Abstract: The present invention discloses macrocyclic compounds of Formula (I), and pharmaceutically acceptable salts, thereof: which inhibit coronavirus replication activity. The invention further relates to pharmaceutical compositions comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof, and methods of treating or preventing a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof.

Abstract: Novel 5-substituted aminopyrimido[6?,1?:2,3]imidazo[4,5-c][2,6]naphthyridine compounds, a method of synthesizing said compounds, a pharmaceutical composition comprising said compounds and a suitable carrier, and a method of using the compounds. The 5-substituted aminopyrimido[6?,1?:2,3]imidazo[4,5-c][2,6]naphthyridine compounds, identified as CK2 inhibitors, are useful as anticancer and/or antitumor agents, and as agents for treating other kinase-associated conditions including inflammation, pain, and certain immunological disorders, and other types of diseases such as diabetes, viral infection, neurodegenerative diseases.

Abstract: The present invention relates to 9-oxo-9,10-dihydro-6H-pyrano[3,2-b:4,5-b?]dipyridine-8-carboxylic acid derivatives, their manufacture, pharmaceutical compositions containing them and their use as a medicament.

Abstract: The present application provides spirocyclic lactam compounds that modulate the activity of the V617F variant of JAK2, which are useful in the treatment of various diseases, including cancer.

Abstract: The present disclosure includes compounds, kits, and assay procedures for use in determining the levels of certain types of drugs in samples that contain specific binding proteins for the drugs. The present disclosure includes analog compounds useful for displacing the drugs from their endogenous binding proteins, and kits including same, as well as methods that utilize these displacers as binding competitors in pharmaceutical assays.

Abstract: Novel 6-substituted aminopyrazino[2?,1?:2,3]imidazo[4,5-c][1,7]naphthyridine compounds, a method of synthesizing said compounds, a pharmaceutical composition comprising said compounds and a suitable carrier, and a method of using the compounds. The 6-substituted aminopyrazino[2?,1?:2,3]imidazo[4,5-c][1,7]naphthyridine compounds, identified as CK2 inhibitors, are useful as anticancer and/or antitumor agents, and as agents for treating other kinase-associated conditions including inflammation, pain, and certain immunological disorders, and other types of diseases such as diabetes, viral infection, neurodegenerative diseases.

Abstract: The present invention relates to Tetracyclic Heterocycle Compounds of Formula (I): and pharmaceutically acceptable salts or prodrug thereof, wherein R1 is as defined herein. The present invention also relates to compositions comprising at least one Tetracyclic Heterocycle Compound, and methods of using the Tetracyclic Heterocycle Compounds for treating or preventing HIV infection in a subject.

Abstract: The disclosure relates to anti-cancer compounds derived from a payload which binds to poly(ADP-ribose) polymerase (PARP) and a nuclear steroid-targeting epitope (B of Formula I), which components are covalently linked via a linker, to products containing the same, as well as to methods of their use and preparation.

Abstract: Provided are a fibroblast activation protein inhibitor (FAPI) dimer compound, an FAPI dimer-based positron emission tomography (PET) imaging agent for tumor diagnosis, and a preparation method and use thereof. An amphiphilic polyethylene glycol (PEG) chain and a dimerized structure of FAPI in the FAPI dimer compound with a structure shown in formula I can improve the in vivo kinetic properties of the compound and prolong a residence time of the compound in a tumor, thereby improving the uptake and imaging effects in the tumor. The accurate tumor diagnosis can be achieved by labeling the FAPI dimer compound with a diagnostic nuclide (68Ga), which has promising application prospects in PET imaging for diagnosis and in the preparation of a therapeutic nuclide (such as 177Lu or 90Y)-labeled drug for treating a FAP-?-expressing tumor.

Abstract: Methods are provided for modulating MRGPRX2 generally, or for treating a MRGPRX2 dependent condition more specifically, by contacting the MRGPRX2 or administering to a subject in need thereof, respectively, an effective amount of a compound having structure (I): or a pharmaceutically acceptable salt, isomer, hydrate, solvate or isotope thereof, wherein D, W, Z, R1, R2 and R3 are as defined herein. Pharmaceutical compositions containing such compounds, as well as the compounds themselves, are also provided.

Abstract: Disclosed herein are heterocyclic compounds, for example, according to the following formula and analogs thereof: that inhibit the activity of FLT3. Also described are specific covalent inhibitors of FLT3. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the FLT3 inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of proliferative diseases or conditions, including hematological malignancies and other diseases or conditions dependent on FLT3 activity.

Abstract: The present invention provides methods for treating pruritus having a neurogenic component in a subject in need thereof comprising administering a therapeutically effective amount of a JAK1 inhibitor based on a benzimidazole core, a purine core, or a pyrrolo pyridine core.

Abstract: Methods and systems for screening therapeutic compositions for the treatment of age-related macular degeneration (AMD) or for the prevention of progression of AMD, wherein retinal pigment epithelium cells (RPE) are cultured and the level of hypoxia-induced exosome release from the RPE cells is subsequently measured. In the present invention, the level of hypoxia-induced exosome release can be correlated with AMD onset and severity.

Abstract: The present invention relates to compounds of formula I: in which Y1, Y2, R1, R2 and R3 are defined in the Summary of the Invention; capable of inhibiting the activity of SHP2. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds and compositions in the management of diseases or disorders associated with the aberrant activity of SHP2.

Abstract: The present invention is related to processes for preparing ruxolitinib, or a salt thereof, and related synthetic intermediates related thereto.

Abstract: The present invention relates to compounds of formula I wherein R1, R4, Ar, W, X and Z are all as defined herein. The compounds of the present invention are known to inhibit the spindle checkpoint function of Monospindle 1 (Mps1—also known as TTK) kinases either directly or indirectly via interaction with the Mps1 kinase itself. In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.

Abstract: The present disclosure provides methods of treatment using ophthalmic compositions comprising semifluorinated alkanes for keratoconjunctivitis sicca and/or Meibomian gland dysfunction, which methods provide for the enrichment of an ophthalmic tissue in the semifluorinated alkane, and optionally methods of delayed release of the semifluorinated alkane from the enriched ophthalmic tissue to the surface of the cornea and/or conjunctiva, and/or to the Meibomian gland.

Abstract: Provided are certain triazolopyridines and triazolopyrazines of Formula 1, wherein X, Y, R1, R2, R3, R4 and R5 have any of the meanings described herein; processes for their preparation, pharmaceutical compositions containing them, and their use in the treatment of cell proliferative disorders.

Abstract: The present invention relates to crystalline forms of cabotegravir sodium and to methods for their preparation. Furthermore, the invention relates to a pharmaceutical composition comprising one of said crystalline forms of cabotegravir sodium, preferably in a predetermined and/or effective amount, and at last one pharmaceutically acceptable excipient. The pharmaceutical composition of the present invention can be used as a medicament, in particular for the treatment and/or prophylaxis of viral infections such as HIV infections.

Abstract: The present disclosure relates to novel compounds, methods, and compositions capable of binding to PCSK9, thereby modulating PCSK9 proprotein convertase enzyme activity, for treatment of a disease or condition mediated, at least in part, by PCSK9. The compounds of the disclosure include compounds Formula (I).