856252-70-5

Upstream product

• 7697-26-9 3-bromo-4-methylbenzoic acid 
• 765-30-0 Cyclopropylamine 
• 21900-33-4 3-bromo-4-methylbenzoyl chloride 

Downstream Products

• 856252-71-6 3-bromo-N-cyclopropyl-4,N-dimethyl-benzamide 
• 515135-67-8 N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolanyl)benzamide 

Relevant academic research and scientific papers

2-OXO-2,3-DIHYDRO-1H-IMIDAZO[4,5-B]PYRIDIN-6-YL)-4-METHYLBENZAMIDE DERIVATIVES AND SIMILAR COMPOUNDS AS RIPK2 INHIBITORS FOR TREATING E.G. AUTOIMMUNE DISEASES

Disclosed are compounds of Formula 1, and pharmaceutically acceptable salts thereof, wherein α, β, R2, R3, R4, R5, R8, R9, X1, X6, and X7 are defined in the specification. The compounds of formula 1 are receptor-interacting protein kinase 2 (RIPK2) inhibitors for treating e.g. type I hypersensitivity reactions, autoimmune diseases, inflammatory disorders, cancer and non-malignant proliferative disorders, such as e.g. allergic rhinitis, asthma, atopic dermatitis, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, lupus nephritis, psoriasis, immune thrombocytopenic purpura, inflammatory bowel disease, chronic obstructive pulmonary disease, Sjogren's syndrome, ankylosing spondylitis, Behcet's disease, graft versus host disease, pemphigus vulgaris, idiopathic plasmacytic lymphadenopathy, atherosclerosis, myocardial infarction and thrombosis. The present description discloses the preparation of exemplary compounds as well as pharmacological data thereof (e.g. pages 107 to 208; examples 1 to 109; table 1). An exemplary compound is e.g. N-cyclopropyl-2-fluoro-5-(l-(2-fluoroethyl)-3-(l-hydroxy-2-methylpropan-2-yl)-2-oxo-2,3-dihydro-lH-imidazo[4,5-b]pyridin-6-yl)-4-methylbenzamide (example 1).

Structure-Based Design, Synthesis, and Biological Evaluation of Imidazo[4,5-b]Pyridin-2-one-Based p38 MAP Kinase Inhibitors: Part 2

We identified novel potent inhibitors of p38 mitogen-activated protein (MAP) kinase using a structure-based design strategy, beginning with lead compound, 3-(butan-2-yl)-6-(2,4-difluoroanilino)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (1). To enhance the inhibitory activity of 1 against production of tumor necrosis factor-α (TNF-α) in human whole blood (hWB) cell assays, we designed and synthesized hybrid compounds in which the imidazo[4,5-b]pyridin-2-one core was successfully linked with the p-methylbenzamide fragment. Among the compounds evaluated, 3-(3-tert-butyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-6-yl)-4-methyl-N-(1-methyl-1H-pyrazol-3-yl)benzamide (25) exhibited potent p38 inhibition, superior suppression of TNF-α production in hWB cells, and also significant in vivo efficacy in a rat model of collagen-induced arthritis (CIA). In this paper, we report the discovery of potent, selective, and orally bioavailable imidazo[4,5-b]pyridin-2-one-based p38 MAP kinase inhibitors.

Phthalazine, aza- and diaza-phthalazine compounds and methods of use

The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation and related conditions. The compounds have a general Formula I wherein A1, A2, B, R1, R2, R3 and R4 are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, uses of such compounds and compositions for treatment of kinase mediated diseases including rheumatoid arthritis, psoriasis and other inflammation disorders, as well as intermediates and processes useful for the preparation of compounds of Formula I.

METHODS FOR TREATING RETINOID RESPONSIVE DISORDERS USING SELECTIVE INHIBITORS OF CYP26A AND CYP26B

The invention provides methods for treating an individual having a retinoid responsive disorder. In one embodiment, a method involves administering to the individual an effective amount of a selective CYP26B inhibitor, the selective CYP26B inhibitor having at least 10-fold selectivity for CYP26B relative to CYP26A. In another embodiment, a method involves administering to the individual an effective amount of a selective CYP26A inhibitor, the selective CYP26A inhibitor having a chemical formula set forth in the specification. The invention further provides screening methods for identifying a selective CYP26A inhibitor or selective CYP26B inhibitor.

COMPOUNDS HAVING SELECTIVE CYTOCHROME P450RAI-1 OR SELECTIVE CYTOCHROME P450RAI-2 INHIBITORY ACTIVITY AND METHODS OF OBTAINING THE SAME

Compounds of formulas 1 through 17 provided in the specification specifically or selectively inhibit either the cytochrome P450RAI-1 enzyme or the cytochrome P450RAI-2 enzyme.