Abstract: The invention relates to disseminated intravascular coagulation. More particularly, the invention relates to medical intervention disseminated intravascular coagulation. The invention provides new peptides arginals, new and better compounds and methods for the treatment of DIC. The compounds and methods according to the invention have inhibitory action on clot-bound thrombin and factor Xa and are also inhibitory against plasmin and plasminogen activators.

Abstract: The invention relates to a new (3R)-3-amino-4-carboxybutyraldehyde derivatives of general formula(I) wherein X represents a C1-4 alkyloxycarbonyl, an optionally substituted phenyl-(C1-2 alkyloxy)-carbonyl, a C1-4 alkylcarbonyl or an optionally substituted phenyl-(C1-3 alkyl)-carbonyl group, n represents 1 or 0, Y represents, in the case when n=1, a tetrapeptide of general formula Y4-Y3-Y2-Y1, a tripeptide of general formula Y3-Y2-Y1 or a dipeptide of general formula Y2-Y1 or an amino acid residue of general formula Y1, or in the case when n=0, an &agr;-hydroxyacyl-tripeptide of general formula Q4-Y3-Y2-Y1, an &agr;-hydroxyacyl-dipeptide of general formula Q3-Y2-Y1 or an &agr;-hydroxyacyl-aminoacyl residue of general formula Q2-Y1; wherein Y1-Y4 represent a residue selected from the group of the following L- or D-amino acids: alanine, alloisoleucine, cyclohexyl-glycine, phenyl-alanine, glutamine, histidine, isoleucine, leucine, lysine, methionine, pipecolic acid, proline, tyrosi

Abstract: The invention relates to new peptidyl-arginine aldehyde compounds of formula (I) Q-D-Xaa-Pro-Arg-H  (I) wherein Q represents an acyl group of formula Q′—OCO, wherein Q′ represents an alkyl-group with 1-3 carbon atoms, D-Xaa represents a 3-cyclobutyl-D-alanyl- or 3-cyclopentyl-D-alanyl group, Pro represents an L-prolyl group, and Arg represents an L-arginyl group, and acid-addition salts thereof, and pharmaceutical compositions comprising them, which are suitable for the prevention and cure of thrombosis and accelerated blood clotting.

Abstract: The present invention deals with LHRH analogs which contain cytotoxic moieties, have influence on the release of gonadotropins from the pituitary in mammals (possess high agonistic or antagonistic activity) and have antineoplastic effect.

Abstract: This invention relates to peptide aldehyde derivatives of formula (I): D-Xaa-Pro-Arg-H, wherein Xaa represent a 2-cycloheptyl-2-hydroxyacetyl or 2-cyclopentyl-2-hydroxyacetyl group, Pro represents an L-prolyl residue and Arg represents an L-arginyl residue, their acid-additon salts formed with an organic or inorganic acid and pharmaceutical compositions containing the same. The compounds of formula (I) of the invention have therapeutic, particularly anticoagulant, antiplatelet and antithrombotic properties.

Abstract: This invention relates to new peptide derivatives of the general formula (I) A-Xaa-Arg-H, wherein A represents a D- or L-isochroman-1-carbonyl, D- or L-isochroman-3-carbonyl group, furthermore an acyl group of the general formula: D- or DL-A'--CH(OH)--CO, wherein A' represents a phenyl, benzyl, 1-naphthyl, 1-naphthylmethyl, 2-naphthyl, 2-naphthylmethyl, 9-fluorenyl, benzhydryl, cyclohexyl, cyclohexylmethyl, 2-pyridyl, 3-pyridyl or 4-pyridyl group, and Xaa represents an L-prolyl or an L-pipecolinic acid residue, and Arg stands for an L-arginine residue, their acid addition salts formed with an organic or inorganic acid and pharmaceutical compositions containing the same. Furthermore the invention relates to a process for preparing them. The compounds of the invention have valuable therapeutic, particularly anticoagulant, properties.

Abstract: The present invention deals with LHRH analogues which contain cytotoxic moieties and have influence on the release of gonadotropins from the pituitary gland of mammals, including humans. The compounds of this invention are represented by the formula:X--R.sup.1 --R.sup.2 --R.sup.3 -Ser-R.sup.5 --R.sup.6 (Q)-Leu-Arg-Pro-R.sup.10 --NH.sub.2whereinR.sup.1 is pGlu, Pro, D-Nal(2), or D-Phe(4Cl),R.sup.2 is His or D-Phe(4Cl),R.sup.3 is Trp, D-Trp or D-Pal(3),R.sup.5 is Tyr or Arg,R.sup.6 is D-Phe or R*.sup.6, where R*.sup.6 is D-Orn, D-Lys or D-Phe(NH.sub.2),R.sup.10 is Gly or D-Ala,X is hydrogen, a lower alkanoyl group of 2-5 carbon atoms or carbamyl,Q is bis-(2-chloroethyl)amino group provided that R.sup.6 is D-Phe,where R.sup.6 is R*.sup.6,Q is a complexed metal-containing acyl group having the formula: ##STR1## wherein Q' is Pt(Y).sub.

Abstract: The present invention deals with LHRH antagonists which possess improved water solubility and while having the high antagonist potency of the basic peptides, are free of the edematogenic effects. These compounds are highly potent in inhibiting the release of gonadotropins from the pituitary gland in mammals, including humans.The compounds of this invention are represented by the formulaX--R.sup.1 --R.sup.2 --R.sup.3 --Ser--Tyr--R.sup.6 --Leu--Arg--Pro--R.sup.10 --NH.sub.2whereinX is an acyl group derived from straight or branched chain aliphatic or alicyclic carboxylic acids having from 1 to 7 carbon atoms, or H.sub.2 N--CO,R.sup.1 is D-- or L--Pro, D-- or L--.DELTA..sup.3 --Pro, D--Phe, D--Phe(4--H1), D--Ser, D--Thr, D--Ala, D--Nal(1) or D--Nal (2),R.sup.2 is D--Phe or D--Phe(4--C1)R.sup.3 is D--Trp, D--Phe, D--Pal(3), D--Nal(1) or D--Nal(2),R.sup.6 is D--Cit, D--Hci, D--Cit(Q) or D--Hci(Q) andR.sup.

Abstract: Human pancreatic GRF (hpGRF), rat hypothalamic GRF (rGRF) and porcine hypothalamic GRF (pGRF) have been earlier characterized and synthesized. The invention provides synthetic peptides which are extremely potent in stimulating the release of pituitary GH in animals, including humans, which have resistance to enzymatic degradation in the body, and which have the sequence: ##STR1## wherein Q.sup.1 is an omega or alpha-omega substituted alkyl,Q.sup.2 is a lower omega-quanidino-alkyl group.R.sub.2 is Ala, D-Ala, or D-N-Methyl-AlaR.sub.3 is Asp, D-Asp, Glu, or D-GluR.sub.8 is Asn, D-Asn, Ser, or D-SerR.sub.10 is Tyr or D-TyrR.sub.12 is Lys, D-Lys Arg or OrnR.sub.13 is Val or IleR.sub.14 is Leu or D-LeuR.sub.15 is Gly, N-Methyl-Gly, or D-AlaR.sub.17 is Leu or D-LeuR.sub.18 is Tyr or SerR.sub.23 is Leu or D-LeuR.sub.24 is Gln or HisR.sub.25 is Asp, D-Asp, Glu, or D-GluR.sub.27 is Met, D-Met, Ala, Nle, Ile, Val, Nva, LeuR.sub.

Abstract: The present invention deals with LHRH antagonists which possess improved water solubility and while having the high antagonist potency of the basic peptides, are free of the edematogenic effects. These compounds are highly potent in inhibiting the release of gonadotropins from the pituitary gland in mammals, including humans.The compounds of this invention are represented by the formulaX-R.sup.1 -R.sup.2 -R.sup.3 -Ser-Tyr-R.sup.6 -Leu-Arg-Pro-R.sup.10 -NH.sub.2whereinX is an acyl group derived from straight or branched chain aliphatic or alicyclic carboxylic acids having from 1 to 7 carbon atoms,R.sup.1 is D- or L-Pro, D- or L- .DELTA. .sup.3 -Pro, D-Phe, D-Phe(4-H1), D-Ser, D-Thr, D-Ala, D-Nal (1) or D-Nal (2),R.sup.2 is D-Phe or D-Phe(4-H1)R.sup.3 is D-Trp, D-Phe, D-Pal, D-Nal(1) or D-Nal (2),R.sup.6 is D-Cit, D-Hci, D-Cit(Q) or D-Hci(Q) andR.sup.

Abstract: The invention relates to new peptide-aldehydes and a process for the preparation thereof, furthermore to pharmaceutical compositions containing the same.According to a feature of the present invention there are provided new peptide-aldehyde derivatives corresponding to the general formula (I) ##STR1## wherein R.sub.1 represents hydrogen or C.sub.1-6 alkyl group,R.sub.2 stands for C.sub.1-6 alkyl group, furthermore R.sub.1 and R.sub.2 are linked to the amino group of the Xxx alpha-amino acid,Xxx represents a D-phenylalanine residue or a D-alpha-amino acid group having in the side chain a C.sub.1-4 alkyl group,Pro stands for L-proline residue,Yyy stands for L-, D- or DL-arginine residue andA represents an acid residue.The new peptide-aldehyde derivatives of the invention possess valuable anticoagulant activity.

Abstract: The invention relates to t-butyloxy-carbonyl-D-phenylalanyl-L-prolyl-L-arginine aldehyde hemisulfate and D-phenylalanyl-L-prolyl-L-arginine aldehyde sulfate, which is highly stable in aqueous solution, and to a process for preparing D-phenylalanyl-L-prolyl-L-arginine aldehyde sulfate from D-phenylalanyl-L-prolyl-L-arginine aldehyde hemisulfate or N.sup.G -carboxy derivative containing an acid-sensitive protecting group at its amino terminal, wherein the acid sensitive amino terminal protecting group or optionally the N.sup.G -carboxy group is removed with 1 to 12 N sulfuric acid, applied in 1 to 12 equivalent amounts and the resulting free tripeptide aldehyde sulfate isolated. The D-phenylalanyl-L-prolyl-L-arginine aldehyde sulfate of the invention possesses valuable anti-coagulant activity.

Abstract: Analgesic compounds having the formula (I):Tyr-A-Gly-Phe-B-X-YwhereinA is a D-aminoacid group having a lower alkyl group or a lower thioalkyl group as a side chain,B is an aminoacid or a cyclic iminoacid group, either of which has a lower alkyl group as a side chain,X is an oxygen atom or an NH group, andY is a hydrogen atom or a lower alkyl group,or a pharmaceutically effective amide, ester or salt thereof.

Abstract: The invention relates to D-phenylalanyl-L-prolyl-L-arginine aldehyde sulfate, highly stable in aqueous solution, and to a process for preparing it from D-phenylalanyl-L-prolyl-L-arginine aldehyde hemisulfate or N.sup.G -carboxy derivative containing an acid-sensitive protecting group at its amino terminal, wherein the acid sensitive amino terminal protecting group or optionally the N.sup.G -carboxy group is removed with 1 to 12 N sulfuric acid, applied in 1 to 12 equivalent amounts and the resulting free tripeptide aldehyde sulfate is isolated. The D-phenylalanyl-L-prolyl-L-arginine aldehyde sulfate of the invention possesses valuable anticoagulant activity.

Abstract: Anti-coagulants of the formula X-Pro-Agm(HB) (.sub.n) whereinX is an alpha-amino acid moiety of the configuration having a phenyl, phenyl-(lower)-alkyl or phenyl-(heteroatom-containing) lower alkyl side chain,Agm is an agmatine group (1-amino-4-guanidino-butane),B is an acid residue, andn is an integer from 0-2, are disclosed.

Abstract: The invention relates to new enkephalin analogues of the general formula (I),Tyr-X-Gly-Phe-Y (I)whereinTyr, Gly and Phe represent L-tyrosyl, glycyl and L-phenylalanyl residue, respectively,X is glycyl residue or a D-.alpha.-aminocarboxylic acid residue with a lower alkyl, lower thioalkyl or phenyl-(lower)-alkyl side chain, andY is the residue of an L, D or DL-.alpha.-aminophosphonic acid or L, D or DL-.alpha.-aminosulfonic acid, each having a lower alkyl side chain,and salts thereof. These compounds are prepared according to the invention so that an L-, D- or DL-.alpha.-aminophosphonic acid or an L-, D- or DL-.alpha.-aminosulfonic acid, each bearing a lower alkyl side chain, is coupled in the proper order, as defined by formula (I), with the amino acids and/or peptide fragments each having a removable protecting group on the terminal amino group, the protecting group is split off from the terminal amino group, and the free peptide is isolated as such or in the form of its salt.

Abstract: Novel peptidyl-arginine aldehyde derivatives and their salts of formula I, ##STR1## wherein X represents a hydrogen atom, benzoyl or tert-butyloxycarbonyl group, and Y is a D-phenylalanine, .beta.-phenyl-D-lactic acid or D-allo-isoleucine moiety, are prepared from peptidyl-arginine aldehydes protected by an urethane type protecting group on their N- or O-terminal and/or a guanidino group, by removing the protecting group in a mixture of lower alkanols and water by means of hydrogenolysis, and eventually converting the product formed into a salt.The compounds of formula I possess valuable antithrombin activity.

Abstract: The invention relates to novel enkephalin analoge of the general formula IH.sub.2 N-C(NH)-Tyr-A-Gly-Phe-B (I)whereinTyr, Gly and Phe stand for an L-tyrosine, glycine and L-phenylalanine residue, resp.A stands for a D-amino acid residue having a lower alkyl group or a lower thioalkyl group as side chain, andB stands for an amino group or an L-proline amide moiety,and their pharmaceutically acceptable salts. These compounds can be prepared from peptides containing terminal amino group corresponding in amino acid sequence by transforming the terminal amino group to guanidino group in a known way and, if desired, by forming a salt with a pharmaceutically acceptable acid.The novel compounds of the general formula I possess valuable morphine-like (enkephalin-like) opiate activities.

Abstract: The invention relates to a novel compound of the formula ##STR1## and the pharmaceuticlly acceptable acid addition salts thereof, wherein R stands for a hydrogen atom or methyl group, x y designates a ##STR2## Q is a hydrogen atom or a benzyloxycarbonyl- or N-tert.-butyloxycarbonyl protective group, and R.sub.1 is the side chain of a natural .alpha.-amino acid selected from the group consisting of Arg--, Tryp-13 , Phe--, Ser--, Leu--, Val--, Meth--, Tyr--, His-- or Prol---side-chain.The compounds according to the invention possess antiserotonin and hypotensive effects and act upon the central nervous system.

Abstract: The invention relates to the preparation of biologically active polypeptides containing the aspartyl group, particularly an aspartyl-glycine moiety, using the active-ester technique.According to the method of the invention, human adrenocorticotropic hormone and its fragments characteristic to the individual species, as well as the blocked derivatives of such compounds are prepared by the pentafluorophenol method, i.e., the carboxy group of the acylating component is activated by converting it into pentafluorophenyl ester in the coupling reaction carried out with blocked peptides containing the aspartyl group or an aspartylglycine moiety. The acylation is carried out preferably using equimolar quantities of the respective reactants. The free peptides obtained after removing the blocking groups can be converted into their acid addition salts or pharmaceutically acceptable complexes or condensates.Human adrenocorticotropic hormone and its derivatives are valuable substances of therapeutical activity.