, Verfahren zu deren Herstellung, diese enthaltende Mittel und deren Verwendung
DE4011171A1 (de)	1991-10-10	Herstellung von (alpha)-aminosaeure-2,2,2,-trifluorethylester
DE2604560A1 (de)	1977-08-11	Phenylalkancarbonsaeure-derivate und verfahren zu ihrer herstellung
DE1812979C (de)	1972-01-27	Aminomethylbicyclo oktan und nonan carbonsaure Verbindungen und Verfahren zu ihrer Herstellung
AT401931B (de)	1996-12-27	Verfahren zur herstellung von (s,s)-(n-(1- ethoxycarbonyl-3-oxo-3-phenylpropyl)-alanin)- (phenylmethyl)ester
DE3811256A1 (de)	1989-10-19	(alpha)-trifluormethylaminosaeure-derivate, verfahren zur herstellung von (alpha)-trifluormethylaminosaeure-derivaten und ihre verwendung als arzneimittel
DE3608083A1 (de)	1987-09-10	Verfahren zur herstellung von peptiden