66377-37-5

Upstream product

• 1204-86-0 4-(4-morpholinyl)benzaldehyde 
• 141-82-2 malonic acid 
• 6341-04-4 p-[N,N-bis(2-chloroethyl)amino]cinnamic acid 
• 1359868-31-7 ethyl (E)-3-(4-morpholinophenyl)acrylate 
• 459-57-4 4-fluorobenzaldehyde 

Relevant academic research and scientific papers

Discovery of Novel Benzothiazepinones as Irreversible Covalent Glycogen Synthase Kinase 3β Inhibitors for the Treatment of Acute Promyelocytic Leukemia

Recently, irreversible inhibitors have attracted great interest in antitumors due to their advantages of forming covalent bonds to target proteins. Herein, some benzothiazepinone compounds (BTZs) have been designed and synthesized as novel covalent GSK-3β inhibitors with high selectivity for the kinase panel. The irreversible covalent binding mode was identified by kinetics and mass spectrometry, and the main labeled residue was confirmed to be the unique Cys14 that exists only in GSK-3β. The candidate 4-3 (IC50 = 6.6 μM) showed good proliferation inhibition and apoptosis-inducing ability to leukemia cell lines, low cytotoxicity on normal cell lines, and no hERG inhibition, which hinted the potential efficacy and safety. Furthermore, 4-3 exhibited decent pharmacokinetic properties in vivo and remarkably inhibited tumor growth in the acute promyelocytic leukemia (APL) mouse model. All the results suggest that these newly irreversible BTZ compounds might be useful in the treatment of cancer such as APL.

Imidazolylamide derivative

The present invention pertains to an imidazolylamide derivative represented by formula (1) that exhibits an exceptional suppressive effect on cancer cell sphere formation ability and that is useful as an antitumor agent that can be administered orally, or a pharmacologically acceptable salt thereof. [In the formula, ring Q1 represents a C6-10 aryl group or the like; m represents 0, 1, 2, 3, 4, or 5; R3, independently when multiple, represent(s) a halogen atom or the like; R1 and R2 independently represent a hydrogen atom or the like; W1 represents a C1-4 alkylene group (said group may be substituted by 1-3 fluorine atoms or C3-7 cycloalkyls); W2 represents —NR4aC(O)— or the like (where R4a represents a hydrogen atom or C1-6 alkyl group); and ring Q2 represents a C6-10 arylgroup or the like]

Discovery of caffeic acid phenethyl ester derivatives as novel myeloid differentiation protein 2 inhibitors for treatment of acute lung injury

Myeloid differentiation protein 2 (MD2) is an essential molecule which recognizes lipopolysaccharide (LPS), leading to initiation of inflammation through the activation of Toll-like receptor 4 (TLR4) signaling. Caffeic acid phenethyl ester (CAPE) from propolis of honeybee hives could interfere interactions between LPS and the TLR4/MD2 complex, and thereby has promising anti-inflammatory properties. In this study, we designed and synthesized 48 CAPE derivatives and evaluated their anti-inflammatory activities in mouse primary peritoneal macrophages (MPMs) activated by LPS. The most active compound, 10s, was found to bind with MD2 with high affinity, which prevented formation of the LPS/MD2/TLR4 complex. The binding mode of 10s revealed that the major interactions with MD2 were established via two key hydrogen bonds and hydrophobic interactions. Furthermore, 10s showed remarkable protective effects against LPS-caused ALI (acute lung injury) in vivo. Taken together, this work provides new lead structures and candidates as MD2 inhibitors for the development of anti-inflammatory drugs.

Synthesis and biological evaluation of N-(4-phenylthiazol-2-yl)cinnamamide derivatives as novel potential anti-tumor agents

In this study, a series of novel N-(4-phenylthiazol-2-yl)cinnamamide derivatives (7a-8n) were synthesized and evaluated for their anti-proliferative activities in vitro by MTT assay and a possible antitumor mechanism was also explored. SAR analysis showed that steric effects played an important role on the anti-tumor activity. The most potent analogue 8f showed excellent inhibitions on the K562, Bel7402, A549 and Jurkat cells ranging from sub-micromolar to nanomolar concentration. Compound 8f inhibited Jurkat cells with an IC50 value of 0.035 μM with no apparent toxicity in different non-cancerous cells. Furthermore, it was suggested that the possible mechanism of 8f might be associated with inducing cancer cell apoptosis following flow cytometer analysis and Hoechst 33358 staining assays.

Design, synthesis, 3D pharmacophore, QSAR, and docking studies of carboxylic acid derivatives as Histone Deacetylase inhibitors and cytotoxic agents

In this study, five series of (E)-6-(4-substituted phenyl)-4-oxohex-5-enoic acids IIb-f (E), (E)-3-(4-(substituted)-phenyl)acrylic acids IIIa-g (E), 4-(4-(substituted)phenylamino)-4-oxobutanoic acids VIa,b,e, 5-(4-(substituted)phenylamino)-5-oxopentanoic acids VIIa,f and 2-[(4-(substituted)phenyl) carbamoyl]benzoic acids VIIIa,e were designed and synthesized. Selected compounds were screened in vitro for their cytotoxic effect on 60 human NCI tumor cell lines. Compound IIf (E) displayed significant inhibitory activity against NCI Non-Small Cell Lung A549/ATCC Cancer cell line (68% inhibition) and NCI-H460 Cancer cell line (66% inhibition). Moreover, the final compounds were evaluated in vitro for their cytotoxic activity on HepG2 Cancer cell line in which histone deacetylase (HDAC) is overexpressed. Compounds IIc (E), IIf (E), IIIb (E), and IIIg (E) exhibited the highest cytotoxic activity against HepG2 human cancer cell lines with IC50ranging from 2.27 to 10.71 μM. In addition, selected compounds were tested on histone deacetylase isoforms (HDAC1-11). Molecular docking simulation was also carried out for HDLP enzyme to investigate their HDAC binding affinity. In addition, generation of 3D-pharmacophore model and quantitative structure activity relationship (QSAR) models were combined to explore the structural requirements controlling the observed cytotoxic properties.