PEPTIDE DERIVATIVES AND PROCESSES FOR THEIR PREPARATION

Peptide ester and amide derivatives of the general formula I: (I) in which X is H or an acyl, A and B are structurally defined amino acid residues, n is an integer of from 1 to 3, Rl is H or a lower alkyl and either R2 or C is a defined optionally modified amino acid residue and the other is a lower alkoxyl, an amino group or a direct chemical bond, are converted under physiologic conditions, by enzymic hydrolysis in pathologically altered tissues and subsequent spontaneous cyclization, into pharmacodynamically active spirocyclic peptide derivatives of the general formula III, (III) in which R3 and R4 are H atoms, optionally substituted alkyl groups or jointly an aliphatic chain forming preferably a 2,5-piperazinedione ring, and hence can act as pro-farmaca (drug precursors) of prolonged biological effect. A process for the production of these derivatives is also disclosed.

BIOLOGICALLY EFFECTIVE ONES TRICHLOROETHYLENE AND TETRAPEPTIDALKYLAMIDE, PROCEDURE FOR THEIR PRODUCTION AND THESE CONTAINING PHARMACEUTICAL PREPARATIONS.

CARBOXYALKANOYLPEPTID ALKYLAMIDE ONE.

AMIDES OF TRIPEPTIDES AND TETRAPEPTIDES

PEPTIDDERIVATE AND PROCEDURE FOR THEIR PRODUCTION.

Amides of tripeptides and tetrapeptides

This invention relates to biologically active tripeptide and tetrapeptide alkylamides of the general formula wherein R1 is an alkyl with 1 to 5 carbon atoms, A is a peptidically bound alanine or proline residue, B is a peptidically bound glycine, alanine or proline residue, n is an integer of 1 or 2, and R2 is an alkylcarbonylamino group with 2 to 12 carbon atoms, an alkenyl with 6 to 12 carbon atoms or a benzyloxycarbonylamino group. The compounds effectively inhibit the enzymatic activity of pancreatic and leucocytal elastase and are expected to find use in the treatment of acute pancreatitis, chronic obstructive pulmonary disease, pulmonary emphysema, and certain forms of arthritis. The invention also relates to processes for the preparation of the title compounds and to pharmaceutical compositions containing them.

BIOLOGICALLY ACTIVE TRIPEPTIDE AND TETRAPEPTIDE ALKYLAMIDES, PROCESSES FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME

The invention relates to novel biologically active tripeptide and tetrapeptide alkylamides of the general formula (I): (I) wherein R1 is an alkyl radical with 1 to 5 carbon atoms, A is a peptidically bound alanine or proline rest, B is a peptidically bound glycine, alanine or proline rest, n is an integer of 1 or 2 and R2 is an alkylcarbonylamino group with 2 to 12 carbon atoms, an alkenyl radical with 6 to 12 carbon atoms or a benzyloxycarbonylamino group. These compounds show a remarkable inhibitory activity towards the pancreatic and leucocytal elastase and are expected to find use in the treatment of acute pancreatitis, chronical obstructive pulmonary disease (pulmonary emphysema) and certain forms of arthrites. The invention also relates to processes for the preparation of the title compounds and to pharmaceutical compositions containing the same.

CONCENTRATES OF COAGULATION FACTORS II, VII, IX AND X, METHOD OF THEIR PREPARATION AND USE

Concentrates of coagulation factors II, VII, IX and X may be prepared by selective sorption on an equilibrated carrier based on hydroxyethylmethacrylate or hydroxyethylacrylate with bound diethylaminoethyl-groups followed by selective desorption. The concentrates of coagulation factors II and X can be used for the determination of coagulation factor VII and in a laboratory method for detection or determination of the extent of mammalian inflammatory diseases.

BIOLOGISCH WIRKSAME TRI- UND TETRAPEPTIDALKYLAMIDE, IHRE HERSTELLUNG UND PHARMAZEUTISCHE VERWENDUNG

ALKYLAMIDES OF CARBOXYALKANOYL PEPTIDES

ABSTRACT OF THE DISCLOSURE: The invention is related to alkylamides of carboxyalkanoyl peptides, novel compounds with notable inhibition of elastase, of general formula

ALKYLAMIDES OF CARBOXYALKANOYL PEPTIDES

Alkylamides of carboxyalkanoyl peptides

A method is described for the preparation of novel alkylamides of carboxyalkanoyl peptides of the formula wherein R is an aralky or an alkyl group of 1-5 carbon atoms, A is a residue of peptidically bound proline or alanine, B is a straight bond or a residue of peptidically bound proline or alanine and X is a CH=CH group or a methylene group of 1-3 carbon atoms. The described compounds are capable of inhibiting elastase.

CARBOXYALKANOYLPEPTID-ALKYLAMIDE, IHRE HERSTELLUNG UND PHARMAZEUTISCHE MITTEL

Peptidderivate und Verfahren zu deren Herstellung.

Peptidderivate und Verfahren zu deren Herstellung.

CONCENTRATE OF COAGULATION FACTOR II, VII, IX AND X AND REPARATION AND USE THEREOF

PURPOSE: To efficiently obtain the concentrate of coagulation factors II, VII, IX, and X used for medical care of blood coagulopathy, etc., by bringing a DEAE-hydroxyethyl methacrylate gel ion exchanger into contact with a biological substance contg. those coagulation factors and eluting them with a specific buffer soln. CONSTITUTION: A starting material comprising a biological substance contg. coagulation factors II, VII, IX, and X is brought into contact with and thereby is adsorbd by an adsorbent mainly comprising a diethylaminoethyl (DEAE) hydroxyethyl methacrylate polymer ion exchanger equilibrated with a buffer soln. having a pH of 7.2-7.6 and a 0.2 mol/l physiological saline. The adsorbent is then washed with a buffer soln. contg. a 0.2 mol/l physiological saline to remove ballast protein, and the adsorbed matters is desorbed with a buffer eluant contg. a 0.3-2.0 mol/d physiological saline having a pH of 7.2-7.6, thus giving the objective concentrate. COPYRIGHT: (C)1989,JPO ...

TRIPEPTIDE- AND TETRAPEPTIDE-ALKYLAMIDES WITH BIOLOGICAL ACTIVITY, USEFUL AS MEDICAMENTS AND METHODS FOR THEIR PREPARATION

TRIPEPTIDE- ET TETRAPEPTIDE-ALKYLAMIDES A ACTIVITE BIOLOGIQUE UTILES COMME MEDICAMENTS ET PROCEDES POUR LEUR PREPARATION; LES COMPOSES DE L'INVENTION REPONDENT A LA FORMULE GENERALE I : (CF DESSIN DANS BOPI) DANS LAQUELLE R EST UN ALKYLE AYANT 1 A 5 ATOMES DE CARBONE, A EST UN RESTE D'ALANINE OU DE PROLINE A LIAISON PEPTIDIQUE, B EST UN RESTE DE GLYCINE, D'ALANINE OU DE PROLINE A LIAISON PEPTIDIQUE, N EST 1 OU 2, ET R EST UN RADICAL ALKYLCARBONYL-AMINO AYANT 2 A 12 ATOMES DE CARBONE, UN RADICAL ALCENYLE AYANT DE 6 A 12 ATOMES DE CARBONE OU UN RADICAL BENZYLOXYCARBONYL-AMINO; DES PROCEDES POUR LA PREPARATION DE CES COMPOSES SONT EGALEMENT DECRITS; CES COMPOSES PRESENTENT UNE REMARQUABLE ACTIVITE D'INHIBITION DE L'ELASTASE PANCREATIQUE ET LEUCOCYTAIRE LES RENDANT UTILES DANS LE TRAITEMENT DE LA PANCREATITE AIGUE, DU SYNDROME RESPIRATOIRE OBSTRUCTIF CHRONIQUE (EMPHYSEME PULMONAIRE) ET DE CERTAINES FORMES D'ARTHRITES. BIOLOGICALLY ACTIVATED TRIPEPTIDE- AND TETRAPEPTIDE-ALKYLAMIDES USEFUL AS MEDICINAL PRODUCTS AND METHODS FOR THEIR PREPARATION; THE COMPOUNDS OF THE INVENTION MEET THE GENERAL FORMULA I: (CF DRAWING IN BOPI) IN WHICH R IS AN ALKYL HAVING 1 TO 5 CARBON ATOMS, A IS A REMAINDER OF ALANINE OR OF PROLINE A PEPTIDIC BOND, B IS A REMAINDER OF PEPTIDIC-LINKED GLYCINE, ALANINE OR PROLINE, N IS 1 OR 2, AND R IS AN ALKYLCARBONYL-AMINO RADICAL WITH 2 TO 12 CARBON ATOMS, AN ALKENYL RADICAL WITH 6 TO 12 CARBON ATOMS OR ONE RADICAL BENZYLOXYCARBONYL-AMINO; METHODS FOR THE PREPARATION OF THESE COMPOUNDS ARE ALSO DESCRIBED; THESE COMPOUNDS SHOW REMARKABLE PANCREATIC AND LEUCOCYTARY ELASTASE INHIBITION ACTIVITY, WHICH MAKES THEM USEFUL IN THE TREATMENT OF ACUTE PANCREATITIS, CHRONIC RESPIRATORY OBSTRUCTIVE SYNDROME (PULMONARY EMPHYSEMA) AND CERTAIN FORMS OF ARTHYSEMA.

TRIPEPTIDE- AND TETRAPEPTIDE-ALKYLAMIDES WITH BIOLOGICAL ACTIVITY, USEFUL AS MEDICAMENTS AND METHODS FOR THEIR PREPARATION

Alkylamides of carboxyalkanoyl peptides and method for preparation thereof

A method is described for the preparation of novel alkylamides of carboxyalkanoyl peptides of the formula ##STR1## wherein R is an aralky or an alkyl group of 1-5 carbon atoms, A is a residue of peptidically bound proline or alanine, B is a straight bond or a residue of peptidically bound proline or alanine and X is a CH═CH group or a methylene group of 1-3 carbon atoms. The described compounds are capable of inhibiting elastase.

Peptides with 1-amino-1-cycloalkane carboxylic acid

Peptide ester and amide derivatives of the general formula I <CHEM> in which X is H or acyl, a C2 to C5 alkanecarbonyl, a C3 to C6 carboxylalkanecarbonyl or a p-toluenesulfonyl, A is a glycine, alanine, leucine, phenylalanine, tyrosine, lysine or arginine residue, B is a glutamine, proline, arginine or lysine residue or a direct chemical bond, n is an integer of from 1 to3, R<1> is H or a C1 to C3 alkyl and R<2> is a C1 to C3 alkoxyl or an amino group when C is a peptidically bound glycine, alanine, leucine, phenylalanine, glutamine or serine residue or R<2> is a peptidically bound glycine, alanine, leucine, phenylalanine or serine methyl ester, ethyl ester or amide residue when C is a direct chemical bond, and pharmaceutically acceptable acid addition salts thereof are converted under physiological conditions, by enzymic hydrolysis in pathologically altered tissues and subsequent spontaneous cyclization, into pharmacodynamically active spirocyclic peptide derivatives of the general formula III, in which R<3> and R<4> are H atoms, optionally substituted alkyl groups of jointly an aliphatic chain forming preferably a 2,5-piperazinedione ring, and hence can act as pro-farmaca (drug precursors) of prolonged biological effect.

Peptide derivatives and processes for their preparation

Peptide ester and amide derivatives of the general formula I <CHEM> in which X is H or acyl, a C2 to C5 alkanecarbonyl, a C3 to C6 carboxylalkanecarbonyl or a p-toluenesulfonyl, A is a glycine, alanine, leucine, phenylalanine, tyrosine, lysine or arginine residue, B is a glutamine, proline, arginine or lysine residue or a direct chemical bond, n is an integer of from 1 to3, R<1> is H or a C1 to C3 alkyl and R<2> is a C1 to C3 alkoxyl or an amino group when C is a peptidically bound glycine, alanine, leucine, phenylalanine, glutamine or serine residue or R<2> is a peptidically bound glycine, alanine, leucine, phenylalanine or serine methyl ester, ethyl ester or amide residue when C is a direct chemical bond, and pharmaceutically acceptable acid addition salts thereof are converted under physiological conditions, by enzymic hydrolysis in pathologically altered tissues and subsequent spontaneous cyclization, into pharmacodynamically active spirocyclic peptide derivatives of the general formula III, in which R<3> and R<4> are H atoms, optionally substituted alkyl groups of jointly an aliphatic chain forming preferably a 2,5-piperazinedione ring, and hence can act as pro-farmaca (drug precursors) of prolonged biological effect.

CARBOXYALCANOYLPEPTIDE ALCOYLAMIDES

Alchilamidi di carbossialcanoilpeptidi.

Tripeptide e tetrapeptide alchilamidi biologicamente attive, processi per la loro preparazione e composizioni farmaceutiche che le contengono.

Způsob výroby 4, 4'-dimetoxybenzhydrylamidu prolinu

Vynález se týká způsobu výroby 4,4' -dimctoxybenzhydrylaminu prolinu ” zorce í ze 4 , 4 ' -dimetoxybenzbydry 1 - amidu benzyloxykarbonyIprol inu vzorce J. I katalytickou hydroqenolýzou s použitím paladia na uhlí v prostředí metanolu nebo etanolu, za zvýšené teploty. Na rozdíl od známého stavu techniky se při způsobu podle vynálezu používá koncentrovaného roztoku výchozí sloučeniny, a to v rozmezí 10 až 60 hmot., zejména 20 až 40 * hmot., za tlaku 0,1 až 10 MPa, s výhodou 0,2 až 1,5 MPa, při teplotě 20 až 60 °C. Způsob podln vynálezu je proti dosud známým postupům produktivnější a levnější. Titulní sloučenina je meziproduktem syntézy hormonu thyreoliberinu , léčiva používaného zejména při poruchách funkce št í tné žlázy.

Analogy hypothalamických hormonů

Process for preparing hydrochloride of 1-amino-1-cyclopentanecarboxylic acid methyl ester

Arginine peptides

Preparation for local therapy of cutaneous and mucosal lesions

Chromogenni substraty pro proteolyticke enzymy stepici v kysele oblasti ph

Způsob výroby hydrochloridu methylesteru kyseliny 1-amino-l-cyklopentankarboxylové

Způsob výroby hydrochloridu methylesteru kyseliny l-amino-l-cyklopentankarboxylové esterifikací kyseliny methanolem, nasyceným chlorovodíkem. Postup se vyznačuje tím, že při dvojím zahuštování reakční směsi se užívá přídavek toluenu, tím se výhodně odstraňuje voda z reakce a posouvá se rovnováha. Produkt, hydrochlorid methylesteru kyseliny 1-amino-l-cyklopentankarboxylové slouží jako meziprodukt syntézy léčiv.

Argininové peptidy

Řešení se týká argininových peptidů vzorce X-A-B-C- Arg - Arg - Y, kde značí: X atom vodíku, cv-karboxyalkanoyl s 3 až 5 atomy uhlíku nebo acyl s 2 až 5 atomy uhlíku, A zbytek glycinu, alaninu, leucinu nebo fenylalaninu, B totéž co A nebo jednoduchou vazbu, C zbytek alaninu, leucinu, prolinu nebo jednoduchou vazbu, Y fluorogenní zbytek 7-amino-4-methylkumarinu. Tyto sloučeniny jsou vysoce citlivé fluorogenní substráty pro proteolytické enzymy, které mohou být použitelné v klinické praxi, zejména k důkazu a/nebo stanovení kathepsinů řady B při diagnostice a/nebo therapii neoplasií.

Koncentrater af koagulationsfaktorer ii, vii, ix og x, fremgangsmaade til deres fremstilling og anvendelse deraf

CHrnmogenní substráty pro priitealytické enzymy štěpící v kyselé oblasti pH

Řešení se týká chromogenníčh substrátů pro proteolytické enzymy, které štěpí v kyselé oblasti pH. Jde o skupinu nových látek typu acylovaných tetrapeptidických derivátů p-nitroanilidu, použitelných při stanovení enzymové aktivity aspartátových proteináz.