Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods that restore DNA binding affinity of p53 mutants. The compounds of the present disclosure can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.

Described herein are novel γ- and δ-propargyl carboxylic acids and esters. The novel compositions are antagonists of CSE and may be used to modulate of the activity of the carotid body, therefore providing therapeutic benefits for sleep-related breathing disorders and related conditions.

An improved process for preparing verdiperstat is disclosed. The process includes the steps of reacting a compound having formula

##STR00001##

or a salt thereof, wherein R is the same or different and is each independently a C1-05 alkyl with 3-(dimethylamino)acrylonitrile to obtain a compound having formula

##STR00002##

and converting the compound having formula

##STR00003##

to verdiperstat.

An improved process for preparing verdiperstat is disclosed. The process includes the steps of reacting a compound having formula

##STR00001##

or a salt thereof, wherein R is the same or different and is each independently a C1-05 alkyl with 3-(dimethylamino)acrylonitrile to obtain a compound having formula

##STR00002##

and converting the compound having formula

##STR00003##

to verdiperstat.

Compounds of formula (II):

##STR00001##

wherein

##STR00002##

R.sup.1, R.sup.2, R.sup.5 and R.sup.13 are described herein, or a stereoisomer, enantiomer or tautomer thereof or mixtures thereof, or a pharmaceutically acceptable salt or solvate thereof, are described herein, as well as other compounds. These compounds have activity as SHIP1 modulators, and thus may be useful in treating a variety of diseases, disorders or conditions that would benefit from SHIP1 modulation. Compositions comprising a compound of the invention are also disclosed, as are methods of SHIP1 modulation by administration of such compounds to an animal in need thereof.

Compounds of formula (II):

##STR00001##

wherein

##STR00002##

R.sup.1, R.sup.2, R.sup.5 and R.sup.13 are described herein, or a stereoisomer, enantiomer or tautomer thereof or mixtures thereof, or a pharmaceutically acceptable salt or solvate thereof, are described herein, as well as other compounds. These compounds have activity as SHIP1 modulators, and thus may be useful in treating a variety of diseases, disorders or conditions that would benefit from SHIP1 modulation. Compositions comprising a compound of the invention are also disclosed, as are methods of SHIP1 modulation by administration of such compounds to an animal in need thereof.

In immunoglobulin light chain amyloidosis (AL), the unique antibody light chain (LC) protein that is secreted by monoclonal plasma cells in each patient misfolds and/or aggregates, a process leading to organ degeneration. For treating AL patients, such as those with substantial cardiac involvement who have difficulty tolerating existing chemotherapy regimens, provided herein are small molecule compounds of Formula Ia, Formula Ib, and Formula II that are kinetic stabilizers of the native dimeric structure of full-length LCs, which compounds can slow or stop the amyloidogenicity cascade at its origin.

In immunoglobulin light chain amyloidosis (AL), the unique antibody light chain (LC) protein that is secreted by monoclonal plasma cells in each patient misfolds and/or aggregates, a process leading to organ degeneration. For treating AL patients, such as those with substantial cardiac involvement who have difficulty tolerating existing chemotherapy regimens, provided herein are small molecule compounds of Formula Ia, Formula Ib, and Formula II that are kinetic stabilizers of the native dimeric structure of full-length LCs, which compounds can slow or stop the amyloidogenicity cascade at its origin.

A compound represented by Formula (I) is provided:

##STR00001##

In Formula (I), R.sup.3, R.sup.4, and R.sup.5 each independently represent an electron-withdrawing group; R.sup.1, R.sup.2, R.sup.6, and R.sup.7 each independently represent a hydrogen atom, a heterocyclic group, a halogen atom, a nitro group, a cyano group, a hydroxy group, a thiol group, a carboxy group, —SCF.sub.3, —SF.sub.5, —SF.sub.3, —SO.sub.3H, —SO.sub.2H, an aliphatic hydrocarbon group having 1 to 25 carbon atoms which may have a substituent, or an aromatic hydrocarbon group having 6 to 18 carbon atoms which may have a substituent; and R.sup.1 and R.sup.2, R.sup.1 and R.sup.6, R.sup.6 and R.sup.7, and R.sup.4 and R.sup.5 may be linked to each other to form a ring.

A compound represented by Formula (I) is provided:

##STR00001##

In Formula (I), R.sup.3, R.sup.4, and R.sup.5 each independently represent an electron-withdrawing group; R.sup.1, R.sup.2, R.sup.6, and R.sup.7 each independently represent a hydrogen atom, a heterocyclic group, a halogen atom, a nitro group, a cyano group, a hydroxy group, a thiol group, a carboxy group, —SCF.sub.3, —SF.sub.5, —SF.sub.3, —SO.sub.3H, —SO.sub.2H, an aliphatic hydrocarbon group having 1 to 25 carbon atoms which may have a substituent, or an aromatic hydrocarbon group having 6 to 18 carbon atoms which may have a substituent; and R.sup.1 and R.sup.2, R.sup.1 and R.sup.6, R.sup.6 and R.sup.7, and R.sup.4 and R.sup.5 may be linked to each other to form a ring.