4801-80-3

Usage

Uses

Used in Pharmaceutical Industry:
Z-PHE-NH2 is used as a protecting agent for the amino group during peptide synthesis. Its role is crucial in ensuring the successful conjugation of amino acids, which is a fundamental process in the creation of peptide-based drugs.
Used in Medicinal Chemistry Research:
In the context of medicinal chemistry, Z-PHE-NH2 serves as a valuable component in the synthesis of new drug molecules. Its presence in the structure of these compounds can contribute to their therapeutic properties and potential applications in treating various diseases.
Used in Organic Synthesis:
Z-PHE-NH2 is also utilized in organic synthesis, where it can be incorporated into the structure of complex organic molecules. This can lead to the development of new compounds with unique chemical properties and potential applications in various industries, including pharmaceuticals, materials science, and agrochemicals.

Upstream product

• 1161-13-3 N-Cbz-L-Phe 
• 35909-92-3 N-carbobenzoxy-L-phenylalanine methyl ester 
• 7524-50-7 methyl (2S)-2-amino-3-phenylpropanoate hydrochloride 
• 501-53-1 benzyl chloroformate 
• 109453-49-8 (C₈H₇O₂)(NHCHCOO)(CH₂C₆H₅)(CO₂C₂H₅) 
• 7664-41-7 ammonia 
• 55740-07-3 (4S)-4-benzyl-5-oxo-1,3-oxazolidine-3-carboxylic acid benzyl ester 
• 928406-59-1 [(S)-1-((S)-1-Amino-3-hydroxy-propylcarbamoyl)-2-phenyl-ethyl]-carbamic acid benzyl ester 
• 127-88-8 N,N-di(2-chloroethyl)amidophosphoric acid dichloride 
• 928406-72-8 [(S)-1-((R)-1-Amino-3-hydroxy-propylcarbamoyl)-2-phenyl-ethyl]-carbamic acid benzyl ester 
• 63-91-2 L-phenylalanine 
• 541-41-3 chloroformic acid ethyl ester 
• 54769-22-1 1-methanesulfonyloxy-1,2,3-benzotriazole 
• 6638-79-5 N,O-dimethylhydroxylamine*hydrochloride 

Downstream Products

• 17186-44-6 (S)-benzyl (1-(tert-butylamino)-1-oxo-3-phenylpropan-2-yl)carbamate 
• 5241-58-7 L-Phenylalanine amide 
• 52396-85-7 Z-(S)-phenylalanine thioamide 
• 91177-54-7 Z-Phe-Δ^ZPhe-OH 
• 88463-10-9 Cbz-Phe-ΔPhe-OH 
• 24730-33-4 (S)-2-amino-3-phenylpropanamide hydrobromide 
• 21947-21-7 (S)-N-benzyloxycarbonyl-2-amino-3-phenyl-propionitrile 
• 62076-57-7 Z-Phe-ΔAla 
• 208665-37-6 2-((S)-2-Benzyloxycarbonylamino-3-phenyl-propionylamino)-3-oxo-butyric acid methyl ester 
• 208665-36-5 2-((S)-2-Benzyloxycarbonylamino-3-phenyl-propionylamino)-malonic acid dimethyl ester 
• 209047-58-5 N-trityl-L-phenylalaninamide 
• 308277-53-4 (S)-2-[2-((S)-2-Benzyloxycarbonylamino-3-phenyl-propionylamino)-2-methoxycarbonyl-acetylamino]-3-methyl-butyric acid methyl ester 
• 112037-34-0 Z-Phe-NCO 
• 876322-97-3 benzyl N-(1-benzyl-2-oxo-2-[1-(phenylsulfonyl)propylamino]ethyl)carbamate 

Relevant academic research and scientific papers

α-Amino Diphenyl Phosphonates as Novel Inhibitors of Escherichia coli ClpP Protease

Increased Gram-negative bacteria resistance to antibiotics is becoming a global problem, and new classes of antibiotics with novel mechanisms of action are required. The caseinolytic protease subunit P (ClpP) is a serine protease conserved among bacteria that is considered as an interesting drug target. ClpP function is involved in protein turnover and homeostasis, stress response, and virulence among other processes. The focus of this study was to identify new inhibitors of Escherichia coli ClpP and to understand their mode of action. A focused library of serine protease inhibitors based on diaryl phosphonate warheads was tested for ClpP inhibition, and a chemical exploration around the hit compounds was conducted. Altogether, 14 new potent inhibitors of E. coli ClpP were identified. Compounds 85 and 92 emerged as most interesting compounds from this study due to their potency and, respectively, to its moderate but consistent antibacterial properties as well as the favorable cytotoxicity profile.

Synthesis and Preclinical Evaluation of the First Carbon-11 Labeled PET Tracers Targeting Substance P1-7

Two potent SP1-7 peptidomimetics have been successfully radiolabeled via [11C]CO2-fixation with excellent yields, purity, and molar activity. l-[11C]SP1-7-peptidomimetic exhibited promising ex vivo biodistribution profile. Metabolite analysis showed that l-[11C]SP1-7-peptidomimetic is stable in brain and spinal cord, whereas rapid metabolic degradation occurs in rat plasma. Metabolic stability can be significantly improved by substituting l-Phe for d-Phe, preserving 70% more of intact tracer and resulting in better brain and spinal cord tracer retention. Positron emission tomography (PET) scanning confirmed moderate brain (1.5 SUV; peak at 3 min) and spinal cord (1.0 SUV; peak at 10 min) uptake for l- and d-[11C]SP1-7-peptidomimetic. A slight decrease in SUV value was observed after pretreatment with natural peptide SP1-7 in spinal cord for l-[11C]SP1-7-peptidomimetic. On the contrary, blocking using cold analogues of l- and d-[11C]tracers did not reduce the tracers' brain and spinal cord exposure. In summary, PET scanning of l- and d-[11C]SP1-7-peptidomimetics confirms rapid blood-brain barrier and blood-spinal-cord barrier penetration. Therefore, further validation of these two tracers targeting SP1-7 is needed in order to define a new PET imaging target and select its most appropriate radiopharmaceutical.

Amidation of carboxylic acids via the mixed carbonic carboxylic anhydrides and its application to synthesis of antidepressant (1S,2R)-tranylcypromine

Primary amidations of carboxylic acids 1 or 3 with NH4Cl in the presence of ClCO2Et and Et3N were developed to afford the corresponding primary amides in 22% to quantitative yields. Additionally, we have applied the amidation to the preparation of various amides containing hydroxamic acids and achieved the synthesis of (1S,2R)-tranylcypromine as an antidepressant medicine via Lossen rearrangement.

Metastin derivatives and use thereof

The invention provides stable metastin derivatives having excellent biological activities (a cancer metastasis suppressing activity, a cancer growth suppressing activity, etc.). By modifying the constituent amino acids of metastin with specific modifying groups, metastin derivatives having more improved blood stability, etc. than native metastin and showing excellent cancer metastasis suppressing activity or cancer growth suppressing activity have been found. Furthermore, it has been found that these metastin derivatives exhibit effects of suppressing gonadotropic hormone secretion, suppressing sex hormone secretion, etc., which are wholly different from the effects heretofore known.

LAT1 activity of carboxylic acid bioisosteres: Evaluation of hydroxamic acids as substrates

Large neutral amino acid transporter 1 (LAT1) is a solute carrier protein located primarily in the blood–brain barrier (BBB) that offers the potential to deliver drugs to the brain. It is also up-regulated in cancer cells, as part of a tumor's increased metabolic demands. Previously, amino acid prodrugs have been shown to be transported by LAT1. Carboxylic acid bioisosteres may afford prodrugs with an altered physicochemical and pharmacokinetic profile than those derived from natural amino acids, allowing for higher brain or tumor levels of drug and/or lower toxicity. The effect of replacing phenylalanine's carboxylic acid with a tetrazole, acylsulfonamide and hydroxamic acid (HA) bioisostere was examined. Compounds were tested for their ability to be LAT1 substrates using both cis-inhibition and trans-stimulation cell assays. As HA-Phe demonstrated weak substrate activity, its structure–activity relationship (SAR) was further explored by synthesis and testing of HA derivatives of other LAT1 amino acid substrates (i.e., Tyr, Leu, Ile, and Met). The potential for a false positive in the trans-stimulation assay caused by parent amino acid was evaluated by conducting compound stability experiments for both HA-Leu and the corresponding methyl ester derivative. We concluded that HA's are transported by LAT1. In addition, our results lend support to a recent account that amino acid esters are LAT1 substrates, and that hydrogen bonding may be as important as charge for interaction with the transporter binding site.

Optimization and Structure-Activity Relationships of Phosphinic Pseudotripeptide Inhibitors of Aminopeptidases That Generate Antigenic Peptides

The oxytocinase subfamily of M1 aminopeptidases, consisting of ER aminopeptidase 1 (ERAP1), ER aminopeptidase 2 (ERAP2), and insulin-regulated aminopeptidase (IRAP), plays critical roles in the generation of antigenic peptides and indirectly regulates human adaptive immune responses. We have previously demonstrated that phosphinic pseudotripeptides can constitute potent inhibitors of this group of enzymes. In this study, we used synthetic methodologies able to furnish a series of stereochemically defined phosphinic pseudotripeptides and demonstrate that side chains at P1′ and P2′ positions are critical determinants in driving potency and selectivity. We identified low nanomolar inhibitors of ERAP2 and IRAP that display selectivity of more than 2 and 3 orders of magnitude, respectively. Cellular analysis demonstrated that one of the compounds that is a selective IRAP inhibitor can reduce IRAP-dependent but not ERAP1-dependent cross-presentation by dendritic cells with nanomolar efficacy. Our results encourage further preclinical development of phosphinic pseudotripeptides as regulators of adaptive immune responses.

Carbohydrates as efficient catalysts for the hydration of α-amino nitriles

Directed hydration of α-amino nitriles was achieved under mild conditions using simple carbohydrates as catalysts exploiting temporary intramolecularity. A broadly applicable procedure using both formaldehyde and NaOH as catalysts efficiently hydrated a variety of primary and secondary susbtrates, and allowed the hydration of enantiopure substrates to proceed without racemization. This work also provides a rare comparison of the catalytic activity of carbohydrates, and shows that the simple aldehydes at the basis of chemical evolution are efficient organocatalysts mimicking the function of hydratase enzymes. Optimal catalytic efficiency was observed with destabilized aldehydes, and with difficult substrates only simple carbohydrates such as formaldehyde and glycolaldehyde proved reliable.

Synthesis of Nitriles from Aldoximes and Primary Amides Using XtalFluor-E

The dehydration reaction of aldoximes and amides for the synthesis of nitriles using [Et2NSF2]BF4 (XtalFluor-E) is described. Overall, the reaction proceeds rapidly (normally 1 h) at room temperature in an environmentally benign solvent (EtOAc) with only a slight excess of the dehydrating agent (1.1 equiv). A broad scope of nitriles can be prepared, including chiral nonracemic ones. In addition, in a number of cases, further purification of the nitrile after the workup was not required.

Exploration and pharmacokinetic profiling of phenylalanine based carbamates as novel substance P 1-7 analogues

The bioactive metabolite of Substance P, the heptapeptide SP1-7 (H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH), has been shown to attenuate signs of hyperalgesia in diabetic mice, which indicate a possible use of compounds targeting the SP1-7 bi