Technische Universitat Munchen

Merck Patent Gesellschaft MIT Beschrankter Haftung

Wilex Ag

Merck Patent Gesellschaft MIT

Merck Patent Gmbh

The University of Arizona

Biotronik Ag

Biomet Deutschland Gmbh

Hoechst Aktiengesellschaft

The Brigham and Women's Hospital, Inc.

Roche Diagnostics Gmbh

Merck Patent Gesellschaft

Asta Medica, Aktiengesellschaft

Merck Patent Gesellschaft MIT Beschraenkter Haftung

Biomet Deutchland Gmbh

Horst Kessler

Alfred Jonczyk

Simon Lawrence Goodman

Beate Diefenbach

Berthold Nies

Martin Kantlehner

Olaf G Wilhelm

Gunter Holzemann

Christoph Gibson

Jochen Wermuth

Brunhilde Felding-Habermann

Roland Haubner

Nils Potthoff

Niko Schmiedeberg

Dirk Finsinger

Tobias Kapp

Oliver Demmer

Bernhard Kutscher

Victor J Hruby

Guenter Hoelzemann

Marcus Koppitz

Alexander Borck

Manfred Schmitt

Viktor Magdolen

Minying Cai

Hans-Jürgen Wester

Margret Schottelius

Matthias Gratz

Friedrich Rippmann

Markus Buergle

Michel Dard

Joerg Meyer

Markus Bürgle

Florian Rechenmacher

G&uuml;nter H&ouml;lzemann

Christoph Riemer

Ingrid Dijkgraaf

Ulrich Hersel

Oleg Maltsev

Gabor Sulyok

Michael Joner

Jörg Meyer

Stefanie Neubauer

Heinrich Graeff

Hans Jürgen Wester

Arne Sutter

J&ouml;rg Simon Schmitt

David A Cheresh

Rainer Obermeier

Guido Melzer

Matthias Wiesner

Hubert Mullner

Ulrich Weidle

Thomas Klenner

Sandor Szabo

Michael Bernd

Martina Anton

Norman Koglin

Theresa Osl

Gunter H&ouml;lzemann

Erich G Roedern

Gerhard Muller

Marion Gurrath

Klaus W Usadel

Florian Reichart

Andreas Konard Buck

Georgette Thumshirn

Michael Dechantsreiter

Dirk Weber

Dirk Gottschling

Gab&oacute;r Sulyok

J&ouml;rg Meyer

Markus Schwaiger

Burkhardt Laufer

Markus B&uuml;rgle

Bernhard K&ouml;nig

Armin Modlinger

Andreas Konrad Buck

Sebastian KNÖR

The present disclosure relates to imaging and endoradiotherapy of diseases involving chemokine receptor 4 (CXCR4). Provided are compounds which bind or inhibit hCXCR4 and mCXCR4 and furthermore carry at least one moiety which is amenable to labeling. Provided are also medical uses of such compounds.

CXCR4-targeted diagnostic and therapeutic agents with reduced species selectivity

Disclosed are compounds represented by the following general formula (I): Cyclo-(Arg-Gly-Asp-X-X-X-X-X) (I) wherein the variables groups Xto Xhave the following meanings X: Leu, Ile, Nle, Val, Tyr, Phe; X: D-amino acid such as D-Pro, N-Me-D-Phe; X: Pro, N-Me-amino acid such as N-Me-Lys, N-Me-Lys(Ac); Pro-Rx3, N-Me-Lys-Rx4; X: Gly, Ala, Ser, Thr; X: Leu, Ala, Tyr, His, Ile, Nle, Val, Phe wherein Pro-Rx3 represents a proline residue that carries at the C-3, C-4 or C-5 carbon atom and preferably the C-4 carbon atom a functional group selected from &#x2014;NH2, &#x2014;OH, &#x2014;NH&#x2014;Ac, &#x2014;NH-hexyne, and wherein Lys-Rrepresents a lysine residue, wherein the &#x3c9;-amino nitrogen atom carries a group of the formula -L4-R4, wherein L4 is selected from the group consisting of covalent bond, &#x2014;C(O)&#x2014;, and &#x2014;C(O)&#x2014;O&#x2014;, . . . , and wherein R4 is selected from the group consisting of &#x2014;(CH2)n-C&#x2261;CH with n=0, 1, 2, 3, 4, 5, 6, 7 or 8, or wherein the sub-sequence -X-X- represents a &#x3b2;-turn mimetic diffe&#x3c9;&#x3c9;ring from the meanings above, or pharmaceutically acceptable salts, esters, solvates, polymorphs or modified forms thereof represented by the following general formula (II): (X)L(X)wherein X0 represents the compound of the general formula (I) as specified above (excluding one hydrogen atom to allow bonding to the linker), L represents a linker, Xrepresents the effector moiety and wherein n1 and n2 are each independently selected from the range of 1 to 5, preferably such that each of n1 and n2 represents 1, wherein n1+n2 represents the number of valencies of the linker and is preferably in the range of from 2 to 6, more preferably 2-5, with the proviso that each of n1 and n2 is at least 1, as well as uses therefore in therapy and imaging.

Ligands for integrin &#x3b1;V&#x3b2;8, synthesis and uses thereof

Disclosed are compound exhibiting highly active and selective binding to &#x3b1;v&#x3b2;6 integrin, which are represented by the following general formula (I): Cyclo-(Arg-X-Asp-X-X-X-X-X-X) (I) wherein the variables groups X to X have the following meanings X: Ser, Gly, Thr, X: Leu, lie, Nle, Val, Phe, X: Gly, Ala, X: Leu, He, Nle, Val, Phe, Lys, Tyr, Trp, Arg, X: D-Pro, N-Me-D-lipophilic amino acids, X: Pro, N-Me-amino acids, N-Me-Lys, N-Me-Lys(Ac), and X; Ala, Leu, He, Nle, Val, Phe, Tyr, Trp or wherein the sub-sequence -X-X- represents a &#x3b2;-turn mimetic differing from the meanings above, or pharmaceutically acceptable salts, esters, solvates, polymorphs or modified forms thereof represented by the following general formula (II): (X)L(X)wherein Xrepresents the compound of the general formula (I) as specified above (excluding one hydrogen atom to allow bonding to the linker), L represents a linker, Xrepresents the effector moiety and wherein n1 and n2 are each independently selected from the range of 1 to 5, wherein n1+n2 represents the number of valencies of the linker and is preferably in the range of from 2 to 6, more preferably 3-5, with the proviso that each of n1 and n2 is at least 1, as well as uses therefore in therapy and imaging.

Ligands for integrin &#x3b1;v&#x3b2;6, synthesis and uses thereof

Compositions and methods of treating a central nervous system (CNS) disorder or mood disorder in a subject in need of such treatment are described. A therapeutically effective amount of a composition comprising a melanocortin 5 receptor (MC5R) peptide ligand in a pharmaceutically acceptable carrier is administered to the subject. The MCSR peptide ligand is a selective MCSR antagonist, in which administration thereof to the subject can treat the CNS disorder or mood disorder with clinical improvement observed in a relatively short time.

Compositions and methods for treating central nervous system (CNS) disorders and mood disorders

Methods of treating a depressive disorder or an anxiety disorder in a subject in need of such treatment are described. A therapeutically effective amount of a composition comprising Ac-Nle-c[Asp-His-(NMe)D-Nal(2')-Arg-Trp-(NMe)Lys]-NH(PEPTIDE 9), in a pharmaceutically acceptable carrier is administered to the subject. PEPTIDE 9 is a selective MC5R antagonist, in which administration thereof to the subject can treat the depressive or generalized anxiety disorder with clinical improvement observed in a relatively short time.

Methods for the treatment of depression and anxiety

The present invention, among others, relates to a compound having a structure according to formula (I) or a pharmaceutically acceptable salt thereof, wherein Xaato Xaaare independently of each other, an optionally N-alkylated natural or unnatural amino acid, R is H or methyl, L is a linker moiety, Ar is a spacer comprising an aromatic moiety, and D comprises, preferably is i) a combination of an organic complexation agent and a detectable label; or ii) a detectable label, an organic complexation agent or an active substance, said active substance particularly being selected from cytotoxic agents, lipids, sugars, sugar conjugates, sugar derivatives, proteins and combinations thereof, with the proviso that -L-Ar-D does not comprise aF-benzoyl residue.

Cyclopentapeptide derivatives and uses thereof

At least some embodiments of the invention relates to an implant having a coating that contains or is composed of a functionalized RGD peptidomimetic RGD-P1 having the formula (1) and/or a functionalized RGD peptidomimetic RGD-P2 having the formula (2), and an associated manufacturing method.

Functionalized RGD peptidomimetics and their manufacture, and implant having a coating containing such functional-ized RGD peptidomimetics

Functionalized RGD peptidomimetics and their manufacture, and implant having a coating containing such functionalized RGD peptidomimetics

Provided herein are compounds or conjugates useful for diagnostic imaging and/or therapeutic purposes. Each compound or conjugate comprises a ligand for the chemokine receptor CXCR4 and a detectable label. The ligand has a binding affinity for the CXCR4 receptor, measured as ICin the presence ofI-CPCR4, of 250 nM or lower, and the ligand comprises a cyclic oligopeptide moiety having the motif B-Arg or B-(Me)Arg within the cyclic moiety, wherein B is a basic amino acid, a derivative thereof, or phenylalanine, provided that the motif is B-Arg when B is a N-methyl derivative of a basic amino acid.

Cancer imaging and treatment

A compound, or a pharmaceutically acceptable salt or ester thereof, comprises the structure: [(P1-S1)-L-(S2-P2)]wherein: P1 and P2, which may be the same or different, are cyclic oligopeptide moieties, at least one of P1 and P2 having the motif B-Arg or B-(Me) Arg within the cyclic moiety, wherein B is a basic amino acid, a derivative thereof, or phenylalanine or a derivative thereof; S1 and S2 are spacer groups, which may be the same or different; L is a linker moiety containing at least two functional groups for attachment of the cyclic oligopeptides or spacer groups; n and q are independently 0 or 1; p and r are independently integers of 1 or more; and t is an integer of 1 or more, provided that, when t, p or r is greater than 1, the cyclic oligopeptide moiety, spacer group and/or the value of j or q may be the same or different between the multiple (P1-S1) moieties or multiple (S2-P2) moieties.

The invention relates to compounds of formula (1) B-Q-X, wherein B is bioactive cell adhesive mediating molecule. Q is absent or is an inorganic spacer molecule and Xis an anchor molecule, selected from the group Lys-(CO&#x2014;CH&#x2014;(CH)&#x2014;POH)(I), -Lys-[-Lys-(CO&#x2014;CH&#x2014;(CH)&#x2014;POH)](ii) or -Lys-(Lys[-Lys-(CO&#x2014;CH&#x2014;(CH)&#x2014;POH](iii), and n independently represents 0, 1, 2 or 3, wherein a free amino group of group B is linked in peptide form to a free carboxyl group of the spacer molecule Q or of the anchor molecule X, or a free amino group of the radical Q is linked in peptide form to a free carboxyl group of the radical X. The invention also relates to the salts thereof. The inventive compounds can be used as integrin inhibitors for the treatment of illnesses, deficiencies, inflammations caused by implants and osteolytic illnesses such as osteoporosis, thrombosis, cardiac infarction and arteriosclerosis, in addition to the acceleration and strengthening of the integration process of implants or the biocompatible surface in tissue.

Peptide and peptide mimetic conjugates with integrin-inhibitor properties

The present invention relates to cyclic peptides as inhibitors of urokinase binding to the urokinase receptor. Said cyclic peptides are suitable as pharmaceutical active substances for disorders mediated by urokinase and its receptor.

Cyclic peptidomimetic urokinase receptor antagonists

The invention relates to compounds of formula (I) B-Q-X, wherein B is a bioactive, cell adhesive mediating molecule, selected from the group (i) and Thr-Trp-Tyr-Lys-Ile-Ala-Phe-Gln-Arg-Asn-Arg-Lys (SEQ ID NO: 1) (ii), Trp-Tyr-Lys-Ile-Ala-Phe-Gln-Arg-Asn-Arg-Lys (SEQ ID NO: 2) (iii), Tyr-Lys-Ile-Ala-Phe-Gln-Arg-Asn-Arg-Lys (SEQ ID NO: 3) (iv), Thr-Trp-Tyr-Lys-Ile-Ala-Phe-Gln-Arg-Asn-Arg (SEQ ID NO: 4) (v), Thr-Trp-Tyr-Lys-Ile-Ala-Phe-Gln-Arg-Asn (SEQ ID NO: 5) (vi), Thr-Trp-Tyr-Lys-Ile-Ala-Phe-Gln-Arg (SEQ ID NO: 6) (vii), wherein (i) X, Y, Z, R, R, R, A, Ar, Hal, Het, Het, n, m, o, p, q, s, t have the meanings cited in claim, Q is absent or is an organic spacer molecule, Xis an anchor molecule selected from the group cited in claim, and the salts thereof, which can be used as integrin inhibitors particularly for treatment of illness, deficiencies and inflammations caused by implants and osteolytic illnesses such as osteoporosis, thrombosis, cardiac infarction and arteriosclerosis, in addition to the acceleration and strengthening of the integration process of implants or the biocompatible surface in tissue.

Peptide and peptide mimetic derivatives with integrin-inhibitors properties II

Isoquinoline derivatives of the general formula (I) in which X, Y, Z, R, Rand n are as defined in Patent Claim (), and physiologically acceptable salts or solvates thereof, are integrin inhibitors and can be employed for combating thromboses, cardiac infarction, coronary heart diseases, arteriosclerosis, inflammation, tumors, osteoporosis, infections and restenosis after angioplasty or in pathological processes which are maintained or propagated by angiogenesis.

Isoquinoline derivatives

Growing community of inventors

Schwalbach, Germany

Horst Kessler