44 results about "Macrocyclic peptide" patented technology

Compounds of formula I: wherein D, R4, R3, L0, L1, L2, R2 and Rc are defined herein; or a pharmaceutically acceptable salt thereof, useful as inhibitors of the HCV NS3 protease.

Compounds of formula (I): wherein R1, R2, X, R3, D, and the dotted line b are as defined herein; or a pharmaceutically acceptable salt or ester thereof, are useful as inhibitors of the HCV NS3 protease.

Compounds of formula (I): wherein R1 is (C1-8)alkyl, (C3-7)cycloalkyl, {(C1-6)alkyl-(C3-7)cycloalkyl} or Het, which are all optionally substituted from 1 to 3 times with halo, cyano, nitro, O—(C1-6)alkyl, amido, amino or phenyl, or R1 is C6 or C10 aryl which is optionally substituted from 1 to 3 times with halo, cyano, nitro, (C1-6)alkyl, O—(C1-6)alkyl, amido, amino or phenyl; or a pharmaceutically acceptable salt thereof, useful as an inhibitor of the HCV NS3 protease.

This invention discloses short chain peptides that have been constrained to adopt an alpha helical conformation and their use as alpha helical scaffolds for directing amino acid side chains into positions analogous to those found in longer chain alpha helical peptides and for attaching peptidic or non-peptidic appendages in order to mimic side chains of longer alpha helical peptides. More particularly the invention discloses alpha helical cyclic pentapeptides and their use as alpha helical scaffolds or macrocyclic alpha helical modules, either alone, or within longer chain peptides or attached to other macrocyclic peptides or attached to non-peptidic structures, for the purpose of mimicking naturally occurring peptides or proteins, and as agonists or antagonists of the biological activity of naturally-occurring peptides or proteins or for the preparation of new materials.

Compounds of formula I:wherein R1 is hydroxy or NHSO2R1A wherein R1A is (C1-8)alkyl, (C3-7)cycloalkyl or {(C1-6)alkyl-(C3-7)cycloalkyl}, which are all optionally substituted from 1 to 3 times with halo, cyano, nitro, O(C1-6)alkyl, amido, amino or phenyl, or R1A is C6 or C10 aryl which is optionally substituted from 1 to 3 times with halo, cyano, nitro, (C1-6)alkyl, O(C1-6)alkyl, amido, amino or phenyl; R2 is (C5-6)cycloalkyl and R3 is cyclopentyl; or a pharmaceutically acceptable salt thereof, useful as inhibitors of the HCV NS3 protease.

Compounds of formula (I): wherein R1 is (C1-8)alkyl, (C3-7)cycloalkyl, {(C1-6)alkyl-(C3-7)cycloalkyl} or Het, which are all optionally substituted from 1 to 3 times with halo, cyano, nitro, O—(C1-6)alkyl, amido, amino or phenyl, or R1 is C6 or C10 aryl which is optionally substituted from 1 to 3 times with halo, cyano, nitro, (C1-6)alkyl, O—(C1-6)alkyl, amido, amino or phenyl; or a pharmaceutically acceptable salt thereof, useful as an inhibitor of the HCV NS3 protease.

Compounds of formula I:wherein D, R4, R3, L0, L1, L2, R2 and RC are defined herein; or a pharmaceutically acceptable salt thereof, useful as inhibitors of the HCV NS3 protease.

Disclosed are cyclosporine derivatives in which the 3-Sarcosine carbon and 5-Valine nitrogen are each substituted by a non-hydrogen substituent, and their use as pharmaceuticals, in particular for the treatment of hepatitis C virus.

Methods and compositions are provided that utilize synthetic molecules and genetically encoded polypeptides to generate macrocyclic peptide-containing molecules with a hybrid peptidic / non-peptidic backbone. Also provided are nucleic acid molecules, polypeptides, and methods for generating libraries of macrocyclic peptide-containing molecules with a hybrid peptidic / non-peptidic backbone. These methods can be used to increase the structural diversity of ligand libraries as well as facilitate the functional screening of these libraries to identify compound(s) with desired activity properties.

The present disclosure provides novel macrocyclic peptides which inhibit the PD-1 / PD-L1 and PD-L1 / CD80 protein / protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.

The present disclosure provides compounds which are immunomodulators and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.

An object of the present invention is to provide a peptide excellent in resistance against metabolism, having a stable structure in vivo, and capable of penetrating a cell membrane and reaching in cells.The present invention provides a macrocyclic peptide having a macrocyclic structure comprised of four or more amino acids. At least two amino acids not adjacent to each other have a hydrophobic side chain and the hydrophobic side chains interact with each other inside the ring of the macrocyclic peptide in a hydrophilic environment.

A macrocyclic peptide deformylase (PDF) inhibitor comprising a peptide or peptide mimetic having three residues, P1′, P2′, and P3′, wherein P2′ connects P1′ and P3′,wherein P1′ and P3′ each have a side chain, and wherein the side chains on P1′ and P3′ are crosslinked to form the macrocyclic PDF inhibitor. The side chains of P1′ and P3′ interact with the PDF active site, and preferably, P2′ has a side chain that interacts with a solvent. Also provided are methods of inhibiting the growth of a bacterium, the methods comprising contacting the bacterium with an anti-bacterial effective amount of the inventive macrocyclic PDF inhibitor. Additionally, a method of treating a bacterial infection in a subject comprising administering an effective amount of a macrocyclic PDF inhibitor to a subject in need of treatment. Additionally, methods of preparing macrocyclic PDF inhibitors comprising a) choosing an acyclic base molecule, having at least some PDF inhibitory activity, the acyclic base molecule having a first residue having a first side chain that interacts with the PDF active site and a second residue having a second that interacts with the PDF active site; and b) crosslinking the first side chain and the second side chain to form a macrocyclic PDF inhibitor.

The present disclosure provides novel macrocyclic peptides which inhibit the PD-1 / PD-L1 and PD-L1 / CD80 protein / protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.

Methods and compositions are provided that utilize synthetic molecules and genetically encoded polypeptides to generate macrocyclic peptide-containing molecules with a hybrid peptidic / non-peptidic backbone. Also provided are nucleic acid molecules, polypeptides, and methods for generating libraries of macrocyclic peptide-containing molecules with a hybrid peptidic / non-peptidic backbone. These methods can be used to increase the structural diversity of ligand libraries as well as facilitate the functional screening of these libraries to identify compound(s) with desired activity properties.

Compounds of formula (I): wherein R1 is hydroxyl or NHSO2R1A, wherein R1A is (C1-8) alkyl, (C3-7) cycloalkyl or {(C1-6) alkyl-(C3-7) cycloalkyl }, all of which are optionally substituted 1 to 3 times with halogen, cyano, nitro, O(C1-6) alkyl, amido, amino or phenyl, or R1A is C6 or C10 aryl, depending on Requires 1 to 3 substitutions with halogen, cyano, nitro, (C1-6) alkyl, O(C1-6) alkyl, amido, amino or phenyl; R2 is (C5-6) ring Alkyl and R3 are cyclopentyl; or a pharmaceutically acceptable salt thereof, useful as an HCV NS3 protease inhibitor.

A macrocyclic peptide deformylase (PDF) inhibitor comprising a peptide or peptide mimetic having three residues, P1′, P2′, and P3′, wherein P2′ connects P1′ and P3′, wherein P1′ and P3′ each have a side chain, and wherein the side chains on P1′ and P3′ are crosslinked to form the macrocyclic PDF inhibitor. The side chains of P1′ and P3′ interact with the PDF active site, and preferably, P2′ has a side chain that interacts with a solvent. Also provided are methods of inhibiting the growth of a bacterium, the methods comprising contacting the bacterium with an anti-bacterial effective amount of the inventive macrocyclic PDF inhibitor. Additionally, a method of treating a bacterial infection in a subject comprising administering an effective amount of a macrocyclic PDF inhibitor to a subject in need of treatment. Additionally, methods of preparing macrocyclic PDF inhibitors comprising a) choosing an acyclic base molecule, having at least some PDF inhibitory activity, the acyclic base molecule having a first residue having a first side chain that interacts with the PDF active site and a second residue having a second that interacts with the PDF active site; and b) crosslinking the first side chain and the second side chain to form a macrocyclic PDF inhibitor.

The present invention relates to novel compounds, in particular peptidic macrocyclic peptides, that are capable of binding to and / or neutralizing influenza viruses, in particular influenza A viruses comprising HA of the H1 subtype 1, and to pharmaceutical compositions comprising such compounds. The invention also relates to the use of the peptidomimetic 5 compounds in the diagnosis, prophylaxis and / or treatment of influenza virus infections.

The invention relates to macrocyclic peptides and pharmaceutical compositions thereof. The invention further relates to pharmaceutical compositions for modulating opioid receptor activity.

Compositions are provided for formulations of θ-defensin and / or a θ-defensin analog that are highly suitable for parenteral administration. Such formulations provide the θ-defensin and / or a θ-defensin analog in a slightly acidic buffer that includes propylene glycol. Surprisingly, Inventors have found that such formulation increase bioavailability of a θ-defensin and / or a θ-defensin analog so provided by at least a factor of 10 relative to conventional isotonic saline solutions, and that such formulations dramatically improved bioavailability in human subjects relative to animal models. Inventors have also found that such formulations advantageously exhibit low viscosity at high peptide concentrations, reducing injection volume permitting sterilization by simple filtration.

The invention relates to macrocyclic peptides and pharmaceutical compositions thereof. The invention further provides macrocyclic tetrapeptides comprising sarcosine. The invention further relates to pharmaceutical compositions for modulating opioid receptor activity. The macrocyclic tetrapeptides provided herein are useful in treating diseases or disorders relating to the activity of one or more opioid receptors, such as neurological disorders.

The invention provides compositions and methods for inhibiting protein-protein interactions with cap-binding protein 80 (CBP80). In one embodiment, the invention provides compositions comprising linear and macrocylic peptides. In one embodiment, the invention provides methods for treating cancer, heart disease, autoimmune disorders, obesity, diabetes, or chronic inflammation disorders associated with the PGC1 family of co-activators.

Provided herein are cyclic peptide inhibitors of autophagy that bind to LC3. These cyclic peptides may be used to treat diseases or disorders associated with autophagy, such as, for example, cancer, diabetes, cardiovascular disease, and neurological disorders. These cyclic peptides may also be used to sensitize cancers to front-line chemotherapy, immunotherapy, and / or radiation therapy.

Disclosed are cyclosporine derivatives in which the 3-Sarcosine carbon and 5-Valine nitrogen are each substituted by a non-hydrogen substituent, and their use as pharmaceuticals, in particular for the treatment of hepatitis C virus.