NO166328B - PROCEDURE FOR THE PREPARATION OF CARBOXYLAL CHOYDIPE Peptides. - Google Patents
PROCEDURE FOR THE PREPARATION OF CARBOXYLAL CHOYDIPE Peptides. Download PDFInfo
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- NO166328B NO166328B NO893332A NO893332A NO166328B NO 166328 B NO166328 B NO 166328B NO 893332 A NO893332 A NO 893332A NO 893332 A NO893332 A NO 893332A NO 166328 B NO166328 B NO 166328B
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- lower alkyl
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- ester
- peptides
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- 238000000034 method Methods 0.000 title claims description 9
- 108090000765 processed proteins & peptides Proteins 0.000 title claims 2
- 102000004196 processed proteins & peptides Human genes 0.000 title claims 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- 108010016626 Dipeptides Proteins 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 150000001875 compounds Chemical class 0.000 claims description 11
- 150000002148 esters Chemical class 0.000 claims description 11
- 125000003118 aryl group Chemical group 0.000 claims description 6
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 235000004279 alanine Nutrition 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 4
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 4
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 4
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 4
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 4
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 4
- 239000004472 Lysine Substances 0.000 claims description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 4
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 4
- 229960000310 isoleucine Drugs 0.000 claims description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 4
- 239000011976 maleic acid Substances 0.000 claims description 4
- 150000002688 maleic acid derivatives Chemical class 0.000 claims description 4
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 4
- 239000004474 valine Substances 0.000 claims description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 3
- 125000004442 acylamino group Chemical group 0.000 claims description 3
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 claims description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 235000010290 biphenyl Nutrition 0.000 claims description 3
- 239000004305 biphenyl Substances 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 125000004181 carboxyalkyl group Chemical group 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- -1 3,3-diphenylpropyl Chemical group 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229960002429 proline Drugs 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 125000005236 alkanoylamino group Chemical group 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 125000005239 aroylamino group Chemical group 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- ZEDXTTHVOCBPLU-JZKFLRDJSA-N benzyl (2s)-1-[(2s)-2-aminopropanoyl]pyrrolidine-2-carboxylate;hydrochloride Chemical compound Cl.C[C@H](N)C(=O)N1CCC[C@H]1C(=O)OCC1=CC=CC=C1 ZEDXTTHVOCBPLU-JZKFLRDJSA-N 0.000 description 1
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000004475 heteroaralkyl group Chemical group 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
Fremstilling og farmasøytisk bruk av nye carboxyalkyldipeptider såvel som derivater og analoger derav, er blitt beskrevet i Europa-patentsøknad 12 401. Forbindelsene beskrevet i angitte Europa-patentsøknad er anvendbare som omdannende enzyminhibitorer og som antihypertensive midler. The production and pharmaceutical use of new carboxyalkyl dipeptides, as well as derivatives and analogues thereof, has been described in European patent application 12 401. The compounds described in said European patent application are useful as converting enzyme inhibitors and as antihypertensive agents.
Foreliggende oppfinnelse angår en fremgangsmåte for fremstilling av carboxyalkyldipeptider av den type som er beskrevet i den ovenfor angitte Europa-patentsøknad. Fremgangsmåten ifølge oppfinnelsen er således rettet mot fremstilling av carboxyalkyldipeptider av formel: The present invention relates to a method for the production of carboxyalkyl dipeptides of the type described in the above-mentioned European patent application. The method according to the invention is thus aimed at producing carboxyalkyl dipeptides of the formula:
hvori R er aryl, som eventuelt er substituert med lavere alkyl, lavere alkoxy, halogen, en heterocyklisk gruppe som eventuelt er substituert med halogen, dihalogen, lavere alkyl, hydroxy, lavere alkoxy, acylamino, halogen-lavere alkyl; hvori aryl betyr fenyl, nafthyl eller bifenyl, og den heterocykliske gruppe betyr indolyl, thienyl, imidazolyl, furyl, benzimidazolyl, pyridyl, kinolinyl, isokinolinyl og benzothienyl, R1 er lavere alkyl med 1 til 4 carbonatomer; -NH-X- er alanin? glycin; isoleucin; leucin; lysin; fenylalanin; valin; wherein R is aryl optionally substituted with lower alkyl, lower alkoxy, halogen, a heterocyclic group optionally substituted with halogen, dihalogen, lower alkyl, hydroxy, lower alkoxy, acylamino, halo-lower alkyl; wherein aryl means phenyl, naphthyl or biphenyl, and the heterocyclic group means indolyl, thienyl, imidazolyl, furyl, benzimidazolyl, pyridyl, quinolinyl, isoquinolinyl and benzothienyl, R 1 is lower alkyl of 1 to 4 carbon atoms; -NH-X- is alanine? glycine; isoleucine; leucine; lysine; phenylalanine; valine;
Y er alanin; glycin; isoleucin; leucin; lysin; fenylalanin; prolin; valin; og Y is alanine; glycine; isoleucine; leucine; lysine; phenylalanine; proline; valine; and
farmasøytisk akseptable salter derav; pharmaceutically acceptable salts thereof;
Foretrukne er forbindelser av formel I: Preferred are compounds of formula I:
R er aryl, som eventuelt er substituert med lavere alkyl, lavere alkoxy, halogen; R is aryl, which is optionally substituted with lower alkyl, lower alkoxy, halogen;
R^, -NH-X- og Y er som ovenfor definert. R 1 , -NH-X- and Y are defined as above.
Mere foretrukne forbindelser av formel I er slike hvori: R er fenyl; More preferred compounds of formula I are those wherein: R is phenyl;
R^ er ethyl; og R 1 is ethyl; and
-NH-X og Y er som ovenfor definert. -NH-X and Y are defined as above.
De mest foretrukne er forbindelser av formel I hvori: R er fenyl; Most preferred are compounds of formula I wherein: R is phenyl;
R^ er ethyl; R 1 is ethyl;
-NH-X er alanin; og -NH-X is alanine; and
Y er prolin. Y is proline.
De foretrukne forbindelser av formel I innbefatter også farmasøytisk akseptable salter derav. The preferred compounds of formula I also include pharmaceutically acceptable salts thereof.
Lavere alkylgruppene innbefatter rettkjedede, for-grenede og umettede hydrocarbonradikaler med 1-6 carbonatomer slik som methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, hexyl. Aralkyl- og heteroaralkylgruppene har fra 1 til 6 carbonatomer i alkyl-delen og innbefatter benzyl, fenethyl, 3,3-difenylpropyl, 3-indolylmethyl. Halogen betegner klor, brom, jod eller fluor. Hvor aryl fremkommer i radikalene, betegner dette fenyl, nafthyl eller bifenyl. Heteroaryl innbefatter indolyl, thienyl, imidazolyl, furyl, benzimidazolyl, pyridyl, kinolinyl, isokinolinyl og benzothienyl. Acylamino angir lavere alkanoylamino og aroylaminogrupper som acetylamino og benzyl-amino. The lower alkyl groups include straight-chain, branched and unsaturated hydrocarbon radicals with 1-6 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, hexyl. The aralkyl and heteroaralkyl groups have from 1 to 6 carbon atoms in the alkyl part and include benzyl, phenethyl, 3,3-diphenylpropyl, 3-indolylmethyl. Halogen denotes chlorine, bromine, iodine or fluorine. Where aryl appears in the radicals, this denotes phenyl, naphthyl or biphenyl. Heteroaryl includes indolyl, thienyl, imidazolyl, furyl, benzimidazolyl, pyridyl, quinolinyl, isoquinolinyl and benzothienyl. Acylamino denotes lower alkanoylamino and aroylamino groups such as acetylamino and benzylamino.
Fremgangsmåten ifølge foreliggende oppfinnelse er kjennetegnet ved at en forbindelse av formel The method according to the present invention is characterized in that a compound of formula
omsettes med et dipeptidbenzylester-hydroklorid under dannelse av en beskyttet dipeptidester; angitte ester under-kastes katalytisk hydrogenering, hvorpå den dannede dipeptidester behandles med acetonnitril og maleinsyre under dannelse av forbindelser av formel I som S,S,S-stereoisomere maleatsalter. is reacted with a dipeptide benzyl ester hydrochloride to form a protected dipeptide ester; specified ester is subjected to catalytic hydrogenation, after which the formed dipeptide ester is treated with acetonitrile and maleic acid to form compounds of formula I as S,S,S-stereoisomeric maleate salts.
Fremgangsmåten ifølge oppfinnelsen illustreres i det etterfølgende reaksjonsskjerna hvori de foretrukne reaktanter er angitt for lettere å illustrere fremgangsmåten ifølge oppfinnelsen . The method according to the invention is illustrated in the subsequent reaction core in which the preferred reactants are indicated to more easily illustrate the method according to the invention.
Som vist i reaksjonsskjemaet omsettes ethyl- fb -benzoyl-acrylat II (fremstilt ved methoden ifølge W. Koga, Nippon Kagaku Zasshi, 7_6. 1053-6 (1955 ) ) med L-alanin-L-prolin-benzylester-hydroklorid HI i nærvær av ethanol og natriumbicarbonat under dannelse av beskyttet dipeptidester IV . Denne dipeptidester IV behandles deretter med ethanol og Raney-Nickel-katalysator (R.H. Mitchell, et. al, Tetrahedron Lett., 2A, 2637 (1980)) under dannelse av dipeptidester V. Behandling av V med maleinsyre tilveiebringer I som S,S,S-stereoisomermaleatsaltet. As shown in the reaction scheme, ethyl-fb-benzoyl-acrylate II (prepared by the method according to W. Koga, Nippon Kagaku Zasshi, 7_6. 1053-6 (1955) ) is reacted with L-alanine-L-proline-benzyl ester hydrochloride HI in the presence of ethanol and sodium bicarbonate to form protected dipeptide ester IV. This dipeptide ester IV is then treated with ethanol and Raney-Nickel catalyst (R.H. Mitchell, et. al, Tetrahedron Lett., 2A, 2637 (1980)) to form dipeptide ester V. Treatment of V with maleic acid affords I as S,S, The S-stereoisomer maleate salt.
Fremgangsmåten ifølge oppfinnelsen tilveiebringer således en enkel, effektiv og økonomisk måte for å syntetisere forbindelser av formel I ettersom utgangsmaterialene og hovedreaktantene enten lett kan fremstilles eller er kommer-sielt tilgjengelige. I en foretrukken utførelsesform kan diesteren IV fremstilles for lagring og transport og kan deretter omdannes til enten monoestersaltet eller en forbindelse av formel I. The process according to the invention thus provides a simple, efficient and economical way to synthesize compounds of formula I as the starting materials and the main reactants can either be easily prepared or are commercially available. In a preferred embodiment, the diester IV can be prepared for storage and transport and can then be converted to either the monoester salt or a compound of formula I.
Oppfinnelsen illustreres nærmere i det etterfølgende eksempel. The invention is illustrated in more detail in the following example.
Eksempel Example
N-( l- carboethoxy- 3- fenylpropyl)- L- alanyl- L- prolin 3,12 g (10 mmol) L-alanyl-L-prolin-benzylester-hydroklorid kombineres med 2,04 g (10 mmol) ethyl-j2>-benzoyl-acrylat, 0,84 g (10 mmol) natriumbicarbonat og 20 ml absolutt ethanol, og blandingen omrøres deretter ved romtemperatur i 24 timer. Blandingen filtreres deretter, hvorpå 2 ml vann og W-7 Raney-nikkel-katalysator (R.H. Mitchell, et at., Tetrahedron Lett., 21, 2637 (1980)) tilsettes, og blandingen hydrogeneres ved 21,09 kg/cm 2 i 24 timer. Etter filtrering for å fjerne katalysatoren og konsentrering til tørrhet taes residuet opp i acetonitril og filtreres. Til filtratet tilsettes en acetonitrilløsning inneholdende en halvmolarekviva-lent av maleinsyre, og etter omrøring i 1 time oppsamles det faste materiale, skylles med acetonitril og tørkes under N-(l-carboethoxy-3-phenylpropyl)-L-alanyl-L-proline 3.12 g (10 mmol) L-alanyl-L-proline benzyl ester hydrochloride is combined with 2.04 g (10 mmol) ethyl- β-benzoyl acrylate, 0.84 g (10 mmol) of sodium bicarbonate and 20 ml of absolute ethanol, and the mixture is then stirred at room temperature for 24 hours. The mixture is then filtered, whereupon 2 ml of water and W-7 Raney nickel catalyst (R.H. Mitchell, et al., Tetrahedron Lett., 21, 2637 (1980)) are added, and the mixture is hydrogenated at 21.09 kg/cm 2 in 24 hours. After filtration to remove the catalyst and concentration to dryness, the residue is taken up in acetonitrile and filtered. An acetonitrile solution containing a half-molar equivalent of maleic acid is added to the filtrate, and after stirring for 1 hour the solid material is collected, rinsed with acetonitrile and dried under
dannelse av maleatsaltet. formation of the maleate salt.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO893332A NO166328C (en) | 1982-06-07 | 1989-08-18 | PROCEDURE FOR THE PREPARATION OF CARBOXYLAL CHOYDIPE Peptides. |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38574582A | 1982-06-07 | 1982-06-07 | |
| US06/462,727 US4442030A (en) | 1982-06-07 | 1983-01-31 | Process for preparing carboxyalkyl dipeptides |
| NO832036A NO166231C (en) | 1982-06-07 | 1983-06-06 | PROCEDURE FOR THE PREPARATION OF CARBOXYAL COOLEDIPE Peptides. |
| NO893332A NO166328C (en) | 1982-06-07 | 1989-08-18 | PROCEDURE FOR THE PREPARATION OF CARBOXYLAL CHOYDIPE Peptides. |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| NO893332L NO893332L (en) | 1983-12-08 |
| NO893332D0 NO893332D0 (en) | 1989-08-18 |
| NO166328B true NO166328B (en) | 1991-03-25 |
| NO166328C NO166328C (en) | 1991-07-03 |
Family
ID=27484081
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO893332A NO166328C (en) | 1982-06-07 | 1989-08-18 | PROCEDURE FOR THE PREPARATION OF CARBOXYLAL CHOYDIPE Peptides. |
Country Status (1)
| Country | Link |
|---|---|
| NO (1) | NO166328C (en) |
-
1989
- 1989-08-18 NO NO893332A patent/NO166328C/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| NO893332L (en) | 1983-12-08 |
| NO166328C (en) | 1991-07-03 |
| NO893332D0 (en) | 1989-08-18 |
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