The present invention relates to a family of S-substituted quinazoline derivatives that inhibitors of the enzyme phosphodiesterase 7 (PDE7), useful for the treatment or prevention of diseases mediated by said enzyme, especially inflammatory, neurodegenerative, neurological, psychiatric and/or autoimmune diseases.

The present invention relates to a family of S-substituted quinazoline derivatives that inhibitors of the enzyme phosphodiesterase 7 (PDE7), useful for the treatment or prevention of diseases mediated by said enzyme, especially inflammatory, neurodegenerative, neurological, psychiatric and/or autoimmune diseases.

The present invention provides a process of producing a trifluoromethoxylated aryl or trifluoromethoxylated heteroaryl having the structure:

##STR00001##

wherein A is an aryl or heteroaryl, each with or without subsutitution; and R.sub.1 is —H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), —NH-(alkyl), —N(alkyl).sub.7, —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 trifluoromethoxylated aryl or trifluoromethoxylated heteroaryl having the structure:

##STR00001##

wherein A is an aryl or heteroaryl, each with or without subsutitution; and R.sub.1 is —H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), —NH-(alkyl), —N(alkyl).sub.7, —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##

A new class of antibiotics effective against methicillin-resistant Staphylococcus aureus (MRSA) is disclosed. Compounds of this class can impair cell-wall biosynthesis by binding to both the allosteric and the catalytic domains of penicillin-binding protein (PBP) 2a. This class of antibiotics holds promise in reversing obsolescence of staphylococcal PBPs as important targets for antibiotics. Embodiments of the invention thus provide novel antibacterial compounds that target penicillin-binding proteins and/or other important cellular targets. Methods for inhibiting the growth and/or replication of bacteria using the compounds described herein are also provided. Various embodiments exhibit activity against gram positive bacteria, including drug-resistant strains of Staphylococcus aureus.

A new class of antibiotics effective against methicillin-resistant Staphylococcus aureus (MRSA) is disclosed. Compounds of this class can impair cell-wall biosynthesis by binding to both the allosteric and the catalytic domains of penicillin-binding protein (PBP) 2a. This class of antibiotics holds promise in reversing obsolescence of staphylococcal PBPs as important targets for antibiotics. Embodiments of the invention thus provide novel antibacterial compounds that target penicillin-binding proteins and/or other important cellular targets. Methods for inhibiting the growth and/or replication of bacteria using the compounds described herein are also provided. Various embodiments exhibit activity against gram positive bacteria, including drug-resistant strains of Staphylococcus aureus.

The present invention relates to novel heterocyclic compounds based on a quinazoline scaffold, which bind effectively to the mitochondrial translocator protein (TSPO), and counteract cell death processes. These compounds can also stimulate neuronal differentiation. The present invention further relates to pharmaceutical compositions including such compounds, and methods of using these compounds for the prevention and treatment of brain damage resulting from brain injury, especially secondary brain damage due to traumatic brain injury (TBI). The compounds of the invention are also useful in preventing, treating, and curing brain damage due to neurodegenerative diseases, including underlying and associated pathological and mental disorders. The compounds can also be used to prevent and treat brain damage due to infection, toxic challenges, and excessive drug use, e.g., recreational, over the counter, or prescription drugs. These compounds can also prevent heart failure, for example associated with brain injuries and brain diseases.

The present invention relates to novel heterocyclic compounds based on a quinazoline scaffold, which bind effectively to the mitochondrial translocator protein (TSPO), and counteract cell death processes. These compounds can also stimulate neuronal differentiation. The present invention further relates to pharmaceutical compositions including such compounds, and methods of using these compounds for the prevention and treatment of brain damage resulting from brain injury, especially secondary brain damage due to traumatic brain injury (TBI). The compounds of the invention are also useful in preventing, treating, and curing brain damage due to neurodegenerative diseases, including underlying and associated pathological and mental disorders. The compounds can also be used to prevent and treat brain damage due to infection, toxic challenges, and excessive drug use, e.g., recreational, over the counter, or prescription drugs. These compounds can also prevent heart failure, for example associated with brain injuries and brain diseases.

The present disclosure relates to compounds, which are useful for inhibition of BET protein function by binding to bromodomains, and their use in therapy.

The present disclosure relates to compounds, which are useful for inhibition of BET protein function by binding to bromodomains, and their use in therapy.