114744-84-2

Upstream product

• 1149-26-4 (S)-N-(benzyloxycarbonyl)valine 
• 6638-79-5 N,O-dimethylhydroxylamine*hydrochloride 
• 87052-60-6 Z-(S)-Val-Cl 
• 623-04-1 4-aminobenzenemethanol 
• 1117-97-1 N,0-dimethylhydroxylamine 
• 6306-52-1 L-valine methylester hydrochloride 
• 24210-19-3 methyl (2S)-3-methyl-[(benzyloxy)carbonylamino]butanoate 
• 501-53-1 benzyl chloroformate 
• 72-18-4 L-valine 
• 17498-50-9 L-valine hydrochloride 
• 13734-41-3 t-Boc-L-valine 

Downstream Products

• 1025840-65-6 [(S)-2-Methyl-1-(2-methyl-2H-tetrazole-5-carbonyl)-propyl]-carbamic acid benzyl ester 
• 1027243-19-1 [(S)-1-(Benzofuran-2-carbonyl)-2-methyl-propyl]-carbamic acid benzyl ester 
• 120629-82-5 (S)-1-(2-Benzothiazolyl)-2-(benzyloxycarbonyl)amino-3-methyl-1-butanone 
• 1025993-82-1 [(S)-1-(3-Ethoxy-pyridine-2-carbonyl)-2-methyl-propyl]-carbamic acid benzyl ester 
• 1027511-54-1 [(S)-1-(Benzo[b]thiophene-2-carbonyl)-2-methyl-propyl]-carbamic acid benzyl ester 
• 1178876-44-2 (S)-benzyl 2-methyl-4-oxohex-5-yn-3-ylcarbamate 
• 331779-26-1 1-chloro-3-methyl-(2S)-2-phenylmethyloxycarbonylamino-butane-1-one oxime 
• 1449512-57-5 (S)-2-benzyloxycarbonylamino-3-methylbutanaldoxime 
• 120629-95-0 3-<(benzyloxycarbonyl)amino>-2-hydroxy-4-methylpentanenitrile 

Relevant academic research and scientific papers

The discovery of potent, selective, and reversible inhibitors of the house dust mite peptidase allergen der p 1: An innovative approach to the treatment of allergic asthma

Blocking the bioactivity of allergens is conceptually attractive as a small-molecule therapy for allergic diseases but has not been attempted previously. Group 1 allergens of house dust mites (HDM) are meaningful targets in this quest because they are globally prevalent and clinically important triggers of allergic asthma. Group 1 HDM allergens are cysteine peptidases whose proteolytic activity triggers essential steps in the allergy cascade. Using the HDM allergen Der p 1 as an archetype for structure-based drug discovery, we have identified a series of novel, reversible inhibitors. Potency and selectivity were manipulated by optimizing drug interactions with enzyme binding pockets, while variation of terminal groups conferred the physicochemical and pharmacokinetic attributes required for inhaled delivery. Studies in animals challenged with the gamut of HDM allergens showed an attenuation of allergic responses by targeting just a single component, namely, Der p 1. Our findings suggest that these inhibitors may be used as novel therapies for allergic asthma.

Synthesis of chiral branched allylamines through dual photoredox/nickel catalysis

Allylamines are versatile building blocks in the synthesis of various naturally occurring products and pharmaceuticals. In contrast to terminal allylamines, the methods of synthesis of their branched congeners with internal, stereodefined double bonds are less explored. This work describes a new approach for the preparation of allylaminesviacross-coupling of alkyl bromides with simple 3-bromoallylamines by merging the photoredox approach and Ni catalysis. The reaction proceeds under mild conditions, under blue light irradiation, and in the presence of an organic dye, 4CzIPN, as a photocatalyst. The scope of suitable reaction partners is broad, including alkyl bromides bearing reactive functionalities (e.g., esters, nitriles, aldehydes, ketones, epoxides) andN-protected allylamines, as well asN-allylated secondary and tertiary amines and heterocycles. The employment of non-racemic starting materials allows for rapid and easy construction of complex multifunctional allylamine derivatives without the loss of enantiomeric purity.

One-pot synthesis of Weinreb amides employing 3,3-dichloro-1,2-diphenylcyclopropene (CPI-Cl) as a chlorinating agent

The synthesis of Nα-protected amino alkyl Weinreb amides starting from the corresponding α-amino acids as well as carboxylic acids has been delineated through the in situ generation of acid chlorides using CPI-Cl as a chlorinating agent. The protocol is simple; the reaction conditions employed were mild, and compatible with all the three commonly used urethane protecting groups namely, Boc, Cbz and Fmoc groups. The resulting Weinreb amides are obtained in good yields as optically pure products.

Discovery of Peptidomimetic Antibody-Drug Conjugate Linkers with Enhanced Protease Specificity

Antibody-drug conjugates (ADCs) have become an important therapeutic modality for oncology, with three approved by the FDA and over 60 others in clinical trials. Despite the progress, improvements in ADC therapeutic index are desired. Peptide-based ADC linkers that are cleaved by lysosomal proteases have shown sufficient stability in serum and effective payload-release in targeted cells. If the linker can be preferentially hydrolyzed by tumor-specific proteases, safety margin may improve. However, the use of peptide-based linkers limits our ability to modulate protease specificity. Here we report the structure-guided discovery of novel, nonpeptidic ADC linkers. We show that a cyclobutane-1,1-dicarboxamide-containing linker is hydrolyzed predominantly by cathepsin B while the valine-citrulline dipeptide linker is not. ADCs bearing the nonpeptidic linker are as efficacious and stable in vivo as those with the dipeptide linker. Our results strongly support the application of the peptidomimetic linker and present new opportunities for improving the selectivity of ADCs.

ALIPHATIC PROLINAMIDE DERIVATIVES

This invention is directed to novel aliphatic prolinamide derivatives of Formula I, and pharmaceutically acceptable salts, solvates, solvates of the salt and prodrugs thereof, useful in the prevention (e.g., delaying the onset of or reducing the risk of developing) and treatment (e.g., controlling, alleviating, or slowing the progression of) of age-related macular degeneration (AMD) and related diseases of the eye. These diseases include dry-AMD, wet-AMD, geographic atrophy, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, and degeneration of retinal or photoreceptor cells. The invention disclosed herein is further directed to methods of prevention, slowing the progress of, and treatment of dry-AMD, wet-AMD, and geographic atrophy, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, and degeneration of retinal or photoreceptor cells, comprising: administration of a therapeutically effective amount of compound of the invention. The compounds of the invention are inhibitors of HTRAl. Thus, the compounds of the invention are useful in the prevention and treatment of a wide range of diseases mediated (in whole or in part) by HTRAl. The compounds of the invention are also useful for inhibiting HTRAl protease activity in an eye or locus of an arthritis or related condition.

α-Amino Aldehydes as Readily Available Chiral Aldehydes for Rh-Catalyzed Alkyne Hydroacylation

Readily available α-amino aldehydes, incorporating a methylthiomethyl (MTM) protecting group on nitrogen, are shown to be efficient substrates in Rh-catalyzed alkyne hydroacylation reactions. The reactions are performed under mild conditions, employing a small-bite-angle bis-phosphine ligand, allowing for good functional group tolerance with high stereospecificity. Amino aldehydes derived from glycine, alanine, valine, leucine, phenylalanine, isoleucine, serine, tryptophan, methionine, and cysteine were successfully employed, as was an enantiomerically enriched α-OMTM-aldehyde derived from phenyllactic acid. The synthetic utility of the α-amino enone products is demonstrated in a short enantioselective synthesis of the natural product sphingosine.

PEPTIDOMIMETIC COMPOUNDS AND ANTIBODY-DRUG CONJUGATES THEREOF

This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, pharmaceutical compositions containing them, and to their use in therapy for the prevention treatment of cancer.

PEPTIDOMIMETIC COMPOUNDS AND ANTIBODY-DRUG CONJUGATES THEREOF

This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.

PEPTIDOMIMETIC COMPOUNDS AND ANTIBODY-DRUG CONJUGATES THEREOF

This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.

Efficient synthesis of N-protected amino/peptide Weinreb amides from T3P and DBU

The reaction of Nα-protected amino/peptide acid with N,O-dimethylhydroxylamine hydrochloride in the presence of T3P and DBU to obtain enantiomerically pure Nα-protected amino/peptidyl Weinreb amides in high yields has been described. Fmoc-Ala-Weinreb amide 2a is obtained as single crystal, and its structure was determined through X-ray crystallography.