68166-40-5

Upstream product

• 33857-66-8 N-benzyloxycarbonyl-L-valine 2-pyridylthiol ester 
• 147-85-3 L-proline 
• 3496-11-5 2,5-dioxopyrrolidin-1-yl (2S)-2-(((benzyloxy)carbonyl)amino)-3-methylbutanoate 
• 609-36-9 rac-Pro-OH 
• 5497-76-7 L-proline tert-butyl ester hydrochloride 
• 2577-48-2 methyl (2S)-pyrrolidine carboxylate 
• 910469-60-2 Z-Val-D-Pro-OMe 
• 1149-26-4 (S)-N-(benzyloxycarbonyl)valine 
• 820239-44-9 benzyl (S)-(1-(1H-benzo[d][1,2,3]triazol-1-yl)-3-methyl-1-oxobutan-2-yl)carbamate 
• 52616-99-6 N-[(Phenylmethoxy)carbonyl]-L-valyl-L-proline tert-butyl ester 
• 51827-14-6 N-[(Phenylmethoxy)carbonyl]-L-valyl-L-proline methyl ester 

Downstream Products

• 221106-06-5 (3S,4RS)-3-<amino>-4-hydroxy-5-phenoxypentanoic acid tert-butyl ester 
• 437756-12-2 {(S)-1-[(S)-2-((S)-1-{[4-(tert-Butyl-dimethyl-silanyloxy)-benzooxazol-2-yl]-hydroxy-methyl}-2-methyl-propylcarbamoyl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid benzyl ester 
• 910469-67-9 [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-[3-N'-[N^α(benzyloxycarbonyl)valyl-prolyl-valylamino]propyl]thymine]-3'-spiro-5''-[4''-amino-1'',2''-oxathiole-2'',2''-dioxide] 
• 884867-04-3 (S)-1-((S)-2-Amino-3-methyl-butyryl)-pyrrolidine-2-carboxylic acid benzylamide 

Relevant academic research and scientific papers

A MedChem toolbox for cereblon-directed PROTACs

A modular chemistry toolbox was developed for cereblon-directed PROTACs. A variety of linkers was attached to a CRBN ligand via the 4-amino position of pomalidomide. We used linkers of different constitution to modulate physicochemical properties. We equipped one terminus of the linker with a set of functional groups, e.g. protected amines, protected carboxylic acids, alkynes, chloroalkanes, and protected alcohols, all of which are considered to be attractive for PROTAC design. We also highlight different opportunities for the expansion of the medicinal chemists' PROTAC toolbox towards heterobifunctional molecules, e.g. with biotin, fluorescent, hydrophobic and peptide tags.

MALT1 INHIBITORS AND USES THEREOF

Provided herein are compounds of Formula (I) and pharmaceutical compositions thereof, which may be useful as MALT1 inhibitors. Also provided are for the treatment of proliferative disorders (e.g., cancer (e.g., non-Hodgkin' s lymphoma, diffuse large B-cell lymphoma, MALT lymphoma), benign neoplasm, a disease associated with angiogenesis,an autoimmune disease, an inflammatory disease, an autoinflammatory disease) by administering a compound of Formula (I).

A new benzotriazole-mediated stereoflexible gateway to hetero-2,5- diketopiperazines

Open chain Cbz-L-aa1-L-Pro-Bt (Bt=benzotriazole) sequences were converted into either the corresponding trans- or cis-fused 2,5- diketopiperazines (DKPs) depending on the reaction conditions. Thermodynamic tandem cyclization/epimerization afforded selectively the corresponding trans-DKPs (69-75%). Complementarily, tandem deprotection/cyclization led to the cis-DKPs (65-72%). A representative set of proline-containing cis- and trans-DKPs has been prepared. A mechanistic investigation, based on chiral HPLC, kinetics, and computational studies enabled a rationalization of the results. Stereoflexible route to DKPs: A convenient, versatile, and flexible benzotriazole-mediated methodology for the synthesis of proline-containing hetero-2,5-diketopiperazines (DKPs) is reported. Depending on the reaction conditions, either cis- or trans-configured DKPs were obtained starting from the same inexpensive l,l-dipeptidoyl benzotriazole key intermediate (see scheme). Kinetics, chiral HPLC, and computational studies forged a background for mechanistic rationalization. Copyright

Design and discovery of a novel dipeptidyl-peptidase IV (CD26)-based prodrug approach

Here we describe a novel type of enzyme-based prodrug approach in which a dipeptide moiety is linked to a nonpeptidic therapeutic drug through an amide bond which is specifically cleaved by the dipeptidyl-peptidase IV (DPP IV/CD26) enzyme activity present in plasma and on the surface of certain cells. DPP IV has high substrate selectivity for peptides with a proline (or an alanine) at the penultimate amino acid position at the N-terminus but tolerates a wide range of natural amino acids at the amino terminal end. A variety of dipeptidyl amide prodrugs of anti-HIV TSAO molecules were synthesized and evaluated for their ability to act as substrates for the enzyme. Our data revealed that DPP IV/CD26 can efficiently recognize such prodrugs as substrates, releasing the parent compound. Moreover, it is possible to modify the half-life and the lipophilicity of the prodrugs by changing the nature of the dipeptide. All conjugates have shown marked in vitro antiviral activities irrespective the the nature of the terminal and/or the penultimate amino acid moiety.

Inhibitors of tripeptidyl peptidase II. 3. Derivation of butabindide by successive structure optimizations leading to a potential general approach to designing exopeptidase inhibitors

The cholecystokinin-8 (CCK-8)-inactivating peptidase is a serine peptidase that has been shown to be a membrane-bound isoform of tripeptidyl peptidase II (EC 3.4.14.10). It cleaves the neurotransmitter CCK-8 sulfate at the Met-Gly bond to give Asp-Tyr(SO

Tripeptidylpeptidase inhibitors

A compound of formula wherein the substituents are defined as in the specification and salts or hydrates thereof is disclosed as well as a method of treating disorders associated with the inactivation or excessive degradation of cholecystokinin.

An Effective Water-Free Aprotic System for Dissolving Free Amino Acids

An effective water-free system was proposed for dissolution and subsequent use in peptide synthesis of free amino acids and their derivatives. It consists of dimethylformamide, a tertiary base, and inorganic additives. Neutral salts (CF3COONa, Ba(ClO4)2, Ca(ClO4)2, NaClO4, BaI2, or Ca(NO3)2) serve as the inorganic additives that increase the solubility of free amino acids in dimethylformamide and provide true 0.2-3 M amino acid solutions. Triethylamine and N-methylmorpholine are most suitable as the tertiary bases. This system was used in reactions with acylating agents: Boc2O, ZOSu, FmocOSu, and activated derivatives of Nα-protected amino acids or peptides. The corresponding amino acid derivatives or Nα-protected di-, tri-, and tetrapeptides were obtained in yields of 80-99 percent at the reaction times of 30-240 min.

Diastereomeric pure trifluoromethyl ketone peptide derivatives as inhibitors of human leukocyte elastase

The present invention relates to pyrrolidine derivatives, and more particularly to the compound (S)-1-?(S)-2-(4-methoxybenzamido)-3-methylbutyryl!-N-?(S)-2-methyl-1-(trifluoroacetyl)propyl!pyrrolidine-2-carboxamide, shown by formula I, and solvates thereo

Peptidyl α-Ketoheterocyclic Inhibitors of Human Neutrophil Elastase. 2. Effect of Varying the Heterocyclic Ring on in Vitro Potency

A series of peptidyl α-ketoheterocycles were synthesized and evaluated for their in vitro inhibition of human neutrophil elastase (HNE).Several heterocycles, including oxazoline and benzoxazole, afforded extremely potent inhibitors of HNE (1p-r) with nano

Synthetic Studies on Antifungal Cyclic Peptides, Echinocandins. Stereoselective Total Synthesis of Echinocandin D via a Novel Peptide Coupling

Synthetic studies on the novel fungicidal oligopeptides, echinocandins (1b and 1c), are described.The constituent amino acids 5-8 were synthesized in a stereocontrolled manner from the chiral starting materials, 5a, 6a and 7a, respectively.The coupling of these amino acids was characterized by the use of unprotected amino acid as the C-terminal and 2-pyridyl thiol ester as the N-terminal, and the coupling was performed in the presence of 1-(trimethylsilyl)imidazole (TMSIm) or a catalytic amount of tert-amine to give C-terminal free dipeptides, 14 and 16a, respectively, which were converted to the pentapeptide 17a, a common intermediate for the synthesis of 1b and 1c.The synthesis of 1c was achieved by the cyclization of the hexapeptide 24b.