864282-43-9

Upstream product

• 57260-73-8 N-BOC-1,2-diaminoethane 
• 1161-13-3 N-Cbz-L-Phe 
• 3397-32-8 N-(benzyloxycarbonyl)-phenylalanine-N-hydroxysuccinimide ester 
• 79513-35-2 N-(tert-butyloxycarbonyl)-1,2-ethanediamine hydrochloride 
• 56602-33-6 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 

Downstream Products

• 112670-62-9 (2S)-2-amino-N-(2-aminoethyl)-3-phenylpropanamide 
• 1028301-57-6 3-benzyl-N-(2-{2-[2-benzyloxycarbonylamino-3-(1H-indol-3-yl)-propionylamino]-3-phenyl-propionylamino}-ethyl)-succinamic acid tert-butyl ester 
• 1025819-78-6 3-benzyl-N-[1-[1-(2-tert-butoxycarbonylamino-ethylcarbamoyl)-2-phenyl-ethylcarbamoyl]-2-(1H-indol-3-yl)-ethyl]-succinamic acid tert-butyl ester 
• 1026725-77-8 N-[1-[1-(2-tert-butoxycarbonylamino-ethylcarbamoyl)-2-phenyl-ethylcarbamoyl]-2-(1H-indol-3-yl)-ethyl]-succinamic acid 
• 1027372-84-4 [1-[1-(2-tert-butoxycarbonylamino-ethylcarbamoyl)-2-phenyl-ethylcarbamoyl]-2-(1H-indol-3-yl)-ethyl]-carbamic acid benzyl ester 
• 957148-23-1 C₁₄H₂₂N₄O₂ 
• 957148-22-0 C₂₀H₂₆N₄O₂ 
• 383187-88-0 N-[2-(tert-butoxycarbonylamino)ethyl]-2-(S)-amino-3-phenylpropionamide 
• 383187-91-5 N-[1-(S)-(2-tert-butoxycarbonylaminoethylcarbamoyl)-2-phenylethyl]-2-(4-oxo-2,3-dihydro-1,5-benzothiazepin-5-yl)acetamide 

Relevant academic research and scientific papers

Synthesis and optimization of hyaluronic acid-methotrexate conjugates to maximize benefit in the treatment of osteoarthritis

We previously reported that a conjugate of hyaluronic acid (HA) and methotrexate (MTX) could be a prototype for future osteoarthritis drugs having the efficacy of the two clinically validated agents but with a reduced risk of the systemic side effects of MTX by using HA as the drug delivery carrier. To identify a clinical candidate, we attempted optimization of a lead, conjugate 1. Initially, in fragmentation experiments with cathepsins, we optimized the peptide part of HA-MTX conjugates to be simpler and more susceptible to enzymatic cleavage. Then we optimized the peptide, the linker, the molecular weight, and the binding ratio of the MTX of the conjugates to inhibit proliferation of human fibroblast-like synoviocytes in vitro and knee swelling in rat antigen-induced monoarthritis in vivo. Consequently, we found conjugate 30 (DK226) to be a candidate drug for the treatment of osteoarthritis.

Hyaluronic Acid-Methotrexate Conjugate

An object of the present invention is to provide a hyaluronic acid-methotrexate conjugate useful as a therapeutic drug for joint disorders. There is provided a hyaluronic acid-methotrexate conjugate useful for the treatment of joint disorders, wherein met

Molecular rotors as simple models to study amide NH-aromatic interactions and their role in the folding of peptide-like structures

(Chemical Equation Presented) The conformational behavior of designed macrocyclic naphthalenophanes (1a,b and 2a,b) derived from amino acids (Phe and Val) has been used for studying NH...π interactions. The cycles having 16- and 17-membered rings showed a dynamic process within the NMR time scale, produced by the flipping of the aromatic naphthalene moiety with respect to the macrocyclic main plane. We used the temperature dependence of 1H NMR to obtain activation parameters of the energetic barrier for the process (variable temperature NMR and line shape analysis). The rate of the movement clearly depends on the macrocyclic ring size and, more interestingly, on the nature of the peptidomimetic side chain, the energetic barrier being higher for the compounds bearing aromatic side chains. A largely negative entropic contribution to the free energy of activation was observed, with clear differences due to the side chain nature. Molecular modeling studies suggest that the aromatic rings interact with intramolecularly H-bonded amide NH groups, protecting them from solvation and thus leading to a larger unfavorable activation entropy. This NH...π interaction has been exploited for the preparation of new systems (1c and meso-1b) with designed conformational preferences, in which aromatic rings tend to fold over amide NH groups. Thus, these minimalistic molecular rotors have served us as simple model systems for the study of NH...π interactions and their implication in the folding of peptide-like molecules.

Small molecule inhibitors of secretion of proteins encoded by ARE-mRNAs

The invention features compounds that inhibit secretion of a protein encoded by an ARE-mRNA or that modulate regulation of an ARE-mRNA. These compounds are useful for the treatment or prevention of conditions involving proteins encoded by ARE-mRNAs, such

Rational design, discovery, and synthesis of a novel series of potent growth hormone secretagogues

In the joint experimental and computational efforts reported here to obtain novel chemical entities as growth hormone secretagogues (GHSs), a small database of peptides and non-peptides known to have GHS activity was used to generate and assess a 3D pharmacophore for this activity. This pharmacophore was obtained using a systematic and efficient procedure, "DistComp", developed in our laboratory. The 3D pharmacophore identified was then used to search 3D databases to explore chemical structures that could be novel GHSs. A number of these were chosen for synthesis and assessment of their ability to release growth hormone (GH) from rat pituitary cells. Among the compounds tested, those with a benzothiazepin scaffold were discovered with micromolar activity. To facilitate lead optimization, a second program, a site-dependent fragment QSAR procedure was developed. This program calculates a library of chemical and physical properties of "fragments" or chemical components in a known pharmacophore and determines which, if any, of these properties are important for the observed activity. The combined use of the 3D pharmacophore and the results of the site-dependent fragment QSAR analysis led to the discovery and synthesis of a novel series of potent GHSs, a number of which had nanomolar in vitro activity.