The present disclosure provides compounds which are immunomodulators 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.

It has been found that the membrane permeability of peptide compounds can be improved by making at least one of amino acids constituting the peptide compound be an amino acid having a side chain capable of forming an intramolecular hydrogen bond.

It has been found that the membrane permeability of peptide compounds can be improved by making at least one of amino acids constituting the peptide compound be an amino acid having a side chain capable of forming an intramolecular hydrogen bond.

The present invention relates to polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which bind to OX40. The invention also relates to multimeric binding complexes of polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold that are functional agonists of OX40. The invention also includes drug conjugates comprising said peptides and complexes, conjugated to one or more effector and/or functional groups, to pharmaceutical compositions comprising said peptide ligands, complexes and drug conjugates and to the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder mediated by OX40.

The present invention relates to polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which bind to OX40. The invention also relates to multimeric binding complexes of polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold that are functional agonists of OX40. The invention also includes drug conjugates comprising said peptides and complexes, conjugated to one or more effector and/or functional groups, to pharmaceutical compositions comprising said peptide ligands, complexes and drug conjugates and to the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder mediated by OX40.

The disclosure relates to inhibitors of PCSK9 useful in the treatment of cholesterol lipid metabolism, and other diseases in which PCSK9 plays a role, having the Formula (I):

##STR00001## or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, N-oxide, or tautomer thereof, wherein X.sub.1, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.6′, R.sub.7, R.sub.7′, R.sub.8, R.sub.9, R.sub.9′, R.sub.10, R.sub.11, R.sub.12, and n are described herein.

The disclosure relates to inhibitors of PCSK9 useful in the treatment of cholesterol lipid metabolism, and other diseases in which PCSK9 plays a role, having the Formula (I):

##STR00001## or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, N-oxide, or tautomer thereof, wherein X.sub.1, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.6′, R.sub.7, R.sub.7′, R.sub.8, R.sub.9, R.sub.9′, R.sub.10, R.sub.11, R.sub.12, and n are described herein.

The invention provides compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein the variables are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12D mutant of Kirsten rat sarcoma (K-Ras) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

##STR00001##

Insect-repellent compositions containing compounds of Formula I: ##STR00001##
wherein R is a 5-membered or 6-membered carbon-containing ring, having zero, one, two, or three double bonds, and having zero, one, two, or three heteroatoms, wherein the one, two, or three heteroatoms, if present, are selected from nitrogen, oxygen, and sulfur; “x” is an integer from 0 to 5; and “y” is an integer from 1 to 10.