90434-92-7

Usage

InChI:InChI=1/C8H12N4O/c9-10-8(13)7-5-3-1-2-4-6(5)11-12-7/h1-4,9H2,(H,10,13)(H,11,12)

Upstream product

• 5396-14-5 ethyl 2-oxo-2-(2-oxocyclohexyl)acetate 
• 108-94-1 cyclohexanone 
• 4492-02-8 ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate 

Downstream Products

• 1381840-62-5 N'-[1-(2,4-dihydroxyphenyl)ethylidene]-4,5,6,7-tetrahydro-1H-indazole-3-carbohydrazone 
• 1381840-66-9 N'-[(3-chloro-4-hydroxy-5-methoxyphenyl)methylene]-4,5,6,7-tetrahydro-1H-indazole-3-carbohydrazone 
• 326018-40-0 N'-[(2-hydroxyphenyl)methylene]-4,5,6,7-tetrahydro-1H-indazole-3-carbohydrazone 
• 1381840-59-0 N'-[(4-cyanophenyl)methylene]-4,5,6,7-tetrahydro-1H-indazole-3-carbohydrazone 
• 303208-18-6 N'-[(2-hydroxynaphthalen-1-yl)methylene]-4,5,6,7-tetrahydro-1H-indazole-3-carbohydrazone 
• 1381840-61-4 N'-[(4-chloro-3-nitrophenyl)methylene]-4,5,6,7-tetrahydro-1H-indazole-3-carbohydrazone 
• 1381840-60-3 N'-[(4-chloro-3-fluorophenyl)methylene]-4,5,6,7-tetrahydro-1H-indazole-3-carbohydrazone 
• 331234-59-4 N'-[(2,4-dihydroxyphenyl)methylene]-4,5,6,7-tetrahydro-1H-indazole-3-carbohydrazone 
• 1477482-60-2 C₁₅H₁₅BrN₄O 
• 1477482-59-9 C₁₆H₁₈N₄O₂ 
• 1477482-57-7 C₁₅H₁₆N₄O₂ 
• 94000-49-4 4,5,6,7-tetrahydro-1⁽²⁾H-indazole-3-carboxylic acid benzylidenehydrazide 
• 92553-19-0 4,5,6,7-tetrahydro-1⁽²⁾H-indazole-3-carboxylic acid (4-chloro-benzylidene)-hydrazide 
• 1477482-50-0 C₁₆H₁₈N₄O 

Relevant academic research and scientific papers

Indazole hydrazide compound and application thereof

The invention provides an indazole hydrazide compound as shown in a formula (I), wherein R is selected from substituted alkyl, substituted alkenyl or substituted phenyl; substituent groups in the substituted alkyl group and the substituted alkenyl group comprise phenyl and/or substituted phenyl; and R' is selected from H or alkyl. Compared with the prior art, the indole hydrazide compound provided by the invention can be used as an integrin avbeta3 receptor antagonist, has obvious anti-prostatic cancer activity, and has a significant inhibition effect on enzalutamide drug-resistant cell lines.

Suprafenacine, an Indazole-hydrazide agent, target Cancer cells through microtubule destabilization

Microtubules are a highly validated target in cancer therapy. However, the clinical development of tubulin binding agents (TBA) has been hampered by toxicity and chemoresistance issues and has necessitated the search for new TBAs. Here, we report the identification of a novel cell permeable, tubulin-destabilizing molecule - 4,5,6,7-tetrahydro-1H-indazole-3- carboxylic acid [1p-tolyl-meth-(E)-ylidene]-hydrazide (termed as Suprafenacine, SRF). SRF, identified by in silico screening of annotated chemical libraries, was shown to bind microtubules at the colchicine-binding site and inhibit polymerization. This led to G2/M cell cycle arrest and cell death via a mitochondria-mediated apoptotic pathway. Cell death was preceded by loss of mitochondrial membrane potential, JNK - mediated phosphorylation of Bcl-2 and Bad, and activation of caspase-3.Intriguingly, SRF was found to selectively inhibit cancer cell proliferation and was effective against drug-resistant cancer cells by virtue of its ability to bypass the multidrug resistance transporter P-glycoprotein. Taken together, our resultssuggest that SRF has potential as a chemotherapeutic agent for cancer treatment and provides an alternate scaffold for the development of improved anti-cancer agents.

TUBULIN INHIBITORS

The present invention relates to a compound of Formula (I) for use as a medicament, wherein: m is 0, 1, 2, 3, 4, or 5; R1 and R2 together form a five-membered, six-membered, or seven-membered ring, wherein R1 and R2 together as a group is -(CH2)3-, -(CH2)4 -, or -(CH2)5-; R3 at each occurrence is independently selected from the group consisting of H, halogen, hydroxyl, alkoxy, and a substituted or unsubstituted C1-C5 alkyl; and R4 is H, halogen, or a substituted or unsubstituted C1-C5 alkyl

Synthesis, Structure-Activity Relationship, and Pharmacophore Modeling Studies of Pyrazole-3-Carbohydrazone Derivatives as Dipeptidyl Peptidase IV Inhibitors

Type 2 diabetes mellitus (T2DM) is a metabolic disease and a major challenge to healthcare systems around the world. Dipeptidyl peptidase IV (DPP-4), a serine protease, has been rapidly emerging as an effective therapeutic target for the treatment for T2DM. In this study, a series of novel DPP-4 inhibitors, featuring the pyrazole-3-carbohydrazone scaffold, have been discovered using an integrated approach of structure-based virtual screening, chemical synthesis, and bioassay. Virtual screening of SPECS Database, followed by enzymatic activity assay, resulted in five micromolar or low-to-mid-micromolar inhibitory level compounds (1-5) with different scaffold. Compound 1 was selected for the further structure modifications in considering inhibitory activity, structural variability, and synthetic accessibility. Seventeen new compounds were synthesized and tested with biological assays. Nine compounds (6e, 6g, 6k-l, and 7a-e) were found to show inhibitory effects against DPP-4. Molecular docking models give rational explanation about structure-activity relationships. Based on eight DPP-4 inhibitors (1-5, 6e, 6k, and 7d), the best pharmacophore model hypo1 was obtained, consisting of one hydrogen bond donor (HBD), one hydrogen bond acceptor (HBA), and two hydrophobic (HY) features. Both docking models and pharmacophore mapping results are in agreement with pharmacological results. The present studies give some guiding information for further structural optimization and are helpful for future DPP-4 inhibitors design.