The present disclosure is concerned with 2-pyrimidone compounds that are capable of inhibiting a viral infection and methods of treating alphavirus viral infections such as, for example, chikungunya, Eastern equine encephalitis (EEEV), Western equine encephalitis (WEEV), and Venezuelan equine encephalitis using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Provided herein is an LpxC inhibitor compound, as well as methods of making and pharmaceutical compositions comprising said compound, and methods of use thereof in the treatment of disease that would benefit from treatment with an LpxC inhibitor, including gram-negative bacterial infections such as urinary tract infections and the like.

The invention provides for a method for screening compounds that bind to and modulate a histone acetyltransferase protein. The invention further provides methods for treating neurodegenerative disorders, conditions associated with accumulated amyloid-beta peptide deposits, Tau protein levels, and/or accumulations of alpha-synuclein as well as cancer by administering a HAT-activating compound to a subject.

The invention provides for a method for screening compounds that bind to and modulate a histone acetyltransferase protein. The invention further provides methods for treating neurodegenerative disorders, conditions associated with accumulated amyloid-beta peptide deposits, Tau protein levels, and/or accumulations of alpha-synuclein as well as cancer by administering a HAT-activating compound to a subject.

A compound represented by Formula (I):

##STR00001##

wherein

##STR00002##

or the like
Y.sup.1 is O or the like; Z.sup.1 is C(R.sup.4) or N; Z.sup.2a is C(R.sup.5a) or the like; Z.sup.3a is C(R.sup.6) or the like; R.sup.4, R.sup.5a and R.sup.6 are each independently a hydrogen atom or the like; R.sup.1 is substituted or unsubstituted aromatic carbocyclyl or the like; R.sup.2a, R.sup.2b, R.sup.2c and R.sup.2d are each independently a hydrogen atom or the like; X is N(R.sup.7a) or the like; R.sup.7a is a hydrogen atom or the like; R.sup.3 is

##STR00003##

or the like
Ring B is a 6-membered aromatic carbocycle or the like; R.sup.9a and R.sup.10a are each independently halogen or the like; n is an integer from 1 to 5; m is an integer from 0 to 4; and p 1 is an integer from 0 to 3,
or a pharmaceutically acceptable salt thereof.

A compound represented by Formula (I):

##STR00001##

wherein

##STR00002##

or the like
Y.sup.1 is O or the like; Z.sup.1 is C(R.sup.4) or N; Z.sup.2a is C(R.sup.5a) or the like; Z.sup.3a is C(R.sup.6) or the like; R.sup.4, R.sup.5a and R.sup.6 are each independently a hydrogen atom or the like; R.sup.1 is substituted or unsubstituted aromatic carbocyclyl or the like; R.sup.2a, R.sup.2b, R.sup.2c and R.sup.2d are each independently a hydrogen atom or the like; X is N(R.sup.7a) or the like; R.sup.7a is a hydrogen atom or the like; R.sup.3 is

##STR00003##

or the like
Ring B is a 6-membered aromatic carbocycle or the like; R.sup.9a and R.sup.10a are each independently halogen or the like; n is an integer from 1 to 5; m is an integer from 0 to 4; and p 1 is an integer from 0 to 3,
or a pharmaceutically acceptable salt thereof.

A compound represented by Formula (I): ##STR00001##
wherein ##STR00002##
or the like,
Y.sup.1 is O or the like; Z.sup.1 is C(R.sup.4) or N; Z.sup.2a is C(R.sup.5a) or the like; Z.sup.3a is C(R.sup.6) or the like; R.sup.4, R.sup.5a and R.sup.6 are each independently a hydrogen atom or the like; R.sup.1 is substituted or unsubstituted aromatic carbocyclyl or the like; R.sup.2a, R.sup.2b, R.sup.2c and R.sup.2d are each independently a hydrogen atom or the like; X is N(R.sup.7a) or the like; R.sup.7a is a hydrogen atom or the like; R.sup.3 is ##STR00003##
or the like,
Ring B is a 6-membered aromatic carbocycle or the like; R.sup.9a and R.sup.10a are each independently halogen or the like; n is an integer from 1 to 5; m is an integer from 0 to 4; and p1 is an integer from 0 to 3,
or a pharmaceutically acceptable salt thereof.

A compound represented by Formula (I): ##STR00001##
wherein ##STR00002##
or the like,
Y.sup.1 is O or the like; Z.sup.1 is C(R.sup.4) or N; Z.sup.2a is C(R.sup.5a) or the like; Z.sup.3a is C(R.sup.6) or the like; R.sup.4, R.sup.5a and R.sup.6 are each independently a hydrogen atom or the like; R.sup.1 is substituted or unsubstituted aromatic carbocyclyl or the like; R.sup.2a, R.sup.2b, R.sup.2c and R.sup.2d are each independently a hydrogen atom or the like; X is N(R.sup.7a) or the like; R.sup.7a is a hydrogen atom or the like; R.sup.3 is ##STR00003##
or the like,
Ring B is a 6-membered aromatic carbocycle or the like; R.sup.9a and R.sup.10a are each independently halogen or the like; n is an integer from 1 to 5; m is an integer from 0 to 4; and p1 is an integer from 0 to 3,
or a pharmaceutically acceptable salt thereof.

Novel compounds and pharmaceutically acceptable salts capable of modulating the activity of kinases, including Akt, ERK and MEK. Such modulation affects biological functions, for example, by inhibiting cell proliferation and/or inducing apoptosis. Also provided are pharmaceutical compositions and medicaments, comprising the compounds or salts of the invention, alone or in combination with other therapeutic agents or palliative agents.

In various embodiments novel allosteric antagonists of the CRFR1 receptor are provided. It discovered that allosteric CRFR1 receptor antagonists are effective to modulate p-Tau levels in Alzheimer's disease (AD) models. In one illustrative embodiment, a compound that is a CRFR1 receptor antagonist is a compound according to the formula ##STR00001## or a pharmaceutically acceptable salt, ester, amide, solvate, or prodrug thereof.