Disclosed are compounds which may be utilized to inhibit transcription by RNA Polymerase II (Pol II), and in particular to disrupt the Super Elongation Complex (SEC). The compounds may be utilized in pharmaceutical compositions and methods for treating diseases and disorders associated with the biological activity of SEC, and in particular, diseases and disorders that are associated with high levels of expression of genes whose expression is SEC-dependent and that promote, support, or otherwise are required for the disease or disorder such as cancers.

Disclosed are compounds which may be utilized to inhibit transcription by RNA Polymerase II (Pol II), and in particular to disrupt the Super Elongation Complex (SEC). The compounds may be utilized in pharmaceutical compositions and methods for treating diseases and disorders associated with the biological activity of SEC, and in particular, diseases and disorders that are associated with high levels of expression of genes whose expression is SEC-dependent and that promote, support, or otherwise are required for the disease or disorder such as cancers.

2-aminothiazole derivatives represented by formula (I), where R.sub.1 and R.sub.2 represent cycloalkyls, respectively; or R.sub.1 represents a substituted aromatic group, and R.sub.2 represents H, a C.sub.1-C.sub.11 alkyl, —CH.sub.2Ph (benzyl), or a methyl ether including a C.sub.1-C.sub.11 alkyl. R.sub.3 is a substituent including an amino group. X represents a carbonyl or a methylene and n is an integer from 0 to 5.

2-aminothiazole derivatives represented by formula (I), where R.sub.1 and R.sub.2 represent cycloalkyls, respectively; or R.sub.1 represents a substituted aromatic group, and R.sub.2 represents H, a C.sub.1-C.sub.11 alkyl, —CH.sub.2Ph (benzyl), or a methyl ether including a C.sub.1-C.sub.11 alkyl. R.sub.3 is a substituent including an amino group. X represents a carbonyl or a methylene and n is an integer from 0 to 5.

The present disclosure relates to chemical entities useful as inhibitors of Ubiquitin Specific Protease 30 (USP30), pharmaceutical compositions comprising the chemical entities, and methods of using the chemical entities. The chemical entities as disclosed herein can be useful in the treatment of a disease, disorder, or condition involving mitochondrial dysfunction, including neurodegenerative diseases, motor neuron diseases, metabolic disorders, and cancers, among other ailments. Chemical entities disclosed herein include compounds of Formula (II): ##STR00001##
wherein A, R.sub.2, R.sub.3, R.sub.4, R.sub.a, R.sub.c, R.sub.d, R.sub.e, R.sub.f, and m are defined herein.

The present disclosure relates to chemical entities useful as inhibitors of Ubiquitin Specific Protease 30 (USP30), pharmaceutical compositions comprising the chemical entities, and methods of using the chemical entities. The chemical entities as disclosed herein can be useful in the treatment of a disease, disorder, or condition involving mitochondrial dysfunction, including neurodegenerative diseases, motor neuron diseases, metabolic disorders, and cancers, among other ailments. Chemical entities disclosed herein include compounds of Formula (II): ##STR00001##
wherein A, R.sub.2, R.sub.3, R.sub.4, R.sub.a, R.sub.c, R.sub.d, R.sub.e, R.sub.f, and m are defined herein.

This invention is in the field of medicinal chemistry. In particular, provided herein are compositions and methods for preventing or reversing T cell exhaustion. In certain embodiments, the present invention relates to methods of preventing or reversing T cell exhaustion by exposing T cells experiencing T cell exhaustion to a new class of small-molecules having a thiazole, imidazolepyridiazine or piperazinyl-methyl-aniline structure, or by expanding genetically engineered T cells in the presence of such small molecules.

Compounds useful as an adjuvant, e.g., formulas (I)-(VI) and uses thereof, for example, with immunogenic moieties or other adjuvants, are provided.

The present disclosure is directed to compounds of formulas (I)-(VII), which are useful as modulators of TRABID. The compounds are further useful in the inhibition of TRABID and the treatment of diseases or disorders associated with the inhibition of TRABID. For instance, the disclosure is concerned with compounds and compositions for inhibition of TRABID, methods of treating diseases associated with the inhibition of TRABID (e.g., autoimmune inflammatory diseases including, but not limited to, psoriasis), and methods of synthesis of these compounds.

The present disclosure is directed to compounds of formulas (I)-(VII), which are useful as modulators of TRABID. The compounds are further useful in the inhibition of TRABID and the treatment of diseases or disorders associated with the inhibition of TRABID. For instance, the disclosure is concerned with compounds and compositions for inhibition of TRABID, methods of treating diseases associated with the inhibition of TRABID (e.g., autoimmune inflammatory diseases including, but not limited to, psoriasis), and methods of synthesis of these compounds.