137992-25-7

Upstream product

• 53267-93-9 O-methyl-N-tert-butoxycarbonyl-L-tyrosine 
• 100-39-0 benzyl bromide 
• 3978-80-1 Boc-Tyr-OH 
• 501-53-1 benzyl chloroformate 

Downstream Products

• 55456-41-2 (S)-benzyl 2-amino-3-(4-methoxyphenyl)propanoate 
• 122225-86-9 N-<(1-methylpiperidin-4-yl)carbonyl>-O-methyltyrosine benzyl ester 
• 122224-96-8 N-<(1-methylpiperidin-4-yl)carbonyl>-O-methyltyrosine 
• 52177-40-9 (L)-4-Methoxy-phenylalanine benzyl ester hydrochloride 

Relevant academic research and scientific papers

Required Immunoproteasome Subunit Inhibition Profile for Anti-Inflammatory Efficacy and Clinical Candidate KZR-616 ((2 S,3 R)- N-((S)-3-(Cyclopent-1-en-1-yl)-1-((R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)-3-hydroxy-3-(4-methoxyphenyl)-2-((S)-2-(2-morpholinoacetamido)propanamido)propenamide)

Selective immunoproteasome inhibition is a promising approach for treating autoimmune disorders, but optimal proteolytic active site subunit inhibition profiles remain unknown. We reveal here our design of peptide epoxyketone-based selective low molecular mass polypeptide-7 (LMP7) and multicatalytic endopeptidase complex subunit-1 (MECL-1) subunit inhibitors. Utilizing these and our previously disclosed low molecular mass polypeptide-2 (LMP2) inhibitor, we demonstrate a requirement of dual LMP7/LMP2 or LMP7/MECL-1 subunit inhibition profiles for potent cytokine expression inhibition and in vivo efficacy in an inflammatory disease model. These and additional findings toward optimized solubility led the design and selection of KZR-616 disclosed here and presently in clinical trials for treatment of rheumatic disease.

Total synthesis of proposed structure of coibamide A, a highly N- and O-methylated cytotoxic marine cyclodepsipeptide

Total synthesis of the originally proposed structure of coibamide A, a highly N- and O-methylated cytotoxic marine cyclodepsipeptide, has been accomplished by using a [(4+1)+3+3]-peptide fragment-coupling strategy and careful examination and optimization

Compounds for enzyme inhibition

One aspect of the invention relates to inhibitors that preferentially inhibit immunoproteasome activity over constitutive proteasome activity. In certain embodiments, the invention relates to the treatment of immune related diseases, comprising administer

ORALLY ACTIVE RENIN INHIBITORS

This invention relates to compounds of the formula STR1 wherein Q, Z, D, E, R 3, R 4, R 5 and R 6 are defined as below, and the pharmaceutically acceptable salts thereof are disclosed. The compounds are useful as antihypertensive agents.

Studies directed toward the design of orally active renin inhibitors. 1. Some factors influencing the absorption of small peptides

A systematic evaluation of structure-absorption relationships using a high throughput intraduodenal rat screening model has led to the delineation of a set of structural parameters that appear to govern bioavailability in a series of peptide-based renin inhibitors. Optimum structures, exemplified by 25 and 41, incorporated a single, solubilizing substituent at the C- or N- terminus combined with a lipophilic P2-site residue. Both inhibitors gave unprecedented plasma drug levels upon intraduodenal administration to monkeys, and the calculated bioavailability for 41 (14 ± 4%) is the highest reported for any peptidic renin inhibitor.

Orally active renin inhibitors

This invention relates to compounds of the formula wherein Q, Z, D, E, R3, R?, R? and R? are defined as below, and the pharmaceutically acceptable salts thereof are disclosed. The compounds are useful as antihypertensive agents.