161876-64-8

Upstream product

• 620-17-7 3-ethylphenol 
• 7647-01-0 hydrogenchloride 
• 7446-70-0 aluminium trichloride 
• 71-43-2 benzene 
• 67-66-3 chloroform 
• 4885-02-3 Dichloromethyl methyl ether 
• 4748-78-1 4-ethylbenzylaldehyde 
• 50-00-0 formaldehyd 

Downstream Products

• 948553-28-4 4-ethyl-3-methoxy-benzoic acid 
• 215660-85-8 4-ethyl-2-[2-(1,1-dimethylethyldimethylsilyloxy)-ethoxy]benzaldehyde 
• 1160694-79-0 C₁₆H₁₆O₂ 
• 221349-19-5 6-ethyl-9-(2-hydroxy-4,4-dimethyl-6-oxocyclohexyl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one 
• 1138027-45-8 4-ethylsalicylamine 
• 1206675-06-0 C₉H₁₁NO₂ 

Relevant academic research and scientific papers

Discovery of a 1-Methyl-3,4-dihydronaphthalene-Based Sphingosine-1-Phosphate (S1P) Receptor Agonist Ceralifimod (ONO-4641). A S1P1 and S1P5 Selective Agonist for the Treatment of Autoimmune Diseases

The discovery of 1-({6-[(2-methoxy-4-propylbenzyl)oxy]-1-methyl-3,4-dihydronaphthalen-2-yl}methyl)azetidine-3-carboxylic acid 13n (ceralifimod, ONO-4641), a sphingosine-1-phosphate (S1P) receptor agonist selective for S1P1 and S1P5, is described. While it has been revealed that the modulation of the S1P1 receptor is an effective way to treat autoimmune diseases such as relapsing-remitting multiple sclerosis (RRMS), it was also reported that activation of the S1P3 receptor is implicated in some undesirable effects. We carried out a structure-activity relationship (SAR) study of hit compound 6 with an amino acid moiety in the hydrophilic head region. Following identification of a lead compound with a dihydronaphthalene central core by inducing conformational constraint, optimization of the lipophilic tail region led to the discovery of 13n as a clinical candidate that exhibited >30 000-fold selectivity for S1P1 over S1P3 and was potent in a peripheral lymphocyte lowering (PLL) test in mice (ED50 = 0.029 mg/kg, 24 h after oral dosing).

Efficient synthesis of chiral benzofuryl β-amino alcohols via a catalytic asymmetric Henry reaction

Chiral β-amino alcohol ligands were found effective for the copper(ii)-catalyzed asymmetric Henry reaction of benzofuran-2-carbaldehydes with nitromethane, which led to the formation of (S)-enriched benzofuryl β-nitro alcohols with satisfactory enantioselectivities (up to 98% ee). Using this catalytic protocol, bioactive (S)-benzofuryl β-amino alcohols could be conveniently prepared in short steps.

Aldehyde-Assisted Ruthenium(II)-Catalyzed C-H Oxygenations

Versatile ruthenium(II) complexes allow for site-selective C-H oxygenations with weakly-coordinating aldehydes. The challenging C-H functionalizations proceed with high chemoselectivity by rate-determining C-H metalation. The new method features an ample substrate scope, which sets the stage for the step-economical preparation of various bioactive heterocycles.

Development of chemical probes: Toward the mode of action of a methylene-linked di(aryl acetate) E1

Analogues of the novel inhibitor of the PI3-K/PKB pathway, 2-[5-(2-chloroethyl)-2-acetoxy-benzyl]-4-(2-chloroethyl)-phenyl acetate (E1), have been prepared and preliminary SAR performed. This established that at least one of the chloroethyl para-substituents could be removed or modified and the ability to inhibit PKB/Akt activation retained. Synthetic methodologies were then developed to methylene-linked aryl acetates for use as molecular probes to identify the target of compound E1.

Characterization of scavengers of γ-ketoaldehydes that do not inhibit prostaglandin biosynthesis

Expression of cyclooxygenase-2 (COX-2) is associated with the development of many pathologic conditions. The product of COX-2, prostaglandin H2 (PGH2), can spontaneously rearrange to form reactive γ-ketoaldehydes called levuglandins (LGs). This γ-ketoaldehyde structure confers a high degree of reactivity on the LGs, which rapidly form covalent adducts with primary amines of protein residues. Formation of LG adducts of proteins has been demonstrated in pathologic conditions (e.g., increased levels in the hippocampus in Alzheimer's disease) and during physiologic function (platelet activation). On the basis of knowledge that lipid modification of proteins is known to cause their translocation and to alter their function, we hypothesize that modification of proteins by LG could have functional consequences. Testing this hypothesis requires an experimental approach that discriminates between the effects of protein modification by LG and the effects of cyclooxygenase-derived prostanoids acting through their G-protein coupled receptors. To achieve this goal, we have synthesized and evaluated a series of scavengers that react with LG with a potency more than 2 orders of magnitude greater than that with the ε-amine of lysine. A subset of these scavengers are shown to block the formation of LG adducts of proteins in cells without inhibiting the catalytic activity of the cyclooxygenases. Ten of these selective scavengers did not produce cytotoxicity. These results demonstrate that small molecules can scavenge LGs in cells without interfering with the formation of prostaglandins. They also provide a working hypothesis for the development of pharmacologic agents that could be used in experimental animals in vivo to assess the pathophysiological contribution of levuglandins in diseases associated with cyclooxygenase up-regulation.

INHIBITORS OF HEPATITIS C VIRUS RNA-DEPENDENT RNA POLYMERASE, AND COMPOSITIONS AND TREATMENTS USING THE SAME

The present invention provides compounds of formula (4), and their pharmaceutically acceptable salts and solvates, which are useful as inhibitors of the Hepatitis C virus (HCV) polymerase enzyme and are also useful for the treatment of HCV infections in HCV-infected mammals. The present invention also provides pharmaceutical compositions comprising compounds of formula (4), their pharmaceutically acceptable salts and solvates. Furthermore, the present invention provides intermediate compounds and methods useful in the preparation of compounds of formula (4).

The synthesis of 2-hydroxymethyl derivatives of phenols

2-Hydroxymethylphenols have been prepared in good yield by reduction with sodium borohydride of the precursor aldehydes, obtained regiospecifically from reaction of phenols with paraformaldehyde in toluene containing stannic chloride and tri-n-butylamine. By contrast, reaction of phenols with either paraformaldehyde under anhydrous conditions or with aqueous formaldehyde results in formation of both the hydroxymethyl and the bishydroxymethyl derivatives. Cyclic acetals of the precursor aldehydes are readily accessible.

Non-metallocene compounds, method for the production thereof and use of the same for the polymerisation of olefins

The invention relates to a method for producing special transition metal compounds, to novel transition metal compounds and to the use of the same for the polymerisation of olefins.

Herbicidal phenylmethoxphenyl heterocycles

Novel herbicidal compounds, compositions containing them, and methods for their use in controling weeds are disclosed. The novel herbicidal compounds are optionally substituted phenylmethoxy or phenylmethylthio heterocycles of the formula: STR1 in which Q is selected from: STR2 R=halogen; R1 =lower alkyl, lower alkoxy, lower haloalkyl, lower haloalkoxy, lower alkylthio, lower sulfonyl, or lower alkylsulfinyl; R2 =lower alkyl, or lower haloalkyl; X=H, halogen, or lower alkyl; W=O or S; Z, Z1, Z2 are independently selected from H, halogen, straight or branched chain lower alkyl, lower alkoxy, is lower haloalkoxy, cyano, lower cyanoalkyloxy, or aryl; or Z and Z1 are adjacent to each other on the benzene ring, and taken together are --(CH2)4 --; or Z2 is OA in the 2-, 3-, or 4-position of the phenyl ring; A is a derivative of an alkanoate bonded to the phenoxy oxygen at the alpha carbon; R3 is H or lower alkyl; R4 =OH or an agriculturally acceptable salt thereof, straight or branched chain lower alkoxy, lower haloalkoxy, alkoxyalkoxy, alkoxyalkoxyalkoxy, amino, lower alkylamino, lower alkylsulfonylamino, or lower (alkyl)(alkylsulfonyl)amino; and R5 =halogen or lower alkyl ester.