621-03-4

Usage

Chemical Properties

yellowish crystalline powder

InChI:InChI=1/C9H8N2O/c10-7-6-9(12)11-8-4-2-1-3-5-8/h1-5H,6H2,(H,11,12)

Upstream product

• 614-16-4 Benzoylacetonitrile 
• 103-71-9 phenyl isocyanate 
• 372-09-8 cyanoacetic acid 
• 151-50-8 potassium cyanide 
• 587-65-5 N-chloroacetyl-aniline 
• 60-29-7 diethyl ether 
• 115057-41-5 cyanoacetyl azide 
• 62-53-3 aniline 
• 105-56-6 ethyl 2-cyanoacetate 
• 36140-83-7 1-cyanoacetyl-3,5-dimethylpyrazole 
• 15397-33-8 3-Oxo-3-phenylpropanal 
• 105-34-0 methyl 2-cyanoacetate 
• 16130-58-8 cyanoacetic acid chloride 
• 56290-86-9 3-cyano-2-oxo-propanoic acid ethyl ester 

Downstream Products

• 57528-64-0 3-amino-propionanilide 
• 19313-82-7 (E)-3-(benzo[d][1,3]dioxol-5-yl)-2-cyano-N-phenylacrylamide 
• 341541-01-3 2-cyano-3ξ-(6-nitro-benzo[1,3]dioxol-5-yl)-acrylic acid anilide 
• 26052-89-1 α-cyanobenzoylacetanilide 
• 96319-17-4 2-cyano-3-ethoxy-N-phenylcrotonamide 
• 114038-07-2 3t-(4-diethylamino-phenyl)-2-cyano-acrylic acid anilide 
• 6690-46-6 2-cyano-acetoacetic acid anilide 
• 53475-36-8 3-cyano-4,6-dimethyl-1-phenyl-2(1H)-pyridone 
• 121217-51-4 2-cyano-3-(2-nitro-phenyl)-acrylic acid anilide 
• 100168-70-5 N_.N-Bis-(2-chlor-ethyl)-3-methyl-4-(2-cyan-2-phenylcarbamoyl-vinyl)-anilin 
• 42003-90-7 N-Phenylcyanacetimidsaeure-ethylester 
• 59749-96-1 3-amino-3-thioxo-N-phenylpropanamide 
• 90484-32-5 Brom-cyan-acetanilid 
• 64735-75-7 4-amino-3-benzyl-2-thioxo-2,3-dihydro-thiazole-5-carboxylic acid anilide 

Relevant academic research and scientific papers

(E)-2-Cyano-3-(1H-Indol-3-yl)-N-phenylacrylamide, a hybrid compound derived from indomethacin and paracetamol: Design, synthesis and evaluation of the anti-inflammatory potential

The compound (E)-2-cyano-3-(1H-indol-3-yl)-N-phenylacrylamide (ICMD-01) was designed and developed based on the structures of clinically relevant drugs indomethacin and paracetamol through the molecular hybridization strategy. This derivative was obtained by an amidation reaction between substituted anilines and ethyl 2-cyanoacetate followed by a Knoevenagel-type condensation reaction with indole aldehyde that resulted in both a viable synthesis and satisfactory yield. In order to assess the immunomodulatory and anti-inflammatory activity, in vitro assays were performed in J774 macrophages, and significant inhibitions (p -1) showed satisfactory activity, as did the group treated with dexamethasone, reducing edema in 2-6 h. In addition, there was no significant inhibition of PGE2, IL-1β or TNFα in vivo. Moreover, in the peritonitis assay that assesses leukocyte migration, ICMD-01 exhibited promising results. Therefore, these preliminary studies demonstrate this compound to be a strong candidate for an anti-inflammatory drug together with an improved gastrointestinal safety profile when compared to the conventional anti-inflammatory drugs.

Identification of Novel Fused Heteroaromatics-Based MALT1 Inhibitors by High-Throughput Screening to Treat B Cell Lymphoma

Development of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) inhibitors is of great value and significance in the treatment of neoplastic disorders and inflammatory and autoimmune diseases. However, there is a lack of effective MALT1 inhibitors in clinic. Herein, a novel class of potent 5-oxo-1-thioxo-4,5-dihydro-1H-thiazolo[3,4-a]quinazoline-based MALT1 inhibitors and their covalent derivatives were first identified and designed through high-throughput screening. We demonstrated that compounds 15c, 15e, and 20c effectively inhibited the MALT1 protease and displayed selective cytotoxicity to activated B cell-like diffuse large B cell lymphoma with low single-digit micromolar potency. Furthermore, compound 20c specifically repressed NF-κB signaling and induced cell apoptosis in MALT1-dependent TMD8 cells in a dose-dependent manner. More importantly, 20c showed good pharmacokinetic properties and antitumor efficacy with no significant toxicity in the TMD8 xenograft tumor model. Collectively, this study provides valuable lead compounds of MALT1 inhibitors for further structural optimization and antitumor mechanism study.

Synthesis and Docking Study of Novel Pyranocoumarin Derivatives

Abstract: A new series of fused tricyclic coumarin derivatives were designed, synthesized by a simple and convenient method, starting from 4-hydroxycoumarin and virtually screened by molecular docking on the target protein 3FRZ (PDB ID: 3FRZ), a HCV RNA-dependent RNA polymerase, for potency against hepatitis C virus (HCV). Efficient binding to the target protein was found for most of the synthesized compounds.

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.

Development of Novel AKR1C3 Inhibitors as New Potential Treatment for Castration-Resistant Prostate Cancer

Aldo-keto reductase (AKR) 1C3 catalyzes the synthesis of active androgens that promote the progression of prostate cancer. AKR1C3 also contributes to androgen-independent cell proliferation and survival through the metabolism of prostaglandins and reactive aldehydes. Because of its elevation in castration-resistant prostate cancer (CRPC) tissues, AKR1C3 is a promising therapeutic target for CRPC. In this study, we found a novel potent AKR1C3 inhibitor, N-(4-fluorophenyl)-8-hydroxy-2-imino-2H-chromene-3-carboxamide (2d), and synthesized its derivatives with IC50 values of 25-56 nM and >220-fold selectivity over other AKRs (1C1, 1C2, and 1C4). The structural factors for the inhibitory potency were elucidated by crystallographic study of AKR1C3 complexes with 2j and 2l. The inhibitors suppressed proliferation of prostate cancer 22Rv1 and PC3 cells through both androgen-dependent and androgen-independent mechanisms. Additionally, 2j and 2l prevented prostate tumor growth in a xenograft mouse model. Furthermore, the inhibitors significantly augmented apoptotic cell death induced by anti-CRPC drugs (abiraterone or enzalutamide).

Co-sensitization of the HD-2 complex with low-cost cyanoacetanilides for highly efficient DSSCs

The photophysical and electrochemical properties of new targeted 2-cyanoacetanilide-based dyes are illustrated. New cyanoacetanilides SA7-10 were synthesized and employed as co-sensitizers in DSSCs. The chemical structures of these 2-cyanoacetanilides differ according to the substituent at the benzene ring (-H,-Me,-OMe and-NEt2), with the anchoring moiety being the same, a-COOH group. Furthermore, a density functional theory (DFT) calculation has shown an effective intermolecular charge transfer character, the HOMOs of SA7-10 are mainly located on the corresponding donor part, and their LUMOs are located on carboxylic acid moieties as the acceptor. Interestingly, using photosensitizers SA7-10 as co-sensitizers with HD-2 dye causes an improvement in their photovoltaic performances. Among the dyes, SA10 co-sensitized with HD-2 displayed an overall efficiency of 8.25%, a JSC of 19.5 mA cm-2, a VOC of 0.65 V and an FF of 64.35 compared to 7.46%, 19 mA cm-2, 0.64 V and 60.54, respectively, of HD-2 only. Moreover, the electrochemical impedance spectroscopy (EIS) data of SA7-10 and HD-2 were found to be in accordance with the obtained photovoltaic parameters. Finally, the results indicated that 2-cyanoacetanilide-based dyes were utilized as promising co-sensitizers due to their easy preparation methods and their relatively small size.

New pyrazolopyrimidine derivatives with anticancer activity: Design, synthesis, PIM-1 inhibition, molecular docking study and molecular dynamics

In this study, new pyrazolopyrimidine derivatives were designed and evaluated for anticancer activity. PIM-1 inhibitiory activity were measured for the most potent compounds. Molecular docking study and molecular dynamics were also done. Thus, the novel derivatives of pyrazolo[1,5-a]pyrimidine have been synthesized and characterized using different spectroscopic techniques. HMBC and NOESY experiments were used to confirm regiospecific structure of pyrimidine ring. The newly synthesized derivatives were evaluated for their antitumor activities against HCT-116 and MCF-7 cell lines. These derivatives showed clear in vitro antitumor activities. Compound 5h showed the highest bioactivity (IC50 = 1.51 μM) against HCT-116 cell line. While, compound 6c was the most potent derivative, its IC50 was 7.68 μM against MCF-7 cell line. Compounds 5c, 5g, 5h, 6a and 6c showed PIM-1 inhibitory activity with IC50 of 1.26, 0.95, 0.60, 1.82, 0.67, respectively μM that could be correlated with their cytotoxic effect. Molecular docking study was done to predict the mode of binding of the target compounds inside PIM-1 active site. The molecular dynamic simulation was conducted in order to evaluate stability of binding of the tested compounds.

Discovery, structure-activity relationship study and biological evaluation of 2-thioureidothiophene-3-carboxylates as a novel class of C-X-C chemokine receptor 2 (CXCR2) antagonists

The C-X-C motif ligand 8 and C-X-C chemokine receptor 2 (CXCL8-CXCR2) axis is involved in pathogenesis of various diseases including inflammation and cancers. Various CXCR2 antagonists are under development for several diseases. Our previous high-throughput cell-based assay specific for CXCR2 has identified a pyrimidine-based compound CX797 acting on CXCR2 down-stream signaling. A lead optimization campaign through scaffold-hopping strategy led to a series of 2-thioureidothiophene-3-carboxylates (TUTP) as novel CXCR2 antagonists. Structure-activity relationship study of TUTPs led to the identification of compound 52 that significantly inhibited CXCR2-mediated β-arrestin recruitment signaling (IC50 = 1.1±0.01 μM) with negligible effect on CXCL8-mediated cAMP signaling and calcium flux. Similar to the known CXCR2 antagonist SB265610, compound 52 inhibited CXCL8-CXCR2 induced phosphorylation of ERK1/2. TUTP compounds also inhibited CXCL8-mediated cell migration and showed synergy with doxorubicin in ovarian cancer cells, thereby supporting TUTPs as promising compounds for cancer treatment.

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.