936330-00-6

Upstream product

• 104-92-7 1-bromo-4-methoxy-benzene 
• 824-94-2 p-methoxybenzyl chloride 
• 123-11-5 4-methoxy-benzaldehyde 
• 57260-71-6 1-t-Butoxycarbonylpiperazine 
• 623-12-1 4-chloromethoxybenzene 
• 1268340-97-1 4-trifluoroboratomethylpiperazine-1-carboxylic acid tert-butyl ester internal salt 
• 2746-25-0 p-Methoxybenzyl bromide 

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• 21867-69-6 1-(4-methoxybenzyl)piperazine 

Relevant academic research and scientific papers

LMO2 PROTEIN INHIBITORS

The present invention relates to compounds of Formula (I) that function as LMO2 activity: Formula (I) wherein R1, X1, X2, X3, Q, R2, R3 and R4 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which LMO2 activity is implicated.

Discovery of Novel Apigenin-Piperazine Hybrids as Potent and Selective Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors for the Treatment of Cancer

Poly (ADP-ribose) polymerase-1 (PARP-1) is a potential target for the discovery of chemosensitizers and anticancer drugs. Amentoflavone (AMF) is reported to be a selective PARP-1 inhibitor. Here, structural modifications and trimming of AMF have led to a series of AMF derivatives (9a-h) and apigenin-piperazine/piperidine hybrids (14a-p, 15a-p, 17a-h, and 19a-f), respectively. Among these compounds, 15l exhibited a potent PARP-1 inhibitory effect (IC50 = 14.7 nM) and possessed high selectivity to PARP-1 over PARP-2 (61.2-fold). Molecular dynamics simulation and the cellular thermal shift assay revealed that 15l directly bound to the PARP-1 structure. In in vitro and in vivo studies, 15l showed a potent chemotherapy sensitizing effect against A549 cells and a selective cytotoxic effect toward SK-OV-3 cells through PARP-1 inhibition. 15l·2HCl also displayed good ADME characteristics, pharmacokinetic parameters, and a desirable safety margin. These findings demonstrated that 15l·2HCl may serve as a lead compound for chemosensitizers and the (BRCA-1)-deficient cancer therapy.

Drug discovery of acetophenone derivatives as BRD4 inhibitors

Background: The bromodomain and extra-terminal proteins (BET), in particular BRD4, has recently emerged as a potential therapeutic target for the treatment of many human disorders such as cancer, inflammation, obesity and cardiovascular disease, which draw more and more attention to discover potent BRD4 inhibitors in the past years. In this article, we described the discovery process of an entirely new chemotype of BRD4 inhibitors. Methods: A fragment-based drug discovery strategy was employed in attempting to find a novel chemotype of BRD4 inhibitors. Thus, the potential hits were firstly identified by docking study with KAc binding pocket and AlphaScreen assay. Then the elected hit was further structurally optimized based on the interaction revealed by the docking study and the Structure-Activity Relationship (SAR). Results: A 1-(2-hydroxyphenyl)ethan-1-one fragment was first identified as an efficient hit to BRD4 with a weak inhibition activity and high ligand efficiency (IC50 = 8.9 μM，LE > 0.5) based on virtual screening and biochemical assay. Then, two-rounds optimization of the hit by a fragment-based drug discovery approach enabled the discovery of a potent BRD4 inhibitor 9, which exhibit nanomolar potency in biochemical assays (IC50 = 0.18 μM). Conclusion: The title compounds displayed potent inhibitory activity to BRD4, implying acetophenone core is an effective KAc residue mimic, suggesting acetophenone derivatives as a new chemotype may be promising for developing novel BRD4 inhibitors. 9.

A class of GPR40 agonist compounds with amide structure, and uses thereof

The present invention relates to a class of amide compounds with a novel structure, and a pharmaceutical composition thereof, wherein the structure of the amide compound is represented by a general formula (I). According to the present invention, the amide compound (I) can regulate GPR40 activity, and can be used for GPR40 activity related diseases such as diabetes and metabolic syndrome. The formula I is defined in the specification.

Substituted O-hydroxyphenyl ketone compound as well as preparation method and application thereof

The invention discloses a substituted O-hydroxyphenyl ketone compound, a preparation method of the substituted O-hydroxyphenyl ketone compound, and an application of the substituted O-hydroxyphenyl ketone compound to preparation of a BRD4 protein activity

ANTI-INFECTIVE COMPOUNDS

The present invention relates to small molecule compounds having the general formula (I): wherein A is a moiety selected from the group consisting of formulae (A) to (K) and their use in the treatment of bacterial infections, in particular Tuberculosis.

Synthesis and receptor binding studies of novel 4,4-disubstituted arylalkyl/arylalkylsulfonyl piperazine and piperidine-based derivatives as a new class of σ1 ligands

This study presents the synthesis and biological evaluation of a new series of arylalkyl/arylalkylsulfonyl piperazine and piperidine-based derivatives as sigma receptor ligands. It was found that a number of halogen substituted sulfonamides display relatively high and low affinities to σ1 and σ2 receptors, respectively. The σ1 affinities and subtype selectivities of four piperidine derivatives were also found to be generally comparable to those of piperazine analogues. Compared to σ1-Rs compounds with n = 0 and 2, those with n = 1 proved to have optimal length of carbon chain by exhibiting higher affinities. Within this series, the 4-benzyl-1-(3-iodobenzylsulfonyl)piperidine sigma ligand was identified with 96-fold σ1/σ2 selectivity ratio (Kiσ1 = 0.96 ± 0.05 nM and K iσ2 = 91.8 ± 8.1 nM).

Reinvestigation of aminomethyltrifluoroborates and their application in suzuki-miyaura cross-coupling reactions

A reinvestigation into the chemical composition of potassium aminomethyltrifluoroborates is reported. These trifluoroborato salts have been reassigned as zwitterionic ammoniomethyltrifluoroborates. Minor adjustments to the previously disclosed reaction conditions are reported that permit a similar level of activity as nucleophiles in Suzuki-Miyaura cross-coupling reactions.

Characterization of tunable piperidine and piperazine carbamates as inhibitors of endocannabinoid hydrolases

Monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH) are two enzymes from the serine hydrolase superfamily that degrade the endocannabinoids 2-arachidonoylglycerol and, anandamide, respectively. We have recently discovered that, MAGL and, FAAH are both inhibited by carbamates bearing an N-piperidine/piperazine group. Piperidine/piperazine carbamates show excellent in vivo activity, raising brain endocannabinoid levels and producing CB1-dependent behavioral effects in mice, suggesting that they represent a promising class of inhibitors for studying the endogenous functions of MAGL and FAAH. Herein, we disclose a full account of the syntheses, structure-activity relationships, and, inhibitory activities of piperidine/piperazine carbamates against members of the serine hydrolase family. These scaffolds can be tuned for MAGL-selective or dual MAGL-FAAH inhibition by the attachment of an, appropriately substituted bisarylcarbinol or aryloxybenzyl moiety, respectively, on the piperidine/piperazine ring. Modifications to the piperidine/piperazine ring ablated inhibitory activity, suggesting a strict requirement for a six-membered ring to maintain potency.

Scope of aminomethylations via Suzuki-Miyaura cross-coupling of orsanotrifluoroborates

(Chemical Equation Presented) We previously reported the Suzuki-Miyaura reaction of N,N-dialkylaminomethyltrifluoroborates with aryl bromides. Herein, we report a further investigation of the scope and limitations of this palladium-catalyzed aminomethylation reaction. Aryl chlorides, iodides, and triflates coupled in good to excellent yields to give N,N-dialkylbenzylic amines. The aminomethylation of alkenyl bromides was also examined.