Abstract: The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of FGFR enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with FGFR signaling with the compounds and compositions of the disclosure.

Abstract: The present disclosure encompasses solid state forms of Belumosudil, in embodiments crystalline polymorphs of Belumosudil or salts thereof, processes for preparation thereof, and pharmaceutical compositions thereof.

Abstract: This invention relates to novel compounds according to Formula (I) which are inhibitors of furin, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy for the treatment of fibrotic diseases, including pulmonary fibrosis, renal fibrosis, liver fibrosis, skin fibrosis, ocular fibrosis, cardiac fibrosis, and other miscellaneous fibrotic conditions. The disclosed compounds may also be useful for treating other furin-mediated conditions, including but not limited to, hypertension, cancer, infectious diseases, and genetic disorders (e.g., cystic fibrosis (CF)), and neurodegenerative disorders.

Abstract: The present invention is directed to, in part, fused heteroaryl compounds and compositions useful for preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. The fused heteroaryl compounds of the disclosure are represented by Formula (I): wherein X, Y, Z, A, R1 and R2 are as defined in the specification. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including Dravet syndrome or epilepsy are also provided herein.

Abstract: Disclosed are heteroaromatic carboxamides of formula (I), wherein Y, R, and Ar are as defined herein, and pharmaceutically acceptable salts thereof. Also disclosed are the use of the compounds of formula (i) for the treatment of diseases which can be influenced by the inhibition of plasma kallikrein.

Abstract: Certain anti-viral compounds, pharmaceutical compositions, and methods related thereto are disclosed.

Abstract: The present invention relates to compounds of Formula (I): or a pharmaceutically acceptable salt thereof, wherein: each of A, B, C, D, and E, independently, is C, N, N—H, O, S, or absent; is a single bond or a double bond; each of X, Y, and Z, independently, is aryl, heteroaryl, aralkyl, H, or absent; each of L1 and L2, independently, is a moiety selected from O, CH2, C?O, C2-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, —((CH2)n—W)—, wherein n=0, 1, 2, 3, 4, or 5, and W is O or S, or absent; and when L2 is absent, Z is aryl or heteroaryl fused with BC. Also provided in the present invention is a method for inhibiting, treating and/or reducing the risk of a neuropsychiatric disorder, comprising administering a subject in need a composition comprising a compound of Formula (I).

Abstract: The invention provides cereblon binders of Formulas: or pharmaceutically acceptable salts thereof, for the degradation of Ikaros or Aiolos by the ubiquitin proteasome pathway along with their use in therapeutic applications to treat medical disorders including, but not limited to cancer.

Abstract: Provided herein are compounds (e.g., compounds of Formulae (I), (II), (III) and (IV), or of Table 1 or Table 4), and pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and kits comprising the same. The compounds provided herein are activin receptor-like kinase (e.g., ALK-5) inhibitors and are, therefore, useful, for example, for treating and/or preventing diseases (e.g., proliferative diseases, such as cancer) in a subject, inhibiting tumor growth in a subject, or inhibiting the activity of an activin receptor-like kinase (e.g., ALK-5) in vitro or in vivo. Also provided herein are methods and synthetic intermediates useful in the preparation of compounds described herein.

Abstract: The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

Abstract: The present invention provides a process of producing a trifluoromcthoxylated aryl or trifluoromothoxylated heteroaryl having the structure: wherein A is an aryl or heteroaryl, each with or without substitution; and R1 is —H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), —NH-(alkyl), —N(alkyl)2, —NH-(alkenyl), —NH-(alkynyl) —NH-(aryl), —NH-(heteroaryl), —O-(alkyl), —O-(alkenyl), —O-(alkynyl), —O-(aryl), —O-(heteroaryl), —S-(alkyl), —S-(alkenyl), —S-(alkynyl), —S-(aryl), or —S-(heteroaryl), comprising: (a) reacting a compound having the structure: with a trifluoromethylating agent in the presence of a base in a first suitable solvent under conditions to produce a compound having the structure: and (b) maintaining the compound produced in step (a) in a second suitable solvent under conditions sufficient to produce the trifluoromethoxylated aryl or trifluormethoxylated heteroaryl having the structure:

Abstract: Compounds are provided that are useful as immunomodulators. The compounds have the Formula (I) including stereoisomers and pharmaceutically acceptable salts thereof, wherein R2a, R2b, R3, R3a, R4, R6, R7, R8, A, Z, X1 and n are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

Abstract: Described herein are crystalline composition comprising a Corticotropin-releasing hormone receptor 1 (CRF1) antagonist, such as Compound 1: methods of making such crystalline composition, pharmaceutical compositions and medicaments comprising such crystalline composition, and methods of using such crystalline composition in the treatment of conditions, diseases, or disorders that would benefit from modulation of CRF.

Abstract: The present disclosure relates to compounds that act as inhibitors of NLRP3 inflammasomes; pharmaceutical compositions comprising the compounds; and methods of treating disorders associated with inflammation and inflammaging, including hearing loss and other diseases associated with aging; wherein the inhibitors of NLRP3 inflammasomes are compounds of Formula VII: or a pharmaceutically acceptable salt thereof.

Abstract: The present application provides compounds, such as compounds of Formula Ia, which are inhibitors of aminoacyl tRNA-synthetase (e.g., prolyl-tRNA-synthetase), and which are useful for treating disorders associated with aminoacyl tRNA-synthetase activity and/or expression. Pharmaceutical compositions comprising the compounds and methods of using the compounds are also provided.

Abstract: Provided herein are compounds and methods for the treatment of cancer. The methods include administering to a subject in need a therapeutically effective amount of a Chk1 inhibitor disclosed herein.

Abstract: The present disclosure relates to compounds of Formula I: that act as inhibitors of NLRP3 inflammasomes; pharmaceutical compositions comprising the compounds; and methods of treating disorders associated with inflammation and inflammaging, including hearing loss and other diseases associated with aging.

Abstract: The present invention relates to pyridazinones and related compounds having Formula I: and pharmaceutically acceptable salts thereof, which are inhibitors of PARP7 and are useful in the treatment of cancer.

Abstract: Disclosed are compounds active towards nuclear receptors, pharmaceutical compositions containing the compounds and use of the compounds in therapy.

Abstract: Described herein are MK2 inhibitors of Formula (II) and pharmaceutical compositions comprising said inhibitors. The subject compounds and compositions are useful for the treatment of autoimmune disorders, chronic inflammatory disorders, acute inflammatory disorders, auto-inflammatory disorders, fibrotic disorders, metabolic disorders, neoplastic disorders, and cardiovascular or cerebrovascular disorders.