24522-26-7

Upstream product

• 372-09-8 cyanoacetic acid 
• 106-40-1 4-bromo-aniline 
• 36140-83-7 1-cyanoacetyl-3,5-dimethylpyrazole 
• 56290-86-9 3-cyano-2-oxo-propanoic acid ethyl ester 
• 105-56-6 ethyl 2-cyanoacetate 

Downstream Products

• 113604-19-6 (Z)-N-(4-Bromo-phenyl)-2-cyano-3-hydroxy-acrylamide 
• 136186-39-5 (Z)-N-(4-Bromo-phenyl)-3-(4-chloro-phenyl)-2-cyano-3-hydroxy-acrylamide 
• 121217-57-0 (Z)-N-(4-Bromo-phenyl)-2-cyano-3-(2-nitro-phenyl)-acrylamide 
• 287474-36-6 N-(4-bromo-phenyl)-2-cyano-2-hydroxyimino-acetamide 
• 24522-48-3 N-(4-bromo phenyl)-4,6-dimethyl-3-cyano-2-pyridone 
• 287474-40-2 2-amino-N-(4-bromo-phenyl)-2-cyano-acetamide 
• 287474-44-6 N-(4-bromo-phenyl)-2-cyano-2-diazo-acetamide 
• 1447585-57-0 N-(4-bromophenyl)-2-{2-[(4-bromophenyl)amino]-2-oxoethyl}-6-thioxo-1,6-dihydropyrimidine-5-carboxamide 
• 1447585-69-4 4-[(2-anilino-2-oxoethyl)thio]-N-(4-bromophenyl)-2-{2-[(4-bromophenyl)amino]-2-oxoethyl}pyrimidine-5-carboxamide 
• 1447585-70-7 4-{[2-(benzylamino)-2-oxoethyl]thio}-N-(4-bromophenyl)-2-{2-[(4-bromophenyl)amino]-2-oxoethyl}pyrimidine-5-carboxamide 
• 1447585-71-8 N-(4-bromophenyl)-2-{2-[(4-bromophenyl)amino]-2-oxoethyl}-4-({2-[(2-methylphenyl)amino]-2-oxoethyl}thio)pyrimidine-5-carboxamide 
• 1447585-72-9 N-(4-bromophenyl)-2-{2-[(4-bromophenyl)amino]-2-oxoethyl}-4-({2-[(4-methylphenyl)amino]-2-oxoethyl}thio)pyrimidine-5-carboxamide 
• 1447585-73-0 N-(4-bromophenyl)-2-{2-[(4-bromophenyl)amino]-2-oxoethyl}-4-({2-[(2-ethylphenyl)amino]-2-oxoethyl}thio)pyrimidine-5-carboxamide 
• 1447585-74-1 N-(4-bromophenyl)-2-{2-[(4-bromophenyl)amino]-2-oxoethyl}-4-({2-[(4-ethylphenyl)amino]-2-oxoethyl}thio)pyrimidine-5-carboxamide 

Relevant academic research and scientific papers

Nickel-promoted oxidative domino Csp3-H/N-H bond double-isocyanide insertion reaction to construct pyrrolin-2-ones

The first nickel-catalyzed oxidative domino Csp3-H/N-H double isocyanide insertion reaction of acetamides with isocyanides has been developed for the synthesis of pyrrolin-2-one derivatives. A wide range of acetamides bearing various functional groups are compatible with this reaction system by utilizing Ni(acac)2as a catalyst. In this transformation, isocyanide could serve as a C1 connector and insert into the inactive Csp3-H bond, representing an effective way to construct heterocycles.

Agonist-mediated switching of ion selectivity in TPC2 differentially promotes lysosomal function

Ion selectivity is a defining feature of a given ion channel and is considered immutable. Here we show that ion selectivity of the lysosomal ion channel TPC2, which is hotly debated (Calcraft et al., 2009; Guo et al., 2017; Jha et al., 2014; Ruas et al., 2015; Wang et al., 2012), depends on the activating ligand. A high-throughput screen identified two structurally distinct TPC2 agonists. One of these evoked robust Ca2+-signals and non-selective cation currents, the other weaker Ca2+-signals and Na+-selective currents. These properties were mirrored by the Ca2+- mobilizing messenger, NAADP and the phosphoinositide, PI(3,5)P2, respectively. Agonist action was differentially inhibited by mutation of a single TPC2 residue and coupled to opposing changes in lysosomal pH and exocytosis. Our findings resolve conflicting reports on the permeability and gating properties of TPC2 and they establish a new paradigm whereby a single ion channel mediates distinct, functionally-relevant ionic signatures on demand.

Synthesis, anti-varicella-zoster virus and anti-cytomegalovirus activity of 4,5-disubstituted 1,2,3-(1H)-triazoles

Background: Clinical drugs for herpesvirus exhibit high toxicity and suffer from significant drug resistance. The development of new, effective, and safe anti-herpesvirus agents with different mechanisms of action is greatly required. Objective: Novel inhibitors against herpesvirus with different mechanisms of action from that of clinical drugs. Methods: A series of novel 5-(benzylamino)-1H-1,2,3-triazole-4-carboxamides were efficiently synthesized and EC50 values against Human Cytomegalovirus (HCMV), Varicella-Zoster Virus (VZV) and Herpes Simplex Virus (HSV) were evaluated in vitro. Results: Some compounds present antiviral activity. Compounds 5s and 5t are potent against both HCMV and VZV. Compounds 5m, 5n, 5s, and 5t show similar EC50 values against both TK+ and TK? VZV strains. Conclusion: 5-(Benzylamino)-1H-1, 2,3-triazole-4-carboxamides are active against herpesviruses and their activity is remarkably affected by the nature and the position of substituents in the benzene ring. The results indicate that these derivatives are independent of the viral thymidine kinase (TK) for activation, which is indispensable for current drugs. Their mechanisms of action may differ from those of the clinic anti-herpesvirus drugs.

Synthesis, cytotoxic characterization, and SAR study of imidazo[1,2-b]pyrazole-7-carboxamides

The synthesis and in vitro cytotoxic characteristics of new imidazo[1,2-b]pyrazole-7-carboxamides were investigated. Following a hit-to-lead optimization exploiting 2D and 3D cultures of MCF-7 human breast, 4T1 mammary gland, and HL-60 human promyelocytic leukemia cancer cell lines, a 67-membered library was constructed and the structure–activity relationship (SAR) was determined. Seven synthesized analogues exhibited sub-micromolar activities, from which compound 63 exerted the most significant potency with a remarkable HL-60 sensitivity (IC50 = 0.183 μM).

2-Imino 2H-chromene and 2-(phenylimino) 2H-chromene 3-aryl carboxamide derivatives as novel cytotoxic agents: synthesis, biological assay, and molecular docking study

The inhibition of AKR1B10 has been recognized as a potential therapeutic approach to the treatment of various types of cancers. A novel series of compounds with imino-2H-chromen and phenylimino-2H-chromen scaffolds were synthesized by Knoevenagel condensation reaction. The in vitro cytotoxic activity of synthesized compounds was evaluated against MOLT-4 and SK-OV-3 cells. Among the tested compounds, N-(3,4-dimethoxyphenyl)-2-(phenylimino)-2H-chromene-3-carboxamide (8g) demonstrated potent inhibitory activity against both examined cell lines. The results of the molecular docking study suggested that this compound is involved in critical hydrogen-bonding interactions with the Val301 and Lue302 of AKR1B10 catalytic site.

AMINO-SUBSTITUTED HETEROCYCLIC DERIVATIVES AS SODIUM CHANNEL INHIBITORS

The present invention relates to novel aminoindazolyl derivative compounds of Formula(I), the use of said compounds in treating diseases mediated by modulation of voltage-gated sodium channels in particular Nav1.7 AND to compositions containing said derivatives.

3,4-Disubstituted isothiazoles: Novel potent inhibitors of VEGF receptors 1 and 2

Novel derivatives of isothiazoles are described as potent ATP-competitive inhibitors of vascular endothelial growth factor receptors I and II (VEGFR-1/2). A number of compounds exhibited VEGFR-2 inhibitory activity comparable to that of Vatalanib in both HTRF enzymatic and cellular assays. Several derivatives featuring bulky meta-substituents in the amide portion of the molecule displayed 4- to 8-fold specificity for VEGFR-2 versus VEGFR-1. Active molecules also showed high intrinsic permeability (>30 × 10-5 cm/min) across Caco-2 cell monolayer.

Synthesis, structure-activity relationships, and pharmacokinetic properties of dihydroorotate dehydrogenase inhibitors: 2-cyano-3-cyclopropyl- 3-hydroxy. N-[3'-methyl-4'-(trifluoromethyl)phenyl]propenamide and related compounds

The active metabolite (2) of the novel immunosuppressive agent leflunomide (1) has been shown to inhibit the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme catalyzes the fourth step in de novo pyrimidine biosynthesis. A series of analogues of the active metabolite 2 have been synthesized. Their in vivo biological activity determined in rat and mouse delayed type hypersensitivity has been found to correlate well with their in vitro DHODH potency. The most promising compound (3) has shown activity in rat and mouse collagen (II)-induced arthritis models (ED50 = 2 and 31 mg/kg, respectively) and has shown a shorter half-life in man when compared with leflunomide. Clinical studies in rheumatoid arthritis are in progress.

Synthesis and Biological Activity of a Series of Diaryl-Substituted α-Cyano-β-hydroxypropenamides, a New Class of Anthelmintic Agents

A series of α-cyano-β-hydroxypropenamides was prepared and tested for anthelmintic activity. α-Cyano-β-hydroxy-N--3-propenamide (1) showed good activity against the nematode Nematospirodes dubius in a mixed parasite infection in mice; several of the analogues were also effective against the cestode Hymenolepis nana.In sheep trials, 1 caused 100percent reduction of the hematophagous nematode Haemonchus contortus after a single dose of 20 mg/kg but did not show satisfactory control of Trichostrongylus colubriformis or Ostertagia circumcincta.Against the liver fluke Fasciola hepatica, 1 suppressed egg production but only temporarily, suggesting that the adult flukes were not eliminated.Mechanism of action studies on 1 using Ascaris mitochondria showed it to be an uncoupler of oxidative phosphorylation.