539855-79-3

Upstream product

• 16642-92-5 4-(trifluoromethyl)cinnamic acid 
• 53473-36-2 3-(4-trifluoromethylphenyl)propionic acid 

Downstream Products

• 808170-34-5 N-(2-benzoyl-4-nitrophenyl)-3-(4-trifluoromethylphenyl)propionic acid amide 
• 808169-95-1 N-(4-amino-2-benzoylphenyl)-3-(4-trifluoromethylphenyl)propionic acid amide 
• 1056445-50-1 N-methoxy-N-methyl-3-(4-trifluoromethylphenyl)propanamide 
• 1056445-32-9 1-(3-Trifluoromethoxy-phenyl)-3-(4-trifluoromethyl-phenyl)-propan-1-one 
• 1174936-23-2 C₂₂H₂₃F₃N₄O 
• 1174936-27-6 C₂₂H₂₃F₃N₄O 
• 1229604-25-4 tert-butyl 5-[4-(trifluoromethyl)phenyl]penta-2,3-dienoate 
• 1144035-06-2 6-(3-{4-[3-(4-trifluoromethylphenyl)propionyl]piperazin-1-yl}-propionyl)-3H-benzoxazol-2-one 
• 1248730-72-4 C₂₄H₃₄F₃N₃O₃ 
• 1314227-72-9 1-[2-(2-acetamidoethyl)-4,5-dimethoxyphenyl]-3-(4-trimethylphenyl)-1-propanone 
• 1169801-38-0 6,7-dimethoxy-1-[2-(4-trifluoromethyl-phenyl)-ethyl]-3,4-dihydro-isoquinoline hydrochloride 
• 1314227-83-2 6,7-dimethoxy-1-[2-(4-trifluormethylphenyl)ethyl]-3,4-dihydroisoquinoline 
• 1314227-74-1 1-[2-(2-propionamidoethyl)-4,5-dimethoxyphenyl]-3-(4-trimethylphenyl)-1-propanone 
• 1401223-47-9 N-isopropyl-N-((3-phenyl-1,2,4-oxadiazol-5-yl)methyl)-3-(4-(trifluoromethyl)phenyl)propanamide 

Relevant academic research and scientific papers

Copper-Catalyzed Oxidative Benzylic C(sp3)?H Cyclization for the Synthesis of β-Lactams

β-Lactams are important structural motifs because of their ubiquity in natural products and pharmaceuticals. We report herein a Cu-catalyzed intramolecular oxidative C(sp3)?H amidation for the synthesis of β-lactams using tBuOOtBu. This method

Cyclohexyl-Fused, Spirobiindane-Derived, Phosphine-Catalyzed Synthesis of Tricyclic ?3-Lactams and Kinetic Resolution of ?3-Substituted Allenoates

A C2-symmetric chiral phosphine catalyst, NUSIOC-Phos, which can be easily derived from cyclohexyl-fused spirobiindane, was introduced. A highly enantioselective domino process involving pyrrolidine-2,3-diones and γ-substituted allenoates catalyzed by NUSIOC-Phos has been disclosed. Diastereospecific tricyclic γ-lactams containing five contiguous stereogenic centers were obtained in high yields and with nearly perfect enantioselectivities. A kinetic resolution process of racemic γ-substituted allenoates was developed for the generation of optically enriched chiral allenoates.

Direct C-C Bond Formation from Alkanes Using Ni-Photoredox Catalysis

A method for direct cross coupling between unactivated C(sp3)-H bonds and chloroformates has been accomplished via nickel and photoredox catalysis. A diverse range of feedstock chemicals, such as (a)cyclic alkanes and toluenes, along with late-stage intermediates, undergo intermolecular C-C bond formation to afford esters under mild conditions using only 3 equiv of the C-H partner. Site selectivity is predictable according to bond strength and polarity trends that are consistent with the intermediacy of a chlorine radical as the hydrogen atom-abstracting species.

Rapid chemoenzymatic route to glutamate transporter inhibitor l-TFB-TBOA and related amino acids

The complex amino acid (l-threo)-3-[3-[4-(trifluoromethyl)benzoylamino]benzyloxy]aspartate (l-TFB-TBOA) and its derivatives are privileged compounds for studying the roles of excitatory amino acid transporters (EAATs) in regulation of glutamatergic neurotransmission, animal behavior, and in the pathogenesis of neurological diseases. The wide-spread use of l-TFB-TBOA stems from its high potency of EAAT inhibition and the lack of off-target binding to glutamate receptors. However, one of the main challenges in the evaluation of l-TFB-TBOA and its derivatives is the laborious synthesis of these compounds in stereoisomerically pure form. Here, we report an efficient and step-economic chemoenzymatic route that gives access to enantio- and diastereopure l-TFB-TBOA and its derivatives at multigram scale.

Ligand-Assisted Palladium(II)/(IV) Oxidation for sp3C H Fluorination

The direct functionalization of inert sp3C H bonds is limited to a few bond types. Although the activation of sp3C H bonds can be accomplished under mild conditions using palladium catalysts, the subsequent functionalization is not trivial due to the high energy required to convert palladium(II) to palladium(IV). We have systematically studied the palladium oxidation using computation-guided experiments for reactions involving strong chelation control. We find that a mild external ligand could significantly accelerate the oxidation of palladium(II) to palladium(IV) for strong bidentate directing groups. The acceleration is believed to be a result of ligand stabilization of both the palladium(II) and palladium(IV) intermediates. (Figure presented.) .

Autotaxin inhibitors

The present invention relates to novel compounds that are autotaxin inhibitors, processes for their preparation, pharmaceutical compositions and medicaments containing them and to their use in diseases and disorders mediated by autotaxin.

Oxadiazole-isopropylamides as potent and noncovalent proteasome inhibitors

Screening of the 50 000 ChemBridge compound library led to the identification of the oxadiazole-isopropylamide 1 (PI-1833) which inhibited chymotrypsin-like (CT-L) activity (IC50 = 0.60 μM) with little effects on the other two major proteasome proteolytic activities, trypsin-like (T-L) and postglutamyl-peptide-hydrolysis-like (PGPH-L). LC-MS/MS and dialysis show that 1 is a noncovalent and rapidly reversible CT-L inhibitor. Focused library synthesis provided 11ad (PI-1840) with CT-L activity (IC50 = 27 nM). Detailed SAR studies indicate that the amide moiety and the two phenyl rings are sensitive toward modifications. Hydrophobic residues, such as propyl or butyl in the para position (not ortho or meta) of the A-ring and a m-pyridyl group as B-ring, significantly improve activity. Compound 11ad (IC50 = 0.37 μM) is more potent than 1 (IC50 = 3.5 μM) at inhibiting CT-L activity in intact MDA-MB-468 human breast cancer cells and inhibiting their survival. The activity of 11ad warrants further preclinical investigation of this class as noncovalent proteasome inhibitors.

Palladium-catalyzed reduction of acid chlorides to aldehydes with hydrosilanes

An efficient synthesis of aldehydes from acid chlorides with hydrosilanes as a reducing agent in the presence of a palladium catalyst has been achieved. A simple mixture of commercially available Pd(dba)2 and Mes 3P as a catalyst realized the reduction of various acid chlorides including aliphatic acid chlorides and a, P-unsaturated acid chlorides to the corresponding aldehydes in good to high yields under mild reaction conditions. Georg Thieme Verlag Stuttgart ? New York.

PROTEASOME CHYMOTRYPSIN-LIKE INHIBITION USING PI-1833 ANALOGS

Focused library synthesis and medicinal chemistry on an oxadiazole- isopropylamide core proteasome inhibitor provided the lead compound that strongly inhibits CT-L activity. Structure activity relationship studies indicate the amide moiety and two phenyl rings are sensitive toward synthetic modifications. Only para-substitution in the A-ring was important to maintain potent CT-L inhibitory activity. Hydrophobic residues in the A-ring?s para-position and meta-pyridyl group at the B- ring significantly improved inhibition. The meta-pyridyl moiety improved cell permeability. The length of the aliphatic chain at the para position of the A-ring is critical with propyl yielding the most potent inhibitor, whereas shorter (i.e. ethyl, methyl or hydrogen) or longer (i.e. butyl, propyl and hexyl) chains demonstrating progressively less potency. Introduction of a stereogenic center next to the ether moiety (i.e. substitution of one of the hydrogens by methyl) demonstrated chiral discrimination in proteasome CT-L activity inhibition (the S-enantiomer was 35-40 fold more potent than the R-enantiomer)

PIPERIDINE AND PIPERAZINE DERIVATIVES AS AUTOTAXIN INHIBITORS

The present invention relates to piperidine and pyrazine derivatives according to formulae (Ia), (Ib) and (II) as autotaxin inhibitors and the use of such compounds for the treatment and/or prophylaxis of physiological and/or pathophysiological conditions, which are caused, mediated and/or propagated by increased lysophosphatic acid levels and/or the activation of autotaxin, in particular of different cancers.