The present disclosure is directed to compounds of formula (I) and pharmaceutically acceptable salts thereof, which are useful as MAP4K1 inhibitors, processes for their preparation, pharmaceutical compositions comprising the compounds, and the use of the compounds or the compositions in the treatment or prevention of various diseases, conditions and/or disorders mediated by MAP4K1.

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Disclosed are a class of quinoline compounds and use thereof. This class of compounds has good inhibitory activity to a fibroblast growth factor receptor 4 (FGFR4), may be used as a receptor tyrosine kinase inhibitor, in particular as an FGFR4 kinase irreversible inhibitor, and is used for preparing drugs for preventing and/or treating FGFR4 overexpression-mediated diseases in organisms and diseases associated with angiogenesis or cancer metastasis.

Background: HIV capsid (CA) is an emerging target for antiretroviral treatment PF-3450074 (P74) is a small-molecule CA binder that has been proposed to inhibit reverse transcription (RT) by accelerating HIV core uncoating. PF74 antiviral potency can depend on cyclophilin A (CypA) binding to CA in some cells and it shares a CA binding site with the host nuclear transport factor CPSF6, which restrict HIV infection when mislocalized to the cell cytoplasm. Here we further interrogate the mechanism of action (MOA) for PF74 in human T cells and clarify its potential dependence on CypA and CPSF6.

Methodology: HIV reporter viruses were produced in HEK293T cells and used to infect MT2 cells and primary CD4+ T cells to determine the antiviral effect of PF74. Compound exposure was controlled by staggered addition and cell washing at various times post-infection. DNA products of infection were analyzed by qPCR. CypA and CPSF6 levels were varied in MT2 cells by overexpression and shRNA knockdown. CA (P90A, N74D) and CPSF6 (FG.sub.50,AA) mutations were used to eliminate CypA or CPSF6 binding to the viral capsid. CPSF6 binding to CA was tested using a CA-NO pull down assay.

Results: PF74 efficiently inhibited late (EC.sub.50=795 nM) and early (EC.sub.50=264 nM) post-entry stages of HIV-1 replication in single-round infectivity assays and stabilized CA-NC polymers in vitro. Stable CypA knockdown or mutation of the CypA binding site of CA (P90A) had no effect on HIV infectivity or PF74 antiviral potency in T cells. CypA-independence of PF74 MOA was confirmed in PBMCs using HIV isolates unable to bind CypA due to CA polymorphisms. Drug washout studies showed that at high concentrations (100× EC.sub.50), PF74 inactivates cell-free virus via core disassembly and also acts concomitant with the RT step in infected cells. At 10× EC.sub.50, however, PF74 acted post-RT and was not virucidal, suggesting antiviral mechanism(s) beyond capsid destabilization. In time-of-addition studies, PF74 (10× EC.sub.50) remained active when added after RT but before vDNA integration, and normal levels of late-RT products but reduced 2-LTR circles were observed under these conditions. In contrast, reduced late-RT products were detected at higher compound concentrations. Although PF74 did compete with CPSF6 binding to CA in vitro, it remained active against the N740 mutant virus that does not bind CPSF6, suggesting a CPSF6-independent MOA.

Conclusions: Although PF74 can accelerate viral capsid disassembly at high concentrations, our results indicate that this compound primarly acts after the RT step, but prior to 2-LTR circle accumulation in human T cells, via a CypA- and CPSF6-in

Provided a polymerizable compound represented by the following Formula A-1 or Formula A-2: In Formula A-1 or Formula A-2, R.sup.1 represents an electron-donating group; n represents an integer from 1 to 5; R.sup.2 represents a hydrogen atom, a halogen atom, or —OR.sup.O, wherein R.sup.O represents a hydrogen atom, an alkyl group, or a protecting group of a hydroxy group; R.sup.3 represents a hydrogen atom or a protecting group of a hydroxy group; and X represents a structure represented by any one of Formula B-1 to Formula B-5.

Provided a polymerizable compound represented by the following Formula A-1 or Formula A-2: In Formula A-1 or Formula A-2, R.sup.1 represents an electron-donating group; n represents an integer from 1 to 5; R.sup.2 represents a hydrogen atom, a halogen atom, or —OR.sup.O, wherein R.sup.O represents a hydrogen atom, an alkyl group, or a protecting group of a hydroxy group; R.sup.3 represents a hydrogen atom or a protecting group of a hydroxy group; and X represents a structure represented by any one of Formula B-1 to Formula B-5.

Provided herein are compounds of formula I: ##STR00001##
wherein the variables are defined herein, processes of making them, and methods of treating cancer comprising administering such compounds.

The invention provides a compound of formula (I): ##STR00001##
wherein R is as described herein. The invention also provides a process for the preparation of the compound.

A crystalline form and/or polymorph of a compound having the following structure (I), including tautomeric and zwitterionic forms thereof, are provided: ##STR00001##
Methods associated with preparation and use of the polymorphs, and pharmaceutical compositions comprising the same are also provided. Also provided are methods for preparing a compound having formula (I), or a salt, tautomer or zwitterionic form thereof.

Described herein are 1,2-dioxetanes that are useful as chemiluminescent probes, diagnostic agents, and imaging agents. Also described herein are compositions containing such compounds and methods of using the same.

Provided herein is a compound represented by structural formula (I-0) or formula (II): or a pharmaceutically acceptable salt or a stereoisomer thereof useful for treating diseases (such as cancer) that are treatable by inhibiting HPK1 activity.

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