Polyphor Ltd.

Unversität Zürich

Universitaet Zuerich

Polyphor Ag

Kerstin Moehle

Daniel Obrecht

Frank Gombert

Steven J Demarco

Christian Ludin

Heiko Henze

Barbara Romagnoli

Jan Wim Vrijbloed

Reshmi Mukherjee

John-Anthony Robinson

John Anthony Robinson

Jürg Zumbrunn

Sergio Lociuro

Odile Sellier

Francoise Jung

Anatol Luther

Steffen Weinbrenner

Christian Bisang

Françoise Jung

William J Drury, Iii

Christian Steuer

William J Drury Iii

Steven J De Marco

The template-fixed &#x3b2;-hairpin peptidomimetics Cyclo(-Tyr-His-X-Cys-Ser-Ala-Pro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys-Pro-Pro), disulfide bond between Cys4 and Cys11, and pharmaceutically acceptable salts thereof, with X being Ala or Tyr, have CXCR4 antagonizing properties and can be used for where cancer is mediated or resulting from CXCR4 receptor activity.

Template-fixed peptidomimetics

Novel backbone-cyclized peptidomimetics of the general formulacyclo[-P-P-P-P-P-P-P-P-T-T-]&#x2003;&#x2003; (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 modulate the GLP-1 receptor. They can be used as medicaments to treat, prevent, or delay the onset of diseases, disorders or conditions in which modulation of the human GLP-1 receptor is beneficial, such as type 2 diabetes. These backbone-cyclized peptidomimetics can be manufactured by a process which is based on a mixed solid&#x2014;and solution phase synthetic strategy.

Backbone-cyclized peptidomimetics with GLP-1R modulating activity

Template-fixed &#x3b2;-hairpin peptidomimetics of the general formulae wherein Z is a chain of 11 &#x3b1;-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid) are Gly, or Pro, or Pro(4NHCOPhe), 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 inhibit proteases, in particular serine proteases, especially Cathepsin G or Elastase or Tryptase. These &#x3b2;-hairpin peptidomimetics can be manufactured by processes which are based on a mixed solid- and solution phase synthetic strategy.

Template-fixed beta-hairpin peptidomimetics with protease inhibitory activity

The template-fixed &#x3b2;-hairpin peptidomimetics Cyclo(-Tyr-His-Cys-Ser-Ala-Pro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys--Pro-Pro), disulfide bond between Cys4 and Gysl1, and pharmaceutically acceptable salts thereof, with X being Ala or Tyr, have CXCR4 antagonizing properties and can be used for where cancer is mediated or resulting from CXCR4 receptor activity.

The template-fixed B-hairpin peptidomimetics Cyclo(-Tyr-His-X-Cys-Ser-Ala-Pro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys--Pro-Pro), disulfide bond between Cys4 and Gys11, and pharmaceutically acceptable salts thereof, with X being Ala or Tyr, have CXCR4 antagonizing properties and can be used for where cancer is mediated or resulting from CXCR4 receptor activity.

Template-fixed &#x3b2;-hairpin peptidomimetics of the general formula (I) wherein Z is a template-fixed chain of 12, 14 or 18 &#x3b1;-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid), are Gly, NMeGly, Pro or Pip, 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 CXCR4 antagonizing properties These &#x3b2;-hairpin peptidomimetics 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

The template-fixed &#x3b2;-hairpin peptidomimetics Cyclo(-Tyr-His-X-Cys-Ser-Ala-Pro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys-Pro-Pro), disulfide bond between Cys4 and Gys11, and pharmaceutically acceptable salts thereof, with X being Ala or Tyr, 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 immuno suppression; or, in particular, for stem cell mobilization of peripheral blood stem cells and/or mesenchymal stem cell (MSC) and/or other stem cells which retention depend on the CXCR4-receptor. These &#x3b2;-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and Solution phase synthetic strategy, using methods which are well known to those adequately skilled in peptide chemistry.

Template-fixed &#x3b2;-hairpin peptidomimetics of the general formula (I) wherein Z is a template-fixed chain of 12, 14 or 18 &#x3b1;-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid), are Gly, NMeGly, Pro or Pip, 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 CXCR4 antagonizing properties. These &#x3b2;-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

The template-fixed &#x3b2;-hairpin peptidomimetics Cyclo(-Tyr-His-X-Cys-Ser-Ala-Pro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys-Pro-Pro), disulfide bond between Cys4 and Cys11, and pharmaceutically acceptable salts thereof, with X being Ala or Tyr, 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 immuno suppression; or for treating inflammation, or, in particular, for stem cell mobilization of peripheral blood stem cells and/or mesenchymal stem cell (MSC) and/or other stem cells which retention depend on the CXCR4-receptor.

Template-fixed &#x3b2;-hairpin peptidomimetics of the General Formula (I); wherein Zand Zare template-fixed chains of 4 and 6 or 5 and 7 &#x3b1;-amino acid residues and salts thereof. They have CXCR4-antagonizing properties and can be used as medicaments. These &#x3b2;-sheet peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy. 

Template-fixed peptidomimetics as medicaments against HIV and cancer

Template-fixed &#x3b2;-hairpin peptidomimetics of the general formula (I) wherein Z is a template-fixed chain of 12, 14 or 18 &#x3b1;-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid), are Gly, NMeGly, Pro or Pip, 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 CXCR4 antagonizing properties. These &#x3b2;-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid&#x2014;and solution phase synthetic strategy.

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Wettswil, Switzerland

Kerstin Moehle