184969-49-1

Basic information

• Product Name: 3,5-BIS(TRIFLUORO-METHYL)CINNAMIC ETHYL ESTER
• Synonyms: 3,5-BIS(TRIFLUOROMETHYL)CINNAMIC ACID ETHYL ESTER;3,5-BIS(TRIFLUORO-METHYL)CINNAMIC ETHYL ESTER;ETHYL 3,5-BIS(TRIFLUOROMETHYL)CINNAMATE;Bis(trifluoro-methyl)cinnamic ethyl ester
• CAS NO: 184969-49-1
• Molecular Formula: C₁₃H₁₀F₆O₂
• Molecular Weight: 312.21
• Mol File: 184969-49-1.mol

Chemical Properties

• Boiling Point: 276.2°C at 760 mmHg
• Flash Point: 83.2°C
• Appearance: /
• Density: 1.334g/cm³
• Vapor Pressure: 0.00486mmHg at 25°C
• Refractive Index: 1.452
• CAS DataBase Reference: 3,5-BIS(TRIFLUORO-METHYL)CINNAMIC ETHYL ESTER(CAS DataBase Reference)
• NIST Chemistry Reference: 3,5-BIS(TRIFLUORO-METHYL)CINNAMIC ETHYL ESTER(184969-49-1)
• EPA Substance Registry System: 3,5-BIS(TRIFLUORO-METHYL)CINNAMIC ETHYL ESTER(184969-49-1)

Safety Data

• Hazardous Substances Data: 184969-49-1(Hazardous Substances Data)

Usage

InChI:InChI=1/C13H10F6O2/c1-2-21-11(20)4-3-8-5-9(12(14,15)16)7-10(6-8)13(17,18)19/h3-7H,2H2,1H3/b4-3+

Upstream product

• 328-70-1 3,6-bis(trifluoromethyl)bromobenzene 
• 140-88-5 ethyl acrylate 
• 867-13-0 diethoxyphosphoryl-acetic acid ethyl ester 
• 401-95-6 3,5-Bis(trifluoromethyl)benzaldehyde 

Downstream Products

• 1147334-65-3 C₁₁H₈F₆O 
• 1340475-16-2 (Z)-3-[3,5-bis(trifluoromethyl)phenyl]acrylic acid 

Relevant articles and documents

Assessment of Tractable Cysteines for Covalent Targeting by Screening Covalent Fragments

Targeted covalent inhibition and the use of irreversible chemical probes are important strategies in chemical biology and drug discovery. To date, the availability and reactivity of cysteine residues amenable for covalent targeting have been evaluated by proteomic and computational tools. Herein, we present a toolbox of fragments containing a 3,5-bis(trifluoromethyl)phenyl core that was equipped with chemically diverse electrophilic warheads showing a range of reactivities. We characterized the library members for their reactivity, aqueous stability and specificity for nucleophilic amino acids. By screening this library against a set of enzymes amenable for covalent inhibition, we showed that this approach experimentally characterized the accessibility and reactivity of targeted cysteines. Interesting covalent fragment hits were obtained for all investigated cysteine-containing enzymes.

An electrophilic warhead library for mapping the reactivity and accessibility of tractable cysteines in protein kinases

Targeted covalent inhibitors represent a viable strategy to block protein kinases involved in different disease pathologies. Although a number of computational protocols have been published for identifying druggable cysteines, experimental approaches are limited for mapping the reactivity and accessibility of these residues. Here, we present a ligand based approach using a toolbox of fragment-sized molecules with identical scaffold but equipped with diverse covalent warheads. Our library represents a unique opportunity for the efficient integration of warhead-optimization and target-validation into the covalent drug development process. Screening this probe kit against multiple kinases could experimentally characterize the accessibility and reactivity of the targeted cysteines and helped to identify suitable warheads for designed covalent inhibitors. The usefulness of this approach has been confirmed retrospectively on Janus kinase 3 (JAK3). Furthermore, representing a prospective validation, we identified Maternal embryonic leucine zipper kinase (MELK), as a tractable covalent target. Covalently labelling and biochemical inhibition of MELK would suggest an alternative covalent strategy for MELK inhibitor programs.

Improved flavodoxin inhibitors with potential therapeutic effects against Helicobacter pylori infection

Helicobacter pylori (Hp) infection affects one-half of the human population and produces a variety of diseases from peptic ulcer to cancer. Current eradication therapies achieve modest success rates (around 70%), resistance to the antibiotics of choice is on the rise, and vaccination has not proved to be successful yet. Using an essential Hp protein, flavodoxin, as target, we identified three low-molecular-weight flavodoxin inhibitors with bactericidal anti-Hp properties. To improve their therapeutic indexes, we have now identified and tested 123 related compounds. We have first tested similar compounds available. Then we have designed, synthesized, and tested novel variants for affinity to flavodoxin, MIC for Hp, cytotoxicity, and bactericidal effect. Some are novel bactericidal inhibitors with therapeutic indexes of 9, 38 and 12, significantly higher than those of their corresponding leads. Developing novel Hp-specific antibiotics will help fighting Hp resistance and may have the advantage of not generally perturbing the bacterial flora.