AT394726B - Verfahren zur herstellung von l-alanyl-l-prolin-derivaten - Google Patents

Verfahren zur herstellung von l-alanyl-l-prolin-derivaten Download PDF

Info

Publication number: AT394726B
Authority: AT; Austria
Prior art keywords: alanyl; proline; phenylpropyl; formula; ethyl acetate
Prior art date: 1988-07-13

Application number

AT168189A

Other languages

German (de)

English (en)

Other versions

ATA168189A (de

Inventor

Marjo Dr Merslavic

Pavel Dr Zupet

Vesna Flego

Miha Dr Japelj

Branko Dr Stanovnik

Janja Cirnski

Original Assignee

Krka Tovarna Zdravil

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.)

1988-07-13

Filing date

1989-07-11

Publication date

1992-06-10

1989-07-11 Application filed by Krka Tovarna Zdravil filed Critical Krka Tovarna Zdravil

1991-11-15 Publication of ATA168189A publication Critical patent/ATA168189A/de

1992-06-10 Application granted granted Critical

1992-06-10 Publication of AT394726B publication Critical patent/AT394726B/de

Links

238000004519 manufacturing process Methods 0.000 title 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 30
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 18
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
-1 (S) -carboxy-3-phenylpropyl Chemical group 0.000 claims description 13
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
238000000034 method Methods 0.000 claims description 9
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
WPWUFUBLGADILS-WDSKDSINSA-N Ala-Pro Chemical class C[C@H](N)C(=O)N1CCC[C@H]1C(O)=O WPWUFUBLGADILS-WDSKDSINSA-N 0.000 claims description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
150000001875 compounds Chemical class 0.000 claims description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
229910052739 hydrogen Chemical group 0.000 claims description 5
239000001257 hydrogen Chemical group 0.000 claims description 5
238000002360 preparation method Methods 0.000 claims description 4
150000003839 salts Chemical class 0.000 claims description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
239000000047 product Substances 0.000 claims description 3
239000011780 sodium chloride Substances 0.000 claims description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
239000003495 polar organic solvent Substances 0.000 claims description 2
239000002244 precipitate Substances 0.000 claims description 2
229920006395 saturated elastomer Polymers 0.000 claims description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 2
230000007062 hydrolysis Effects 0.000 claims 2
238000006460 hydrolysis reaction Methods 0.000 claims 2
229910000041 hydrogen chloride Inorganic materials 0.000 claims 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims 1
239000002904 solvent Substances 0.000 claims 1
229960002429 proline Drugs 0.000 description 7
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
YXIWHUQXZSMYRE-UHFFFAOYSA-N 1,3-benzothiazole-2-thiol Chemical group C1=CC=C2SC(S)=NC2=C1 YXIWHUQXZSMYRE-UHFFFAOYSA-N 0.000 description 5
229960003767 alanine Drugs 0.000 description 4
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
101800000734 Angiotensin-1 Proteins 0.000 description 3
102400000344 Angiotensin-1 Human genes 0.000 description 3
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 3
239000007858 starting material Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
108010058865 angiotensinase Proteins 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
239000011976 maleic acid Substances 0.000 description 2
239000000725 suspension Substances 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
239000005051 trimethylchlorosilane Substances 0.000 description 2
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
ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
102000005862 Angiotensin II Human genes 0.000 description 1
101800000733 Angiotensin-2 Proteins 0.000 description 1
102000004881 Angiotensinogen Human genes 0.000 description 1
108090001067 Angiotensinogen Proteins 0.000 description 1
108010064733 Angiotensins Proteins 0.000 description 1
102000015427 Angiotensins Human genes 0.000 description 1
102000004506 Blood Proteins Human genes 0.000 description 1
108010017384 Blood Proteins Proteins 0.000 description 1
208000024172 Cardiovascular disease Diseases 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
150000008534 L-alanines Chemical class 0.000 description 1
229930182821 L-proline Natural products 0.000 description 1
125000000174 L-prolyl group Chemical class [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 1
108090000783 Renin Proteins 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
108010087924 alanylproline Proteins 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
229950006323 angiotensin ii Drugs 0.000 description 1
230000036772 blood pressure Effects 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
230000000694 effects Effects 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
STPXIOGYOLJXMZ-UHFFFAOYSA-N ethyl 2-oxo-4-phenylbutanoate Chemical compound CCOC(=O)C(=O)CCC1=CC=CC=C1 STPXIOGYOLJXMZ-UHFFFAOYSA-N 0.000 description 1
150000002431 hydrogen Chemical group 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
125000000896 monocarboxylic acid group Chemical group 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000000758 substrate Substances 0.000 description 1
150000007970 thio esters Chemical class 0.000 description 1

Landscapes

Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyrrole Compounds (AREA)

AT168189A 1988-07-13 1989-07-11 Verfahren zur herstellung von l-alanyl-l-prolin-derivaten AT394726B (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
YU135588A YU46919B (sh)	1988-07-13	1988-07-13	Postupak za dobijanje derivata l-alanil-l-prolina

Publications (2)

Publication Number	Publication Date
ATA168189A ATA168189A (de)	1991-11-15
AT394726B true AT394726B (de)	1992-06-10

Family

ID=25553829

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
AT168189A AT394726B (de)	1988-07-13	1989-07-11	Verfahren zur herstellung von l-alanyl-l-prolin-derivaten

Country Status (10)

Country	Link
JP (1)	JP2714447B2 (pl)
AT (1)	AT394726B (pl)
DD (1)	DD284028B5 (pl)
ES (1)	ES2015723A6 (pl)
NO (1)	NO172894C (pl)
PL (1)	PL154625B1 (pl)
SI (1)	SI8811355A (pl)
SU (1)	SU1757471A3 (pl)
UA (1)	UA18634A1 (pl)
YU (1)	YU46919B (pl)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2005010028A1 (en) *	2003-07-31	2005-02-03	Lupin Limited	Alpha-amino acid benzothiazolylthio ester as intermediates for manufacture of ace inhibitors and process for preparation thereof

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5847135A (en) *	1994-06-17	1998-12-08	Vertex Pharmaceuticals, Incorporated	Inhibitors of interleukin-1β converting enzyme
CN101484411A (zh) *	2006-06-27	2009-07-15	桑多斯股份公司	盐的新制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0099239A2 (en) *	1982-07-06	1984-01-25	E.R. Squibb & Sons, Inc.	Method for treating glaucoma
EP0215335A2 (en) *	1985-08-27	1987-03-25	Kanegafuchi Kagaku Kogyo Kabushiki Kaisha	Process for preparing N-/1(S)-ethoxycarbonyl-3-phenylpropyl/-L-alanyl-L-proline

1988
- 1988-07-13 SI SI8811355A patent/SI8811355A/sl unknown
- 1988-07-13 YU YU135588A patent/YU46919B/sh unknown
1989
- 1989-07-07 NO NO892813A patent/NO172894C/no unknown
- 1989-07-10 ES ES8902425A patent/ES2015723A6/es not_active Expired - Lifetime
- 1989-07-11 AT AT168189A patent/AT394726B/de not_active IP Right Cessation
- 1989-07-11 PL PL28052689A patent/PL154625B1/pl unknown
- 1989-07-11 DD DD33068889A patent/DD284028B5/de active IP Right Maintenance
- 1989-07-12 UA UA4614532A patent/UA18634A1/uk unknown
- 1989-07-12 SU SU894614532A patent/SU1757471A3/ru active
- 1989-07-13 JP JP1179211A patent/JP2714447B2/ja not_active Expired - Lifetime

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0099239A2 (en) *	1982-07-06	1984-01-25	E.R. Squibb & Sons, Inc.	Method for treating glaucoma
EP0215335A2 (en) *	1985-08-27	1987-03-25	Kanegafuchi Kagaku Kogyo Kabushiki Kaisha	Process for preparing N-/1(S)-ethoxycarbonyl-3-phenylpropyl/-L-alanyl-L-proline

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2005010028A1 (en) *	2003-07-31	2005-02-03	Lupin Limited	Alpha-amino acid benzothiazolylthio ester as intermediates for manufacture of ace inhibitors and process for preparation thereof

Also Published As

Publication number	Publication date
PL154625B1 (en)	1991-08-30
NO892813D0 (no)	1989-07-07
UA18634A1 (uk)	1997-12-25
SU1757471A3 (ru)	1992-08-23
JPH0272195A (ja)	1990-03-12
NO172894B (no)	1993-06-14
PL280526A1 (en)	1990-02-05
NO892813L (no)	1990-01-15
SI8811355A (en)	1995-04-30
NO172894C (no)	1993-09-22
JP2714447B2 (ja)	1998-02-16
ATA168189A (de)	1991-11-15
YU135588A (en)	1990-02-28
ES2015723A6 (es)	1990-09-01
DD284028B5 (de)	1996-08-08
YU46919B (sh)	1994-06-24

Legal Events

Date	Code	Title	Description
2003-07-15	ELJ	Ceased due to non-payment of the annual fee

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DE3687103T2 (de)	1993-03-25	Verfahren zur herstellung von n-(1(s)-ethoxycarbonyl-3-phenylpropyl)-l-alanyl-l-proline.
EP0517589A2 (fr)	1992-12-09	Dérivés de tachykinines, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent
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EP0203450B1 (de)	1992-04-01	Neue Derivate bicyclischer Aminosäuren, Verfahren zu ihrer Herstellung, diese enthaltende Mittel und deren Verwendung
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AT394726B - Verfahren zur herstellung von l-alanyl-l-prolin-derivaten - Google Patents

Info

Links

Landscapes

Applications Claiming Priority (1)

Publications (2)

Family

ID=25553829

Family Applications (1)

Country Status (10)

Cited By (1)

Families Citing this family (2)

Citations (2)

Patent Citations (2)

Cited By (1)

Also Published As

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