Compounds and methods are provided for the treatment of pathogen infections. In some embodiments, the anti-infective compounds have broad spectrum activity against a variety of infective diseases, where the diseases are caused by pathogens containing a basic amino acid PIP-2 pincer (BAAPP) domain that interacts with phosphatidylinositol 4,5-bisphosphate (PIP-2) to mediate pathogen replication. Also provided are methods of inhibiting a PI4-kinase and methods of inhibiting viral infection. In some embodiments, the compound is a PI4-kinase inhibiting compound that is a 5-aryl-thiazole or a 5-heteroaryl-thiazole. The subject compounds may be formulated or provided to a subject in combination with a second anti-infective agent, e.g. interferon, ribavirin, and the like.

Compounds and methods are provided for the treatment of pathogen infections. In some embodiments, the anti-infective compounds have broad spectrum activity against a variety of infective diseases, where the diseases are caused by pathogens containing a basic amino acid PIP-2 pincer (BAAPP) domain that interacts with phosphatidylinositol 4,5-bisphosphate (PIP-2) to mediate pathogen replication. Also provided are methods of inhibiting a PI4-kinase and methods of inhibiting viral infection. In some embodiments, the compound is a PI4-kinase inhibiting compound that is a 5-aryl-thiazole or a 5-heteroaryl-thiazole. The subject compounds may be formulated or provided to a subject in combination with a second anti-infective agent, e.g. interferon, ribavirin, and the like.

The invention relates to compounds of formula (I) ##STR00001##
with low cytotoxicity for blocking the ubiquitination-proteasome system in diseases. Accordingly, these compounds can be used in treatment of disorders including, but not limited to, cancers.

The invention relates to compounds of formula (I) ##STR00001##
with low cytotoxicity for blocking the ubiquitination-proteasome system in diseases. Accordingly, these compounds can be used in treatment of disorders including, but not limited to, cancers.

The present invention relates to a process for the preparation 2-chloro-1-(2-chlorothiazol-5-yl)ethanone.

Inhibitor compounds and agents of Cathepsin C, CELA1, CELA3A and/or structurally related molecules thereto, compositions comprising the same, and uses thereof in the inhibition and/or prevention of cell and/or tissue necrosis are described. The compounds include imidazoles of Formula VI: ##STR00001## wherein G1 is pyrrolidine, pyrazolidine, imidazolidine piperidine, or piperazine and G2 is alkyl, cycloalkyl, heterocycle, or aryl. The pyrrolidine, pyrazolidine, imidazolidine, piperidine, or piperazine of G1 and the alkyl, cycloalkyl, heterocycle, or aryl of G2 are optionally substituted with one or more substituents independently selected from the group consisting of halogen, NO2, CN, C1-C6 alkyl, C1-C6 haloalkyl, NH2, OH, OC1-C6 alkyl, C(O)H, C(O)C1-C6 alkyl, C(O)NH2, C(O)OH, and C(O)OC1-C6 alkyl. Variations applications for the described compounds, and combination therapies are further described as well.

Inhibitor compounds and agents of Cathepsin C, CELA1, CELA3A and/or structurally related molecules thereto, compositions comprising the same, and uses thereof in the inhibition and/or prevention of cell and/or tissue necrosis are described. The compounds include imidazoles of Formula VI: ##STR00001## wherein G1 is pyrrolidine, pyrazolidine, imidazolidine piperidine, or piperazine and G2 is alkyl, cycloalkyl, heterocycle, or aryl. The pyrrolidine, pyrazolidine, imidazolidine, piperidine, or piperazine of G1 and the alkyl, cycloalkyl, heterocycle, or aryl of G2 are optionally substituted with one or more substituents independently selected from the group consisting of halogen, NO2, CN, C1-C6 alkyl, C1-C6 haloalkyl, NH2, OH, OC1-C6 alkyl, C(O)H, C(O)C1-C6 alkyl, C(O)NH2, C(O)OH, and C(O)OC1-C6 alkyl. Variations applications for the described compounds, and combination therapies are further described as well.

Amino, amido, and heterocyclic compounds are disclosed. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, diabetes complications, inflammation, and neurodegeneration, obesity, cancer, ischemia/reperfusion injury, cardiovascular disease and other diseases related to RAGE activity.

The present disclosure relates to crystalline Form 1, Form 2, Form 3 of Ponesimod, a selective S1P1 receptor modulator, and preparation methods thereof. The X-ray powder diffraction pattern of Form 1 shows characteristic peaks at 2theta values of 18.10.2, 14.60.2, 11.30.2; the X-ray powder diffraction pattern of Form 2 shows characteristic peaks at 2theta values of 3.80.2, 10.80.2, 6.10.2; the X-ray powder diffraction pattern of Form 3 shows characteristic peaks at 2theta values of 12.20.2, 6.20.2, 5.60.2. The crystalline forms in present disclosure not only have better stability but also have higher solubility compared with the prior art forms, they are more suitable for the formulation development of Ponesimod.

The present disclosure relates to crystalline Form 1, Form 2, Form 3 of Ponesimod, a selective S1P1 receptor modulator, and preparation methods thereof. The X-ray powder diffraction pattern of Form 1 shows characteristic peaks at 2theta values of 18.10.2, 14.60.2, 11.30.2; the X-ray powder diffraction pattern of Form 2 shows characteristic peaks at 2theta values of 3.80.2, 10.80.2, 6.10.2; the X-ray powder diffraction pattern of Form 3 shows characteristic peaks at 2theta values of 12.20.2, 6.20.2, 5.60.2. The crystalline forms in present disclosure not only have better stability but also have higher solubility compared with the prior art forms, they are more suitable for the formulation development of Ponesimod.