A61P37/06

Methyoxy-Substituted Pyrrolopyridine Modulators of RORC2 and Methods of Use Thereof

The present invention provides methoxy-substituted pyrrolopyridines, pharmaceutical compositions thereof, methods of modulating RORγ activity and/or reducing the amount of IL-17 in a subject, and methods of treating various medical disorders using such pyrrolopyridines and pharmaceutical compositions thereof.

VIRAL RNA SEGMENTS AS IMMUNOMODULATORY AGENTS AND VACCINE COMPONENTS

The disclosure provides compositions and methods involving viral RNA segments for use in modulating immune responses, including inhibition inflammation related to pathogenic T-cell activation. In addition, modification of the viral sequences responsible for modulating immune response provides for improved vaccine formulations.

INFLAMMATORY DISEASE DIAGNOSIS AND METHODS OF TREATMENT USING LIPOPOLYSACCHARIDE-RESPONSIVE BEIGE-LIKE ANCHOR

Anti-cytokine therapy has revolutionized immunological disease treatment, but is not always effective and subject to treatment resistance as the cytokine cascade is highly redundant and multiple cytokines are involved in inflammation. Targeting a critical common regulator of inflammatory effectors is desirable. Lipopolysaccharide (LPS)-responsive beige-like anchor (LRBA) is a master regulator of multiple genes important for inflammation. Subcellular localization shows that LRBA translocated to the nucleus upon LPS stimulation and colocalized with multiple proteins associated with the endosome membrane system, indicating a critical role in membrane/vesicle trafficking essential for deposition, secretion and signal transduction of immune effectors. Deregulation, deficiency, down-regulation and overexpression of LRBA causes defective trafficking and signaling of immune effector molecules, resulting in immunodeficiency and autoimmunity diseases associated with a broader spectrum of severe symptoms when compared to other CVID genes. Modulating LRBA through antibodies, dominant negative mutants, or small interference RNA can be used to treat inflammatory diseases.

TRICYCLIC SULFONES AS ROR GAMMA MODULATORS

There are described RORγ modulators of the formula (I),

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and formula (II)

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or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.

SYNTHESIS OF HETEROCYCLIC COMPOUNDS
20180002332 · 2018-01-04 ·

Provided herein are intermediates and processes useful for facile synthesis of compounds of formula (I):

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or a pharmaceutically acceptable salt, a solvate, a tautomer, an isomer or a deuterated analog thereof, wherein Q, P.sup.1 and P.sup.2 are as defined in this disclosure.

METHODS AND AGENTS FOR TREATING DISEASE

The present invention provides compounds having the general structural formula (I) [formula should be inserted here] and pharmaceutically acceptable derivatives thereof, as described generally and in classes and subclasses herein, and additionally provides pharmaceutical compositions thereof, and methods for the use thereof for the treatment of any of a number of conditions or diseases involving elevated levels of aldosterone or abnormal or excessive fibrosis, such as kidney disease and hypertension.

TRICYCLIC SPIRO COMPOUND

A medicinal agent for the prevention and/or treatment of diseases caused by EP.sub.4 receptor activation. A compound having antagonistic activity against the EP.sub.4 receptor is contained as an active ingredient in the medicinal agent. The compound represented by the following general formula (I) as defined in the specification, a salt, an N-oxide, or a solvate thereof, or a prodrug of these is useful as a medicinal component having antagonistic activity against the EP.sub.4 receptor for the prevention and/or treatment of diseases caused by EP.sub.4 receptor activation.

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HETEROCYCLIC INHIBITORS OF MONOCARBOXYLATE TRANSPORTERS

The invention provides compounds that inhibit monocarboxylate transporters, such as MCT1 and MCT4. Compounds of the invention can be used for treatment of a condition in a patient, wherein the condition is characterized by the heightened activity or by the high prevalence of MCT1 and/or MCT4, such as cancer or type II diabetes.

SUBSTITUTED IMIDAZO[1, 2-A]PYRIDIN-2-YLAMINE COMPOUNDS, AND PHARMACEUTICAL COMPOSITIONS AND METHODS OF USE THEREOF
20180002328 · 2018-01-04 ·

Provided herein are substituted imidazo[1,2-a]pyridin-2-ylamine compounds, for example, of formula (A), and pharmaceutical compositions thereof; and methods of their use for treating, preventing, or ameliorating one or more symptoms of a Janus kinase-mediated disease.

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OPTIMIZED ANTIBODIES THAT TARGET CD19

The present invention describes antibodies that target CD19, wherein the antibodies comprise at least one modification relative to a parent antibody, wherein the modification alters affinity to an FcγR or alters effector function as compared to the parent antibody. Also disclosed are methods of using the antibodies of the invention.