259808-63-4

Usage

Uses

Used in Pharmaceutical Industry:
4-(4-BROMO-BENZENESULFONYL)-PIPERAZINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER is used as an intermediate in the synthesis of various pharmaceuticals and organic compounds. Its structural features and functional groups make it a valuable component in the development of new drugs and therapeutic agents.
Used in Medicinal Chemistry:
In the field of medicinal chemistry, 4-(4-BROMO-BENZENESULFONYL)-PIPERAZINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER is utilized for its potential to contribute to the design and synthesis of novel drug candidates. Its unique properties may enable the creation of compounds with specific therapeutic effects and improved pharmacological profiles.
Safety Considerations:
It is crucial to handle 4-(4-BROMO-BENZENESULFONYL)-PIPERAZINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER with caution and adhere to proper safety protocols when working with it in a laboratory setting. This ensures the safety of researchers and the integrity of the experimental process.

Upstream product

• 98-58-8 4-bromobenzenesulfonyl chloride 
• 57260-71-6 1-t-Butoxycarbonylpiperazine 

Downstream Products

• 486422-54-2 (4-((4-(tert-butoxycarbonyl)piperazin-1-yl)sulfonyl)phenyl)boronic acid 
• 1227370-73-1 4-(4-trimethylsilanylethynyl-benzenesulfonyl)-piperazine-1-carboxylic acid tert-butyl ester 
• 910907-48-1 4-[4-(5-nitro-pyrimidin-2-ylamino)-benzenesulfonyl]-piperazine-1-carboxylic acid tert-butyl ester 
• 179334-20-4 1-(4-bromophenylsulphonyl)piperazine 
• 1291057-96-9 1-benzo[b]thiophen-3-yl-3-[4-(4-bromobenzenesulfonyl)piperazin-1-yl]propan-1-one hydrochloride 
• 1291141-96-2 1-benzo[b]thiophen-3-yl-3-[4-(4-bromobenzenesulfonyl)piperazin-1-yl]propan-1-one 

Relevant academic research and scientific papers

Tetra-arylborate lipophilic anions as targeting groups

Tetraphenylborate (TPB) anions traverse membranes but are excluded from mitochondria by the membrane potential (Δψ). TPB-conjugates also distributed across membranes in response to Δψ, but surprisingly, they rapidly entered cells. They accumulated within

Structure activity refinement of phenylsulfonyl piperazines as antimalarials that block erythrocytic invasion

The emerging resistance to combination therapies comprised of artemisinin derivatives has driven a need to identify new antimalarials with novel mechanisms of action. Central to the survival and proliferation of the malaria parasite is the invasion of red blood cells by Plasmodium merozoites, providing an attractive target for novel therapeutics. A screen of the Medicines for Malaria Venture Pathogen Box employing transgenic P. falciparum parasites expressing the nanoluciferase bioluminescent reporter identified the phenylsulfonyl piperazine class as a specific inhibitor of erythrocyte invasion. Here, we describe the optimization and further characterization of the phenylsulfonyl piperazine class. During the optimization process we defined the functionality required for P. falciparum asexual stage activity and determined the alpha-carbonyl S-methyl isomer was important for antimalarial potency. The optimized compounds also possessed comparable activity against multidrug resistant strains of P. falciparum and displayed weak activity against sexual stage gametocytes. We determined that the optimized compounds blocked erythrocyte invasion consistent with the asexual activity observed and therefore the phenylsulfonyl piperazine analogues described could serve as useful tools for studying Plasmodium erythrocyte invasion.

Preparation of targeted GSK3 alpha/beta degradation agent and medical application thereof

The invention discloses preparation of a targeted GSK3 alpha/beta degradation agent and a medical application thereof. The pharmaceutical composition comprises compounds or pharmaceutically acceptable salts thereof as shown in general formulas (I) and (II), R is selected from Cl and I, m is selected from 2, 3, 4, 5 and 6, and n is selected from 1, 2 and 4. The invention provides the degradation agent, and the compound disclosed by the invention can effectively degrade cell GSK3 alpha/beta in a targeting manner, and can be used as a therapeutic agent for Alzheimer's disease or other GSK3 protein related diseases.

Discovery of PT-65 as a highly potent and selective Proteolysis-targeting chimera degrader of GSK3 for treating Alzheimer's disease

GSK3 is a promising target for the treatment of Alzheimer's disease. Here, we describe the design and synthesize of a series of GSK3 degraders based on a click chemistry platform. A series of highly potent GSK3 degraders were obtained. Among them, PT-65 exhibited most potent degradation potency against GSK3α (DC50 = 28.3 nM) and GSK3β (DC50 = 34.2 nM) in SH-SY5Y cells. SPR assay confirmed that PT-65 binds to GSK3β with high affinity (KD = 12.41 nM). The proteomic study indicated that PT-65 could selectively induced GSK3 degradation. Moreover, PT-65 could effectively suppress GSK3β and Aβ mediated tau hyperphosphorylation in a dose-dependent manner and protect SH-SY5Y cells from Aβ caused cell damage. We also confirmed that PT-65 could suppress OA induced tau hyperphosphorylation and ameliorate learning and memory impairments in vivo model of AD. In summary, PT-65 might be a promising candidate for the treatment of AD.

Discovery of Novel Chromone Derivatives Containing a Sulfonamide Moiety as Anti-ToCV Agents through the Tomato Chlorosis Virus Coat Protein-Oriented Screening Method

A number of novel chromone derivatives containing sulfonamide moieties were designed and synthesized, and the activity of compounds against tomato chlorosis virus (ToCV) was assessed using the ToCVCP-oriented screening method. Comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) models were established based on the dissociation constant (Kd) values of the target compounds, and compound 35 was designed and synthesized with the aid of CoMFA and CoMSIA models. The study of affinity interaction indicated that compound 35 exhibited excellent affinity with ToCVCP with a Kd value of 0.11 μM, which was better than that of the positive control agents xiangcaoliusuobingmi (0.44 μM) and ningnanmycin (0.79 μM). In addition, the in vivo inhibitory effect of compound 35 on the ToCVCP gene was evaluated by the quantitative real-time polymerase chain reaction. ToCVCP gene expression levels of the compound 35 treatment group were reduced by 67.2%, which was better than that of the positive control agent ningnanmycin (59.5%). Therefore, compound 35 can be used as a potential anti-ToCV drug in the future.

MERTK DEGRADERS AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same.

IRAK DEGRADERS AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same.

Structure-Guided Modification of Heterocyclic Antagonists of the P2Y14 Receptor

The P2Y14 receptor (P2Y14R) mediates inflammatory activity by activating neutrophil motility, but few classes of antagonists are known. We have explored the structure-activity relationship of a 3-(4-phenyl-1H-1,2,3-triazol-1-yl)-5-(aryl)benzoic acid antagonist scaffold, assisted by docking and molecular dynamics (MD) simulation at a P2Y14R homology model. A computational pipeline using the High Throughput MD Python environment guided the analogue design. Selection of candidates was based upon ligand-protein shape and complementarity and the persistence of ligand-protein interactions over time. Predictions of a favorable substitution of a 5-phenyl group with thiophene and an insertion of a three-methylene spacer between the 5-aromatic and alkyl amino moieties were largely consistent with empirical results. The substitution of a key carboxylate group on the core phenyl ring with tetrazole or truncation of the 5-aryl group reduced affinity. The most potent antagonists, using a fluorescent assay, were a primary 3-aminopropyl congener 20 (MRS4458) and phenyl p-carboxamide 30 (MRS4478).

New Pyridinones and Isoquinolinones as Inhibitors of the Bromodomain BRD9

The present invention encompasses compounds of general formula (I) wherein the groups R1 to R9, X1 and X2 have the meanings given in the claims and in the specification. The compounds of the invention are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation, e.g. cancer, pharmaceutical preparations containing such compounds and their uses as a medicament.

Medicinal chemistry optimization of antiplasmodial imidazopyridazine hits from high throughput screening of a softfocus kinase library: Part 2

On the basis of our recent results on a novel series of imidazopyridazine-based antimalarials, we focused on identifying compounds with improved aqueous solubility and hERG profile while maintaining metabolic stability and in vitro potency. Toward this objective, 41 compounds were synthesized and evaluated for antiplasmodial activity against NF54 (sensitive) and K1 (multidrug resistant) strains of the malaria parasite Plasmodium falciparum and evaluated for both aqueous solubility and metabolic stability. Selected compounds were tested for in vitro hERG activity and in vivo efficacy in the P. berghei mouse model. Several compounds were identified with significantly improved aqueous solubility, good metabolic stability, and a clean hERG profile relative to a previous frontrunner lead compound. A sulfoxide-based imidazopyridazine analog 45, arising from a prodrug-like strategy, was completely curative in the Plasmodium berghei mouse model at 4 × 50 mg/kg po.