106930-52-3

Upstream product

• 56877-41-9 methyl 2(S)-2-benzyloxycarbonylamino-4-tert-butoxycarbonylbutanoate 
• 16881-41-7 di-tert-butyl N-Cbz-L-glutamate 
• 3886-08-6 5-tert-butyl N-benzyloxycarbonyl-L-glutamate 
• 1155-62-0 N-benzyloxycarbonyl-L-glutamic acid 
• 62188-74-3 H-Glu(O-t-Bu)-OBzl 
• 541-41-3 chloroformic acid ethyl ester 
• 4666-16-4 5-tert-butyl 1-(2,5-dioxopyrrolidin-1-yl) (S)-2-{[(phenylmethoxy)carbonyl]amino}glutarate 
• 106930-50-1 Z-D-Glu-(O-t-Bu)-O-t-Bu 
• 51644-83-8 N-(benzyloxy)carbonyl-D-glutamic acid 5-tert-butyl ester 
• 63648-73-7 N-benzyloxycarbonyl-D-glutamic acid 

Downstream Products

• 92506-78-0 4(S)-benzyloxycarbonylamino-5-oxo-pentanoic acid tert-butyl ester 
• 130338-65-7 tert-butyl 4-<(benzyloxycarbonyl)amino>-5-(O-tosyl)pentanoate 
• 426253-92-1 tert-butyl (4S)-4-{[(benzyloxy)carbonyl]amino}-5-bromopentanoate 
• 426253-93-2 tert-butyl (4R)-4-{[(benzyloxy)carbonyl]amino}pentanoate 
• 95716-10-2 Z-L-(glu)Thz-OH 
• 95716-09-9 Z-L-(glu)Thz-OMe 
• 92506-79-1 (R)-2-((S)-1-Benzyloxycarbonylamino-3-tert-butoxycarbonyl-propyl)-thiazolidine-4-carboxylic acid methyl ester 
• 95716-08-8 Z-L-(glu(OBu^t))Thz-OMe 
• 92506-82-6 Z-(gly)Thz-L-Pro-L-Leu-L-Val-L-(gln)Thz-OMe 
• 1194058-59-7 tert-butyl (4S)-4-benzyloxycarbonylamino-5-tert-butyl(diphenyl)silyloxy-pentanoate 
• 92506-78-0 (R)-4-Benzyloxycarbonylamino-5-oxo-pentanoic acid tert-butyl ester 
• 426253-83-0 tert-butyl (4R)-4-{[(benzyloxy)carbonyl]amino}-5-(methoxymethoxy)pentanoate 
• 475266-25-2 tert-butyl (4R)-4-{[(benzyloxy)carbonyl]amino}-5-bromopentanoate 
• 106930-63-6 Z-D-Thz-O-Me 

Relevant academic research and scientific papers

Preparative synthesis of β-amino alcohols from α-amino dicarboxylic acid derivatives

A low-expensive preparative procedure has been developed for the synthesis of protected β-amino alcohols from α-amino dicarboxylic acid derivatives.

Photoactivated Colibactin Probes Induce Cellular DNA Damage

Colibactin is a small molecule produced by certain bacterial species of the human microbiota that harbour the pks genomic island. Pks+ bacteria induce a genotoxic phenotype in eukaryotic cells and have been linked with colorectal cancer progression. Colibactin is produced in a benign, prodrug form which, prior to export, is enzymatically matured by the producing bacteria to its active form. Although the complete structure of colibactin has not been determined, key structural features have been described including an electrophilic cyclopropane motif, which is believed to alkylate DNA. To investigate the influence of the putative “warhead” and the prodrug strategy on genotoxicity, a series of photolabile colibactin probes were prepared that upon irradiation induced a pks+ like phenotype in HeLa cells. Furthermore, results from DNA cross-linking and imaging studies of clickable analogues enforce the hypothesis that colibactin effects its genotoxicity by directly targeting DNA.

Nanoaggregates of biodegradable amphiphilic random polycations for delivering water-insoluble drugs

Cationic amphiphilic random copolyesters were obtained by copolymerization of 5-Z-amino-δ-valerolactone and ε-caprolactone. The amino content of the final copolymers was controlled by the polymerization feed ratio and was in the range 10 to 100%. Copolymers solubility and aggregation behavior was assessed by conductometric and zeta potential analyses. A critical aggregation concentration of ca. 0.05% (w/v) was found for all water-soluble copolymers that formed nanoaggregates. Two populations were found to be present in equilibrium with hydrodynamic diameters in the range of 30-50 and 100-250 nm. The capacity to use the amphiphilic and cationic character of the nanoaggregates to encapsulate highly hydrophobic compounds was further investigated. Finally, copolymers hemo- and cytocompatibility were evaluated by hemagglutination, hemolysis, and cells proliferation tests. The results showed that the proposed cationic amphiphilic random copolyesters are biocompatible.

Efficient access to enantiopure γ4-amino acids with proteinogenic side-chains and structural investigation of γ4- asn and γ4-ser in hybrid peptide helices

Hybrid peptides composed of α- and β-amino acids have recently emerged as new class of peptide foldamers. Comparatively, γ- and hybrid γ-peptides composed of γ4-amino acids are less studied than their β-counterparts. However, recent investigations reveal that γ4-amino acids have a higher propensity to fold into ordered helical structures. As amino acid side-chain functional groups play a crucial role in the biological context, the objective of this study was to investigate efficient synthesis of γ4-residues with functional proteinogenic side-chains and their structural analysis in hybrid-peptide sequences. Here, the efficient and enantiopure synthesis of various N- and C-terminal free-γ4-residues, starting from the benzyl esters (COOBzl) of N-Cbz-protected (E)-α,β-unsaturated γ-amino acids through multiple hydrogenolysis and double-bond reduction in a single-pot catalytic hydrogenation is reported. The crystal conformations of eight unprotected γ4-amino acids (γ4-Val, γ4-Leu, γ4-Ile, γ4-Thr(OtBu), γ4-Tyr, γ4-Asp(OtBu), γ4- Glu(OtBu), and γ-Aib) reveals that these amino acids adopted a helix favoring gauche conformations along the central Cγi￡ Cβ bond. To study the behavior of γ4- residues with functional side chains in peptide sequences, two short hybrid γ-peptides P1 (Ac-Aib-γ4-Asn-Aib-γ4-Leu- Aib-γ4-Leu-CONH2) and P2 (Ac-Aib- γ4-Ser-Aib-γ4-Val-Aib-γ4-Val- CONH2) were designed, synthesized on solid phase, and their 12-helical conformation in single crystals were studied. Remarkably, the γ4-Asn residue in P1 facilitates the tetrameric helical aggregations through interhelical H bonding between the side-chain amide groups. Furthermore, the hydroxyl side-chain of γ4-Ser in P2 is involved in the interhelical H bonding with the backbone amide group. In addition, the analysis of 87 γ4-residues in peptide single-crystals reveal that the γ4-residues in 12-helices are more ordered as compared with the 10/12- and 12/14-helices. Copyright

Synthesis of threo-β-aminoalcohols from aminoaldehydes via chelation-controlled additions. Total synthesis of l-threo sphingosine and safingol

Chelation-controlled addition of organocuprates to N-carbamoyl aminoaldehydes, prepared from functionalized amino acids, generated predominately the threo-β-amino alcohol derivatives through chelation with the carbamoyl moiety. The carbamate group is a stronger chelating group than other potentially good chelators, for example ethers, esters, thioethers, and gives good diastereoselectivity with cuprates. Thus addition of lithium divinylcuprate to the aldehyde generated from the serine derivative 25 in the presence of extra copper for chelation afforded the threo compound 26 in 83% yield. Cross-metathesis and cleavage of the protecting groups furnished l-threo sphingosine 21. In addition the lyso-sphingolipid protein kinase C inhibitor, safingol, 22, was prepared from commercially available O-benzyl N-BOC serine 28 in six steps and 56% overall yield by this method.

NOVEL HETEROCYCLYL COMPOUNDS

The invention is concerned with novel bicyclic compounds of formula (I), wherein n, m, p, A, L, R1, R2, R3, R4, R5, R6, R7, R7, R8, R9, and R10 are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds are antagonists of CCR2 receptor, CCR5 receptor and/or CCR3 receptor may be used, for example, in the prevention and/or treatment of inflammatory diseases, particularly peripheral arterial occlusive diseases or atherothrombosis.

DIAZEPAM DERIVATIVES AS MODULATORS OF CHEMOKINE RECEPTORS

The invention is concerned with novel bicyclic compounds of Formula (I), wherein n, m, p, A, L, R1, R2, R3, R4, R5, R6, R7, R7, R8, R9 and R10 are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds are antagonists of CCR2 receptor, CCR5 receptor and/or CCR3 receptor and can be used as medicaments.

Structure-affinity relationships of glutamine mimics incorporated into phosphopeptides targeted to the SH2 domain of signal transducer and activator of transcription 3

In cancer cells, signal transducer and activator of transcription 3 (Stat3) participates in aberrant growth, survival, angiogenesis, and invasion signals and is a validated target for anticancer drug design. We are targeting its SH2 domain to prevent docking to cytokine and growth factor receptors and subsequent signaling. One of the important elements of the recognition sequence, pTyr-Xxx-Xxx-Gln, is glutamine. We incorporated novel Gln mimics into a lead peptide, pCinn-Leu-Pro-Gln-NHBn, and found that a linear, unconstrained side chain and carboxamide are necessary for high affinity, and the benzamide can be eliminated. Replacement of Gln-NHBn with (R)-4-aminopentanamide or 2-aminoethylurea produced inhibitors with equal or greater potency than that of the lead, as judged by fluorescence polarization (IC50 values were 110 and 130 nM, respectively). When Pro was replaced with cis-3,4- methanoproline, the glutamine mimic, (4R,5S)-4-amino-5-benzyloxyhexanamide resulted in an IC50 of 69 nM, the highest affinity Stat3 inhibitor reported to date. 2009 American Chemical Society.

ANTIBACTERIAL FLUOROQUINOLONE ANALOGS

Compounds having antibacterial activity are disclosed. The compunds have the following structure (I): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein A, B, D, E, G, R1, R2, R3, R4, R5, R6 and R7 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

NOVEL BETA-LACTAM COMPOUNDS AND PROECSS FOR PRODUCING THE SAME

1. A β-lactam compound of the formula [1]; ???wherein R1 is a lower alkyl, a lower alkyl substituted by a hydroxy; R2 is a hydrogen, a lower alkyl; X is O, S, NH; m and n are 0 to 4, Y1 is a halogen, cyano, a hydroxy, an amino, a lower alkyloxy, a lower alkylamino, a carboxy, a carbamoyl, a lower alkyl, etc., Y2 is hydrogen, an alkyl, cyano, -C(R3)=NR4 (wherein R3 and R4 are hydrogen, an amino, an alkyl, etc., or R3 and R4 may combine each other together with the nitrogen atom to form a 5- to 7-membered heterocyclic group), or a pharmaceutically acceptable salt thereof, or a non-toxic ester thereof, which has an excellent antibacterial activity against Gram-positive bacteria, especially against MRSA and MRCNS.