Polyphor Ltd.

Universitaet Zuerich

Unversität Zürich

Polyphor Ag

Reshmi Mukherjee

Daniel Obrecht

Frank Gombert

Barbara Romagnoli

Christian Ludin

Heiko Henze

Steven J Demarco

Jan Wim Vrijbloed

Kerstin Moehle

John-Anthony Robinson

John Anthony Robinson

Jürg Zumbrunn

Sergio Lociuro

Alexander Lederer

Christian Bisang

Françoise Jung

Odile Sellier-Kessler

Francoise Jung

Kerstin Möhle

Steve J DeMarco

Steve J Demarco

Barbara Romanoli

Alex Lederer

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

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.

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.

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.

Template-fixed &#x3b2;-hairpin peptidomimetics of the general formula (I) 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. 

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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Pasadena, CA, United States of America

Reshmi Mukherjee