894399-90-7

Upstream product

• 5414-19-7 1,1'-oxybis(2-bromo-ethane) 
• 41841-16-1 (4-bromo-phenyl)-acetic acid methyl ester 
• 111-44-4 3-oxa-1,5-dichloropentane 

Downstream Products

• 894399-83-8 4-(4-bromophenyl)-4-(methoxymethyl)tetrahydro-2H-pyran 
• 894399-94-1 [4-(4-bromophenyl)tetrahydro-2H-pyran-4-yl]methanol 

Relevant academic research and scientific papers

Achiral Derivatives of Hydroxamate AR-42 Potently Inhibit Class i HDAC Enzymes and Cancer Cell Proliferation

AR-42 is an orally active inhibitor of histone deacetylases (HDACs) in clinical trials for multiple myeloma, leukemia, and lymphoma. It has few hydrogen bond donors and acceptors but is a chiral 2-arylbutyrate and potentially prone to racemization. We report achiral AR-42 analogues incorporating a cycloalkyl group linked via a quaternary carbon atom, with up to 40-fold increased potency against human class I HDACs (e.g., JT86, IC50 0.7 nM, HDAC1), 25-fold increased cytotoxicity against five human cancer cell lines, and up to 70-fold less toxicity in normal human cells. JT86 was ninefold more potent than racAR-42 in promoting accumulation of acetylated histone H4 in MM96L melanoma cells. Molecular modeling and structure-activity relationships support binding to HDAC1 with tetrahydropyran acting as a hydrophobic shield from water at the enzyme surface. Such potent inhibitors of class I HDACs may show benefits in diseases (cancers, parasitic infections, inflammatory conditions) where AR-42 is active.

1,3-DISUBSTITUTED-4-PHENYL-1 H-PYRIDIN-2-ONES

The present invention relates to novel compounds, in particular novel pyridinone derivatives according to Formula (I) wherein all radicals are as defined in the application and claims. The compounds according to the invention are positive allosteric modul

THERAPEUTIC OR PROPHYLACTIC AGENT FOR LEUKEMIA

A therapeutic or prophylactic agent for leukemia is disclosed. The therapeutic or prophylactic agent comprises as an effective ingredient a glycine derivative having a specific structure or a pharmaceutically acceptable salt thereof, for example, the below-described compound [(E)-2-(2,6-dichlorobenzamido)-5-[4-(isopropyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid]. The therapeutic or prophylactic agent for leukemia according to the present invention shows the excellent absorbability and in vivo stability when orally administered, and exhibits prominent therapeutic or prophylactic effects.

THERAPEUTIC OR PROPHYLACTIC AGENT FOR ALLERGIC DERMATITIS

A therapeutic or prophylactic agent for allergic dermatitis is disclosed. The therapeutic or prophylactic agent comprises as an effective ingredient a glycine derivative having a specific structure or a pharmaceutically acceptable salt thereof, for example, the below-described compound [(E)-2-(2,6-dichlorobenzamido)-5-[4-(isopropyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid]. The therapeutic or prophylactic agent for allergic dermatitis according to the present invention has high therapeutic or prophylactic effect.

THERAPEUTIC OR PROPHYLACTIC AGENT FOR MULTIPLE SCLEROSIS

A therapeutic or prophylactic agent for multiple sclerosis is disclosed. The therapeutic or prophylactic agent comprises as an effective ingredient a glycine derivative having a specific structure or a pharmaceutically acceptable salt thereof, for example, the below-described compound [(E)-2-(2,6-dichlorobenzamido)-5-[4-(isopropyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid]. The therapeutic or prophylactic agent for multiple sclerosis according to the present invention shows the excellent absorbability and in vivo stability when orally administered, and exhibits high therapeutic or prophylactic effects.

GLYCINE DERIVATIVE AND USE THEREOF

The compounds in the present invention, for example, the compound represented by the formula: has an excellent therapeutic and prophylactic effects against inflammatory bowel disease. Further, they are excellent in absorption and in vivo stability when administered orally in comparison with conventional compounds. That is, the compounds can be administered orally, and can have excellent therapeutic or prophylactic effect sustained for a longer period of time.

GLYCINE DERIVATIVE AND USE THEREOF

A glycine derivative which is, e.g., the following compound (Chemical formula (1)). It is highly effective in the treatment and prevention of inflammatory bowel diseases. Compared to conventional compounds, the compound is excellent in absorbability in oral administration and in vivo stability. The compound can be orally administered and can retain an excellent therapeutic or preventive effect over a longer period.