5453-07-6

Usage

Uses

Used in Pharmaceutical Industry:
3-amino-5-methyl-1H-pyrazole-4-carbonitrile is used as a pharmaceutical intermediate for the development of new drugs. Its unique structure and properties make it a promising candidate for medicinal chemistry research and drug design, potentially leading to the creation of innovative therapeutic agents.
Used in Medicinal Chemistry Research:
In the field of medicinal chemistry, 3-amino-5-methyl-1H-pyrazole-4-carbonitrile is used as a research compound to explore its potential in drug discovery. Its distinctive chemical features allow scientists to investigate its interactions with biological targets and evaluate its efficacy in treating various diseases.
Used in Agrochemicals:
3-amino-5-methyl-1H-pyrazole-4-carbonitrile may also have potential applications in the agrochemical industry. Its unique chemical structure could be harnessed to develop new agrochemical products, such as pesticides or herbicides, that can effectively control pests and weeds while minimizing environmental impact.
Used in Material Science:
In the realm of material science, 3-amino-5-methyl-1H-pyrazole-4-carbonitrile could be utilized in the development of novel materials with specific properties. Its chemical structure may contribute to the creation of advanced materials with applications in various fields, such as electronics, energy storage, or nanotechnology.

InChI:InChI=1/C5H6N4/c1-3-4(2-6)5(7)9-8-3/h1H3,(H3,7,8,9)

Upstream product

• 5417-82-3 (1-ethoxyethylidene)malononitrile 
• 75-36-5 acetyl chloride 
• 109-77-3 malononitrile 
• 2644-70-4 hydrazine hydrochloride 
• 5515-16-2 2-(methoxyethylidene)propanedinitrile 
• 1187-11-7 acetylmalonodinitrile 
• 1202180-98-0 benzyl 5-amino-4-cyano-3-methyl-1H-pyrazole-1-carboxylate 

Downstream Products

• 5399-44-0 3-methyl-4-amino-1H-pyrazolo[3,4-d]pyrimidine 
• 908808-35-5 5-amino-3-methyl-1H-pyrazole-4-carboxamide 
• 138254-43-0 2,5-dimethyl-7-phenyl-pyrazolo[1,5-a]pyrimidine-3-carbonitrile 
• 73001-75-9 2-methyl-7-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carbonitrile 
• 1159591-69-1 4,4'-bis(3-(4-cyano-3-methyl-1H-pyrazol-5-yl)thioureido)-1,1'-diphenylsulfone 
• 1159591-68-0 4,4'-bis(6,7-dihydro-3-methyl-4-imino-6-thioxo-1H,5H-pyrazolo[3,4-d]-pyrimidin-5-yl)-1,1'-diphenylsulfone 
• 1202181-02-9 7-methyl-4-oxo-3-phenethyl-3,4-dihydropyrazolo[5,1-d]-[1,2,3,5]tetrazine-8-carbonitrile 
• 1202180-99-1 7-methyl-4-oxo-3-phenyl-3,4-dihydropyrazolo[5,1-d][1,2,3,5]tetrazine-8-carbonitrile 
• 1202181-01-8 3-benzyl-7-methyl-4-oxo-3,4-dihydropyrazolo[5,1-d]-[1,2,3,5]tetrazine-8-carbonitrile 
• 83451-26-7 1-(2-Nitrobenzoyl)-4-cyan-5-methyl-3-aminopyrazole 
• 83451-31-4 1-(2-Nitrobenzoyl)-4-cyan-3-methyl-5-aminopyrazole 
• 115955-47-0 7-(2,5-dichlorophenyl)-2-methyl-pyrazolo(1,5-a)pyrimidine-3-carbonitrile 
• 1693-94-3 2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one 

Relevant academic research and scientific papers

Pyrazolo[3,4-d]pyrimidine derivatives as irreversible Bruton's tyrosine kinase inhibitors

4,6-Disubstituted pyrazolo[3,4-d]pyrimidine derivatives were explored as irreversible Bruton's tyrosine kinase (BTK) inhibitors. The structure–activity relationship was established with over 20 derivatives synthesized to determine initial hit compounds, based on activities against BTK enzyme and TMD8 cells. It turns out that introducing 1-acrylamido-4-aminopiperdine (1b) at the C4 position of pyrazolopyrimidine as in 5e, and 3-acrylamido-aniline (1j) as 4-position substituent, such as in 9d, 10d, and 10e, delivered potent in vitro enzyme activities as well as TMD8 cell-based cytotoxicities. Considering kinase selectivity profiles, 5e was selected for in vivo efficacy studies with a murine xenograft model using TMD8 cells, where 5e exhibited moderate tumor growth inhibition activities. Further optimization of 5e and 9d may lead to clinically useful compounds to overcome B-cell-mediated hematologic cancers.

Revisiting Pyrazolo[3,4- d]pyrimidine Nucleosides as Anti- Trypanosoma cruzi and Antileishmanial Agents

Chagas disease and visceral leishmaniasis are two neglected tropical diseases responsible for numerous deaths around the world. For both, current treatments are largely inadequate, resulting in a continued need for new drug discovery. As both kinetoplastid parasites are incapable of de novo purine synthesis, they depend on purine salvage pathways that allow them to acquire and process purines from the host to meet their demands. Purine nucleoside analogues therefore constitute a logical source of potential antiparasitic agents. Earlier optimization efforts of the natural product tubercidin (7-deazaadenosine) involving modifications to the nucleobase 7-position and the ribofuranose 3′-position led to analogues with potent anti-Trypanosoma brucei and anti-Trypanosoma cruzi activities. In this work, we report the design and synthesis of pyrazolo[3,4-d]pyrimidine nucleosides with 3′- and 7-modifications and assess their potential as anti-Trypanosoma cruzi and antileishmanial agents. One compound was selected for in vivo evaluation in an acute Chagas disease mouse model.

Fused-pyrimidine derivatives, preparation method thereof, and pharmaceutical composition for use in preventing or treating Bruton's tyrosine kinase activity related diseases containing the same as an active ingredient

The present invention relates to a conjugated pyrimidine derivative, a method for manufacturing the same, and a pharmaceutical composition for preventing or treating Bruton′s tyrosine kinase activity-related diseases containing the same as an active ingredient. The conjugated pyrimidine derivative according to the present invention is excellent in the ability to inhibit the activity of Bruton′s tyrosine kinase or TMD80, and thus can be usefully used for prevention or treatment of diseases related to Bruton′s tyrosine kinase activity, particularly cancer or autoimmune diseases.COPYRIGHT KIPO 2019

ATG7 INHIBITORS AND THE USES THEREOF

Disclosed are chemical entities which are compounds of formula (I) : or a pharmaceutically acceptable salt thereof, wherein R1, R2, and Ra have the values described herein. Chemical entities according to the disclosure can be useful as inhibitors of ATG7. Further provided are pharmaceutical compositions comprising a chemical entity of the disclosure and methods of using the compositions in the treatment of cancer.

3-cyanopyrazolopyrimidine [1,5-a] derivative as well as preparation method and application thereof

The invention belongs to the field of chemical medicines and specifically relates to a 3-cyanopyrazolopyrimidine [1,5-a] derivative as well as a preparation method and application thereof. The invention provides the 3-cyanopyrazolopyrimidine [1,5-a] derivative, and the structure of the 3-cyanopyrazolopyrimidine [1,5-a] derivative is shown as a formula I. The invention further provides the preparation method and the application of the 3-cyanopyrazolopyrimidine [1,5-a] derivative. (The formula I is shown in the description).

Discovery of pyrazolo[1,5-a]pyrimidine-3-carbonitrile derivatives as a new class of histone lysine demethylase 4D (KDM4D) inhibitors

Herein we report the discovery of a series of new small molecule inhibitors of histone lysine demethylase 4D (KDM4D). Molecular docking was first performed to screen for new KDM4D inhibitors from various chemical databases. Two hit compounds were retrieved. Further structural optimization and structure-activity relationship (SAR) analysis were carried out to the more selective one, compound 2, which led to the discovery of several new KDM4D inhibitors. Among them, compound 10r is the most potent one with an IC50 value of 0.41?±?0.03?μM against KDM4D. Overall, compound 10r could be taken as a good lead compound for further studies.

HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK

Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.

Facile synthesis of 1H-imidazo[1,2-b]pyrazoles via a sequential one-pot synthetic approach

5-Aminopyrazole-4-carbonitrile and ethyl 5-aminopyrazole-4-carboxylate, as potential trifunctional building blocks are introduced in a facile, chemo- and regioselective multicomponent assembly of imidazo[1,2-b]pyrazoles via the Groebke-Blackburn-Bienaym reaction (GBB reaction). Besides the synthetic elaboration of a green-compatible isocyanide-based access in three-component mode, we describe an operationally simple, one-pot two-step GBB protocol for the rapid construction of a 46 membered imidazo[1,2- b ] pyrazole library with yields up to 83%.

1,3-disubstituted-4-aminopyrazolo [3, 4-d] pyrimidines, a new class of potent inhibitors for phospholipase D

Phospholipase D enzymes cleave lipid substrates to produce phosphatidic acid, an important precursor for many essential cellular molecules. Phospholipase D is a target to modulate cancer-cell invasiveness. This study reports synthesis of a new class of phospholipase D inhibitors based on 1,3-disubstituted-4-amino-pyrazolopyrimidine core structure. These molecules were synthesized and used to perform initial screening for the inhibition of purified bacterial phospholipase D, which is highly homologous to the human PLD1. Initially tested with the bacterial phospholipase D enzyme, then confirmed with the recombinant human PLD1 and PLD2 enzymes, the molecules presented here exhibited inhibition of phospholipase D activity (IC50) in the low-nanomolar to low-micromolar range with both monomeric substrate diC4PC and phospholipid vesicles and micelles. The data strongly indicate that these inhibitory molecules directly block enzyme/vesicle substrate binding. Preliminary activity studies using recombinant human phospholipase Ds in in vivo cell assays measuring both transphosphatidylation and head-group cleavage indicate inhibition in the mid- to low-nanomolar range for these potent inhibitory novel molecules in a physiological environment. This study reports synthesis of a new class of PLD inhibitors based on 1,3-disubstituted-4-amino-pyrazolopyrimidine core structure. These molecules exhibited inhibition of human recombinant PLD activity (IC 50) in the low-nanomolar to low-micromolar range with monomeric substrate diC4PC and phospholipid vesicles and micelles. Preliminary activity studies using recombinant human PLDs in in vivo cell assays measuring both transphosphatidylation and head-group cleavage indicates inhibition in the mid- to low-nanomolar range for these potent inhibitory novel molecules in a physiological environment.

The interplay of hydrogen bonds in the solid state structure of NH-pyrazoles bearing cyano and amino substituents

The annular tautomeric equilibrium of two 4-cyano-3(5)-aminopyrazoles having hydrogen atom or methyl group in position 5(3) was studied by X-ray crystallography for the solid compounds and by DFT B3LYP/6-31G and CBS-QB3 calculations for the free molecules. The 3-amino tautomer was found to be the more favorable form for the free molecules and the sole form in the solid state.