223433-51-0

Upstream product

• 140-77-2 3-cyclopentylpropionic acid 
• 104-97-2 cyclopentanepropanoyl chloride 
• 90719-32-7 (S)-4-Benzyl-2-oxazolidinone 
• 5292-43-3 bromoacetic acid tert-butyl ester 

Downstream Products

• 1351523-68-6 C₁₀H₁₆O₄ 
• 204637-77-4 (R)-2-cyclopentyl-methyl-succinic acid 4-tert-butyl ester 
• 1351523-32-4 (R)-3-(cyclopentylmethyl)-4-(cyclopropyl(4-(2-(6-(2-methoxyethoxy)pyridin-3-yl)phenyl)thiazol-2-yl)amino)-4-oxobutanoic acid 
• 1351523-99-3 (R)-tert-butyl 3-(cyclopentylmethyl)-4-(cyclopropyl(4-(2-(6-(2-methoxyethoxy)pyridin-3-yl)phenyl)thiazol-2-yl)amino)-4-oxobutanoate 
• 1229363-89-6 (R)-3-(cyclopentylmethyl)-4-(cyclopropyl(4-(2-(6-methoxypyridin-3-yl)phenyl)thiazol-2-yl)amino)-4-oxobutanoic acid 
• 1229363-78-3 (R)-4-((4-(2-chlorophenyl)thiazol-2-yl)(methyl)amino)-3-(cyclopentylmethyl)-4-oxo butanoic acid 
• 1351523-54-0 (R)-4-((4-(2-(6-(1H-pyrazol-1-yl)pyridin-3-yl)phenyl)thiazol-2-yl)(cyclopropyl)amino)-3-(cyclopentylmethyl)-4-oxobutanoic acid 

Relevant academic research and scientific papers

Synthesis and Anticancer Activity of Novel Actinonin Derivatives as HsPDF Inhibitors

Human mitochondrial peptide deformylase (HsPDF) is responsible for removing the formyl group from N-terminal formylmethionines of newly synthesized mitochondrial proteins and plays important roles in maintaining mitochondria function. It is overexpressed

N-Thiazolylamide-based free fatty-acid 2 receptor agonists: Discovery, lead optimization and demonstration of off-target effect in a diabetes model

Free fatty acid-2 (FFA2) receptor is a G-protein coupled receptor of interest in the development of therapeutics in metabolic and inflammatory disease areas. The discovery and optimization of an N-thiazolylamide carboxylic acid FFA2 agonist scaffold is described. Dual key objectives were to i) evaluate the potential of this scaffold for lead optimization in particular with respect to safety de-risking physicochemical properties, i.e. lipophilicity and aromatic content, and ii) to demonstrate the utility of selected lead analogues from this scaffold in a pertinent in vivo model such as oral glucose tolerance test (OGTT). As such, a concomitant improvement in bioactivity together with lipophilic ligand efficiency (LLE) and fraction sp3 content (Fsp3) parameters guided these efforts. Compound 10 was advanced into studies in mice on the basis of its optimized profile vs initial lead 1 (ΔLLE = 0.3, ΔFsp3 = 0.24). Although active in OGTT, 10 also displayed similar activity in the FFA2-knockout mice. Given this off-target OGTT effect, we discontinued development of this FFA2 agonist scaffold.

Synthesis method of (R) 4 (tert-butoxy) 2 (cyclopentyl methyl) 4 oxobutyric acid

The invention belongs to the field of organic chemistry, and discloses a synthesis method of a compound (R) 4 (tert-butoxy) 2 (cyclopentyl methyl) 4 oxobutyric acid of which the formula 5 is shown in the description. According to the technical scheme, 3-cyclopentyl propionyl chloride is adopted as a raw material, through chiral prothetic group induction, an alkylation reaction and a hydrolysis reaction, the compound of which the formula 5 is shown in the description is prepared. According to the synthesis method of the compound (R) 4 (tert-butoxy) 2 (cyclopentyl methyl) 4 oxobutyric acid, by adjusting the temperatures in chiral prothetic group induction, the alkylation reaction and the hydrolysis reaction and the catalysts used in chiral prothetic group induction, the alkylation reaction and the hydrolysis reaction, the compound of which the formula 5 is shown in the description is synthesized with high yield. The path is short, the aftertreatment is simple, the total yield through the three-step reaction can reach 65%, and the optical purity can reach 95% or above.

NOVEL COMPOUNDS, PHARMACEUTICAL COMPOSITION AND METHODS FOR USE IN TREATING METABOLIC DISORDERS

The present invention is directed to novel compounds of formula (I) and their use in treating metabolic diseases.

Synthesis and SAR of succinamide peptidomimetic inhibitors of cathepsin S

Peptidic, non-covalent inhibitors of lysosomal cysteine protease cathepsin S (1 and 2) were investigated due to low oral bioavailability, leading to an improved series of peptidomimetic inhibitors. Utilizing phenyl succinamides as the P2 residue increased the oral exposure of this lead series of compounds, while retaining selective inhibition of the cathepsin S isoform. Concurrent investigation of the P1 and P2 subsites resulted in the discovery of several potent and selective inhibitors of cathepsin S with good pharmacokinetic properties due to the elimination of saturated aliphatic P2 residues.

INHIBITORS OF CATHEPSIN S

The present invention provides compounds, compositions and methods for the selective inhibition of cathepsin S. In a preferred aspect, cathepsin S is selectively inhibited in the presence of at least one other cathepsin isozyme. The present invention also