Polyphor Ag

Unversität Zürich

Frank Otto Gombert

Daniel Obrecht

Alexander Lederer

Barbara Romagnoli

Johann Zimmermann

Odile Sellier-Kessler

Sophie Barthélémy

Christian Oefner

Christian Ludin

John Anthony Robinson

Heiko Henze

Christian Bisang

Steffen Weinbrenner

Françoise Jung

Jürg Zumbrunn

Kerstin Möhle

Eric Chevalier

Ralf Löwe

Guillaume Lemercier

Kalpana Patel

Krystyna Patora-Komisarska

Tobias Remus

Ralf Loewe

Manuella Schmitt-Billet

Markus Seitz

Ludovic T Maillard

Roba Mounme

&#x3b2;-Hairpin peptidomimetics of the general formula cyclo(-Xaa-Xaa-Thr-Xaa-Ser-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-) and pharmaceutically acceptable salts thereof, with Xaa, Xaa, Xaa, Xaa, Xaa, Xaa, Xaa, Xaa, Xaa, Xaaand Xaabeing amino acid residues which are defined in the description and the claims, have elastase inhibitory properties, especially against human neutrophil elastase, and can be used for preventing infections or diseases related to such infections in healthy individuals or for slowing infections in infected patients. The compounds of the invention can further be used where cancer, or immunological diseases, or pulmonary diseases, or cardiovascular diseases, or neurodegenerative diseases, or inflammation, or diseases related to inflammation, are mediated or resulting from elastase activity. These peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

Beta-hairpin peptidomimetics as selective elastase inhibitors

&#x3b2;-Hairpin peptidomimetics of the general formula cyclo(-Tyr-His-Xaa-Cys-Ser-Xaa-Pro-Xaa-Arg-Tyr-Cys-Tyr-Xaa-Xaa-Xaa-Pro-), disulfide bond between Cysand Cys, and pharmaceutically acceptable salts thereof, with Xaa, Xaa, Xaa, Xaa, Xaaand Xaabeing amino acid residues of certain types which are defined in the description and the claims, have favorable pharmacological properties and can be used for preventing HIV infections in healthy individuals or for slowing and halting viral progression in infected patients; or where cancer is mediated or resulting from CXCR4 receptor activity; or where immunological diseases are mediated or resulting from CXCR4 receptor activity; or for treating immunosuppression; or during apheresis collections of peripheral blood stem cells and/or as agents to induce mobilization of stem cells to regulate tissue repair. These peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

&#x3b2;-hairpin peptidomimetics

&#x3b2;-Hairpin peptidomimetics of the general formula cyclo(-Xaa-Xaa-Thr-Xaa-Ser-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-) and pharmaceutically acceptable salts thereof, with Xaa, Xaa, Xaa, Xaa, Xaa, Xaa, Xaa, Xaa, Xaa, Xaaand Xaabeing amino acid residues of certain types which are defined in the description and the claims, have elastase inhibitory properties, especially against human neutrophil elastase, and can be used for preventing infections or diseases related to such infections in healthy individuals or for slowing infections in infected patients. The compounds of the invention can further be used where cancer, or immunological diseases, or pulmonary diseases, or cardiovascular diseases, or neurodegenerative diseases, or inflammation, or diseases related to inflammation, are mediated or resulting from elastase activity. These peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

&#x3b2;-Hairpin peptidomimetics of the general formula cyclo(-Tyr-His-Xaa-Cys-Ser-Xaa-DPro-Xaa-Arg-Tyr-Cys-Tyr-Xaa-Xaa-Xaa-Pro-), disulfide bond between Cysand Cys, and pharmaceutically acceptable salts thereof, with Xaa, Xaa, XaaXaa, Xaaand Xaabeing amino acid residues of certain types which are defined in the description and the claims, have favorable pharmacological properties and can be used for preventing HIV infections in healthy individuals or for slowing and halting viral progression in infected patients; or where cancer is mediated or resulting from CXCR4 receptor activity; or where immunological diseases are mediated or resulting from CXCR4 receptor activity; or for treating immunosuppression; or during apheresis collections of peripheral blood stem cells and/or as agents to induce mobilization of stem cells to regulate tissue repair. These peptidomimetics can be manufactured by a process which is based on a mixed solid-and solution phase synthetic strategy.

Beta-hairpin peptidomimetics

&#x3b2;-Hairpin peptidomimetics of the general formula cyclo(-Tyr-His-Xaa-Cys-Ser-Ala-Xaa-Xaa-Arg-Tyr-Cys-Tyr-Xaa-Aaa-Pro-Pro-), disulfide bond between Cysand Cys, and pharmaceutically acceptable salts thereof, with Xaa, Xaa, Xaa, Xaaand Xaabeing amino acid residues of certain types which are defined in the description and the claims, have favorable pharmacological properties and can be used for preventing HIV infections in healthy individuals or for slowing and halting viral progression in infected patients; or where cancer is mediated or resulting from CXCR4 receptor activity; or where immunological diseases are mediated or resulting from CXCR4 receptor activity; or for treating immunosuppression; or during apheresis collections of peripheral blood stem cells and/or as agents to induce mobilization of stem cells to regulate tissue repair. These peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

Beta-hairpin peptidomimetics as CXC4 antagonists

&#x3b2;-Hairpin peptidomimetics of the general formula Cyclo(-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Arg-Tyr-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-), disulfide bond between Cysand Cys, and pharmaceutically acceptable salts thereof, with Xaa, Xaa, Xaa, Xaa, Xaa, Xaa, Xaa, Xaa, Xaa, Xaa, Xaaand Xaabeing amino acid residues of certain types which are defined in the description and the claims, have CXCR4 antagonizing properties and can be used for preventing HIV infections in healthy individuals or for slowing and halting viral progression in infected patients; or where cancer is mediated or resulting from CXCR4 receptor activity; or where immunological diseases are mediated or resulting from CXCR4 receptor activity; or for treating immunosuppression; or during apheresis collections of peripheral blood stem cells and/or as agents to induce mobilization of stem cells to regulate tissue repair. These peptides can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

Beta-hairpin peptidomimetics having CXCR4 antagonizing activity

&#x3b2;-Hairpin peptidomimetics of the general formula cyclo(-Tyr-His-Xaa-Cys-Ser-Ala-Xaa-Xaa-Arg-Tyr-Cys-Tyr-Xaa-XaaPro-Pro-), disulfide bond between Cysand Cys, and pharmaceutically acceptable salts thereof, with Xaa, Xaa, Xaa, Xaaand Xaabeing amino acid residues of certain types which are defined in the description and the claims, have favorable pharmacological properties and can be used for preventing HIV infections in healthy individuals or for slowing and halting viral progression in infected patients; or where cancer is mediated or resulting from CXCR4 receptor activity; or where immunological diseases are mediated or resulting from CXCR4 receptor activity; or for treating immunosuppression; or during apheresis collections of peripheral blood stem cells and/or as agents to induce mobilization of stem cells to regulate tissue repair. These peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

&#x3b2;-Hairpin peptidomimetics of the general formula Cyclo(-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-), enantiomers and pharmaceutically acceptable salts thereof, with Xaa-Xaabeing amino acid residues of certain types which are defined in the description and the claims, have anti-infective activity, e.g. to selectively inhibit the growth of or to kill microorganisms such asand/or. They can be used as medicaments to treat or prevent infections or as disinfectants for foodstuffs, cosmetics, medicaments or other nutrient-containing materials. These peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

Template-fixed peptidomimetics formula (Ia) formula (Ib) wherein Z is a template-fixed chain of 14 &#x3b1;-amino and/or &#x3b1;-hydroxy acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid), are Pro, Gly, a glycolic acid residue or of certain types which, as the remaining symbols in the above formulae, are defined in the description and the claims, and salts thereof, have CXCR4 antagonizing properties and can be used for preventing HIV infections in non-infected individuals or for slowing and halting viral progression in infected patients; or where cancer is mediated or resulting from CXCR4 receptor activity; or where immunological diseases are mediated or resulting from CXCR4 receptor activity; or for treating immuno suppression; or during apheresis collections of peripheral blood stem cells and/or as agents to induce mobilization of stem cells to regulate tissue repair. These depsipeptides can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy. 

Template-fixed beta-hairpin peptidomimetics with CXCR4 antagonizing activity

&#x3b2;-Hairpin peptidomimetics of the general formula Cyclo(-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Arg-Tyr-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-), disulfide bond between Cysand Cys11, and pharmaceutically acceptable salts thereof, with Xaa, Xaa, Xaa, Xaa, Xaa, Xaa, Xaa, Xaa, Xaa, Xaa, Xaaand Xaabeing amino acid residues of certain types which are defined in the description and the claims, have CXCR4 antagonizing properties and can be used for preventing HIV infections in healthy individuals or for slowing and halting viral progression in infected patients; or where cancer is mediated or resulting from CXCR4 receptor activity; or where immunological diseases are mediated or resulting from CXCR4 receptor activity; or for treating immunosuppression; or during apheresis collections of peripheral blood stem cells and/or as agents to induce mobilization of stem cells to regulate tissue repair. These peptides can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

Novel template-fixed &#x3b2;-hairpin peptidomimetics of the general formula (I) wherein the single elements T or P are &#x3b1;-amino acid residues connected in either direction which, depending on their positions in the chain, are as defined in the description and the claims, and salts thereof, have the property to antagonize the receptor CCR10. They can be used as medicaments to treat or prevent diseases or conditions in the area of dermatological and cutaneous disorders, inflammation, allergic disorders, respiratory diseases, diseases of the gastro-intestinal tract, ophthalmic diseases, haematology and cancer. These &#x3b2;-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy. 

Template-fixed peptidomimetics with CCR10 antagonistic activity

&#x3b2;-Hairpin peptidomimetics of the general formula Cyclo(-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-), and pharmaceutically acceptable salts thereof, with Xaa 1-Xaa 16 being amino acid residues of certain types which are defined in the description and the claims, have CXCR4 antagonizing properties and prolonged half-lives in vivo and can be used for preventing HIV infections in healthy individuals or for slowing and halting viral progression in infected patients; or where cancer is mediated or resulting from CXCR4 receptor activity; or where immunological diseases are mediated or resulting from CXCR4 receptor activity; or for treating immunosuppression; or during apheresis collections of peripheral blood stem cells and/or as agents to induce mobilization of stem cells to regulate tissue repair. These peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

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Basel, Switzerland

Frank Otto Gombert