Structure-activity studies of PTPRD phosphatase inhibitors identify a 7-cyclopentymethoxy illudalic acid analog candidate for development.

Interest in development of potent, selective inhibitors of the phosphatase from the receptor type protein tyrosine phosphatase PTPRD as antiaddiction agents is supported by human genetics, mouse models and studies of our lead compound PTPRD phosphatase inhibitor, 7-butoxy illudalic acid analog 1 (7-BIA). We now report structure-activity relationships for almost 70 7-BIA-related compounds and results that nominate a 7- cyclopentyl methoxy analog as a candidate for further development. While efforts to design 7-BIA analogs with substitutions for other parts failed to yield potent inhibitors of PTPRD's phosphatase, ten 7-position substituted analogs displayed greater potency at PTPRD than 7-BIA.

Facile Synthesis of 2-Benzo[]Chromenes via an Arylamine-Catalyzed Mannich Cyclization Cascade Reaction.

A simple arylamine-catalyzed Mannich-cyclization cascade reaction was developed for facile synthesis of substituted 2-benzo[]chromenes. The notable feature of the process included the efficient generation of -quinone methides (-QMs) catalyzed by a simple aniline. The mild reaction conditions allowed for a broad spectrum of 1- and 2-naphthols and -cinnamaldehydes to engage in the cascade sequence with high efficiency.

Design, synthesis, molecular modeling, and biological evaluation of acrylamide derivatives as potent inhibitors of human dihydroorotate dehydrogenase for the treatment of rheumatoid arthritis.

Human dihydroorotate dehydrogenase (DHODH) is a viable target for the development of therapeutics to treat cancer and immunological diseases, such as rheumatoid arthritis (RA), psoriasis and multiple sclerosis (MS). Herein, a series of acrylamide-based novel DHODH inhibitors as potential RA treatment agents were designed and synthesized. 2-Acrylamidobenzoic acid analog was identified as the lead compound for structure-activity relationship (SAR) studies.

Structural Optimization and Structure-Activity Relationship of 4-Thiazolidinone Derivatives as Novel Inhibitors of Human Dihydroorotate Dehydrogenase.

Human dihydroorotate dehydrogenase (DHODH), one of the attractive targets for the development of immunosuppressive drugs, is also a potential target of anticancer drugs and anti-leukemic drugs. The development of promising DHODH inhibitors is in high demand. Based on the unique binding mode of our previous reported 4-thiazolidinone derivatives, via molecular docking method, three new series 4-thiazolidinone derivatives were designed and synthesized as DHODH inhibitors.

Catalyst-free synthesis of thiazolidines via sequential hydrolysis/rearrangement reactions of 5-arylidenethiazolidin-4-ones at room temperature.

A catalyst-free sequential reaction involving hydrolysis and intramolecular aza-Michael addition was developed for synthesizing functionalized thiazolidines from 5-arylidenethiazolidin-4-ones at room temperature. A series of thiazolidine-5-carboxylic acids were prepared in good to excellent yields (up to 97% yield) and excellent diastereoselectivities (up to >20 : 1 dr). This methodology was applicable to the construction of derivatives of thiacloprid and flutianil with good yields.

Synthesis, structure-activity relationship and binding mode analysis of 4-thiazolidinone derivatives as novel inhibitors of human dihydroorotate dehydrogenase.

A series of 4-thiazolidinone derivatives were synthesized and evaluated as novel human dihydroorotate dehydrogenase (DHODH) inhibitors. Compounds and displayed IC values of 1.75 and 1.