Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases; disorders and conditions.

This invention relates to compounds which selectively bind to the survival protein MCL-1 with high affinity and selectivity, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for modulating MCL-1 activity and for treating hyperproliferative disorders, angiogenesis disorders, cell cycle regulation disorders, autophagy regulation disorders, inflammatory disorders, and/or infectious disorders and/or for enhancing cellular engraftment and/or wound repair, as a sole agent or in combination with other active ingredients.

This invention relates to compounds which selectively bind to the survival protein MCL-1 with high affinity and selectivity, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for modulating MCL-1 activity and for treating hyperproliferative disorders, angiogenesis disorders, cell cycle regulation disorders, autophagy regulation disorders, inflammatory disorders, and/or infectious disorders and/or for enhancing cellular engraftment and/or wound repair, as a sole agent or in combination with other active ingredients.

The invention pertains to novel FLT3 receptor antagonists of general formula (1). The compounds are useful for the treatment or the prevention of pain disorders, cancer and autoimmune diseases. ##STR00001##

The invention pertains to novel FLT3 receptor antagonists of general formula (1). The compounds are useful for the treatment or the prevention of pain disorders, cancer and autoimmune diseases. ##STR00001##

The present invention is directed toward novel compounds and novel methods of use of said compounds of the formula (I), useful as nucleocapsid assembly inhibitors for the treatment of viruses, especially but not exclusively, including pregenomic RNA encapsidation inhibitors of HBV for the treatment of Hepatitis B virus (HBV) infection and related conditions.

##STR00001##

including hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof, wherein A, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are defined herein.

The present invention is directed toward novel compounds and novel methods of use of said compounds of the formula (I), useful as nucleocapsid assembly inhibitors for the treatment of viruses, especially but not exclusively, including pregenomic RNA encapsidation inhibitors of HBV for the treatment of Hepatitis B virus (HBV) infection and related conditions.

##STR00001##

including hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof, wherein A, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are defined herein.

The present disclosure relates to polycyclic (e.g., fused tetracyclic) liver X receptor (LXR) modulators, synthetic methods for preparing such LXR modulators, and methods of using such LXR modulators to treat a disease or condition that would benefit from LXR modulation. Exemplary compounds have quaternary centers at C9 and C13 and a substituted sulfonamide moiety at C16.

Compounds according to Formula I:

##STR00001##

or a pharmaceutically acceptable salt wherein: A.sub.1 is NR.sub.1 or CR.sub.1, with R.sub.1 herein; the cyclopropyl moiety with one or more methyl and one or more F; A.sub.2-A.sub.5 are N or CR.sub.2-CR.sub.5, with no more than two of the four positions A in A.sub.2-A.sub.5 can be simultaneously N; R.sub.2-R.sub.5 are described; R.sub.6 and R.sub.7 are independently H, F, methyl, ethyl, hydroxyl or methoxy or R.sub.6 and R.sub.7 together is carbonyl, all alkyl groups, if substituted with one or more F; R.sub.8 is H or C(1-6)alkyl; A.sub.9-A.sub.12 are N or CR.sub.9-CR.sub.12, with no more than two of the four positions A in A.sub.9-A.sub.12 can be simultaneously N; R.sub.9-R.sub.12 herein; R.sub.13 and R.sub.14 herein; or R.sub.13 and R.sub.14 fused forming a ring having 5 to 7 atoms by joining R.sub.13 being C(1-6)alkyl or C(2-6)alkenyl. The ROR compounds can treat ROR mediated diseases.

Compounds according to Formula I:

##STR00001##

or a pharmaceutically acceptable salt thereof wherein: A.sub.1 is NR.sub.1 or CR.sub.1, with R.sub.1 being H or methyl, with methyl, if present, optionally being substituted with one or more F; the cyclopropyl moiety can be optionally substituted with one or more methyl and one or more F; A.sub.2-A.sub.5 are N or CR.sub.2-CR.sub.5, respectively, with the proviso that no more than two of the four positions A in A.sub.2-A.sub.5 can be simultaneously N; R.sub.2-R.sub.5 are independently H, halogen, amino, C(1-3)alkoxy, (di)C(1-3)alkylamino or C(1-6)alkyl; R.sub.6 and R.sub.7 are independently H, F, methyl, ethyl, hydroxyl or methoxy or R.sub.2 and R.sub.3 together is carbonyl, all alkyl groups, if present, optionally being substituted with one or more F; R.sub.8 is H or C(1-6)alkyl; R.sub.9 is selected from the group consisting of Formula II, III, IV and V

##STR00002##

The compounds can be used as inhibitors of ROR and are useful for the treatment of ROR mediated diseases.