The invention relates to oleoyl-lysophosphatidylinositol (oleoyl-LPI) and new synthetic derivatives thereof and uses thereof, and to pharmaceutical compositions comprising such compounds. The invention provides activators and/or up-regulators of glucoregulatory hormones such as glucagon like peptide-1 (GLP-1), and more specifically to agonists, partial agonists and reverse antagonists of GPR119 or activators of GLP-1 activity and/or synthesis and/or secretion, and pharmaceutical compositions comprising same, uses thereof in therapy of diabetes, obesity and other metabolic disorders.

The invention relates to oleoyl-lysophosphatidylinositol (oleoyl-LPI) and new synthetic derivatives thereof and uses thereof, and to pharmaceutical compositions comprising such compounds. The invention provides activators and/or up-regulators of glucoregulatory hormones such as glucagon like peptide-1 (GLP-1), and more specifically to agonists, partial agonists and reverse antagonists of GPR119 or activators of GLP-1 activity and/or synthesis and/or secretion, and pharmaceutical compositions comprising same, uses thereof in therapy of diabetes, obesity and other metabolic disorders.

The present application provides malonamide compounds, and derivatives thereof (e.g., N-aryl malonamides (NAM), acetamides, oxalamides, and the like), that are useful, for example, for the treatment of acute, chronic/persistent, and/or relapsing infections. Pharmaceutical compositions, methods of treating diseases (e.g., bacterial infections), and methods of reducing bacterial virulence are also provided.

The present application provides malonamide compounds, and derivatives thereof (e.g., N-aryl malonamides (NAM), acetamides, oxalamides, and the like), that are useful, for example, for the treatment of acute, chronic/persistent, and/or relapsing infections. Pharmaceutical compositions, methods of treating diseases (e.g., bacterial infections), and methods of reducing bacterial virulence are also provided.

This application relates to processes and intermediates for the preparation of the PD-1/PD-L1 inhibitor (R)-1-((7-cyano-2-(3′-((2-(difluoromethyl)-7-((3-hydroxypyrrolidin-1-yl)methyl)pyrido[3,2-d]pyrimidin-4-yl)amino)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)benzo[d]oxazol-5-yl)methyl)piperidine-4-carboxylic acid, and salts and crystalline forms thereof, where the PD-1/PD-L1 inhibitor and solid forms and salt forms thereof are useful in the treatment of various diseases including infectious diseases and cancer.

The present invention relates to processes of preparing PD-1/PD-L1 inhibitor (R)-1-((7-cyano-2-(3′-(3-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-1,7-naphthyridin-8-ylamino)-2,2′-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)pyrrolidine-3-carboxylic acid, or salts thereof, related synthetic intermediates, and salts of the intermediates, where the PD-1/PD-L1 inhibitor is useful in the treatment of various diseases including infectious diseases and cancer.

The present invention provides a process of producing a trifluoromcthoxylated aryl or trifluoromothoxylated heteroaryl having the structure: ##STR00001##
wherein
A is an aryl or heteroaryl, each with or without substitution; and
R.sub.1 is —H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), —NH-(alkyl), —N(alkyl).sub.2, —NH-(alkenyl), —NH-(alkynyl) —NH-(aryl), —NH-(heteroaryl), —O-(alkyl), —O-(alkenyl), —O-(alkynyl), —O-(aryl), —O-(heteroaryl), —S-(alkyl), —S-(alkenyl), —S-(alkynyl), —S-(aryl), or —S-(heteroaryl), comprising:
(a) reacting a compound having the structure: ##STR00002##
with a trifluoromethylating agent in the presence of a base in a first suitable solvent under conditions to produce a compound having the structure: ##STR00003##
and
(b) maintaining the compound produced in step (a) in a second suitable solvent under conditions sufficient to produce the trifluoromethoxylated aryl or trifluormethoxylated heteroaryl having the structure: ##STR00004##

The present invention provides a process of producing a trifluoromcthoxylated aryl or trifluoromothoxylated heteroaryl having the structure: ##STR00001##
wherein
A is an aryl or heteroaryl, each with or without substitution; and
R.sub.1 is —H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), —NH-(alkyl), —N(alkyl).sub.2, —NH-(alkenyl), —NH-(alkynyl) —NH-(aryl), —NH-(heteroaryl), —O-(alkyl), —O-(alkenyl), —O-(alkynyl), —O-(aryl), —O-(heteroaryl), —S-(alkyl), —S-(alkenyl), —S-(alkynyl), —S-(aryl), or —S-(heteroaryl), comprising:
(a) reacting a compound having the structure: ##STR00002##
with a trifluoromethylating agent in the presence of a base in a first suitable solvent under conditions to produce a compound having the structure: ##STR00003##
and
(b) maintaining the compound produced in step (a) in a second suitable solvent under conditions sufficient to produce the trifluoromethoxylated aryl or trifluormethoxylated heteroaryl having the structure: ##STR00004##

The present invention provides a process of producing a trifluoromcthoxylated aryl or trifluoromothoxylated heteroaryl having the structure: ##STR00001##
wherein
A is an aryl or heteroaryl, each with or without substitution; and
R.sub.1 is —H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), —NH-(alkyl), —N(alkyl).sub.2, —NH-(alkenyl), —NH-(alkynyl) —NH-(aryl), —NH-(heteroaryl), —O-(alkyl), —O-(alkenyl), —O-(alkynyl), —O-(aryl), —O-(heteroaryl), —S-(alkyl), —S-(alkenyl), —S-(alkynyl), —S-(aryl), or —S-(heteroaryl), comprising:
(a) reacting a compound having the structure: ##STR00002##
with a trifluoromethylating agent in the presence of a base in a first suitable solvent under conditions to produce a compound having the structure: ##STR00003##
and
(b) maintaining the compound produced in step (a) in a second suitable solvent under conditions sufficient to produce the trifluoromethoxylated aryl or trifluormethoxylated heteroaryl having the structure: ##STR00004##

Provided herein are compounds of formula I, compositions comprising the compounds and method of treating various diseases with the compounds and compositions.