105095-22-5

Upstream product

• 6908-41-4 4-(methoxycarbonyl)benzyl alcohol 
• 3006-96-0 3-hydroxymethyl-benzoic acid 
• 7693-46-1 4-Nitrophenyl chloroformate 

Downstream Products

• 201211-65-6 4-{[Bis-(4-tert-butoxycarbonylamino-butyl)-carbamoyloxy]-methyl}-benzoic acid 
• 191277-09-5 4-{[(4-tert-Butoxycarbonylamino-butyl)-(3-tert-butoxycarbonylamino-propyl)-carbamoyloxy]-methyl}-benzoic acid 
• 201211-58-7 4-{[Bis-(3-tert-butoxycarbonylamino-propyl)-carbamoyloxy]-methyl}-benzoic acid 
• 191277-08-4 4-({(4-tert-Butoxycarbonylamino-butyl)-[3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-propyl]-carbamoyloxy}-methyl)-benzoic acid methyl ester 
• 177897-11-9 4-{[Bis-(4-tert-butoxycarbonylamino-butyl)-carbamoyloxy]-methyl}-benzoic acid methyl ester 
• 177897-09-5 4-{[(4-tert-Butoxycarbonylamino-butyl)-(3-tert-butoxycarbonylamino-propyl)-carbamoyloxy]-methyl}-benzoic acid methyl ester 
• 177897-10-8 4-{[Bis-(3-tert-butoxycarbonylamino-propyl)-carbamoyloxy]-methyl}-benzoic acid methyl ester 

Relevant academic research and scientific papers

Development of potent and selective tissue transglutaminase inhibitors: Their effect on TG2 function and application in pathological conditions

Potent-selective peptidomimetic inhibitors of tissue transglutaminase (TG2) were developed through a combination of protein-ligand docking and molecular dynamic techniques. Derivatives of these inhibitors were made with the aim of specific TG2 targeting to the intra- and extracellular space. A cell-permeable fluorescently labeled derivative enabled detection of in situ cellular TG2 activity in human umbilical cord endothelial cells and TG2-transduced NIH3T3 cells, which could be enhanced by treatment of cells with ionomycin. Reaction of TG2 with this fluorescent inhibitor in NIH3T3 cells resulted in loss of binding of TG2 to cell surface syndecan-4 and inhibition of translocation of the enzyme into the extracellular matrix, with a parallel reduction in fibronectin deposition. In human umbilical cord endothelial cells, this same fluorescent inhibitor also demonstrated a reduction in fibronectin deposition, cell motility, and cord formation in Matrigel. Use of the same inhibitor in a mouse model of hypertensive nephrosclerosis showed over a 40% reduction in collagen deposition.

ACYLPIPERAZINES AS INHIBITORS OF TRANSGLUTAMINASE AND THEIR USE IN MEDICINE

The present invention relates to novel compounds of Formula I capable of inhibiting tissue transglutaminase, and uses of the same in medicine. In particular, the invention provides compounds for use in the treatment of prevention of disease and conditions such as fibrosis (e.g. cystic fibrosis), scarring, neurodegenerative diseases (e.g. Alzheimer's disease, Huntington's disease and Parkinson's disease), autoimmune diseases (e.g. multiple sclerosis and coeliac disease), thrombosis, proliferative disorders (e.g. cancers), AIDS, psoriasis and inflammation (e.g. chronic inflammatory diseases).

Solid phase synthesis of polyamine conjugates for the study of trypanothione reductase

A number of polyamine scaffolds were synthesised, enabling the facile preparation of a variety of polyamine conjugates using both Boc and Fmoc protecting group strategies. Products were released from the solid support by treatment with either triflic acid/trifluoroacetic acid or trifluoroacetic acid. The trypanosomal metabolite N1, N6-bis(glurathionyl)spermidine [trypanothione], and a range of related analogues were prepared for biological evaluation as previously communicated.

Solid phase polyamine linkers - Their utility in synthesis and the preparation of directed libraries against trypanothione reductase

A variety of diprotected polyamines are anchored to a solid support and used in solid phase chemistry and library generation.

PEPTIDE DERIVATIVES

The invention concerns pharmaceutically useful trifluoromethyl ketone substituted di-, tri-and tetra-peptide derivatives of the formulae Ia, Ib, Ic set out hereinafter, and salts thereof, which are inhibitors of human leukocyte elastase. Also described herein are pharmaceutical compositions containing a peptide derivative and processes and intermediates for use in the manufacture of the peptide derivatives.