Polyphor Ag

Polyphor Ltd.

Other

Unversität Zürich

Alexander Lederer

Daniel Obrecht

Barbara Romagnoli

Frank Otto Gombert

Christian Bisang

Frank Gombert

Christian Ludin

Anatol Luther

Johann Zimmermann

Francesca Bernardini

Sophie Barthélémy

Peter Zbinden

Odile Sellier-Kessler

Heiko Henze

Reshmi Mukherjee

Francoise Jung

Christian Oefner

Ralf Löwe

Steve J DeMarco

Kalpana Patel

John Anthony Robinson

Jan Wim Vrijbloed

Steffen Weinbrenner

Françoise Jung

Jürg Zumbrunn

Eric Chevalier

Kerstin Möhle

Sergio Locurio

Guillaume Lemercier

Shivaprasad Shankaramma

Ralf Loewe

Manuella Schmitt-Billet

Gildas Deniau

Tobias Remus

Markus Seitz

Ludovic T Maillard

Roba Mounme

Beta-hairpin peptidomimetics of the general formula (I), cyclo[P-P-P-P-P-P-P-P-P-P-P-P-T-T], and pharmaceutically acceptable salts thereof, with Pto P, Tand Tbeing elements as defined in the description and the claims, have Gram-negative antimicrobial activity to e.g. inhibit the growth or to kill microorganisms such asand/orand/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.

Beta-hairpin peptidomimetics

Beta-hairpin peptidomimetics of the general formula (I), and pharmaceutically acceptable salts thereof, with P, T, Q, and optionally L being elements as defined in the description and the claims, have Gram-negative antimicrobial activity to e.g. inhibit the growth or to kill microorganisms such asand/orand/orand/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.

Beta-hairpin peptidomimetics of the general formula (I), cyclo[P-P-P-P-P-P-P-P-P-P-P-P-T-T] and pharmaceutically acceptable salts thereof, with Pto P, Tand Tbeing elements as defined in the description and the claims, have Gramnegative antimicrobial activity to e.g. inhibit the growth or to kill microorganisms such asand/orand/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.

&#x3b2;-hairpin peptidomimetics

&#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 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.

Beta-hairpin peptidomimetics as selective elastase inhibitors

Beta-hairpin peptidomimetics of the general formula (I), cyclo[P-P-P-P-P-P-P-P-P-P-P-P-T-T], and pharmaceutically acceptable salts thereof, with Pto P, Tand Tbeing elements as defined in the description and the claims, have Gram-negative antimicrobial activity to e.g. inhibit the growth or to kill microorganisms such asand/orand/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 &#x3b2;-hairpin peptidomimetics of the general formula wherein Z is a template-fixed chain of 4 &#x3b1;-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid) are Gly, or of certain types which, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have the property to agonize or to antagonize GPCR receptors such as CXCR3, urotensin and CCR10. They can be used as medicaments to treat or prevent diseases such as cardiovascular disorders, dermatological disorders, endocrine system and hormone disorders, metabolic diseases, inflammatory diseases, neurological diseases, respiratory diseases, haematological diseases 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

Novel template-fixed &#x3b2;-hairpin peptidomimetics of the general formula (I) wherein the single elements T or P are &#x3b1;-amino acid residues connected from the carbonyl (C&#x2550;O) point of attachment to the nitrogen (N) of the next element in clockwise direction and wherein said elements, depending on their positions in the chain, are defined in the description and the claims have the property to act on the receptor CXCR7. Thus, these &#x3b2;-hairpin peptidomimetics can be useful in the treatment or prevention of diseases or conditions in the area of dermatological disorders, metabolic diseases, inflammatory diseases, fibrotic diseases, infectious diseases, neurological diseases, cardiovascular diseases, respiratory diseases, gastro-intestinal tract disorders, urological diseases, ophthalmic diseases, stomatological diseases, haematological diseases and cancer; or the mobilization of stem cells.

Template-fixed peptidomimetics with CXCR7 modulating activity

&#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.

&#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

Novel template-fixed &#x3b2;-hairpin peptidomimetics of the general formula (I), wherein the single elements T or P are &#x3b1;-amino acid residues connected from the carbonyl (C&#x2550;O) point of attachment to the nitrogen (N) of the next element in clockwise direction and wherein said elements, depending on their positions in the chain, are defined in the description and the claims have the property to act on the receptor CXCR7. Thus, these &#x3b2;-hairpin peptidomimetics can be useful in the treatment or prevention of diseases or conditions in the area of dermatological disorders, metabolic diseases, inflammatory diseases, fibrotic diseases, infectious diseases, neurological diseases, cardiovascular diseases, respiratory diseases, gastro-intestinal tract disorders, urological diseases, ophthalmic diseases, stomatological diseases, haematological diseases and cancer; or the mobilization of stem cells. 

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

Alexander Lederer