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Usage

Uses

Used in Chemical Synthesis:
1-Boc-1,8-diaminooctane is used as a chemical intermediate for the synthesis of various compounds, such as polyurethanes, polyamides, and other polymers. Its reactive amine group allows it to form covalent bonds with carboxylic acids, activated NHS esters, and carbonyls (ketone, aldehyde), making it a useful building block in organic synthesis.
Used in PROTAC Linker Synthesis:
1-Boc-1,8-diaminooctane is used as a PROTAC linker in the synthesis of proteolysis-targeting chimeras (PROTACs). The Boc group can be deprotected under mild acidic conditions to form the free amine, which can then be used to attach the PROTAC molecule to a target protein, promoting its degradation and regulating cellular pathways.
Used in Pharmaceutical Industry:
1-Boc-1,8-diaminooctane is used as a starting material for the synthesis of various pharmaceutical compounds, such as antibiotics, antiviral agents, and anticancer drugs. Its Boc protection allows for selective deprotection and functionalization, enabling the development of new and effective therapeutic agents.
Used in Research and Development:
1-Boc-1,8-diaminooctane is used as a research tool in the development of new chemical reactions, synthetic methods, and drug discovery. Its unique structure and reactivity make it a valuable compound for exploring new chemical space and understanding the mechanisms of various reactions.

InChI:InChI=1/C13H28N2O2/c1-13(2,3)17-12(16)15-11-9-7-5-4-6-8-10-14/h4-11,14H2,1-3H3,(H,15,16)

Upstream product

• 1070-19-5 N-(tert-butyloxycarbonyl) azide 
• 373-44-4 1,8-diaminooctan 
• 24424-99-5 di-tert-butyl dicarbonate 
• 142356-35-2 8-amino>octyl bromide 
• 144183-31-3 N-(8-hydroxyoctyl)carbamic acid tert-butyl ester 
• 57395-46-7 8-azidooctan-1-ol 
• 23144-52-7 8-chlorooctan-1-ol 
• 19008-71-0 8-aminooctan-1-ol 
• 1538-75-6 2,2-dimethylpropanoic anhydride 
• 6627-89-0 tert-butyl phenyl carbonate 
• 556065-55-5 N-(8-aminooctyl)-2,2,2-trifluoroacetamide 
• 556065-56-6 tert-butyl N-{8-[(trifluoroacetyl)amino]octyl}carbamate 
• 82409-00-5 N,N'-bis(t-butoxycarbonyl)-1,8-octanediamine 

Downstream Products

• 395063-10-2 Fmoc-Tyr(O-Pic)-NH-(CH₂)8-NH-Boc 
• 556065-57-7 4-[(1E)-3-({8-[(tert-butoxycarbonyl)amino]octyl}amino)-3-oxoprop-1-enyl]phenyl acetate 
• 1374209-90-1 N-(8-(5,11-dioxo-5H-indeno[1,2-c]isoquinolin-6(11H)-yl)octyl)-4-methylbenzenesulfonamide 

Relevant academic research and scientific papers

Construction of dye-stapled Quenchbodies by photochemical crosslinking to antibody nucleotide-binding sites

We successfully converted an antibody single-chain variable fragment and a full-sized antibody to Quenchbodies, which are a type of powerful fluorescent immunosensor, through ultraviolet-based photochemical crosslinking of an indole-3-butyric acid-conjugated fluorescent dye to the nucleotide-binding sites near the antigen-binding sites.

7-Nitrobenzofurazan (NBD) derivatives of 5′-N-ethylcarboxamidoadenosine (NECA) as new fluorescent probes for human A3 adenosine receptors

New fluorescent ligands for adenosine receptors (ARs), obtained by the insertion, in the N6 position of NECA, of NBD-moieties with linear alkyl spacers of increasing length, proved to possess a high affinity and selectivity for the A3 subtype expressed in CHO cells. In fluorescence microscopy assays, compound 2d, the most active and selective for human A3-AR, permitted visualization and localization of this human receptor subtype, showing its potential suitability for internalization and trafficking studies in living cells.

Design, Synthesis, and Evaluation of VHL-Based EZH2 Degraders to Enhance Therapeutic Activity against Lymphoma

Traditional EZH2 inhibitors are developed to suppress the enzymatic methylation activity, and they may have therapeutic limitations due to the nonenzymatic functions of EZH2 in cancer development. Here, we report proteolysis-target chimera (PROTAC)-based EZH2 degraders to target the whole EZH2 in lymphoma. Two series of EZH2 degraders were designed and synthesized to hijack E3 ligase systems containing either von Hippel-Lindau (VHL) or cereblon (CRBN), and some VHL-based compounds were able to mediate EZH2 degradation. Two best degraders, YM181 and YM281, induced robust cell viability inhibition in diffuse large B-cell lymphoma (DLBCL) and other subtypes of lymphomas, outperforming a clinically used EZH2 inhibitor EPZ6438 (tazemetostat) that was only effective against DLBCL. The EZH2 degraders displayed promising antitumor activities in lymphoma xenografts and patient-derived primary lymphoma cells. Our study demonstrates that EZH2 degraders have better therapeutic activity than EZH2 inhibitors, which may provide a potential anticancer strategy to treat lymphoma.

JNK Inhibitor. Pharmaceutical compositions and uses thereof

Provided herein are compounds represented by the following formula (I), racemates, stereoisomers, tautomers, isotopically labels, solvates, polymorphs, nitrogen oxides or pharmaceutically acceptable salts thereof, which can be used as JNK inhibitors. A method for preparing a compound represented by formula (I), a pharmaceutical composition comprising a compound represented by formula (I), and (I), for the preparation of a medicament for the treatment of a disease treatable by inhibition JNK activity.

Design, synthesis and biological evaluation of tyrosinase-targeting PROTACs

The human tyrosinase is the most prominent therapeutic target for pigmentary skin disorders. However, the overwhelming majority efforts have been devoted to search mushroom tyrosinase inhibitors, which show poor inhibitory activity on human tyrosinase and certain side effects that cause skin damage in practical application. Herein, a series of degraders that directly targeted human tyrosinase was firstly designed and synthesized based on newly developed PROTAC technology. The best PROTAC TD9 induced human tyrosinase degradation obviously in dose and time-dependent manner, and its mechanism of inducing tyrosinase degradation has also been clearly demonstrated. Besides, encouraging results that low-toxicity PROTAC TD9 was applied to reduce zebrafish melanin synthesis have been obtained, highlighting the potential to treatment of tyrosinase-related disorders. Moreover, this work has innovatively expanded the application scope of PROTAC technology and laid a solid foundation for further development of novel drugs treating pigmentary skin disorders.

Genetically Engineered Polypeptide Adhesive Coacervates for Surgical Applications

Adhesive hydrogels have been developed for wound healing applications. However, their adhesive performance is impaired dramatically due to their high swelling on wet tissues. To tackle this challenge, we fabricated a new type of non-swelling protein adhesive for underwater and in vivo applications. In this soft material, the electrostatic complexation between supercharged polypeptides with oppositely charged surfactants containing 3,4-dihydroxylphenylalanine or azobenzene moieties plays an important role for the formation of ultra-strong adhesive coacervates. Remarkably, the adhesion capability is superior to commercial cyanoacrylate when tested in ambient conditions. Moreover, the adhesion is stronger than other reported protein-based adhesives in underwater environment. The ex vivo and in vivo experiments demonstrate the persistent adhesive performance and outstanding behaviors for wound sealing and healing.

Target protein degradation inducing compound, preparation method thereof and pharmaceutical composition for preventing or treating targeted protein related diseases containing the same as an active ingredient

The present invention relates to a degraducer for inducing the decomposition of target protein, a producing method thereof, and a pharmaceutical composition for preventing or treating target protein-related diseases by containing the degraducer as an active ingredient. A novel compound represented by chemical formula 1, ULB-L-PTM, by the present invention, as a degraducer compound inducing the decomposition of target protein using cereblon E3 ubiquitin ligase, is able to significantly achieve a target protein degradation-inducing activity with an excellent binding activity of a cereblon E3 ubiquitin ligase binder thereby, being able to achieve an excellent protein degradation activity by targeting protein or polypeptide related to various diseases. The bromodomain-containing pharmaceutical composition for preventing or treating protein-related diseases or conditions contains the novel compound represented by chemical formula 1 as an active ingredient and has a useful effect of providing a health functional food composition for prevention or improvement.(AA) Example 22 (nM, 24h)COPYRIGHT KIPO 2020

Structure-Activity Relationship of Hetarylpropylguanidines Aiming at the Development of Selective Histamine Receptor Ligands?

New classes of alkylated hetarylpropylguanidines with different functionality and variation in spacer length were synthesized to determine their behavior at the four histamine receptor (H1R, H2R, H3R, H4R) subtypes. Alkylated guanidines with different terminal functional groups and varied basicity, like amine, guanidine and urea were developed, based on the lead structure SK&F 91486 (2). Furthermore, heteroatomic exchange at the guanidine structure of 2 led to simple analogues of the lead compound. Radioassays at all histamine receptor subtypes were accomplished, as well as organ bath studies at the guinea pig (gp) ileum (gpH1R) and right atrium (gpH2R). Ligands with terminal functionalization led to, partially, highly affine and potent structures (two digit nanomolar), which showed up a bad selectivity profile within the histamine receptor family. While the benzoylurea derivative 144 demonstrated a preference towards the human (h) H3R, S-methylisothiourea analogue 143 obtained high affinity at the hH4R (pKi=8.14) with moderate selectivity. The molecular basis of the latter finding was supported by computational studies.

REGULATING CHIMERIC ANTIGEN RECEPTORS

This invention is in the area of compositions and methods for regulating chimeric antigen receptor immune effector cell, for example T-cell (CAR-T), therapy to modulate associated adverse inflammatory responses, for example, cytokine release syndrome and tumor lysis syndrome, using targeted protein degradation.

Fluorescent Benzothiazinone Analogues Efficiently and Selectively Label Dpre1 in Mycobacteria and Actinobacteria

Benzothiazinones (BTZ) are highly potent bactericidal inhibitors of mycobacteria and the lead compound, BTZ043, and the optimized drug candidate, PBTZ169, have potential for the treatment of tuberculosis. Here, we exploited the tractability of the BTZ scaffold by attaching a range of fluorophores to the 2-substituent of the BTZ ring via short linkers. We show by means of fluorescence imaging that the most advanced derivative, JN108, is capable of efficiently labeling its target, the essential flavoenzyme DprE1, both in cell-free extracts and after purification as well as in growing cells of different actinobacterial species. DprE1 displays a polar localization in Mycobacterium tuberculosis, M. marinum, M. smegmatis, and Nocardia farcinica but not in Corynebacterium glutamicum. Finally, mutation of the cysteine residue in DprE1 in these species, to which BTZ covalently binds, abolishes completely the interaction with JN108, thereby highlighting the specificity of this fluorescent probe.