The present disclosure discloses compounds capable of modulating the activity of α-amino-β-carboxymuconic acid semialdehyde decarboxylase (ACMSD), which are useful for the prevention and/or the treatment of diseases and disorders associated with defects in NAD.sup.+ biosynthesis, e.g., metabolic disorders, neurodegenerative diseases, chronic inflammatory diseases, kidney diseases, and diseases associated with ageing. The present application also discloses pharmaceutical compositions comprising said compounds and the use of such compounds as a medicament.

This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.

This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.

The present invention relates to a benzamide compound and a preparation method, use and pharmaceutical composition thereof. The benzamide compound represented by formula (I) is a STAT3 inhibitor, and can be used to prevent and/or treat a disease related to STAT3 activity, such as a tumor, autoimmune disease, renal disease, cardiovascular disease, inflammation, metabolic/endocrine dysfunction, and neurological disease.

##STR00001##

The disclosure relates to compounds and pharmaceutical compositions capable of modulating the hydroxysteroid 17-beta dehydrogenase (HSD17B) family member proteins including inhibiting the HSD17B member proteins, e.g. HSD17B13. The disclosure further relates to methods of treating liver diseases, disorders, or conditions with the compounds and pharmaceutical compositions disclosed herein, in which the HSD17B family member protein plays a role.

The disclosure relates to compounds and pharmaceutical compositions capable of modulating the hydroxysteroid 17-beta dehydrogenase (HSD17B) family member proteins including inhibiting the HSD17B member proteins, e.g. HSD17B13. The disclosure further relates to methods of treating liver diseases, disorders, or conditions with the compounds and pharmaceutical compositions disclosed herein, in which the HSD17B family member protein plays a role.

The invention provides compositions and methods for providing a cardioprotective effect in a subject. Specifically, the invention relates to compositions and methods for treating cardiovascular ailments, such as compositions and methods for attenuating or ameliorating the development of cardiac contractile dysfunction, myocardial fibrosis or maladaptive remodeling in a subject having or having had a myocardial infarction (MI) or at risk of having a myocardial infarction by administering a retinoic acid receptor-beta (RARβ) agonist.

The invention provides compositions and methods for providing a cardioprotective effect in a subject. Specifically, the invention relates to compositions and methods for treating cardiovascular ailments, such as compositions and methods for attenuating or ameliorating the development of cardiac contractile dysfunction, myocardial fibrosis or maladaptive remodeling in a subject having or having had a myocardial infarction (MI) or at risk of having a myocardial infarction by administering a retinoic acid receptor-beta (RARβ) agonist.

Compounds of the formula I ##STR00001## in which R.sup.1 denotes A, Ar, Cyc, Het, COA or CN, R.sup.2 denotes SO.sub.2A, SOA, SA, SO.sub.2NHA, SO.sub.2NA.sub.2, S(═NH,═O)A, S(═NH).sub.2A, NO.sub.2, Hal, CN, A, Het.sup.1, COOH or COOA, R.sup.3 denotes H or Hal, R.sup.4 denotes H or Hal, n denotes 1, 2 or 3, A denotes unbranched or branched alkyl having 1-6 C-atoms, Cyc denotes cyclic alkyl with 3 to 7 C-atoms, Ar denotes phenyl, Het denotes a mono- or bicyclic aromatic, unsaturated or saturated heterocycle having 1 to 4 N, O, and/or S atoms, Het.sup.1 denotes a mono- or bicyclic aromatic, unsaturated or saturated heterocycle having 1 to 4 N, O, and/or S atoms, and Hal denotes F, Cl, Br, or I, are inhibitors of HIF-2α, and can be employed for the treatment of diseases such as cancer.

Compounds of the formula I ##STR00001## in which R.sup.1 denotes A, Ar, Cyc, Het, COA or CN, R.sup.2 denotes SO.sub.2A, SOA, SA, SO.sub.2NHA, SO.sub.2NA.sub.2, S(═NH,═O)A, S(═NH).sub.2A, NO.sub.2, Hal, CN, A, Het.sup.1, COOH or COOA, R.sup.3 denotes H or Hal, R.sup.4 denotes H or Hal, n denotes 1, 2 or 3, A denotes unbranched or branched alkyl having 1-6 C-atoms, Cyc denotes cyclic alkyl with 3 to 7 C-atoms, Ar denotes phenyl, Het denotes a mono- or bicyclic aromatic, unsaturated or saturated heterocycle having 1 to 4 N, O, and/or S atoms, Het.sup.1 denotes a mono- or bicyclic aromatic, unsaturated or saturated heterocycle having 1 to 4 N, O, and/or S atoms, and Hal denotes F, Cl, Br, or I, are inhibitors of HIF-2α, and can be employed for the treatment of diseases such as cancer.