Disclosed is a compound capable of inhibiting interleukin 17A (IL-17A), which is represented by formula (I). An application of the compound or a stereoisomer thereof in the preparation of drugs for inhibiting IL-17A is also provided.

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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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A method for subjecting a compound [A] having a hydroxyl group or a primary or secondary amino group and a compound [B] having a substituent containing a phosphorus atom to a condensation reaction to prepare a compound [C] represented by the following general formula [C]: ##STR00001##
wherein the condensation reaction is carried out in a mixed solvent containing a polar solvent and a halogen solvent as a reaction solvent.

The invention relates to complexing agents of formula (I):

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wherein Chrom.sub.1, Chrom.sub.2 and Chrom.sub.3 are as defined in the description. The invention also relates to lanthanide complexes obtained from these complexing agents.

Provided herein are compounds, compositions, and methods useful for inhibiting protein tyrosine phosphatase, e.g., protein tyrosine phosphatase non-receptor type 2 (PTPN2) and/or protein tyrosine phosphatase non-receptor type 1 (PTPN1), and for treating related diseases, disorders and conditions favorably responsive to PTPN1 or PTPN2 inhibitor treatment, e.g., a cancer or a metabolic disease.

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.

Mitochondrial targeting compounds for the treatment of cancer and other disorders associated with mitochondrial function, including diabetes, autoimmune diseases, inflammatory diseases, cardiovascular diseases and neurodegenerative diseases and their preparation. The present invention is also directed to the pharmaceutical compositions and treatment methods, prodrugs based on those compounds and the use thereof.

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

The present invention relates to the compounds of Formula I, methods of using these compounds as EGFR inhibitors, and pharmaceutical compositions comprising compounds thereof. The compounds are used for treating, preventing or ameliorating diseases or disorders such as cancer or infections.

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Complement Factor D inhibitors, pharmaceutical compositions, and uses thereof, as well as processes for their manufacture are provided. The compounds provided include Formula I, Formula II, Formula III, Formula IV, and Formula V, or a pharmaceutically acceptable salt, prodrug, isotopic analog, N-oxide, or isolated isomer thereof, optionally in a pharmaceutically acceptable composition. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade.