95501-60-3

Upstream product

• 13734-41-3 t-Boc-L-valine 
• 41324-66-7 H-Pro-OBzl 
• 3392-12-9 Boc-Val-ONSu 
• 16652-71-4 benzyl (2S)-2-pyrrolidinecarboxylate hydrochloride 
• 58872-03-0 1--L-valyl>-L-proline phenylmethyl ester 

Downstream Products

• 144393-55-5 Boc-Gly-Val-Pro-OBzl 
• 1374975-59-3 C₃₅H₅₄N₆O₉ 
• 170742-56-0 Boc-Gly-Asp(OCHx)-Gly-Val-Pro-OBzl 
• 123206-35-9 1--L-proline phenylmethyl ester 
• 123206-18-8 N-{(S)-1-[(S)-2-(1-Benzyl-3,3,3-trifluoro-2-oxo-propylcarbamoyl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-succinamic acid methyl ester 
• 123206-15-5 N-(4-methoxy-1,4-dioxobutyl)-L-valyl-N-<3,3,3-trifluoro-2-hydroxy-1-(phenylmethyl)propyl>-L-prolinamide 
• 224577-27-9 N_α-<<4-<<<(2-methylphenyl)amino>carbonyl>amino>phenyl>acetyl>-N_ε-<6-hexanoyl>-L-lysinyl-L-(α-O-benzylaspartyl)-L-valyl-L-proline benzyl ester 
• 224577-25-7 N_ε-<6-hexanoyl>-N_α-(tert-butyloxycarbonyl)-L-lysinyl-L-(α-O-benzylaspartyl)-L-valyl-L-proline benzyl ester 
• 224577-26-8 N_ε-<6-hexanoyl>-L-lysinyl-L-(α-O-benzylaspartyl)-L-valyl-L-proline benzyl ester 
• 224577-21-3 N-<<4-<<<(2-methylphenyl)amino>carbonyl>amino>phenyl>acetyl>-L-leucyl-L-(α-O-benzylaspartyl)-L-valyl-O-benzyl proline 

Relevant academic research and scientific papers

Structure-Based Rationale Design and Synthesis of Aurantiamide Acetate Analogues - Towards a New Class of Potent Analgesic and Anti-inflammatory Agents

A series of new aurantiamide acetate analogues were synthesized by modifying its N-terminal substitution and the amino acid residue. The structure of all these compounds was established on the basis of analytical and spectral studies. All the new derivatives were evaluated in vivo for their analgesic activity by tail flick method in mice and anti-inflammatory activity against carrageenan-induced oedema in albino rats at different doses (25, 50 and 100mg/kg body weight). All the compounds exhibited significant pharmacological activity with no ulcerogenic liability. In particular, pentapeptides and tricosamers (30 amino acids) containing analogues have demonstrated high potency than the reference standards. These compounds hold promise for further development.

Synthesis of elastin based peptides conjugated to benzisoxazole as a new class of potent antimicrobials - A novel approach to enhance biocompatibility

The peptides of elastin sequences chosen for the present study included tetrapeptides, pentapeptides and tricosapeptides (30 amino acids), synthesized by classical solution phase method and conjugated to [3-(4-piperidyl)-6-fluoro- 1,2-benzisoxazole]. The

Synthesis and crystal structure of tripeptide fragment of elastin

Boc-Gly-Val-Pro-OBzl, a protected tripeptide fragment of repeating sequences of mammalian elastic protein elastin was synthesized and characterized by X-ray diffraction method. The sequence C24 H35 N 3 O6 crysta

Discovery of potent antagonists of the antiapoptotic protein XIAP for the treatment of cancer

Inhibitor of apoptosis (IAP) proteins are overexpressed in many cancers and have been implicated in tumor growth, pathogenesis, and resistance to chemo- or radiotherapy. On the basis of the NMR structure of a SMAC peptide complexed with the BIR3 domain of X-linked IAP (XIAP), a novel series of XIAP antagonists was discovered. The most potent compounds in this series bind to the baculovirus IAP repeat 3 (BIR3) domain of XIAP with single-digit nanomolar affinity and promote cell death in several human cancer cell lines. In a MDA-MB-231 breast cancer mouse xenograft model, these XIAP antagonists inhibited the growth of tumors. Close structural analogues that showed only weak binding to the XIAP-BIR3 domain were inactive in the cellular assays and showed only marginal in vivo activity. Our results are consistent with a mechanism in which ligands for the BIR3 domain of XIAP induce apoptosis by freeing up caspases. The present study validates the BIR3 domain of XIAP as a target and supports the use of small molecule XIAP antagonists as a potential therapy for cancers that overexpress XIAP.

Selective, tight-binding inhibitors of integrin α4β1 that inhibit allergic airway responses

Integrin α4β1 mediates leukocyte recruitment, activation, mediator release, and apoptosis inhibition, and it plays a central role in inflammatory pathophysiology. High-affinity, selective inhibitors of α4β1, based on the Leu-Asp-Val (LDV) sequence from the alternatively spliced connecting segment-1 (CS-1) peptide of cellular fibronectin, are described that employ a novel N-terminal peptide 'cap' strategy. One inhibitor, BIO- 1211, was ~106-fold more potent than the starting peptide and exhibited tight-binding properties (k(off) = 1.4 x 10-4 s-1, K(D) = 70 pM), a remarkable finding for a noncovalent, small-molecule inhibitor of a protein receptor. BIO-1211 was also 200-fold selective for the activated form of α4β1, and it stimulated expression of ligand-induced epitopes on the integrin β1 subunit, a property consistent with occupancy of the receptor's ligand-binding site. Pretreatment of allergic sheep with a 3-mg nebulized dose of BIO-1211 inhibited early and late airway responses following antigen challenge and prevented development of nonspecific airway hyperresponsiveness to carbachol. These results show that highly selective and potent small- molecule antagonists can be identified to integrins with primary specificity for peptide domains other than Arg-Gly-Asp (RGD); they confirm the generality of integrins as small molecule targets; and they validate α4β1 as a therapeutic target for asthma.

Non-linear hydrophobic-induced pKa shifts: Implications for efficiency of conversion to chemical energy

By using one Asp or one Glu per thirty residues in a polytricosapeptide capable of exhibiting a hydrophobic folding and assembly transition and stepwise converting a set of the five Val residues( most proximal to the Asp or Glu residue) to more-hydrophobi

TRIFLUOROMETHYLKETONE DERIVATIVES, PROCESSES FOR PREPARATION THEREOF AND USE THEREOF

The trifluoromethylketone derivatives (I) and pharmaceutically acceptable salts thereof have a human leukocyte elastase inhibiting activity and are useful as human leukocyte elastase inhibitors for treating or preventing degenerative diseases. The trifluoromethylketone derivatives (I) have the following formula: STR1 wherein R 1 is C. sub.1-6 alkyl which has one or two substituents selected from carboxy, esterified carboxy and di-C. sub.1-6 alkylcarbamoyl; phenyl(C 1-6) alkyl, the phenyl moiety of which may have halogen or nitro or amino substituents and the alkyl moiety of which may have carboxy or esterified carboxy substituents; halo-phenyl; morpholino; or morpholino(C 1-6) alkyl,R 2 and R 3 are each C 1-6 alkyl,X is--or--NH--, andY is STR2 and pharmaceutically acceptable salts thereof.

Synthesis of peptidyl fluoromethyl ketones and peptidyl α-keto esters as inhibitors of porcine pancreatic elastase, human neutrophil elastase, and rat and human neutrophil cathepsin G

Comparison of MeO-Suc-Val-Pro-Phe-CO2Me (29) and MeO-Suc-Ala-Ala-Pro-Phe-CO2Me (25) with their corresponding trifluoromethyl ketones 9a and 9b, respectively, in rat and human neutrophil cathepsin G assays showed the α-keto esters to

PROLINE DERIVATIVES

Proline derivatives of the formulae: STR1 wherein R 1 through R 11 have defined values, and acid-and base-addition salts thereof, and equilibrium addition compounds of the aldehyde group thereof; processes for their preparation; pharmaceutical compositions; and intermediates for preparing said proline derivatives. The proline derivatives are human leukocyte elastase inhibitors which are useful, for example, in treating pulmonary emphysema.