3-Carbonylamino-8-aminoisoquinoline compounds of formula (I): ##STR00001##
variations thereof, and their use as inhibitors of HPK1 (hematopoietic kinase 1) are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the 3-carbonylamino-8-aminoisoquinoline compounds.

3-Carbonylamino-8-aminoisoquinoline compounds of formula (I): ##STR00001##
variations thereof, and their use as inhibitors of HPK1 (hematopoietic kinase 1) are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the 3-carbonylamino-8-aminoisoquinoline compounds.

Tricyclic PI3k inhibitor compounds of Formula I with anti-cancer activity, anti-inflammatory activity, or immunoregulatory properties, and more specifically with PI3 kinase modulating or inhibitory activity are described. Methods are described for using the tricyclic PI3K inhibitor compounds of Formula I for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, organisms, or associated pathological conditions.

##STR00001##

Formula I compounds include stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof. The dashed lines indicate an optional double bond, and at least one dashed line is a double bond. The substituents are as described.

Tricyclic PI3k inhibitor compounds of Formula I with anti-cancer activity, anti-inflammatory activity, or immunoregulatory properties, and more specifically with PI3 kinase modulating or inhibitory activity are described. Methods are described for using the tricyclic PI3K inhibitor compounds of Formula I for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, organisms, or associated pathological conditions.

##STR00001##

Formula I compounds include stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof. The dashed lines indicate an optional double bond, and at least one dashed line is a double bond. The substituents are as described.

The current invention provides urea derivatives, in particular compounds having the core structure heteroaryl-NH—CO—NH-aryl-O-heteroaryl, for use in treating, ameliorating, delaying, curing and/or preventing a disease or condition associated with muscle cells and/or satellite cells, such as Duchenne muscular dystrophy, Becker muscular dystrophy, cachexia or sarcopenia.

The present invention provides an immunomodulatory composition useful for treating or preventing joint damage comprising at least a set of peptides possessing an amino acid sequence having at least 80%, 85% and 90% sequence identity with the peptides corresponding to SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4 and a method for the treatment or prevention of joint damage comprising the steps of a) extract monocytes from a patient with a rheumatological disease; b) culture the monocytes extracted in the previous step in AIM-V medium with GM-CSF and IL-4; c) wash the monocytes and add dexamethasone; d) load the tDCs with the immunomodulatory composition comprising autoantigenic peptides; e) add MPLA; and f) incorporate the tDCs loaded with autoantigenic peptides into the patient. The present invention includes methods for the treatment or prevention of rheumatological disease comprising a wide range of tDCs performed by different protocols.

The present invention provides an immunomodulatory composition useful for treating or preventing joint damage comprising at least a set of peptides possessing an amino acid sequence having at least 80%, 85% and 90% sequence identity with the peptides corresponding to SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4 and a method for the treatment or prevention of joint damage comprising the steps of a) extract monocytes from a patient with a rheumatological disease; b) culture the monocytes extracted in the previous step in AIM-V medium with GM-CSF and IL-4; c) wash the monocytes and add dexamethasone; d) load the tDCs with the immunomodulatory composition comprising autoantigenic peptides; e) add MPLA; and f) incorporate the tDCs loaded with autoantigenic peptides into the patient. The present invention includes methods for the treatment or prevention of rheumatological disease comprising a wide range of tDCs performed by different protocols.

The present disclosure relates to novel compounds for use in therapeutic treatment of a disease associated with peptidylarginine deiminases (PADs), such as peptidylarginine deiminase type 4 (PAD4). The present disclosure also relates to processes and intermediates for the preparation of such compounds, methods of using such compounds and pharmaceutical compositions comprising the compounds described herein.

The present disclosure relates to novel compounds for use in therapeutic treatment of a disease associated with peptidylarginine deiminases (PADs), such as peptidylarginine deiminase type 4 (PAD4). The present disclosure also relates to processes and intermediates for the preparation of such compounds, methods of using such compounds and pharmaceutical compositions comprising the compounds described herein.

The invention provides novel compounds having the general formula I:

##STR00001##

wherein R.sup.1, R.sup.2, the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds and methods of using the compounds.