98116-49-5

Upstream product

• 98116-50-8 3-(3-cyanophenyl)-2-(E)-propen-1-ol 
• 24964-64-5 3-Cyanobenzaldehyde 
• 2136-75-6 (triphenylphosphoranylidene)acetaldehyde 
• 3054-95-3 acrylaldehyde diethyl acetal 
• 6952-59-6 3-cyanobromobenzene 

Downstream Products

• 337519-98-9 3-((E)-3-{4-[1-(t-butoxycarbonyl)piperidin-4-yloxy]phenylamino}-1-propenyl)benzonitrile 
• 210963-32-9 3-[(1E)-3-bromo-1-propenyl]benzonitrile 
• 233281-62-4 methyl 5-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]-N-[(E)-3-cyanocinnamyl]anthranilate 
• 771584-87-3 3-((1E)-3-{[4-(4-methyl-1,4-diazepan-1-yl)phenyl]amino}prop-1-en-1-yl)benzonitrile 
• 454437-24-2 3-(3-{4-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]anilino}propyl)benzonitrile 
• 98116-50-8 3-(3-cyanophenyl)-2-(E)-propen-1-ol 
• 405887-25-4 tert-butyl (E)-4-{3-[4-(3-cyanophenyl)-2-hydroxy-3-buten-1-yl]-4-nitrophenoxy}piperidine-1-carboxylate 
• 405887-61-8 C₂₇H₃₀ClN₃O₆ 
• 405887-55-0 C₂₇H₃₀ClN₃O₆ 
• 405887-48-1 C₂₇H₃₀FN₃O₆ 
• 405887-44-7 C₂₇H₃₀FN₃O₆ 
• 406220-41-5 C₂₈H₃₀F₃N₃O₆ 
• 405887-84-5 C₂₈H₃₀F₃N₃O₆ 
• 405887-78-7 C₂₈H₃₃N₃O₆ 

Relevant academic research and scientific papers

Potent Inhibition of Nicotinamide N-Methyltransferase by Alkene-Linked Bisubstrate Mimics Bearing Electron Deficient Aromatics

Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (vitamin B3) to generate 1-methylnicotinamide (MNA). NNMT overexpression has been linked to a variety of diseases, most prominently human cancers, indicating its potential as a therapeutic target. The development of small-molecule NNMT inhibitors has gained interest in recent years, with the most potent inhibitors sharing structural features based on elements of the nicotinamide substrate and the S-adenosyl-l-methionine (SAM) cofactor. We here report the development of new bisubstrate inhibitors that include electron-deficient aromatic groups to mimic the nicotinamide moiety. In addition, a trans-alkene linker was found to be optimal for connecting the substrate and cofactor mimics in these inhibitors. The most potent NNMT inhibitor identified exhibits an IC50 value of 3.7 nM, placing it among the most active NNMT inhibitors reported to date. Complementary analytical techniques, modeling studies, and cell-based assays provide insights into the binding mode, affinity, and selectivity of these inhibitors.

COMPOUNDS, COMPOSITIONS AND METHODS

The present disclosure relates generally to methods and compositions for preventing or arresting cell death and/or inflammation.

Tubulin inhibitor

The invention provides a novel tubulin inhibitor and an application thereof. The novel tubulin inhibitor is a series of substituted heterocyclic skeleton-based compounds with colchicine binding sites in tubulins as targets. The compounds have the following structure as shown in the specification, wherein the formula is as shown in the specification; n independently represents an integer of 0-5 under the condition that n is less than or equal to 5; A represents a monosubstituted or polysubstituted group; and the group is selected from H, C1-C20 acylamino, C1-C20 acyloxy, C1-C20 alkanoyl, C1-C20 alkoxycarbonyl, C1-C20 alkoxy, C1-C20 alkylamino, C1-C20 alkylcarboxy amino, aroyl, arylalkanoyl, carboxyl, cyano, halogen, hydroxyl, nitro and methylthienyl.

Emission wavelength prediction of a full-color-tunable fluorescent core skeleton, 9-aryl-1,2-dihydropyrrolo[3,4-b]indolizin-3-one

In this paper we report on a novel fluorescent core skeleton, 9-aryl-1,2-dihydropyrrolo[3,4-b]indolizin-3-one, which we named Seoul-Fluor, having tunable and predictable photophysical properties. Using a concise and practical one-pot synthetic procedure, a 68-member library of new fluorescent compounds was synthesized with diverse substituents. In Seoul-Fluor, the electronic characteristics of the substituents, as well as their positional changes, have a close correlation with their photophysical properties. The systematic perturbation of electronic densities on the specific positions of Seoul-Fluor, guided with the Hammett constant, allows emission wavelength tunability covering the full color range. On the basis of these observations and a computational analysis, we extracted a simple first-order correlation of photophysical properties with the theoretical calculation and accurately predicted the emission wavelength of Seoul-Fluors through the rational design. In this study, we clearly demonstrate that Seoul-Fluor can provide a powerful gateway for the generation of desired fluorescent probes without the need for a tiresome synthesis and trial-and-error process.

Cinnamylindoline derivatives: Synthesis and factor Xa (FXa) inhibitory activities

A series of cinnamylindoline derivatives were synthesized, and their factor Xa (FXa) inhibitory activities and selectivity over trypsin were evaluated. Among them, some novel derivatives showed potent FXa inhibitory activities and good selectivity over trypsin. Especially, (E)-2-{5-[1-(acetimidoyl)piperidin-4- yloxy]-2-[2-(5-amidino-2-hydroxyphenyl)ethen-1-yl]indolin-1-ylsulfonyl}acetic acid (22f) having 2-hydroxycinnamyl moiety exhibited the most potent FXa inhibitory activity in vitro. Furthermore, 22f also exhibited potent anticoagulant activities in vitro.

BENZAMIDINE DERIVATIVE

Compounds of general formula (1) and pharmacologically acceptable salts thereof: ???[wherein ??????R1 represents a hydrogen atom, a halogen atom, an alkyl group or a hydroxyl group; ??????R2 represents a hydrogen atom or a halogen atom; ??????R3 represents a hydrogen atom, an alkyl group which may be substituted, an aralkyl group, an alkylcarbonyl group which may be substituted, an alkylsulfonyl group which may be substituted or the like; ??????each of R4 and R5 represents a hydrogen atom, a halogen atom, an alkyl group which may be substituted, a carbamoyl group or the like; ??????R6 represents a heterocycle or the like; ??????each of R7 and R8 represents a hydrogen atom, an alkyl group or the like; ??????n represents 0, 1 or 2] ???exhibit excellent activated blood coagulation factor X inhibitory activity and are useful for the prevention or treatment of blood coagulation-related diseases.

BENZAMIDINE DERIVATIVES

Benzamidine derivatives of formula (I) or pharmaceutically acceptable salts thereof exhibit excellent inhibitory activity against factor Xa and are useful for treating or preventing blood coagulation disorders: wherein R 1represents a hydrogen atom, a halogen atom, an alkyl group or a hydroxyl group; R 2represents a hydrogen atom, a halogen atom or an alkyl group, R 3represents a hydrogen atom, an optionally substituted alkyl group, an aralkyl group, an optionally substituted alkanoyl group or an optionally substituted alkylsulfonyl group, R 4and R 5 are the same as or different from each other and each represent a hydrogen atom, a halogen atom, an optionally substituted alkyl group, an alkoxy group, a carboxyl group, an alkoxycarbonyl group or an optionally substituted carbamoyl group, and R 6represents a substituted pyrrolidine group or substituted piperidine group.

The discovery of YM-60828: a potent, selective and orally-bioavailable factor Xa inhibitor.

Since Factor Xa (FXa) is well known to play a central role in thrombosis and hemostasis, inhibition of FXa is an attractive target for antithrombotic strategies. As a part of our investigation of a non-peptide, orally available FXa inhibitor, we found tha

Benzimidazole-Based fXa inhibitors with improved thrombin and trypsin selectivity

Optimization of the benzimidazole-based fXa inhibitors for selectivity versus thrombin and trypsin was achieved by substitution on the benzimidazole ring and replacement of the naphthylamidine group. Substitution of a nitro group at the 4-position on the benzimidazole improves both potency against fXa and selectivity versus thrombin. Alternatively, replacement of the naphthylamidine with either a biphenylamidine or propenylbenzamidine not only improves fXa potency and selectivity versus thrombin, but selectivity versus trypsin as well.