861851-74-3

Upstream product

• 28920-43-6 (fluorenylmethoxy)carbonyl chloride 
• 35661-51-9 N-(9-fluorenylmethyloxycarbonyl)hydrazine 
• 147688-35-5 C₂₇H₂₈N₂O₄ 

Downstream Products

• 861851-75-4 1-Fmoc-2-benzyl-4-(o-chlorobenzyl)semicarbazide 
• 1380421-41-9 C₄₂H₆₃N₉O₁₁S 
• 1380421-53-3 C₄₃H₆₅N₉O₁₁S 
• 1093755-66-8 His-D-Ala-Ala-AzaPhe-D-Phe-Lys-NH₂ 
• 1093755-65-7 His-D-Trp-Ala-AzaPhe-D-Ala-Lys-NH₂ 
• 1093755-35-1 His-AzaPhe-Ala-Trp-D-Ala-Lys-NH₂ 
• 1093754-92-7 His-D-Trp-Ala-AzaPhe-D-Phe-Lys-NH₂ 
• 1383736-71-7 (D/L)His-AzaPhe-Ala-Trp-D-Phe-Lys-NH₂ 
• 1093755-67-9 H-Ala-D-Trp-Ala-azaPhe-D-Phe-Lys-NH₂ 
• 1093755-41-9 Ala-AzaPhe-Ala-Trp-D-Phe-Lys-NH₂ 
• 1093755-64-6 His-D-Trp-Ala-AzaPhe-D-Phe-Ala-NH₂ 
• 1093755-32-8 His-AzaPhe-Ala-Trp-D-Phe-Ala-NH₂ 

Relevant academic research and scientific papers

THIOSEMICARBAZATES AND USES THEREOF

Thioesters, thiocarbamates, thiocarbazates, semithiocarbazates, peptides, aza-amino acid conjugates, and azapeptides; and a chemoselective and site-specific functionalization protocol of protected thiocarbazates and semithiocarbazates are described. The protocol features the use of Mitsunobu reaction to alkylate specifically the nitrogen atom close to the acylthiol moiety with alcohols to produce protected mono-substituted thiocarbazates that can be stored for months, activated under mild conditions at low temperature using halonium reagents and integrated orthogonally to make substituted semicarbazides that can be used, e.g., as synthons in synthesis of aza-amino acid conjugates, azapeptides and other peptidomimetics. Methods for preparing and using ureases, carbazides, semicarbazides, beta-peptides, azapeptides, and other peptidomimetics and azapeptide conjugates, and uses of ureases, carbazides, semicarbazides, beta-peptides, azapeptides in drug discovery, diagnosis, inhibition, prevention and treatment of diseases are also described.

Cyclic aza-peptide integrin ligand synthesis and biological activity

Aza-peptides are obtained by replacement of the α-C-atom of one or more amino acids by a nitrogen atom in a peptide sequence. Introduction of aza-residues into peptide sequences may result in unique structural and pharmacological properties, such that aza-scanning may be used to probe structure-activity relationships. In this study, a general approach for the synthesis of cyclic aza-peptides was developed by modification of strategies for linear aza-peptide synthesis and applied in the preparation of cyclic aza-pentapeptides containing the RGD (Arg-Gly-Asp) sequence. Aza-amino acid scanning was performed on the cyclic RGD-peptide Cilengitide, cyclo[R-G-D-f-N(Me)V] 1, and its parent peptide cyclo(R-G-D-f-V) 2, potent antagonists of the αvβ3, αvβ5, and α5β1 integrin receptors, which play important roles in human tumor metastasis and tumor-induced angiogenesis. Although incorporation of the aza-residues resulted generally in a loss of binding affinity, cyclic aza-peptides containing aza-glycine retained nanomolar activity toward the αvβ3 receptor.

Novel semicarbazide-derived inhibitors of human dipeptidyl peptidase I (hDPPI)

Human dipeptidyl peptidase I (hDPPI, cathepsin C, EC 3.4.14.1) is a novel putative drug target for the treatment of inflammatory diseases. Using 1 as a starting point (IC50 > 10 μM), we have improved potency by more than 500-fold and successfully identified novel inhibitors of DPPI via screening of a one-bead-two-compounds library of semicarbazide derivatives. Selected compounds were shown to inhibit intracellular DPPI in RBL-2H3 cells. These compounds were further characterized for adverse effects on HepG2 cells (cytotoxicity and viability) and their metabolic stability in rat liver microsomes was estimated. One of the most potent inhibitors, 8 (IC50 = 31 ± 3 nM; Ki = 45 ± 2 nM, competitive inhibition), is selective for DPPI over other cysteine and serine proteases, has a half-life of 24 min in rat liver microsomes, shows approximately 50% inhibition of intracellular DPPI at 20 μM and is noncytotoxic.