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Upstream product

• 402-45-9 4-hydroxybenzotrifluoride 
• 32315-10-9 bis(trichloromethyl) carbonate 
• 75-44-5 phosgene 

Downstream Products

• 1002100-95-9 C₁₈H₁₅F₃N₂O₃ 
• 1266378-19-1 cinnamyl (4-(trifluoromethyl)phenyl) carbonate 
• 14733-68-7 5-(trifluoromethyl)-3H-1,3-benzoxazol-2-one 

Relevant academic research and scientific papers

Novel artemisinin derivatives with potent anticancer activities and the anti-colorectal cancer effect by the mitochondria-mediated pathway

Many artemisinin derivatives have good inhibitory effects on malignant tumors. In this work, a novel series of artemisinin derivatives containing piperazine and fluorine groups were designed and synthesized and their structures were confirmed by 1H NMR, 13C NMR and HRMS technologies. The in vitro cytotoxicity against various cancer cell lines was evaluated. Among the derivatives, compound 12h was found to exhibit not only the best activity against HCT-116 cells (IC50 = 0.12 ± 0.05 μM), but also low toxicity against normal cell line L02 (IC50 = 12.46 ± 0.10 μM). The mechanisms study revealed that compound 12h caused the cell cycle arrest in G1 phase, induced apoptosis in a concentration-dependent manner, significantly reduced mitochondrial membrane potential, increased intracellular ROS and Ca2+ levels, up-regulated the expression of Bax, cleaved caspase-9, cleaved caspase-3, and down-regulated the expression of Bcl-2 protein. A series of analyses confirmed that 12h can inhibit HCT-116 cells migration and induce apoptosis by a mechanism of the mitochondria-mediated pathway in the HCT-116 cell line. The present work indicates that compound 12h may merit further investigation as a potential therapeutic agent for colorectal cancer.

Asymmetric o-to-c aryloxycarbonyl migration of indolyl carbonates using single-handed dynamic helical polyquinoxalines bearing 4-aminopyridyl groups as chiral nucleophilic catalysts

Use of single-handed dynamic helical macromolecules as nucleophilic catalysts in asymmetric Steglich-type O-to-C aryloxycarbonyl rearrangement of 3-substituted indol-2-yl aryl carbonates is demonstrated. Among several single-handed poly-(quinoxaline-2,3-diyl) copolymers (PQXap) bearing achiral 4-aminopyridin-3-yl groups at the 5-position of the quinoxaline rings, PQXmdpp and PQXapy, containing N-methylpyrrolidine-fused pyridin-3-yl and 4-(1-azetidinyl)pyridin-3-yl groups, respectively, showed higher enantioselectivity and catalytic activity than PQXdmap, bearing 4-dimethylamino-pyridine-3-yl groups. Substrates bearing p-(trifluoromethyl)phenyloxycarbonyl groups on both the nitrogen and oxygen atoms showed high reactivity, giving oxindoles with a quaternary stereogenic carbon center at their 3-positions in up to 97:3 enantiomeric ratio in THF. The macromolecular catalysts underwent inversion of their helix sense by solvent effect, allowing the same catalyst to give the opposite enantiomer in a mixture of methyl t-butyl ether and 1,1,2-trichloroethane (3:1). The macromolecular catalysts could be easily recovered by adding acetonitrile to the reaction mixture and were reused four times without reduction in enantioselectivity.

Versatile Cp*Co(III)(LX) Catalyst System for Selective Intramolecular C-H Amidation Reactions

Herein, we report the development of a tailored cobalt catalyst system of Cp*Co(III)(LX) toward intramolecular C-H nitrene insertion of azidoformates to afford cyclic carbamates. The cobalt complexes were easy to prepare and bench-stable, thus offering a convenient reaction protocol. The catalytic reactivity was significantly improved by the electronic tuning of the bidentate LX ligands, and the observed regioselectivity was rationalized by the conformational analysis and DFT calculations of the transition states. The superior performance of the newly developed cobalt catalyst system could be broadly applied to both C(sp2)-H and C(sp3)-H carbamation reactions under mild conditions.

Artemisinin derivatives containing piperazine ring and fluorine element, and preparation method and application of artemisinin derivatives

The invention provides artemisinin derivatives containing a piperazine ring and a fluorine element, and a preparation method and an application of the artemisinin derivatives. The structures of the compounds are verified through 1H NMR, 13C NMR and HRMS technologies, and in vitro cytotoxicity to MCF-7, A549, PC12, SH-SY5Y, U87MG, U118MG and HCT116 cancer cell lines is evaluated through MTT analysis. Results show that the artemisinin derivatives provided by the invention can more effectively inhibit the growth of cancer cell lines than artemisinin, and has potential application value in preparation of antitumor drugs.

Evaluation of the analgesic effect of 4-anilidopiperidine scaffold containing ureas and carbamates

Fentanyl is a powerful opiate analgesic typically used for the treatment of severe and chronic pain, but its prescription is strongly limited by the well-documented side-effects. Different approaches have been applied to develop strong analgesic drugs with reduced pharmacologic side-effects. One of the most promising is the design of multitarget drugs. In this paper we report the synthesis, characterization and biological evaluation of twelve new 4-anilidopiperidine (fentanyl analogues). In vivo hot-Plate test, shows a moderate antinociceptive activity for compounds OMDM585 and OMDM586, despite the weak binding affinity on both μ and δ-opioid receptors. A strong inverse agonist activity in the GTP-binding assay was revealed suggesting the involvement of alternative systems in the brain. Fatty acid amide hydrolase inhibition was evaluated, together with binding assays of cannabinoid receptors. We can conclude that compounds OMDM585 and 586 are capable to elicit antinociception due to their multitarget activity on different systems involved in pain modulation.

Regio- and Enantioselective Allylation of Phenols via Decarboxylative Allylic Etherification of Allyl Aryl Carbonates Catalyzed by (Cyclopentadienyl)ruthenium(II) Complexes and Pyridine-Hydrazone Ligands

(Cyclopentadienyl)tris(acetonitrile)ruthenium hexafluorophosphate [CpRu(CH3CN)3][PF6] in combination with pyridine-hydrazone ligands efficiently catalyzes the asymmetric decarboxylative allylic rearrangement of allyl aryl carbonates. Formation of C-O bonds with high regio- and enantioselectivity ratios (up to 95:5 and 98% ee) is obtained. Good stereocontrol of the pseudotetrahedral geometry of the CpRu moiety is achieved by the hydrazone ligand and its "electron-poor" nature is evidenced through the epimerization of the hexacoordinated TRISPHAT-N anion.

Modulation of thermo-transient receptor potential (thermo-TRP) channels by thymol-based compounds

A series of thirty-three thymol, p-cymene-3-carboxylic acid, and 3-amino-p-cymene derivatives was synthesized and tested on TRPA1, TRPM8, and TRPV3 channels. Most of them acted as strong modulators of TRPA1, TRPM8, and TRPV3 channels with EC50 and/or IC50 values distinctly lower than those of thymol and related monoterpenoids. Some of the compounds examined, that is, 3c, 4e, f, 6b, and 8b exhibited an appreciable subtype-selectivity.

(Cyclopentadienyl)ruthenium-catalyzed regio- and enantioselective decarboxylative allylic etherification of allyl aryl and alkyl carbonates

(Cyclopentadienyl)tris(acetonitrile)ruthenium hexafluorophosphate {[CpRu(NCMe)3][PF6] or (cyclopentadienyl) (I·6-naphthalene)ruthenium hexafluorophosphate {[CpRu(I·6-naphthalene)][PF6]} in combination with a pyridine oxazoline ligand efficiently catalyze the decarboxylative allylic rearrangement of allyl aryl carbonates. Good levels of regio- and enantioselectivity are obtained. Starting from enantioenriched secondary carbonates, the reaction is stereospecific and the corresponding allylic ethers are obtained with net retention of configuration. An intermolecular version of this transformation was also developed using allyl alkyl carbonates as substrates. Conditions were found to obtain the corresponding products with similar selectivity as in the intramolecular process. Through the use of a hemi-labile hexacoordinated phosphate counterion, a zwitterionic air- and moisture-stable chiral ruthenium complex was synthesized and used in the enantioselective etherification reactions. This highly lipophilic metal complex can be recovered and efficiently reused in subsequent catalysis runs. Copyright

Synthesis and biological evaluation of piperazinyl carbamates and ureas as fatty acid amide hydrolase (FAAH) and transient receptor potential (TRP) channel dual ligands

The evaluation of a series of piperazinyl carbamates and ureas, designed on the basis of previously reported TRPV1 antagonists and FAAH inhibitors, led to the identification of some 'dual-action' compounds targeting both FAAH and TRPV1 or TRPA1 receptors.

New N-arachidonoylserotonin analogues with potential "dual" mechanism of action against pain

N-Arachidonoylserotonin (AA-5-HT, 1a) is an inhibitor of fatty acid amide hydrolase (FAAH) that acts also as an antagonist of transient receptor potential vanilloid-type 1 (TRPV1) channels and is analgesic in rodents. We modified the chemical structure of 1a with the aim of developing "hybrid" FAAH/TRPV1 blockers more potent than the parent compound or obtaining analogues with single activity at either of the two targets to study the mechanism of the analgesic action of 1a. Thirty-eight AA-5-HT analogues, containing a serotonin "head" bound to a variety of lipophilic moieties via amide, urea, or carbamate functionalities, were synthesized. Unlike 1a, most of the new compounds possessed activity at only one of the two considered targets. The amides 1b and 1c of α- and γ-linolenic acid, however, showed "hybrid" activity similar to 1a. The carbamate 3f (OMDM106), although unable to antagonize TRPV1 receptors, was the most potent FAAH inhibitor in this study (IC50 = 0.5 μM). Compounds 3f and 1m (OMDM129), which exhibited activity at only FAAH or TRPV1, respectively, were 10-fold less potent than 1a at preventing formalin-induced hyperalgesia in mice.