116884-64-1

Basic information

• Product Name: 5-AMINO-1-(4-METHOXYPHENYL)-1H-PYRAZOLE-4-CARBONITRILE
• Synonyms: BUTTPARK 34\09-21;AKOS B030078;5-AMINO-1-(4-METHOXYPHENYL)-1H-PYRAZOLE-4-CARBONITRILE
• CAS NO: 116884-64-1
• Molecular Formula: C₁₁H₁₀N₄O
• Molecular Weight: 214.22
• Mol File: 116884-64-1.mol

Chemical Properties

• Melting Point: 125-128
• Appearance: /
• Density: 1.27±0.1 g/cm3 (20 ºC 760 Torr)
• CAS DataBase Reference: 5-AMINO-1-(4-METHOXYPHENYL)-1H-PYRAZOLE-4-CARBONITRILE(CAS DataBase Reference)
• NIST Chemistry Reference: 5-AMINO-1-(4-METHOXYPHENYL)-1H-PYRAZOLE-4-CARBONITRILE(116884-64-1)
• EPA Substance Registry System: 5-AMINO-1-(4-METHOXYPHENYL)-1H-PYRAZOLE-4-CARBONITRILE(116884-64-1)

Safety Data

• Hazard Codes: Xi
• Statements: 41
• Safety Statements: 26-39
• HazardClass: IRRITANT
• Hazardous Substances Data: 116884-64-1(Hazardous Substances Data)

Upstream product

• 123-06-8 Ethoxymethylenemalononitrile 
• 3471-32-7 4-Methoxyphenylhydrazine 
• 19501-58-7 4-methoxyphenylhydrazine hydrochloride 

Downstream Products

• 650628-53-8 1-(4-methoxy-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ol 
• 116884-63-0 (5-amino-1-(4-methoxyphenyl)-1H-pyrazole-4-carboxamide) 
• 925006-60-6 C₁₂H₁₁N₅O 
• 1094618-81-1 1-(4-methoxyphenyl)-5,6,7,8-tetrahydro-1H-pyrazolo[3,4-b]quinolin-4-amine 
• 1225470-47-2 6-methyl-1-(4-methyloxyphenyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-one 
• 1293979-14-2 5-chloro-1-(4-methoxyphenyl)-1H-pyrazole-4-carbonitrile 
• 116884-15-2 7-(4-methoxyphenyl)-3H-pyrazolo[3,4-d][1,2,3]triazin-4(7H)-one 
• 118718-59-5 1-(4-methoxyphenyl)-1H-pyrazole-4-carbonitrile 
• 1301185-12-5 1-(4-methoxyphenyl)-1H-pyrazole-4-carboximidamide 
• 1381260-77-0 C₁₄H₁₃N₅O₂ 
• 1381556-62-2 C₁₅H₁₅N₅O₂ 
• 650628-52-7 4-hydrazino-1-[4-methoxyphenyl]-1H-rzl[3,4-d]pyrimidine 

Relevant articles and documents

COMBINATION THERAPY FOR TREATING MPS1

The application is directed to compounds of formula (I) and their salts and solvates, wherein B, R1, R2, R3, R3', R4, R4', and R5 are as set forth in the specification, as well as to methods for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of, e.g., MPS1, optionally in combination with α-L-iduronidase or an analog or variant thereof, e.g., laronidase.

Synthesis of pyrazole-carboxamides and pyrazole-carboxylic acids derivatives: Simple methods to access powerful building blocks

Hybrid systems containing pyrazole moiety show a wide spectrum of biological activities. To access novel hybrids with pyrazole ring, in this work we synthesized twenty pyrazole-carboxylic acids and twenty pyrazole-carboxamides, using simple synthetic methods, to be used as building blocks in the development of new structures.

Microwave-assisted efficient synthesis of pyrazole-fibrate derivatives as stimulators of glucose uptake in skeletal muscle cells

The design and synthesis of a series of pyrazolo[3,4-d]pyrimidinones containing fibrate side chains have been accomplished by utilizing the concept of molecular hybridization. All the synthesized compounds were evaluated for the glucose uptake stimulatory effect in L6 rat skeletal muscle cells. Four compounds (3f, 3g, 3j and 3q) were found to show significant stimulation of glucose uptake. Further these four compounds have been examined for their Glut4 translocation stimulatory effect in L6-Glut4myc myotubes. Compound 3q was found to exert maximum increase in GLUT4myc translocation.

A Convenient Synthesis of Pyrazole-imidazoline Derivatives by Microwave Irradiation

A series of 28 hybrids pyrazole-imidazolines 1a–n and 2a–n were synthesized by a new methodology using microwave irradiation, in short time (20–30?min), in low power (50–70?W), and in 34–92% yield. Among all methodologies evaluated, no side products were obtained. All derivatives were completely characterized by FT–IR, 1H and 13C NMR, GC–MS, and HRMS.

Synthesis, structure-activity relationship and trypanocidal activity of pyrazole-imidazoline and new pyrazole-tetrahydropyrimidine hybrids as promising chemotherapeutic agents for Chagas disease

Drug therapy for Chagas disease remains a major challenge as potential candidate drugs have failed clinical trials. Currently available drugs have limited efficacy and induce serious side effects. Thus, the discovery of new drugs is urgently needed in the fight against Chagas' disease. Here, we synthesized and evaluated the biological effect of pyrazole-imidazoline (1a-i) and pyrazole-tetrahydropyrimidine (2a-i) derivatives against relevant clinical forms of Trypanosoma cruzi. The structure-activity relationship (SAR), drug-target search, physicochemical and ADMET properties of the major active compounds in vitro were also assessed in silico. Pyrazole derivatives showed no toxicity in Vero cells and also no cardiotoxicity. Phenotypic screening revealed two dichlorinated pyrazole-imidazoline derivatives (1c and 1d) with trypanocidal activity higher than that of benznidazole (Bz) against trypomastigotes; these were also the most potent compounds against intracellular amastigotes. Replacement of imidazoline with tetrahydropyrimidine in the pyrazole compounds completely abolished the trypanocidal activity of series 2(a-i) derivatives. The physicochemical and ADMET properties of the compounds predicted good permeability, good oral bioavailability, no toxicity and mutagenicity of 1c and 1d. Pyrazole nucleus had high frequency hits for cruzipain in drug-target search and structure activity relationship (SAR) analysis of pyrazole-imidazoline derivatives revealed enhanced activity when chlorine atom was inserted in meta-positions of the benzene ring. Additionally, we found evidence that both compounds (1c and 1d) have the potential to interact non-covalently with the active site of cruzipain and also inhibit the cysteine proteinase activity of T. cruzi. Collectively, the data presented here reveal pyrazole derivatives with promise for further optimization in the therapy of Chagas disease.

Computer-aided molecular design of pyrazolotriazines targeting glycogen synthase kinase 3

Numerous studies have highlighted the implications of the glycogen synthase kinase 3 (GSK-3) in several processes associated with Alzheimer’s disease (AD). Therefore, GSK-3 has become a crucial therapeutic target for the treatment of this neurodegenerative disorder. Hereby, we report the design and multistep synthesis of ethyl 4-oxo-pyrazolo[4,3-d][1–3]triazine-7-carboxylates and their biological evaluation as GSK-3 inhibitors. Molecular modelling studies allow us to develop this new scaffold optimising the chemical structure. Potential binding mode determination in the enzyme and the analysis of the key features in the catalytic site are also described. Furthermore, the ability of pyrazolotriazinones to cross the blood–brain barrier (BBB) was evaluated by passive diffusion and those who showed great GSK-3 inhibition and permeation to the central nervous system (CNS) showed neuroprotective properties against tau hyperphosphorylation in a cell-based model. These new brain permeable pyrazolotriazinones may be used for key in vivo studies and may be considered as new leads for further optimisation for the treatment of AD.

Thermal Ring-Opening of Pyrazolo[3,4-d][1,2,3]triazin-4-ones: An Experimental and Theoretical Study

Several 3-pyrazolylcarbonyl-pyrazolo[3,4-d][1,2,3]triazin-4-ones have been prepared from 5-amino-1H-pyrazole-4-carbonitriles through a simple sequence. In the first step, diazotization of the corresponding aminopyrazoles afforded pyrazolo[3,4-d][1,2,3]triazin-4-ones. Next, thermal rearrangement of these compounds through nitrogen elimination gave the final products. The proposed mechanism for the ring-opening of the pyrazolotriazinones to give the pyrazolylcarbonyl-pyrazolotriazinones involves the generation of an iminoketene intermediate, which reacts with a second molecule of pyrazolotriazinone. The complete mechanism of product formation involving the iminoketene intermediate, and all other reasonable pathways, have been explored in detail through DFT calculations. Furthermore, additional experiments to corroborate the presence of the iminoketene intermediate were carried out.

Synthesis and biological evaluation of new tacrine analogues under microwave irradiation

Efficient routes to various kinds of heterocycles incorporating the p-halophenyl moiety have been synthesized. Different pyrrole derivatives have been synthesized, as well, by Thorpe–Ziegler cyclization. Therefore, we synthesized different analogues of tacrine by Friedl?nder reaction of o-amino nitriles (pyrazolo, furano and pyrrolo) with different cycloalkanones. The use of microwave irradiation leads to shorter production times and high product conversion. These synthesized compounds were biologically evaluated by Ellman’s test on acetylcholinesterase inhibition.

Synthesis, in vitro and in vivo anticancer activity of novel 1-(4-imino-1-substituted-1H-pyrazolo[3,4-d]pyrimidin-5(4H)-yl)urea derivatives

A series of pyrazolo[3,4-d]pyrimidine and urea hybrids have been designed, synthesized and evaluated for their anticancer activity in vitro and in vivo cancer models. Among them, compounds 28, 30, 33, 36 and 37 showed promising cytotoxicity against tested cancer cell lines. Compound 37 (CBS-1) appeared as the most active derivative and it exhibited better cytotoxicity against all tested cell lines as compared to doxorubicin. CBS-1 successfully inhibited cell cycle progression and displayed good apoptosis in A549 cells. CBS-1 significantly induced caspase-3 activation and suppressed NF-κB and IL-6 activation in immunocytochemistry, qPCR and western blot analysis. Additionally, CBS-1 prominently displayed tumoricidal effects in lung adenocarcinoma in vivo xenograft nude mice model.

Identification of novel GLUT inhibitors

The compound class of 1H-pyrazolo[3,4-d]pyrimidines was identified using HTS as very potent inhibitors of facilitated glucose transporter 1 (GLUT1). Extensive structure–activity relationship studies (SAR) of each ring system of the molecular framework was established revealing essential structural motives (i.e., ortho-methoxy substituted benzene, piperazine and pyrimidine). The selectivity against GLUT2 was excellent and initial in vitro and in vivo pharmacokinetic (PK) studies are encouraging.