5417-82-3

Usage

Uses

Used in Chemical Synthesis:
(1-Ethoxyethylidene)malononitrile is used as a synthetic intermediate for the production of various chemical compounds. It is particularly utilized in the synthesis of benzyl 5-amino-4-cyano-3-methyl-1H pyrazole-1-carboxylate and 2-amino-6-mercaptopyridine-3,5-dicarbonitrile derivatives. Its unique chemical properties make it a valuable component in the creation of these complex molecules.
Used in Agriculture:
In the agricultural industry, (1-Ethoxyethylidene)malononitrile is used as a herbicide and growth regulator. Its application helps control the growth of unwanted plants and promotes the healthy development of crops. This dual function makes it a valuable tool for farmers and agricultural professionals.

InChI:InChI=1/C7H8N2O/c1-3-10-6(2)7(4-8)5-9/h3H2,1-2H3

Upstream product

• 78-39-7 Triethyl orthoacetate 
• 109-77-3 malononitrile 

Downstream Products

• 34684-87-2 4-amino-2,6-dimethylpyrimidine-5-carbonitrile 
• 5346-56-5 5-amino-3-methyl-1-phenyl-1H-pyrazole-4-carbonitrile 
• 54820-92-7 1,3-dimethyl-5-amino-1H-pyrazole-4-carbonitrile 
• 5453-07-6 5-amino-3-methyl-1H-pyrazole-4-carbonitrile 
• 35261-01-9 3-methyl-4-cyano-5-aminoisoxazole 
• 95689-38-6 1,1-dicyano-4-(N,N-dimethylamino)-2-methoxy-1,3-butadiene 
• 85092-72-4 methyl 3-amino-4-cyano-5-methylthiophene-2-carboxylate 
• 2228-12-8 6-methyl-4-phenyl-2-thioxo-1,2-dihydropyrimidine-5-carbonitrile 
• 76982-33-7 5-Amino-4-cyan-1-(2,4-dinitrophenyl)-3-methylpyrazol 
• 76982-34-8 5-Amino-4-cyan-3-methyl-1-(2-nitro-4-trifluormethylphenyl)pyrazol 
• 76982-35-9 5‐amino‐1‐(4‐bromophenyl)‐3‐methyl‐1H‐pyrazole‐4‐carbonitrile 
• 76989-44-1 5-Amino-4-cyan-1-(2,3-dichlorphenyl)-3-methylpyrazol 
• 76982-29-1 5-Amino-4-cyan-1-(2,5-dichlorphenyl)-3-methylpyrazol 
• 95881-70-2 6-Amino-5-cyano-4-methyl-3-benzenesulfonyl-2-pyridone 

Relevant academic research and scientific papers

Novel pyrazolo[3,4-d]pyrimidine derivatives inhibit human cancer cell proliferation and induce apoptosis by ROS generation

The paucity of effective anticancer drugs for successful treatment is a major concern, indicating the strong need for novel therapeutic compounds. In the quest of new molecules, the present study aimed to explore the potential of pyrazolo[3,4-d]pyrimidine derivatives as antiproliferative agents. In vitro anticancer screening of selected compounds was done by the National Cancer Institute's Developmental Therapeutics Programme against a panel of 60 cancer cell lines. The lead compound PP-31d considerably inhibited the growth of cancer cells, such as NCI-H460 (non-small-cell lung cancer), OVCAR-4 (ovarian cancer), 786-0 (renal cancer), A549 (non-small-cell lung cancer), and ACHN (renal cancer), showing strong anticancer potential, among other derivatives. Kinetic studies of PP-31d on NCI-H460 cells revealed a dose-dependent effect with an IC50 of 2 μM. The observed inhibition by PP-31d is attributed to the generation of reactive oxygen species and the subsequent induction of cellular apoptosis, as evidenced by the increase in the hypodiploid (subG1) population, the early apoptotic cell population, and caspase-3/7 activity, the loss of the mitochondrial membrane potential, and the degradation of nuclear DNA. Collectively, our results demonstrated that pyrazolo[3,4-d]pyrimidine derivatives inhibit cancer cell proliferation by inducing apoptosis and, thus, have the potential to be further explored for anticancer properties.

Design, Synthesis, and Antifungal Activity of 2,6-Dimethyl-4-aminopyrimidine Hydrazones as PDHc-E1 Inhibitors with a Novel Binding Mode

A series of novel 2,6-dimethyl-4-aminopyrimidine hydrazones 5 were rationally designed and synthesized as pyruvate dehydrogenase complex E1 (PDHc-E1) inhibitors. Compounds 5 strongly inhibited Escherichia coli (E. coli) PDHc-E1 (IC50 values 0.94-15.80 μM). As revealed by molecular docking, site-directed mutagenesis, enzymatic, and inhibition kinetic analyses, compounds 5 competitively inhibited PDHc-E1 and bound in a "straight"pattern at the E. coli PDHc-E1 active site, which is a new binding mode. In in vitro antifungal assays, most compounds 5 at 50 μg/mL showed more than 80% inhibition against the mycelial growth of six tested phytopathogenic fungi, including Botrytis cinerea, Monilia fructigena, Colletotrichum gloeosporioides, andBotryosphaeria dothidea. Notably, 5f and 5i were 1.8-380 fold more potent against M. fructigena than the commercial fungicides captan and chlorothalonil. In vivo, 5f and 5i controlled the growth of M. fructigena comparably to the commercial fungicide tebuconazole. Thus, 5f and 5i have potential commercial value for the control of peach brown rot caused by M. fructigena.

An efficient and practical synthesis of 2,4-substituted pyrido[4,3-d]pyrimidin-5(6H)-ones

We describe an efficient synthesis of 2,4-substituted pyrido[4,3-d]pyrimidin-5(6H)-ones, which involves the acid-promoted cyclization of cyano enamine 15 to afford 2,4-bis(methylthio)pyrido[4,3-d]pyrimidin-5(6H)-one 17 as a key intermediate. Selective displacement of the 4-methylthio group by a wide range of anilines followed by oxidation of the 2-methylthio group and subsequent substitution by amines enabled the synthesis of a variety of 2,4-disubstituted pyrido[4,3-d]pyrimidin-5(6H)-ones.

Novel pyrazolo[3,4-d]pyrimidines: design, synthesis, anticancer activity, dual EGFR/ErbB2 receptor tyrosine kinases inhibitory activity, effects on cell cycle profile and caspase-3-mediated apoptosis

A series of novel pyrazolo[3,4-d]pyrimidines was synthesised. Twelve synthesised compounds were evaluated for their anticancer activity against 60 human tumour cell lines by NCI (USA). Compound 7d proved prominent anticancer activity. It showed 1.6-fold more potent anti-proliferative activity against OVCAR-4 cell line with IC50 = 1.74 μM. It also exhibited promising potent anticancer activity against ACHN cell line with IC50 value 5.53 μM, representing 2.2-fold more potency than Erlotinib. Regarding NCI-H460 cell line, compound 7d (IC50 = 4.44 μM) was 1.9-fold more potent than Erlotinib. It inhibited EGFR and ErbB2 kinases at sub-micromolar level (IC50 = 0.18 and 0.25 μM, respectively). Dual inhibition of EGFR and ErbB2 caused induction of apoptosis which was confirmed by a significant increase in the level of active caspase-3 (11-fold). It showed accumulation of cells in pre-G1 phase and cell cycle arrest at G2/M phase.

KINASE INHIBITORS AND USES THEREOF

The present disclosure relates generally to compounds and compositions, intermediates, processes for their preparation, and their use as kinase inhibitors.

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

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.

Simple access to highly functional bicyclic γ- and δ-lactams: Origins of chirality transfer to contiguous tertiary/quaternary stereocenters assessed by DFT

This paper describes the synthesis of both polysubstituted oxazolo-pyrrolidinones and -piperidinones by a domino process. The methodology is based on the reaction between hydroxyl halogenoamides and Michael acceptors, which leads efficiently to bicyclic lactams. The process is compatible with unsymmetrical electron-withdrawing groups on the Michael acceptor, which allows the formation of two contiguous and fully controlled tertiary and quaternary stereocenters. In the case of tetrasubstituted Michael acceptors, two adjacent quaternary stereocenters are formed in good yield. Starting from (R)-phenylglycinol derived amides results in the formation of enantioenriched bicyclic lactams in low to good yields and with high levels of stereo-selectivity, thus greatly increasing the scope and interest of this strategy. The origins of chirality transfer and diastereoselectivity were studied by DFT calculations and have been attributed to a kinetic control in one of the last two steps of the reaction sequence. This selectivity is dependent upon both the substituents on the Michael acceptor and the sodium cation chelation.

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.

BICYCLIC INHIBITORS OF ALK

The present invention relates to compounds of formula (1) or pharmaceutical acceptable salts, Formula (1) wherein R1, R2, R3, X, Y, Z, A, B, G1, m, and n are defined in the description. The present invention relates also to compositions containing said compounds which are useful for inhibiting kinases such as ALK and methods of treating diseases such as cancer.