The present invention relates to pharmaceutical combinations comprising a peptidic CXCR4 inhibitor and a taxane for use in a method for the prevention, delay of progression or treatment of cancer.
A61K 31/337 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à quatre chaînons, p. ex. taxol
The present invention relates to pharmaceutical combinations comprising a compound of formula T or a pharmaceutically acceptable salt thereof and cyclo(-Tyr-His-Ala-Cys-Ser-Ala-DPro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys-DPro-Pro-) having a disulfide bond between Cys4 and Cys11 or a pharmaceutically acceptable salt thereof and their use in a method for the prevention, delay of progression or treatment of cancer in a subject.
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 31/357 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant plusieurs atomes d'oxygène dans le même cycle, p. ex. éthers en couronne, guanadrel
The present invention relates to pharmaceutical combinations comprising a peptidic CXCR4 inhibitor and a taxane for use in a method for the prevention, delay of progression or treatment of cancer.
A61K 31/337 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à quatre chaînons, p. ex. taxol
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
The present invention is directed to peptidomimetics having antibacterial activity, especially against Gram-negative bacteria. The peptidomimetics of the invention are compounds of the general formula (I), P1-P2-P3-P4-P5-P6-P7-P8-P9-P10-P11-P12-P13-P14-P15-P16(I) and pharmaceutically acceptable salts thereof, as described in the description and in the claims. The invention is also directed to therapeutic uses of the peptidomimetics for the treatment or prevention of bacterial infections and diseases related to bacterial infections and to non-therapeutic uses of the peptidomimetics for preserving or disinfecting foodstuffs, cosmetics, medicaments or other nutrient-containing materials. In addition, the present invention provides an efficient synthetic process by which these compounds can, if desired, be made in parallel library-format. Moreover, the peptidomimetics of the invention show improved antimicrobial activity, low or no hemolysis of red blood cells and reduced cytotoxicity.
C07K 7/08 - Peptides linéaires ne contenant que des liaisons peptidiques normales ayant de 12 à 20 amino-acides
C07K 14/47 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés provenant de mammifères
The present invention is directed to peptidomimetics having antibacterial activity, especially against Gram-negative bacteria. The peptidomimetics of the invention are compounds of the general formula (I), [X3tt-[X2SS-X1-P1-P2-P3-P4-P5-P6-P7-P8-P9-P10-P11-P12-P13-P14-P15-P16 and pharmaceutically acceptable salts thereof, as described in the description and in the claims. The invention is also directed to therapeutic uses of the peptidomimetics for the treatment or prevention of bacterial infections and diseases related to bacterial infections and to non-therapeutic uses of the peptidomimetics for preserving or disinfecting foodstuffs, cosmetics, medicaments or other nutrient-containing materials. In addition, the present invention provides an efficient synthetic process by which these compounds can, if desired, be made in parallel library-format. Moreover, the peptidomimetics of the invention show improved antimicrobial activity, low or no hemolysis of red blood cells and reduced cytotoxicity.
C07K 7/08 - Peptides linéaires ne contenant que des liaisons peptidiques normales ayant de 12 à 20 amino-acides
C07K 14/47 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés provenant de mammifères
DPro-Pro-), or any pharmaceutically acceptable salt thereof, for use in a method for the prevention, management or treatment of diseases or conditions of the lungs being mediated by or resulting from human neutrophil elastase activity in a subject.
DPro-Pro-), or any pharmaceutically acceptable salt thereof, for use in a method for the prevention, management or treatment of diseases or conditions of the lungs being mediated by or resulting from human neutrophil elastase activity in a subject.
Escherichia coli.
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.
DPro-Pro-), or any pharmaceutically acceptable salt thereof, for use in a method for the prevention, management or treatment of diseases or conditions of the lungs being mediated by or resulting from human neutrophil elastase activity in a subject.
Klebsiella pneumoniaeAcinetobacterbaumannii Escherichia coliPseudomonas aeruginosa Enterobacter cloacaeEnterobacter cloacae. 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.
The present invention relates to pharmaceutical combinations comprising a compound of formula I or a pharmaceutically acceptable salt thereof and cyclo(-Tyr-His-Ala-Cys-Ser- Ala-DPro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys-DPro-Pro-) having a disulfide bond between Cys4 and Cysl 11 or a pharmaceutically acceptable salt thereof and their use in a method for the prevention, delay of progression or treatment of cancer in a subject.
A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
A61K 31/357 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant plusieurs atomes d'oxygène dans le même cycle, p. ex. éthers en couronne, guanadrel
Escherichia coli.
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.
wherein the single elements T or P are α-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—and solution phase synthetic strategy.
C07K 7/54 - Peptides cycliques contenant au moins une liaison peptidique anormale comportant au moins une liaison peptidique anormale dans le cycle
C07K 7/64 - Peptides cycliques ne comportant que des liaisons peptidiques normales
C07K 14/72 - RécepteursAntigènes de surface cellulaireDéterminants de surface cellulaire pour des hormones
A61K 38/02 - Peptides à nombre indéterminé d'amino-acidesLeurs dérivés
C07K 1/04 - Procédés généraux de préparation de peptides sur des supports
C07K 14/00 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés
C07K 14/47 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés provenant de mammifères
C07K 14/705 - RécepteursAntigènes de surface cellulaireDéterminants de surface cellulaire
C40B 50/14 - Synthèse en phase solide, c.-à-d. dans laquelle au moins un bloc servant à créer la bibliothèque est lié à un support solide au cours de la création de la bibliothèqueProcédés particuliers de clivage à partir du support solide
A61K 38/00 - Préparations médicinales contenant des peptides
Pseudomonas aeruginosa.
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.
Escherichia coli. 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.
The present invention relates to pharmaceutical aerosols comprising a β-hairpin peptidomimetic of formula cyclo(-OctG-Glu-Thr-Ala-Ser-lle-Pro-Pro-Gln-Lys-Tyr-DPro-Pro-), or a pharmaceutically acceptable salt thereof, having inhibitory activity against human neutrophil elastase. It further relates to solid or liquid pharmaceutical compositions and kits for preparing and administering such aerosols. The invention can be used for the prevention, management or treatment of pulmonary diseases, such as alpha-1 antitrypsin deficiency (AATD), cystic fibrosis (CF), non-cystic fibrosis bronchiactasis (NCFB), or chronic obstructive pulmonary disease (COPD), or infections, or diseases, or conditions of the lungs, being mediated by or resulting from human neutrophil elastase activity. Thus, the invention further relates to a pharmaceutical composition or a pharmaceutical aerosol comprising the active compound cyclo(-OctG-Glu-Thr-Ala-Ser-lle-Pro-Pro-Gln-Lys-Tyr-DPro-Pro-), or any pharmaceutically acceptable salt thereof, for use in a method for the prevention, management or treatment of diseases or conditions of the lungs being mediated by or resulting from human neutrophil elastase activity in a subject.
The present invention relates to pharmaceutical aerosols comprising a β-hairpin peptidomimetic of formula cyclo(-OctG-Glu-Thr-Ala-Ser-lle-Pro-Pro-Gln-Lys-Tyr- DPro-Pro-), or a pharmaceutically acceptable salt thereof, having inhibitory activity against human neutrophil elastase. It further relates to solid or liquid pharmaceutical compositions and kits for preparing and administering such aerosols. The invention can be used for the prevention, management or treatment of pulmonary diseases, such as alpha-1 antitrypsin deficiency (AATD), cystic fibrosis (CF), non-cystic fibrosis bronchiactasis (NCFB), or chronic obstructive pulmonary disease (COPD), or infections, or diseases, or conditions of the lungs, being mediated by or resulting from human neutrophil elastase activity. Thus, the invention further relates to a pharmaceutical composition or a pharmaceutical aerosol comprising the active compound cyclo(-OctG-Glu-Thr-Ala-Ser-lle-Pro-Pro-Gln-Lys-Tyr-DPro-Pro-), or any pharmaceutically acceptable salt thereof, for use in a method for the prevention, management or treatment of diseases or conditions of the lungs being mediated by or resulting from human neutrophil elastase activity in a subject.
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
03 - Produits cosmétiques et préparations de toilette; préparations pour blanchir, nettoyer, polir et abraser.
05 - Produits pharmaceutiques, vétérinaires et hygièniques
42 - Services scientifiques, technologiques et industriels, recherche et conception
Produits et services
Chemical products for use in industry, science, photography,
as well as in agriculture, horticulture and forestry;
unprocessed artificial resins, unprocessed plastics; soil
fertilizers; fire-extinguishing compositions; tempering and
soldering preparations; chemical substances for preserving
foodstuffs; tanning materials; adhesives for use in
industry. Bleaching preparations and other substances for laundry use;
cleaning, polishing, degreasing and abrasive preparations;
soaps; perfumery, essential oils, cosmetics, hair lotions;
dentifrices. Pharmaceutical and veterinary products as well as
preparations for health care; dietetic substances for
medical use, food for babies; plasters, materials for
dressings; material for dental fillings and dental
impressions; disinfectants; products for destroying
vermin; fungicides, herbicides. Scientific and technological services as well as research
and design services relating thereto; industrial analysis
and research services; design and development of computers
and software.
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
03 - Produits cosmétiques et préparations de toilette; préparations pour blanchir, nettoyer, polir et abraser.
05 - Produits pharmaceutiques, vétérinaires et hygièniques
42 - Services scientifiques, technologiques et industriels, recherche et conception
Produits et services
Chemical products for use in industry, science, photography,
as well as in agriculture, horticulture and forestry;
unprocessed artificial resins, unprocessed plastics; soil
fertilizers; fire-extinguishing compositions; tempering and
soldering preparations; chemical substances for preserving
foodstuffs; tanning materials; adhesives for use in
industry. Bleaching preparations and other substances for laundry use;
cleaning, polishing, degreasing and abrasive preparations;
soaps; perfumery, essential oils, cosmetics, hair lotions;
dentifrices. Pharmaceutical and veterinary products as well as
preparations for health care; dietetic substances for
medical use, food for babies; plasters, materials for
dressings; material for dental fillings and dental
impressions; disinfectants; products for destroying
vermin; fungicides, herbicides. Scientific and technological services as well as research
and design services relating thereto; industrial analysis
and research services; design and development of computers
and software.
Escherichia coli. 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.
15 being 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.
Conformationally constrained macrocyclic compounds of formula (I), including substituents E, G, and Q, as defined in the description and the claims, and salts thereof, have the property to modulate the activity of the peptidyl-prolyl cis/trans isomerases Pin1. Thus, these compounds and pharmaceutical compositions containing said compounds may be useful in the treatment and/or prevention of diseases or conditions in the area of proliferative disorders and diseases, such as e.g. cancer, inflammatory diseases, transplant rejection, viral infections, osteolytic bone diseases, cardiac diseases, cardiovascular diseases, respiratory diseases, acute neurological diseases, neurodegenerative diseases, immune disorders, and lymphoproliferative theileriosis.
Conformationally constrained macrocyclic compounds of formula (I), including substituents E, G, and Q, as defined in the description and the claims, and salts thereof, have the property to modulate the activity of the peptidyl-prolyl cis/trans isomerases Pin1. Thus, these compounds and pharmaceutical compositions containing said compounds may be useful in the treatment and/or prevention of diseases or conditions in the area of proliferative disorders and diseases, such as e.g. cancer, inflammatory diseases, transplant rejection, viral infections, osteolytic bone diseases, cardiac diseases, cardiovascular diseases, respiratory diseases, acute neurological diseases, neurodegenerative diseases, immune disorders, and lymphoproliferative theileriosis.
Formula (I); Conformationally constrained macrocyclic compounds of formula (I), including substituents E with at least one ester moiety, G and Q, as defined in the description and the claims, and salts thereof, can be metabolized to compounds that have the property to modulate the activity of the peptidyl-prolyl cis/trans isomerase Pin1. In addition, they show antiproliferative activity on various cancer cell lines. Thus, these compounds and pharmaceutical compositions containing said compounds may be useful in the treatment and/or prevention of diseases or conditions in the area of proliferative disorders and diseases, such as e.g. cancer, inflammatory diseases, transplant rejection, viral infections, osteolytic bone diseases, cardiac diseases, cardiovascular diseases, respiratory diseases, acute neurological diseases, neurodegenerative diseases, immune disorders, and lymphoproliferative theileriosis.
Conformationally constrained macrocyclic compounds of formula (I), including substituents E with at least one ester moiety, G and Q, as defined in the description and the claims, and salts thereof, can be metabolized to compounds that have the property to modulate the activity of the peptidyl-prolyl cis/trans isomerase Pin1. In addition, they show antiproliferative activity on various cancer cell lines. Thus, these compounds and pharmaceutical compositions containing said compounds may be useful in the treatment and/or prevention of diseases or conditions in the area of proliferative disorders and diseases, such as e.g. cancer, inflammatory diseases, transplant rejection, viral infections, osteolytic bone diseases, cardiac diseases, cardiovascular diseases, respiratory diseases, acute neurological diseases, neurodegenerative diseases, immune disorders, and lymphoproliferative theileriosis.
13 being 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.
13 being 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.
Novel backbone-cyclized peptidomimetics of the general formula cyclo[-P1-P2-P3-P4-P5-P6-P7-P8-T1-T2-] (I) wherein the single elements T or P are α-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- and solution phase synthetic strategy.
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 as Klebsiella pneumoniae and/or Acinetobacter baumannii and/or Escherichia coli and/or Pseudomonas aeruginosa. They ca n 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.
C07K 7/08 - Peptides linéaires ne contenant que des liaisons peptidiques normales ayant de 12 à 20 amino-acides
C07K 7/60 - Peptides cycliques contenant au moins une liaison peptidique anormale comportant au moins une liaison peptidique anormale dans le cycle cyclisés par le groupe amino-4 de l'acide diamino-2,4 butanoïque
C07K 7/64 - Peptides cycliques ne comportant que des liaisons peptidiques normales
Beta-hairpin peptidomimetics of the general formula (I), cyclo[P1-P2-P3-P4-P5-P6- P7-P8-P9-P10 -P11 -P12 -T1-T2], and pharmaceutically acceptable salts thereof, with P1 to P12, T1 and T2 being elements as defined in the description and the claims, have Gramegative antimicrobial activity to e.g. inhibit the growth or to kill microorganisms such as Klebsiella pneumoniae and/or Acinetobacter baumannii and/or Escherichia coli. 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[P1-P2-P3-P4-P5-P6- P7-P8-P9-P10-P11-P12-T1-T2] a nd pharmaceutically acceptable salts thereof, with P1 to P12, T1 and T2 being elements as defined in the description and the claims, have Gramnegative antimicrobial activity to e.g. inhibit the growth or to kill microorganisms such as Klebsiella pneumoniae and/or Acinetobacter baumannii and/or Escherichia coli. 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.
Escherichia coli. 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.
Escherichia coli. 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.
Novel template-fixed β-hairpin peptidomimetics of the general formula (I)
wherein the single elements T or P are α-amino acid residues connected from the carbonyl (C═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 β-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.
C07K 14/715 - RécepteursAntigènes de surface cellulaireDéterminants de surface cellulaire pour des cytokinesRécepteursAntigènes de surface cellulaireDéterminants de surface cellulaire pour des lymphokinesRécepteursAntigènes de surface cellulaireDéterminants de surface cellulaire pour des interférons
C07K 14/705 - RécepteursAntigènes de surface cellulaireDéterminants de surface cellulaire
A61K 38/00 - Préparations médicinales contenant des peptides
A61K 38/17 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains
14 being 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.
15 being 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.
β-Hairpin peptidomimetics of the general formula cyclo(-Xaa1-Xaa2-Thr3-Xaa4-Ser5- Xaa6-Xaa7-Xaa8-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-) and pharmaceutically acceptable salts thereof, with Xaa1, Xaa2, Xaa4, Xaa6, Xaa7, Xaa8, Xaa9, Xaa10, Xaa11, Xaa12 and Xaa13 being 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.
β-Hairpin peptidomimetics of the general formula cyclo(-Xaa1-Xaa2-Thr3-Xaa4-Ser5-Xaa6-Xaa7-Xaa8-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-) and pharmaceutically acceptable salts thereof, with Xaa1, Xaa2, Xaa4, Xaa6, Xaa7, Xaa8, Xaa9, Xaa10, Xaa11, Xaa12 and Xaa13 being 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.
The conformationally restricted, spatially defined macrocyclic ring system of formula (I) is constituted by three distinct molecular parts: Template A, conformation Modulator B and Bridge C. Macrocycles described by this ring system I are readily manufactured by parallel synthesis or combinatorial chemistry in solution or on solid phase. They are designed to interact with a variety of specific biological target classes, examples being agonistic or antagonistic activity on G-protein coupled receptors (GPCRs), inhibitory activity on enzymes or antimicrobial activity. In particular, these macrocycles show inhibitory activity on endothelin converting enzyme of subtype 1 (ECE-1) and/or the cysteine protease cathepsin S (CatS), and/or act as antagonists of the oxytocin (OT) receptor, thyrotropin-releasing hormone (TRH) receptor and/or leukotriene B4 (LTB4) receptor, and/or as agonists of the bombesin 3 (BB3) receptor, and/or show antimicrobial activity against at least one bacterial strain. Thus they are showing great potential as medicaments for a variety of diseases.
C07D 273/02 - Composés hétérocycliques contenant des cycles comportant des atomes d'azote et d'oxygène comme uniques hétéro-atomes du cycle, non prévus par les groupes comportant deux atomes d'azote et un seul atome d'oxygène
C07D 291/08 - Composés hétérocycliques contenant des cycles comportant des atomes d'azote, d'oxygène et de soufre comme uniques hétéro-atomes du cycle condensés avec des carbocycles ou avec des systèmes carbocycliques
C07D 515/22 - Composés hétérocycliques contenant dans le système condensé au moins un hétérocycle comportant des atomes d'azote, d'oxygène et de soufre comme uniques hétéro-atomes du cycle, non prévus dans les groupes , ou dans lesquels le système condensé contient au moins quatre hétérocycles
16 being 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 of the general formula (I), cyclo[P1-p2-p3-p4-p5-p6- p7-p8.p9- p10-p11-p12-T1-T2], a nd pharmaceutically acceptable salts thereof, with P1 to P12, T1 and T2 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 as Klebsiella pneumoniae and/or Acinetobacter baumannii and/or Escherichia coli. 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(P1-p2-p3-p4-p5-p6- p7p8p9-p10-p11-p12-T1-T2], a nd pharmaceutically acceptable salts thereof, with P1 to P12, T1 and T2 being elements as defined in the description and the claims, have broad spectrum Gram-negative antimicrobial activity to e.g. inhibit the growth or to kill microorganisms such as Klebsiella pneumoniae and/or Acinetobacter baumannii and/or Escherichia coli. 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.
2] wherein the single elements T or P are α-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 of antagonizing the biological effect of the receptor FPR1. They can be used as medicaments to treat or prevent diseases or conditions in the areas of inflammatory diseases, allergic conditions, immunological disorders, neuroinflammation, neurological disorders, obstructive airway diseases, infectious diseases, ischemic reperfusion injuries and proliferative disorders such as e.g. cancer. These β-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.
A61K 38/00 - Préparations médicinales contenant des peptides
C07K 14/47 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés provenant de mammifères
A01N 37/18 - Biocides, produits repoussant ou attirant les animaux nuisibles, ou régulateurs de croissance des végétaux, contenant des composés organiques comportant un atome de carbone possédant trois liaisons à des hétéro-atomes, avec au plus deux liaisons à un halogène, p. ex. acides carboxyliques contenant le groupe —CO—N, p. ex. amides ou imides d'acide carboxyliqueLeurs thio-analogues
A61P 17/00 - Médicaments pour le traitement des troubles dermatologiques
A61P 29/00 - Agents analgésiques, antipyrétiques ou anti-inflammatoires non centraux, p. ex. agents antirhumatismauxMédicaments anti-inflammatoires non stéroïdiens [AINS]
14 being 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.
A novel combination comprising a β-hairpin peptidomimetic of the formula cyclo(-Thr-Trp-lle-Dab-Orn-DDab-Dab-Trp-Dab-Dab-Ala-Ser-DPro-Pro) (I), and a compound of the glycylcycline class, especially tigecycline, that enable therapeutic control of specific bacterial infections in human or animals at doses of the individual compounds lower than either of the compounds administered alone. The combination can be used as a medicament to treat e.g. skin or soft tissue infections; eye, ear, blood stream, or intra-abdominal infections; infections related to respiratory diseases, to bone diseases, to cardiovascular diseases, to genitourinal diseases, or to gastrointestinal diseases.
A novel combination comprising a β-hairpin peptidomimetic of the formula cyclo(-Thr-Trp-Ile-Dab-Orn-DDab-Dab-Trp-Dab-Dab-Ala-Ser-DPro-Pro) (I), and a further compound with antibiotic activity, that enable therapeutic control of specific bacterial infections in human or animals at doses of the individual compounds lower than either of the compounds administered alone. The combination can be used as a medicament to treat e.g. skin or soft tissue infections; eye, ear, blood stream, or intra-abdominal infections; infections related to respiratory diseases, to bone diseases, to cardiovascular diseases, to genitourinal diseases, or to gastrointestinal diseases.
β-Hairpin peptidomimetics of the general formula cyclo(-Tyr1-His2-Xaa3-Cys4-Ser5-Xaa6-DPro7-Xaa8-Arg9-Tyr10-Cys11-Tyr12-Xaa13-Xaa14-Xaa15-Pro16-), disulfide bond between Cys4 and Cys11, and pharmaceutically acceptable salts thereof, with Xaa3, Xaa6, Xaa8, Xaa13, Xaa14 and Xaa15 being 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.
The conformationally restricted, spatially defined macrocyclic ring system of formula (I) is constituted by three distinct molecular parts: Template A, conformation Modulator B and Bridge C. Macrocycles described by this ring system I are readily manufactured by parallel synthesis or combinatorial chemistry in solution or on solid phase. They are designed to interact with a variety of specific biological target classes, examples being agonistic or antagonistic activity on G-protein coupled receptors (GPCRs), inhibitory activity on enzymes or antimicrobial activity. In particular, these macrocycles show inhibitory activity on endothelin converting enzyme of subtype 1 (ECE-1 ) and/or the cysteine protease cathepsin S (CatS), and/or act as antagonists of the oxytocin (OT) receptor, thyrotropin-releasing hormone (TRH) receptor and/or leukotriene B4 (LTB4) receptor, and/or as agonists of the bombesin 3 (BB3) receptor, and/or show antimicrobial activity against at least one bacterial strain. Thus they are showing great potential as medicaments for a variety of diseases.
C07D 273/02 - Composés hétérocycliques contenant des cycles comportant des atomes d'azote et d'oxygène comme uniques hétéro-atomes du cycle, non prévus par les groupes comportant deux atomes d'azote et un seul atome d'oxygène
C07D 515/22 - Composés hétérocycliques contenant dans le système condensé au moins un hétérocycle comportant des atomes d'azote, d'oxygène et de soufre comme uniques hétéro-atomes du cycle, non prévus dans les groupes , ou dans lesquels le système condensé contient au moins quatre hétérocycles
C07D 291/08 - Composés hétérocycliques contenant des cycles comportant des atomes d'azote, d'oxygène et de soufre comme uniques hétéro-atomes du cycle condensés avec des carbocycles ou avec des systèmes carbocycliques
A61K 31/395 - Composés hétérocycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. guanéthidine ou rifamycines
Shigella boydii. 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.
Novel template-fixed β-hairpin peptidomimetics of the general formula (I): cyclo[P1-P2-P3-P4-P5-P6-P7-P8-P9-P10-P11-P12-P13-P14-T1-T2] wherein the single elements T or P are α-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 of antagonizing the biological effect of the receptor FPR1. They can be used as medicaments to treat or prevent diseases or conditions in the areas of inflammatory diseases, allergic conditions,immunological disorders, neuroinflammation, neurological disorders, obstructive airway diseases, infectious diseases, ischemic reperfusion injuries and proliferative disorders such as e.g. cancer. These β-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.
Specific template-fixed β-hairpin peptidomimetics of the general formula (I) wherein the single elements T or P are α-amino acid residues connected from the carbonyl (C═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 β-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.
β-Hairpin peptidomimetics of the general formula cyclo(-Tyr1-His2-Xaa3-Cys4-Ser5- Ala6-Xaa7-Xaa8-Arg9-Tyr10-Cys11-Tyr12-Xaa13-Xaa14-DPro15-Pro16-), disulfide bond between Cys4 and Cys11, and pharmaceutically acceptable salts thereof, with Xaa3, Xaa7, Xaa8, Xaa13 and Xaa14 being 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.
16-), 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.
v1.3 and as inhibitors of the β-catenin-dependent “canonical” Wnt pathway. Thus they are showing great potential as medicaments for a variety of diseases.
C07D 273/02 - Composés hétérocycliques contenant des cycles comportant des atomes d'azote et d'oxygène comme uniques hétéro-atomes du cycle, non prévus par les groupes comportant deux atomes d'azote et un seul atome d'oxygène
A61K 31/407 - Composés hétérocycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. guanéthidine ou rifamycines ayant des cycles à cinq chaînons avec un azote comme seul hétéro-atome d'un cycle, p. ex. sulpiride, succinimide, tolmétine, buflomédil condensés avec des systèmes hétérocycliques, p. ex. kétorolac, physostigmine
C07D 273/00 - Composés hétérocycliques contenant des cycles comportant des atomes d'azote et d'oxygène comme uniques hétéro-atomes du cycle, non prévus par les groupes
A61K 31/4985 - Pyrazines ou pipérazines condensées en ortho ou en péri avec des systèmes hétérocycliques
A61K 31/437 - Composés hétérocycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. guanéthidine ou rifamycines ayant des cycles à six chaînons avec un azote comme seul hétéro-atome d'un cycle condensés en ortho ou en péri avec des systèmes hétérocycliques le système hétérocyclique contenant un cycle à cinq chaînons ayant l'azote comme hétéro-atome du cycle, p. ex. indolizine, bêta-carboline
A61P 1/00 - Médicaments pour le traitement des troubles du tractus alimentaire ou de l'appareil digestif
A61P 25/28 - Médicaments pour le traitement des troubles du système nerveux des troubles dégénératifs du système nerveux central, p. ex. agents nootropes, activateurs de la cognition, médicaments pour traiter la maladie d'Alzheimer ou d'autres formes de démence
A61P 29/00 - Agents analgésiques, antipyrétiques ou anti-inflammatoires non centraux, p. ex. agents antirhumatismauxMédicaments anti-inflammatoires non stéroïdiens [AINS]
2B receptor), and on the prostaglandin F2•receptor (FP receptor). They are thus potentially useful for the treatment of hypomotility disorders of the gastrointestinal tract such as diabetic gastroparesis and constipation type irritable bowl syndrome; of CNS related diseases like migraine, schizophrenia, psychosis or depression; of ocular hypertension such as associated with glaucoma and preterm labour.
C07D 273/02 - Composés hétérocycliques contenant des cycles comportant des atomes d'azote et d'oxygène comme uniques hétéro-atomes du cycle, non prévus par les groupes comportant deux atomes d'azote et un seul atome d'oxygène
A61K 31/407 - Composés hétérocycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. guanéthidine ou rifamycines ayant des cycles à cinq chaînons avec un azote comme seul hétéro-atome d'un cycle, p. ex. sulpiride, succinimide, tolmétine, buflomédil condensés avec des systèmes hétérocycliques, p. ex. kétorolac, physostigmine
C07D 273/00 - Composés hétérocycliques contenant des cycles comportant des atomes d'azote et d'oxygène comme uniques hétéro-atomes du cycle, non prévus par les groupes
A61K 31/4985 - Pyrazines ou pipérazines condensées en ortho ou en péri avec des systèmes hétérocycliques
A61K 31/437 - Composés hétérocycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. guanéthidine ou rifamycines ayant des cycles à six chaînons avec un azote comme seul hétéro-atome d'un cycle condensés en ortho ou en péri avec des systèmes hétérocycliques le système hétérocyclique contenant un cycle à cinq chaînons ayant l'azote comme hétéro-atome du cycle, p. ex. indolizine, bêta-carboline
16 being 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.
β-Hairpin peptidomimetics of the general formula Cyclo (-Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-Xaa10-Xaa11- Xaa12-Xaa13-Xaa14-), enantiomers and pharmaceutically acceptable salts thereof, with Xaa1 - Xaa14 being 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 as Bacillus subtilis and/or Shigella boydii. 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.
C07K 14/435 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains
58.
Template-fixed beta-hairpin peptidomimetics with CXCR4 antagonizing activity
Template-fixed peptidomimetics formula (Ia) formula (Ib) wherein Z is a template-fixed chain of 14 α-amino and/or α-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.
A01N 37/18 - Biocides, produits repoussant ou attirant les animaux nuisibles, ou régulateurs de croissance des végétaux, contenant des composés organiques comportant un atome de carbone possédant trois liaisons à des hétéro-atomes, avec au plus deux liaisons à un halogène, p. ex. acides carboxyliques contenant le groupe —CO—N, p. ex. amides ou imides d'acide carboxyliqueLeurs thio-analogues
A61K 38/00 - Préparations médicinales contenant des peptides
A61P 29/00 - Agents analgésiques, antipyrétiques ou anti-inflammatoires non centraux, p. ex. agents antirhumatismauxMédicaments anti-inflammatoires non stéroïdiens [AINS]
Novel template-fixed β-hairpin peptidomimetics of the general formula (I), wherein the single elements T or P are α-amino acid residues connected from the carbonyl (C=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 β-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 mobilisation of stem cells.
Novel template-fixed β-hairpin peptidomimetics of the general formula (I) wherein the single elements T or P are α-amino acid residues connected from the carbonyl (C=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 β-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 mobilisation of stem cells.
Specific template-fixed β- hairpin peptidomimetics of the general formula (I) wherein the single elements T or P are α-amino acid residues connected from the carbonyl (C=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 β-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 mobilisation of stem cells.
β-Hairpin peptidomimetics of the general formula Cyclo(-Xaa1 -Xaa2 -Xaa3 -Xaa4 -Xaa5 -Xaa6 -Xaa7 -Xaa8 -Xaa9 -Xaa10 -Xaa11 - Xaa12 -Xaa13 -Xaa14 -Xaa15 -Xaa16 -), and pharmaceutically acceptable salts thereof, with Xaa 1 -Xaa 16 being amino acid residues of certain types which are defined in thedescription 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.
Novel template-fixed β-hairpin peptidomimetics of the general formula (I) wherein the single elements T or P are α-amino acid residues connected in either direction which, depending on their positions in the chain are 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, haematological diseases and cancer. These β-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.
Novel template-fixed β-hairpin peptidomimetics of the general formula (I) wherein the single elements T or P are α-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 β-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.
Conformationally restricted, spatially defined 12-30 membered macrocyclic ring systems of formulae Ia and Ib are constituted by three distinct molecular parts: Template A, conformation Modulator B and Bridge C. These macrocycles Ia and Ib are readily manufactured by parallel synthesis or combinatorial chemistry in solution or on solid phase. They are designed to interact with a variety of specific biological target classes, examples being the agonistic or antagonistic activity on G-protein coupled receptors (GPCRs), ion channels and signal transduction pathways. In particular, these macrocycles act as antagonists of the motilin receptor, the FP receptor and the purinergic receptors P2Y1, as modulators of the serotonin receptor of subtype 5-HT2B, as blockers of the voltage-gated potassium channel Kv1.3 and as inhibitors of the β-catenin-dependent "canonical" Wnt pathway. Thus they are showing great potential as medicaments for a variety of diseases.
C07F 7/08 - Composés comportant une ou plusieurs liaisons C—Si
A61K 31/4745 - QuinoléinesIsoquinoléines condensées en ortho ou en péri avec des systèmes hétérocycliques condensées avec des systèmes cycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. phénanthrolines
Conformationally restricted, spatially defined 12-30 membered macrocyclic ring systems of type (I) are constituted by three distinct building blocks: an aromatic template a, a conformation modulator b and a spacer moiety c as detailed in the description and the claims. Macrocycles of type (I) are readily manufactured by parallel synthesis or combinatorial chemistry. They are designed to interact with specific biological targets. In particular, they show agonistic or antagonistic activity on the motilin receptor (MR receptor), on the serotonin receptor of subtype 5-HT2B (5-HT2B receptor), and on the prostaglandin F2 • receptor (FP receptor). They are thus potentially useful for the treatment of hypomotility disorders of the gastrointestinal tract such as diabetic gastroparesis and constipation type irritable bowl syndrome; of CNS related diseases like migraine, schizophrenia, psychosis or depression; of ocular hypertension such as associated with glaucoma and preterm labour.
C07F 7/08 - Composés comportant une ou plusieurs liaisons C—Si
A61K 31/4745 - QuinoléinesIsoquinoléines condensées en ortho ou en péri avec des systèmes hétérocycliques condensées avec des systèmes cycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. phénanthrolines
β-Hairpin peptidomimetics of the general formula Cyclo(-Xaa1-Xaa2-Xaa3-Cys4-Xaa5-Xaa6-Xaa7-Xaa8-Arg9-Tyr10-Cys11- Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-), disulfide bond between Cys4 and Cys11, and pharmaceutically acceptable salts thereof, with Xaa1, Xaa2, Xaa3, Xaa5, Xaa6, Xaa7, Xaa8, Xaa12, Xaa13, Xaa14, Xaa15 and Xaa16 being 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.
C07K 7/08 - Peptides linéaires ne contenant que des liaisons peptidiques normales ayant de 12 à 20 amino-acides
C07K 7/02 - Peptides linéaires contenant au moins une liaison peptidique anormale
A61K 38/10 - Peptides ayant de 12 à 20 amino-acides
A61P 29/00 - Agents analgésiques, antipyrétiques ou anti-inflammatoires non centraux, p. ex. agents antirhumatismauxMédicaments anti-inflammatoires non stéroïdiens [AINS]
A61P 31/18 - Antiviraux pour le traitement des virus ARN du HIV
Template-fixed peptidomimetics formula (Ia) formula (Ib) wherein Z is a template-fixed chain of 14 α-amino and/or α-hydroxy acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid), are Pro, GIy, 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 β-hairpin peptidomimetics of the general formula (I) wherein Z is a template-fixed chain of 8 α-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid), are GIy or Pro 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 agonizing or antagonizing activity against urotensin II or show inhibition of the STAT6/NCoA-1 interaction and can be used for preventing or treating diseases or disorders related to urotensin II, STAT6 and NCoA-1. These β-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.
C07K 7/56 - Peptides cycliques contenant au moins une liaison peptidique anormale comportant au moins une liaison peptidique anormale dans le cycle cyclisés autrement que par l'acide diamino-2,4 butanoïque
C07K 7/64 - Peptides cycliques ne comportant que des liaisons peptidiques normales
C07K 1/02 - Procédés généraux de préparation de peptides en solution
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
03 - Produits cosmétiques et préparations de toilette; préparations pour blanchir, nettoyer, polir et abraser.
05 - Produits pharmaceutiques, vétérinaires et hygièniques
42 - Services scientifiques, technologiques et industriels, recherche et conception
Produits et services
Chemicals used in industry, science and photography, as well
as in agriculture, horticulture and forestry; unprocessed
artificial resins, unprocessed plastics; fertilizers; fire
extinguishing compositions; tempering and soldering
preparations; chemical substances for preserving foodstuffs;
tanning substances; adhesives used in industry. Bleaching preparations and other substances for laundry use;
cleaning, polishing, scouring and abrasive preparations;
soaps; perfumery, essential oils, cosmetics, hair lotions;
dentifrices. Pharmaceutical and veterinary preparations; sanitary
preparations for medical purposes; dietetic substances
adapted for medical use, food for babies; plasters,
materials for dressings; material for stopping teeth, dental
wax; disinfectants; preparations for destroying vermin;
fungicides, herbicides. Scientific and technological services and research and
design relating thereto; industrial analysis and research
services; design and development of computers and software.
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
03 - Produits cosmétiques et préparations de toilette; préparations pour blanchir, nettoyer, polir et abraser.
05 - Produits pharmaceutiques, vétérinaires et hygièniques
42 - Services scientifiques, technologiques et industriels, recherche et conception
Produits et services
Chemical products for use in industry, science, photography,
as well as agriculture, horticulture and forestry;
unprocessed artificial resins, unprocessed plastics;
fertilizers; fire extinguishing compositions; tempering and
soldering preparations; chemical substances for preserving
foodstuffs; tanning substances; adhesives used in industry. Bleaching preparations and other substances for laundry use;
cleaning, polishing, scouring and abrasive preparations;
soaps; perfumery, essential oils, cosmetics, hair lotions;
dentifrices. Pharmaceutical and medico-veterinary preparations as well as
preparations for health care; dietetic substances adapted
for medical use, food for babies; plasters, materials for
dressings; material for stopping teeth and dental wax;
disinfectants; preparations for destroying vermin;
fungicides, herbicides. Scientific and technological services and research and
design relating thereto; industrial analysis and research
services; design and development of computers and software.
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
02 - Couleurs, vernis, laques
03 - Produits cosmétiques et préparations de toilette; préparations pour blanchir, nettoyer, polir et abraser.
05 - Produits pharmaceutiques, vétérinaires et hygièniques
42 - Services scientifiques, technologiques et industriels, recherche et conception
Produits et services
Chemicals used in industry, science, photography as well as
in agriculture, horticulture and silviculture; unprocessed
artificial resins, unprocessed plastics; soil fertilizers;
chemical substances for preserving foodstuffs; tanning
substances; adhesives used in industry. Paints, varnishes, lacquers; preservatives against rust and
deterioration of wood; dyestuffs; mordants. Bleaching preparations and other substances for laundry use;
cleaning, polishing, grease removing and abrasive
preparations; soaps; perfumery, essential oils, cosmetics,
hair lotions; dentifrices. Pharmaceutical, veterinary and sanitary products;
disinfectants; products for destroying vermin; fungicides,
herbicides. Research, consultancy, planning and development based on
internal and customer data in the field of chemicals and
resins.
