67308-26-3

Usage

Uses

Used in Pharmaceutical Research and Development:
2-[(tert-butoxycarbonyl)amino]-3-(5-bromo-1H-indol-3-yl)propanoic acid is utilized as a key intermediate in the synthesis of peptide and protein-based pharmaceuticals due to its Boc protecting group, which facilitates the controlled exposure of reactive amine groups.
Used in Organic Synthesis:
In the realm of organic synthesis, 2-[(tert-butoxycarbonyl)amino]-3-(5-bromo-1H-indol-3-yl)propanoic acid is employed as a building block for the creation of complex organic molecules, capitalizing on its structural features and the reactivity of the 5-bromoindole moiety.
Used in Drug Discovery:
2-[(tert-butoxycarbonyl)amino]-3-(5-bromo-1H-indol-3-yl)propanoic acid is leveraged in drug discovery processes, where its biological activity and the presence of the Boc group make it suitable for the development of new therapeutic agents with potential applications in various medical fields.
Used in the Synthesis of Bioactive Molecules:
2-[(tert-butoxycarbonyl)amino]-3-(5-bromo-1H-indol-3-yl)propanoic acid is used as a precursor in the synthesis of bioactive molecules, given its inherent biological activity and the ability to be selectively modified for specific therapeutic targets.

InChI:InChI=1S/C16H19BrN2O4/c1-16(2,3)23-15(22)19-13(14(20)21)6-9-8-18-12-5-4-10(17)7-11(9)12/h4-5,7-8,13,18H,6H2,1-3H3,(H,19,22)(H,20,21)

Upstream product

• 58632-95-4 2-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrile 
• 6548-09-0 5-bromo-DL-tryptophan 
• 10075-50-0 5-bromo-1H-indole 
• 133766-37-7 N-Boc-5-bromo-DL-tryptophan ethyl ester 
• 24424-99-5 di-tert-butyl dicarbonate 
• 133766-35-5 ethyl 2-hydroximino-3-(5-bromoindol-3-yl)propanoate 

Downstream Products

• 103343-28-8 3-(5-Bromo-1H-indol-3-ylmethyl)-5-phenyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one 

Relevant academic research and scientific papers

Preparation and evaluation of L- and D-5-[18F]fluorotryptophan as PET imaging probes for indoleamine and tryptophan 2,3-dioxygenases

Indoleamine and tryptophan 2,3-dioxygenases (IDO1 and TDO2) are pyrrolases catalyzing the oxidative cleavage of the 2,3-double bond of L-tryptophan in kynurenine pathway. In the tumor microenvironment, their increased activity prevents normal immune function, i.e. tumor cell recognition and elimination by cytotoxic T-cells. Consequently, inhibition of the kynurenine pathway may enhance the activity of cancer immunotherapeutics by reversing immune dysfunction. We sought to investigate the properties of radiolabeled 5-[18F]fluorotryptophan with respect to its ability for measuring IDO1 and TDO2 activity by positron emission tomography (PET). Results L-5-[18F]fluorotryptophan and D-5-[18F]fluorotryptophan were synthesized by Cu(I) catalyzed [18F]fluorodeboronylation of Boc/tBu protected precursors in moderate yields (1.5?±?0.6%) sufficient for pre-clinical studies. The specific activity of the product was 407–740?GBq/μmol, radiochemical purity >99% and enantiomeric excess 90–99%. Enzymatic assay confirmed that L-5-fluorotryptophan is an IDO1 and TDO2 substrate whereas the D-isomer is not. In-vitro cell uptake experiments using CT26 cells with doxycycline-induced overexpression of human-IDO1 and human-TDO2 revealed an elevated cell uptake of L-5-[18F]fluorotryptophan upon induction of IDO1 or TDO2 enzymes compared to baseline; however, the uptake was observed only in the presence of low L-tryptophan levels in media. PET imaging experiments performed using tumor bearing mouse models expressing IDO1 at various levels (CT26, CT26-hIDO1, 17082A, 17095A) showed tumor uptake of the tracer elevated up to 8%ID/g; however, the observed tumor uptake could not be attributed to IDO1 activity in the tumor tissue. The metabolism of L- and D- isomers was markedly different in vivo, the D-isomer was excreted by a combination of hepatobiliary and renal routes, the L-isomer underwent extensive metabolism to [18F]fluoride. Conclusion The observed in vivo tumor uptake of the tracer could not be attributed to IDO1 or TDO2 enzyme activity in the tumor, presumably due to competition with endogenous tryptophan as well as rapid tracer metabolism.

Substrate Fragmentation for the Design of M. tuberculosis CYP121 Inhibitors

The cyclo-dipeptide substrates of the essential M. tuberculosis (Mtb) enzyme CYP121 were deconstructed into their component fragments and screened against the enzyme. A number of hits were identified, one of which exhibited an unexpected inhibitor-like binding mode. The inhibitory pharmacophore was elucidated, and fragment binding affinity was rapidly improved by synthetic elaboration guided by the structures of CYP121 substrates. The resulting inhibitors have low micromolar affinity, good predicted physicochemical properties and selectivity for CYP121 over other Mtb P450s. Spectroscopic characterisation of the inhibitors′ binding mode provides insight into the effect of weak nitrogen-donor ligands on the P450 heme, an improved understanding of factors governing CYP121–ligand recognition and speculation into the biological role of the enzyme for Mtb.

Synthesis and biological evaluation of 18F-labeled fluoropropyl tryptophan analogs as potential PET probes for tumor imaging

In the search for an efficient, fluorine-18 labeled amino acid based radiotracer for tumor imaging with positron emission tomography (PET), two new tryptophan analogs were synthesized and characterized in vitro and in vivo. Both are tryptophan alkyl-derivatives, namely 2-(3-[18F]fluoropropyl)-dl- tryptophan ([18F]2-FPTRP) and 5-(3-[18F]fluoro-propyl)-dl- tryptophan ([18F]5-FPTRP). Standard reference compounds and precursors were prepared by multi step approaches. Radiosynthesis was achieved by no-carrier-added nucleophilic [18F]fluorination in 29-34% decay corrected yields with radiochemical purity over 99%. In vitro cell uptake assays showed that both compounds are substrates for amino acid transport and enter small cell lung cancer cells (NCI-H69) most probably almost exclusively via large neutral amino acids transporter(s) (LAT). Small animal PET imaging with xenograft bearing mice revealed high tumor/background ratios for [ 18F]2-FPTRP comparable to the well established tyrosine analog O-(2-[18F]fluroethyl)-l-tyrosine ([18F]FET). Radiometabolite studies showed no evidence of involvement of a biotransformation step in tumor accumulation.

5-Bromo-DL-tryptophan and Protected Intermediates for Peptide Synthesis

A convenient synthesis of 5-bromotryptophan and protected intermediates for peptide synthesis is reported.Only three steps are required to convert ethyl pyruvate into 5-bromo-tryptophan ethyl ester.

Hemoglobin S antigelation agents based on 5-bromotryptophan with potential for sickle cell anemia

5-Bromotryptophan (5-BrTrp) is the most potent amino acid derivative reported in the literature to inhibit the gelation of hemoglobin S (from sickle cell anemia patients). Trp-Trp is also more potent than Trp as an antigelation agent. Therefore, we have prepared a series of dipeptides containing 5-BrTrp and evaluated the antigelation activity. 5-BrTrp-5-BrTrp is the most potent, i.e., 5.9 times the activity of Trp, followed by 5-BrTrp-Trp and then Trp-5-BrTrp. This improved antigelation potency for 5-BrTrp-5-BrTrp and 5-BrTrp-Trp is very significant and will be pursued further as lead compounds with potential for sickle cell anemia.