117422-78-3

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 2935-35-5 (S)-2-phenylglycine 
• 2900-27-8 (2S)-2-[(tert-butoxycarbonyl)amino]-2-phenylethanoic acid 
• 100-46-9 benzylamine 
• 3287-99-8 benzylamine hydrochloride 
• 201152-47-8 Boc-Phg-OSu 

Downstream Products

• 1620481-07-3 (S)-4-(3-(2-(benzylamino)-2-oxo-1-phenylethyl)ureido)-N-(6-(hydroxyamino)-6-oxohexyl)benzamide 
• 1620481-09-5 (S)-methyl 6-(4-(3-(2-(benzylamino)-2-oxo-1-phenylethyl)ureido)benzamido)hexanoate 
• 135832-68-7 {(1S,2S,4R)-1-Benzyl-4-[((S)-benzylcarbamoyl-phenyl-methyl)-carbamoyl]-2-hydroxy-5-phenyl-pentyl}-carbamic acid tert-butyl ester 
• 155322-81-9 (S)-2-amino-N-benzyl-2-phenylacetamide 

Relevant academic research and scientific papers

Asymmetric phosphoric acid-catalyzed four-component Ugi reaction

The Ugi reaction constructs a-acylaminoamide compounds by combining an aldehyde or ketone,an amine,a carboxylic acid,and an isocyanide in a single flask.Its appealing features include inherent atom and step economy together with the potential to generate products of broad structural diversity.However,control of the stereochemistry in this reaction has proven to be a formidable challenge.We describe an efficient enantioselective four-component Ugi reaction catalyzed by a chiral phosphoric acid derivative that delivers more than 80 a-acylaminoamides in good to excellent enantiomeric excess.Experimental and computational studies establish the reaction mechanism and origins of stereoselectivity.

SAR evolution towards potent C-terminal carboxamide peptide inhibitors of Zika virus NS2B-NS3 protease

Zika virus (ZIKV) is a member of the Flaviviridae family that can cause neurological disorders and congenital malformations. The NS2B-NS3 viral serine protease is an attractive target for the development of new antiviral agents against ZIKV. We report here a SAR study on a series of substrate-like linear tripeptides that inhibit in a non-covalent manner the NS2B-NS3 protease. Optimization of the residues at positions P1, P2, P3 and of the N-terminal and C-terminal portions of the tripeptide allowed the identification of inhibitors with sub-micromolar potency with phenylglycine as arginine-mimicking group and benzylamide as C-terminal fragment. Further SAR exploration and application of these structural changes to a series of peptides having a 4-substituted phenylglycine residue at the P1 position led to potent compounds showing double digit nanomolar inhibition of the Zika protease (IC50 = 30 nM) with high selectivity against trypsin-like proteases and the proteases of other flavivirus, such as Dengue 2 virus (DEN2V) and West Nile virus (WNV).

l-tert-Leucine-Derived AmidPhos-Silver(I) Chiral Complexes for the Asymmetric [3+2] Cycloaddition of Azomethine Ylides

The l-tert-leucine-derived AmidPhos/silver(I) catalytic system has been developed for the asymmetric [3+2] cycloaddition of azomethine ylides with electronic-deficient alkenes with or without Et3N. Under optimal conditions, highly functionalized endo-4-pyrrolidines were obtained with modest to high yields (up to 99% yield) and enantioselectivities (up to 98% ee).

B(OCH2CF3)3-mediated direct amidation of pharmaceutically relevant building blocks in cyclopentyl methyl ether

The use of B(OCH2CF3)3 for mediating direct amidation reactions of a wide range of pharmaceutically relevant carboxylic acids and amines is described, including numerous heterocycle-containing examples. An initial screen of solvents for the direct amidation reaction suggested that cyclopentyl methyl ether, a solvent with a very good safety profile suitable for use over a wide temperature range, was an excellent replacement for the previously used solvent acetonitrile. Under these conditions amides could be prepared from 18 of the 21 carboxylic acids and 18 of the 21 amines examined. Further optimisation of one of the low yielding amidation reactions (36% yield) via a design of experiments approach enabled an 84% yield of the amide to be obtained.

Discovery of a series of hydroximic acid derivatives as potent histone deacetylase inhibitors

To develop potent histone deacetylase inhibitors as antitumor agents, structural modification was performed. The synthesized molecules were tested by enzymatic inhibition assay and anti-proliferation assay. Several molecules show improved activities in the enzymatic inhibition assay. However, in the MTT assays, all these derived molecules have limited performance compared with SAHA. The IC50 values of molecule ((S)-N-(6-(hydroxyamino)-6-oxohexyl)-4-(3-(2-oxo-1-phenyl-2-((3-(trifluoromethyl)phenyl)amino)ethyl)ureido)benzamide, L8) which has the best enzymatic inhibition activity (with an IC50 value of 11.7nm and 967nm against Hela nucleus extract and HDAC8, respectively) were calculated compared with SAHA. Molecular docking was performed to predict the binding mode of molecule L8 in the active site of HDAC2 and HDAC8. Hydrophobic interaction, chelate binding, electrostatic attraction and H-bond interaction in combination make contribution to the ligand-receptor interactions.

Discovery of potent and orally active MTP inhibitors as potential anti-obesity agents

We have successfully identified a number of novel MTP inhibitors with single digit nanomolar potency. Analogues 10aq and 10dq demonstrated in vivo efficacy in a murine gut retention assay.

Microsomal triglyceride transfer protein inhibitor

The present invention provides inhibitors of microsomal triglyceride transfer protein (MTP) and/or apolipoprotein B (Apo B) secretion having Formula (I) which are useful for the treatment of obesity and related diseases, as well as prevention and treatment of atherosclerosis and its clinical sequelae, for lowering serum lipids, and in the prevention and treatment of related diseases. The invention further relates to pharmaceutical compositions comprising the compounds of the present invention and to methods of treating obesity, atherosclerosis, and related diseases and/or conditions with the compounds of the present invention, either alone or in combination with other medicaments, including lipid-lowering agents.

Triamide-substituted heterobicyclic compounds

The invention relates to triamide MTP/ApoB inhibitors of the formula 1 wherein R1-R8 are as defined in the specification, as well as pharmaceutical compositions and uses thereof, and processes for preparing the compounds. The compounds of the invention are useful for the treatment of obesity and lipid disorders.

Design and synthesis of HIV protease inhibitors. Variations of the carboxy terminus of the HIV protease inhibitor L-682,679

A series of tetrapeptide analogues of 1 (L-682,679), in which the carboxy terminus has been shortened and modified, was prepared and their inhibitory activity measured against the HIV protease in a peptide cleavage assay. Selected examples were tested as inhibitors of virus spread in cell culture. Compound 12 was a 10-fold more potent enzyme inhibitor than 1 in vitro and 30-fold more potent in inhibiting the viral spread in cells.