66447-55-0

Upstream product

• 13734-41-3 t-Boc-L-valine 
• 501-53-1 benzyl chloroformate 
• 100-51-6 benzyl alcohol 
• 53772-44-4 benzyloxydiphenylphosphine 
• 58561-04-9 N-tert-butoxycarbonyl-L-valine methyl ester 
• 100-44-7 benzyl chloride 
• 72-18-4 L-valine 
• 24424-99-5 di-tert-butyl dicarbonate 
• 100-39-0 benzyl bromide 
• 100-46-9 benzylamine 

Downstream Products

• 174602-80-3 benzyl (2S)-2-[[(tert-butoxy)carbonyl](methyl)amino]-3-methylbutanoate 
• 13734-41-3 t-Boc-L-valine 
• 2462-34-2 L-valine benzyl ester hydrochloride 
• 21760-98-5 L-valine benzyl ester 
• 910117-28-1 C₆₂H₇₉N₉O₁₅S 
• 93674-99-8 RGDV 
• 152020-29-6 H-Asp(OcHx)-Val-OBzl 
• 152020-28-5 Boc-Asp(OcHex)-Val-OBzl 
• 152020-31-0 (S)-2-[(S)-2-(2-Amino-acetylamino)-3-cyclohexyloxycarbonyl-propionylamino]-3-methyl-butyric acid benzyl ester 
• 152020-30-9 Boc-Gly-Asp(OcHex)-Val-OBzl 
• 152020-32-1 Boc-Arg(Tos)-Gly-Asp(OcHex)-Val-OBzl 
• 20902-47-0 N-tert-butoxycarbonyl-L-valyl-L-phenylalanine methyl ester 
• 108334-64-1 N-tert-butyloxycarbonyl-L-valyl-L-phenylalanine 
• 60209-59-8 (N-tert-butoxycarbonyl-L-alanyl)-L-valine 

Relevant academic research and scientific papers

Transition Metal-Free N-Arylation of Amino Acid Esters with Diaryliodonium Salts

A transition metal-free approach for the N-arylation of amino acid derivatives has been developed. Key to this method is the use of unsymmetric diaryliodonium salts with anisyl ligands, which proved important to obtain high chemoselectivity and yields. The scope includes the transfer of both electron deficient, electron rich and sterically hindered aryl groups with a variety of different functional groups. Furthermore, a cyclic diaryliodonium salt was successfully employed in the arylation. The N-arylated products were obtained with retained enantiomeric excess.

TRANSGLUTAMINASE 2 (TG2) INHIBITORS

Described herein are compounds and pharmaceutical compositions containing such compounds which inhibit transglutaminase 2 (TG2). Also described herein are methods for using such TG2 inhibitors, alone or in combination with other compounds, for treating diseases or conditions that would benefit from TG2 inhibition.

Catalytic Transfer Hydrodebenzylation with Low Palladium Loading

A highly-efficient catalytic system for hydrodebenzylation reaction is described. The cleavage of O-benzyl and N-benzyl protecting groups was performed using an uncommonly low palladium loading (0.02–0.3 mol%; TON up to 5000) in a relatively short reaction time. The approach was used for a variety of substrates including pharmaceutically important precursors, and gram-scale deprotection reaction was shown. Transfer conditions together with easy-to-make Pd/C catalyst are the key features of this debenzylation scheme. (Figure presented.).

Identification of a 4-fluorobenzyl L-valinate amide benzoxaborole (AN11736) as a potential development candidate for the treatment of Animal African Trypanosomiasis (AAT)

Novel L-valinate amide benzoxaboroles and analogues were designed and synthesized for a structure-activity-relationship (SAR) investigation to optimize the growth inhibitory activity against Trypanosoma congolense (T. congolense) and Trypanosoma vivax (T. vivax) parasites. The study identified 4-fluorobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate (5, AN11736), which showed IC50 values of 0.15 nM against T. congolense and 1.3 nM against T. vivax, and demonstrated 100% efficacy with a single dose of 10 mg/kg against both T. congolense and T. vivax in mouse models of infection (IP dosing) and in the target animal, cattle, dosed intramuscularly. AN11736 has been advanced to early development studies.

Heterogeneous H-Bonding in a Foldamer Helix

Structural characterization of new α/γ-peptide foldamers containing the cyclically constrained γ-amino acid I is described. Crystallographic and 2D NMR analysis shows that γ residue I promotes the formation of a 12/10-helical secondary structure in α/γ-pe

Chiral recognition of carboxylates by a static library of thiourea receptors with amino acid arms

Chiral recognition is based on a large network of very subtle interactions whose outcome is difficult to predict. A combinatorial approach is therefore the most suitable to search for the most efficient receptor and obtain a structure-enantioselectivity correlation. We synthesized a set of 12 receptors constructed with 1,9-diaminoantracene and α-amino acid esters, linked via thiourea groups. The association constants and enantioselectivities for the complexes with mandelate and N-acetylphenylalanine were determined by competitive NMR titrations. Association constants quite regularly depend on the substituents in the receptor structure, but the distribution of enantioselectivities across the library could not easily be rationalized.

Design, synthesis and biological evaluation of potent azadipeptide nitrile inhibitors and activity-based probes as promising anti-Trypanosoma brucei agents

Trypanosoma cruzi and Trypanosoma brucei are parasites that cause Chagas disease and African sleeping sickness, respectively. There is an urgent need for the development of new drugs against both diseases due to the lack of adequate cures and emerging drug resistance. One promising strategy for the discovery of small-molecule therapeutics against parasitic diseases has been to target the major cysteine proteases such as cruzain for T. cruzi, and rhodesain/TbCatB for T. brucei. Azadipeptide nitriles belong to a novel class of extremely potent cysteine protease inhibitors against papain-like proteases. We herein report the design, synthesis, and evaluation of a series of azanitrile-containing compounds, most of which were shown to potently inhibit both recombinant cruzain and rhodesain at low nanomolar/picomolar ranges. A strong correlation between the potency of rhodesain inhibition (i.e., target-based screening) and trypanocidal activity (i.e., whole-organism-based screening) of the compounds was observed. To facilitate detailed studies of this important class of inhibitors, selected hit compounds from our screenings were chemically converted into activity-based probes (ABPs), which were subsequently used for in situ proteome profiling and cellular localization studies to further elucidate potential cellular targets (on and off) in both the disease-relevant bloodstream form (BSF) and the insect-residing procyclic form (PCF) of Trypanosoma brucei. Overall, the inhibitors presented herein show great promise as a new class of anti-trypanosome agents, which possess better activities than existing drugs. The activity-based probes generated from this study could also serve as valuable tools for parasite-based proteome profiling studies, as well as bioimaging agents for studies of cellular uptake and distribution of these drug candidates. Our studies therefore provide a good starting point for further development of these azanitrile-containing compounds as potential anti-parasitic agents. Copyright

Catalyst and solvent-free amidation of inactive esters of N-protected amino acids

A catalyst free procedure for the preparation of amides from inactive esters of N-protected amino acids and various amines is demonstrated under mild reaction conditions. Our effort to recover excess amine and generated alcohol is an approach towards environment friendly and cost effective synthesis under easy operational conditions.

Low molecular weight MPEG-assisted organic synthesis

A toolkit of low molecular weight MPEG-supported coupling agents ( MIIDQ, MEDCI), reagents for the Mitsunobu reaction ( MDEAD, MTPP), an alternative to diazomethane, and scavengers can be used in the solution-phase synthesis of amides, esters and ureas and are easily removed after use by solid-phase extraction (MSPE) using normal silica.

Toward the back-up of Boceprevir (SCH 503034): Discovery of new extended P4-capped ketoamide inhibitors of hepatitis C virus NS3 serine protease with improved potency and pharmacokinetic profiles

Hepatitis C is the most prevalent liver disease. Viral hepatitis C (HCV), a small (+)-RNA virus, infects chronically an estimated 300 million people worldwide. Results of Phase I clinical studies with our first generation HCV inhibitor Boceprevir, SCH 503034 (1), presented at the 56th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) were encouraging, and thus, additional human clinical studies are underway. In view of the positive data from our first generation compound, further work aimed at optimizing its overall profile was undertaken. Herein, we report that extension of our earlier inhibitor to the P4 pocket and optimization of the P1′ capping led to the discovery of new ketoamide inhibitors of the HCV NS3 serine protease with improved in vitro potency. In addition to being potent inhibitors of HCV subgenomic RNA replication, some of the new P4-capped inhibitors were also found to have improved PK profile.