This disclosure relates to new phthalimide and isoindolinone derivatives and other PFKFB3 inhibitors for use in the treatment of diseases. The invention further relates to pharmaceutical compositions containing such PFKFB3 inhibitors, methods of preparation thereof, methods for their use as therapeutic agents, and methods of preparation of a medicament for use in therapy, as well as kits and other inventions comprising such PFKFB3 inhibitors. These PFKFB3 inhibitors are useful for the treatment and prophylaxis of cancer, neurodegenerative diseases, autoimmune diseases, inflammatory disorders, multiple sclerosis, metabolic diseases, inhibition of angiogenesis and other diseases and conditions, where the modulation of PFKFB3 and/or PFKFB4 has beneficial effect as well as neuroprotection.

The present invention provides compounds of Formula (I) which can be used as CCR8 inhibitors, which can be used as treatment or prevention of cancer using CCR8 inhibitors targeted tumor specific T regulatory cells.

##STR00001##

Disclosed is a compound of formula (I)

##STR00001## or a stereoisomer thereof, or a salt of any of the foregoing and to processes for its preparation. The compounds of formula (I) are useful in the treatment TRPML1-mediated disorders or diseases.

Disclosed is a compound of formula (I)

##STR00001## or a stereoisomer thereof, or a salt of any of the foregoing and to processes for its preparation. The compounds of formula (I) are useful in the treatment TRPML1-mediated disorders or diseases.

An N-methyl-substituted triacetonamine compound can be produced by reacting at least one triacetonamine compound with formaldehyde under reductive conditions.

An N-methyl-substituted triacetonamine compound can be produced by reacting at least one triacetonamine compound with formaldehyde under reductive conditions.

Binding of the transcriptional co-activator, YAP1, to the transcription factor Oct4, induces Sox2, which is a transcription actor necessary for the self-renewal of stem-like cells from non-small cell lung cancer. The WW domain of YAP1 binds to the PPxY motif of Oct4 to induce Sox2. Delivering a peptide corresponding to the WW domain could prevent the induction of Sox2 and sternness. Similarly, peptides and mimetics of the PPxY motif would be able to inhibit sternness. Disclosed are compounds that affect the Yap1:Oct4 interaction.

The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, A compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, (I) wherein: Z is a group of formula: (II) wherein P and Q are each independently CR.sub.12R.sub.13; or one of P and Q is NR.sub.14 and the other is CR.sub.12R.sub.13; the group X—Y is —NHSO.sub.2— or —SO2NH—; R.sub.1 is H, CN or alkyl; R.sub.2 is selected from COOH and a tetrazolyl group; R.sub.3 is selected from H, Cl and alkyl; R.sub.4 is selected from H and halo; R.sub.5 is selected from H, alkyl, haloalkyl, SO.sub.2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R.sub.6 is H; R.sub.7 is selected from H, CN, haloalkyl, halo, SO.sub.2-alkyl, heteroaryl, SO.sub.2NR.sub.16R.sub.17, CONR.sub.10R.sub.11 and alkyl, wherein said heteroaryl group is optionally substituted by one or more substituents selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; R.sub.8 is selected from H, alkyl, haloalkyl and halo; R.sub.9 is H or halo; and R.sub.10, R.sub.11, R.sub.12, R.sub.13, R.sub.14, R.sub.16 and R.sub.17 are each independently H or alkyl; R.sub.15 is selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; and m and n are each independently 0, 1, 2 or 3. Further aspects of the invention relate to such compounds for use in the field of immune-oncology and related applications.

##STR00001##

The invention relates to a process for preparing an AFX-structure zeolite comprising at least the following steps: i) mixing, in an aqueous medium, an FAU-structure zeolite having an SiO.sub.2 (FAU)/Al.sub.2O.sub.3 (FAU) molar ratio of between 6.00 and 200, limits included, an organic nitrogenous compound R, at least one source of at least one alkali and/or alkaline-earth metal M, the reaction mixture having the following molar composition: (SiO.sub.2 (FAU))/(Al.sub.2O.sub.3 (FAU)) between 6.00 and 200, H.sub.2O/(SiO.sub.2 (FAU)) between 1.00 and 100, R/(SiO.sub.2 (FAU)) between 0.01 and 0.60, M.sub.2/nO/(SiO.sub.2 (FAU)) between 0.005 and 0.45, limits included, until a homogeneous precursor gel is obtained; ii) hydrothermal treatment of said precursor gel obtained on conclusion of step i) at a temperature of between 120° C. and 220° C., for a time of between 12 hours and 15 days.

The invention relates to a process for preparing an AFX-structure zeolite comprising at least the following steps: i) mixing, in an aqueous medium, an FAU-structure zeolite having an SiO.sub.2 (FAU)/Al.sub.2O.sub.3 (FAU) molar ratio of between 6.00 and 200, limits included, an organic nitrogenous compound R, at least one source of at least one alkali and/or alkaline-earth metal M, the reaction mixture having the following molar composition: (SiO.sub.2 (FAU))/(Al.sub.2O.sub.3 (FAU)) between 6.00 and 200, H.sub.2O/(SiO.sub.2 (FAU)) between 1.00 and 100, R/(SiO.sub.2 (FAU)) between 0.01 and 0.60, M.sub.2/nO/(SiO.sub.2 (FAU)) between 0.005 and 0.45, limits included, until a homogeneous precursor gel is obtained; ii) hydrothermal treatment of said precursor gel obtained on conclusion of step i) at a temperature of between 120° C. and 220° C., for a time of between 12 hours and 15 days.