162046-66-4

Usage

Uses

Used in Medicinal Chemistry:
4-[4-(tert-Butoxycarbonyl)piperazino]benzoic acid is used as a building block for the synthesis of various pharmaceuticals and bioactive molecules. Its unique structure, including the piperazine ring and the t-Boc protecting group, makes it a valuable component in the development of new drugs.
Used in Central Nervous System Disorders:
4-[4-(tert-Butoxycarbonyl)piperazino]benzoic acid is used as a potential candidate for drug design and development in the field of central nervous system disorders. Its piperazine ring structure may contribute to the compound's ability to interact with specific receptors or targets in the nervous system, offering potential therapeutic benefits.
Used in Psychiatric Medications:
4-[4-(tert-Butoxycarbonyl)piperazino]benzoic acid is used as a potential candidate for the development of psychiatric medications. The presence of the piperazine ring in its structure may allow it to modulate neurotransmitter systems or other biological pathways involved in psychiatric conditions, providing a new avenue for treatment.
Used in Organic Synthesis:
4-[4-(tert-Butoxycarbonyl)piperazino]benzoic acid is used as a protected amine intermediate in organic synthesis. The t-Boc protecting group temporarily blocks the reactive amine group, enabling selective functionalization of other parts of the molecule. This feature is particularly useful in the synthesis of complex organic compounds and pharmaceuticals, where precise control over the reaction is required.

InChI:InChI=1/C16H22N2O4/c1-16(2,3)22-15(21)18-10-8-17(9-11-18)13-6-4-12(5-7-13)14(19)20/h4-7H,8-11H2,1-3H3,(H,19,20)/p-1

Upstream product

• 80518-57-6 ethyl 4-(piperazin-1-yl)benzoate 
• 158985-36-5 4-(4-methoxycarbonyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester 
• 451-46-7 4-fluorobenzoic acid ethyl ester 
• 57260-71-6 1-t-Butoxycarbonylpiperazine 
• 619-42-1 4-methoxycarbonylphenyl bromide 
• 24424-99-5 di-tert-butyl dicarbonate 
• 403-33-8 methyl 4-flurobenzoate 
• 619-45-4 4-methoxycarbonyl aniline 
• 163210-97-7 methyl 4-(piperazin-1-yl)benzoate 
• 234082-33-8 4-(4-ethoxycarbonylphenyl)piperazine-1-carboxylic acid tert-butyl ester 

Downstream Products

• 406231-38-7 4-{4-[3-nitro-4-(2-phenylsulfanyl-ethylamino)-benzenesulfonylaminocarbonyl]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester 
• 1447331-89-6 {6-[4-(4-boc-piperazin-1-yl)benzoylamino]-1-oxo-1,3-dihydroisoindol-2-yl}acetic acid 
• 1447330-19-9 [1-oxo-6-(4-piperazinium-1-yl-benzoylamino)-1,3-dihydroisoindol-2-yl]acetic acid trifluoroacetate 
• 1447331-32-9 {6-[4-(4-boc-piperazin-1-yl)benzoylamino]-1-oxo-1,3-dihydroisoindol-2-yl}acetic acid methyl ester 

Relevant academic research and scientific papers

Protein degradation targeting chimera for degrading androgen receptor

The invention relates to a novel difunctional molecule compound based on VHL ligand induction and application of the difunctional molecule compound in synthesis of the compounds and pharmaceutical compositions thereof. The compound is shown as a formula I. The compound can selectively induce AR protein degradation and can be used for treating cancers such as prostatic cancer and breast cancer.

Benzothiazole compounds and medical application

The invention discloses a benzothiazole compound and medical application thereof, particularly relates to a benzothiazole compound shown as a formula I and medical application thereof, and especiallyrelates to application of the benzothiazole compound serving as a USP7C-terminal structural domain regulating agent in medicines for preventing and treating myelodysplastic syndromes and malignant tumors. The benzothiazole compound shown in the formula I or the pharmaceutically acceptable salt or solvate of the benzothiazole compound has strong binding force with USP7C-terminal protein; and the protein level of DNMT1 in tumor cells can be reduced, so that the compound can be applied to the preparation of USP7 regulators, has a remarkable anti-tumor cell proliferation effect, and can be used for preparing medicines for preventing or treating myelodysplastic syndrome and malignant tumors.

Design and characterization of cereblon-mediated androgen receptor proteolysis-targeting chimeras

Proteolysis-targeting chimera (PROTAC)-mediated protein degradation is a rapidly emerging therapeutic intervention that induces the degradation of targeted proteins. Herein, we report the design and biological evaluation of a series of androgen receptor (AR) PROTAC degraders for the treatment of metastatic castration-resistant prostate cancer. Predominantly, instead of thalidomide, we utilized the TD-106 scaffold, a novel cereblon (CRBN) binder that was identified in our previous study. Our results suggest that the linker position in the TD-106 CRBN binder is critical for the efficiency of AR degradation. The compounds attached to the 6-position of TD-106 promoted better degradation of AR than those at the 5- and 7-positions. Among the synthesized AR PROTACs, the representative degrader 33c (TD-802) effectively induced AR protein degradation, with a degradation concentration 50% of 12.5 nM and a maximum degradation of 93% in LNCaP prostate cancer cells. Additionally, most AR PROTAC degraders, including TD-802, displayed good liver microsomal stability and in vivo pharmacokinetic properties. Finally, we showed that TD-802 effectively inhibited tumor growth in an in vivo xenograft study.

SELECTIVE HDAC1,2 INHIBITORS

Provided herein are compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat diseases or disorders associated with HDAC1 and/or HDAC2 activity.

Benzamide capped peptidomimetics as non-ATP competitive inhibitors of CDK2 using the REPLACE strategy

Inhibition of cyclin dependent kinase 2 (CDK2) in complex with cyclin A in G1/S phase of the cell cycle has been shown to promote selective apoptosis of cancer cells through the E2F1 pathway. An alternative approach to catalytic inhibition is to target the substrate recruitment site also known as the cyclin binding groove (CBG) to generate selective non-ATP competitive inhibitors. The REPLACE strategy has been applied to identify fragment alternatives and substituted benzoic acid derivatives were evaluated as a promising scaffold to present appropriate functionality to mimic key peptide determinants. Fragment Ligated Inhibitory Peptides (FLIPs) are described which potently inhibit both CDK2/cyclin A and CDK4/cyclin D1 and have preliminary anti-tumor activity. A structural rationale for binding was obtained through molecular modeling further demonstrating their potential for further development as next generation non ATP competitive CDK inhibitors.

Mechanisms of action of novel influenza A/M2 viroporin inhibitors derived from hexamethylene amiloride

The increasing prevalence of influenza viruses with resistance to approved antivirals highlights the need for new anti-influenza therapeutics. Here we describe the functional properties of hexamethylene amiloride (HMA)'derived compounds that inhibit the wildtype and adamantane-resistant forms of the influenza A M2 ion channel. For example, 6-(azepan-1-yl)-N-carbamimidoylnicotinamide (9) inhibits amantadine-sensitive M2 currents with 3- to 6-fold greater potency than amantadine or HMA (IC50 5 0.2 vs. 0.6 and 1.3 μM, respectively). Compound 9 competes with amantadine for M2 inhibition, and molecular docking simulations suggest that 9 binds at site(s) that overlap with amantadine binding. In addition, tert-butyl 4′-(carbamimidoylcarbamoyl)-2′,3-dinitro- [1,1′-biphenyl]-4-carboxylate (27) acts both on adamantanesensitive and a resistantM2variant encoding a serine to asparagine 31 mutation (S31N) with improved efficacy over amantadine and HMA (IC5050.6 μMand4.4mM, respectively).Whereas 9 inhibited in vitro replication of influenza virus encoding wild-type M2 (EC505 2.3 μM), both 27 and tert-butyl 4′-(carbamimidoylcarbamoyl)-2′,3- dinitro-[1,1′-biphenyl]-4-carboxylate (26) preferentially inhibited viruses encoding M2(S31N) (respective EC50 5 18.0 and 1.5 μM). This finding indicates thatHMAderivatives can be designed to inhibit viruses with resistance to amantadine. Our study highlights the potential of HMA derivatives as inhibitors of drug-resistant influenza M2 ion channels.

Discovery of Substituted 1H-Pyrazolo[3,4-b]pyridine Derivatives as Potent and Selective FGFR Kinase Inhibitors

Fibroblast growth factor receptors (FGFRs) are important targets for cancer therapy. Herein, we describe the design, synthesis, and biological evaluation of a novel series of 1H-pyrazolo[3,4-b]pyridine derivatives as potent and selective FGFR kinase inhibitors. On the basis of its excellent in vitro potency and favorable pharmacokinetic properties, compound 7n was selected for in vivo evaluation and showed significant antitumor activity in a FGFR1-driven H1581 xenograft model. These results indicated that 7n would be a promising candidate for further drug development.

Synthesis, biological evaluation, X-ray molecular structure and molecular docking studies of RGD mimetics containing 6-amino-2,3-dihydroisoindolin-1-one fragment as ligands of integrin αiIbβ3

A series of novel RGD mimetics containing phthalimidine fragment was designed and synthesized. Their antiaggregative activity determined by Born's method was shown to be due to inhibition of fibrinogen binding to αIIbβ3. Molecular docking of RGD mimetics to αIIbβ3 receptor showed the key interactions in this complex, and also some correlations have been observed between values of biological activity and docking scores. The single crystal X-ray data were obtained for five mimetics.

NOVEL INHIBITORS OF HEPATITIS C VIRUS

The invention provides compounds of formula (I): wherein the variables are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are inhibitors of replication of the hepatitis C virus. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat hepatitis C viral infections, and processes and intermediates useful for preparing such compounds.

Synthesis and SAR of piperazinyl-N-phenylbenzamides as inhibitors of hepatitis C virus RNA replication in cell culture

The RNA replication machinery of HCV is a multi-subunit membrane-associated complex. NS5A has emerged as an active component of HCV replicase, possibly involved in regulation of viral replication and resistance to the antiviral effect of interferon. We report here substituted piperazinyl-N-(aryl)benzamides as potent inhibitors of HCV replication exerted via modulation of the dimerization of NS5A.