Richter Gedeon Vegyeszeti Gyar Rt

The Administrators of the Tulane Educational Fund

Gyogyszerkutato Intezet Kft.

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Patentbureau Danubia

Sandor Bajusz

Eva Barabas

Daniel Bagdy

Andrew V Schally

Attila Juhasz

Erzsebet Szell Nee Hasenohrl

Imre Moravcsik

Jozsef Szekely

Gyula Horvath

Gabor Toth

Jozsef Lango

Andras Ronai

Andras Feher

Gabriella Szabo

Laszlo Graf

Zsuzsanna Mohai Nee Nagy

Laszlo Szporny

Lajos Kisfaludy

Istvan Schon

Istvan Polgari

Endre Csanyi

Jozsef Borsi

Erzsebet Mago Nee Karacsony

Tamas Szirtes

Miklos Low

Istvan Pallagi

Ildiko Kiraly

Andras Ronay

Kalman Medzihradszky

Tamas Janaky

Jozsef Gulyas

Emilia Lavich Nee Oszko

Gaborne Szeker

Laszlone Mohai

Janosne Lavich

Belane Veghelyi

Iren Veghelyi Nee Fauszt

Gyorgyne Szell

Klara Makk Nee Ocskay

Katalin Palne Aranyosi

Emilia Lavich

Anna Maria Szalkay Nee Hollosi

Rosa Beks

Zsuzsanna Taschler Nee Pasztor

Maria Sz Sarkozi

Klara Nemeth

Zsuzsanna Mohai

Andrae Turan

Agnes Szeker Nee Peszeky

Zsuzsa Mohai Nee Nagy

Erzsbet Szell Nee Hasenohrl

Iren Veghelyi

Eva Tomori Nee Jozst

Mariann Dioszegi

Zsuzsa Fittler

Ferencz Jozsa

Zsuzsanna Taschler

Eva Kaszas

(3R)-3-amino-4-carboxybutyraldehyde derivatives inhibiting the release of interleukin-1/beta

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. The compounds of this invention are represented by Formula I: X-R,-R,-R,-Ser-R,-R,(Q)-Leu-Arg-Pro-R,-NH,, wherein R,is pGlu or D-Nal(2), R,is His or D-Phe(4Cl), R,is Trp, D-Trp or D-Pal(3), R,is Tyr or Arg, R,is D-Lys or D-Orn, R,is Gly or D-Ala, X is hydrogen or a lower alkanoyl group of 2-5 carbon atoms, Q is a cytotoxic moiety having the formula &mdash;Q,or &mdash;A(Q,) or &mdash;B(Q,),or &mdash;B(AQ,),, wherein A is &mdash;NH&mdash;(CH,),&mdash;CO&mdash; or &mdash;OC&mdash;(CH,),&mdash;CO&mdash; where n is 2-6, B is &mdash;NH&mdash;CH,&mdash;(CH,),&mdash;CH(NH)&mdash;(CH,),&mdash;CO&mdash; where m is 0 or 1, n is 0 or 1, the &mdash;CO moiety of A&mdash; and of B&mdash; being bonded to an amino group on R,, and in the group B(AQ,),, the &mdash;CO moiety of A&mdash; and of B&mdash; being bonded to the episilon or delta amino group of R,when R,is Lys or Orn respectively, and in the group B(AQ,),, the &mdash;CO moiety of A being bonded to an amino group on B, Q,is D or L-Mel, cyclopropanealkanoyl, aziridine-2-carbonyl, epoxyalkyl or 1,4-naphthoquinone-5-oxy-carbonyl-ethyl, Q,is Q,, 2-anthraquinonyl-methylenoxy or doxorubicinyl, Q,is Q,, mitomicinyl, esperamycinyl or methotrexoyl, Q,is Q,or methotrexoyl and pharmaceutically acceptable salts thereof and methods of use pertaining these compounds.

Luteinizing hormone releasing hormone analogs with cytotoxic moiety

Anticoagulant peptide aldehyde derivatives

Anticoagulant peptide derivatives and pharmaceutical compositions

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:

LHRH analogues with cytotoxic moieties at the sixth position

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 formula

LHRH antagonists

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,

Synthetic GHRH analogs

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,

Peptide-aldehydes, process for the preparation thereof and

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.

T-Butyloxy-carbonyl-D-phenylalanyl-L-prolyl-L-arginine aldehyde

Analgesic compounds having the formula (I):

Pentapeptides and process for their preparation

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.

D-Phenylalanyl-L-prolyl-L-arginine aldehyde sulfate and process for the

Anti-coagulants of the formula X-Pro-Agm(HB) (.sub.n) wherein

Novel anticoagulant agmatine derivatives and process for the preparation

The invention relates to new enkephalin analogues of the general formula (I),

Enkephalin analogs and a process for the preparation thereof

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.

Novel peptidyl-arginine aldehyde derivatives and process for the

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Budapest, Hungary

Sandor Bajusz