- Xanthenylacetic Acid Derivatives Effectively Target Lysophosphatidic Acid Receptor 6 to Inhibit Hepatocellular Carcinoma Cell Growth
-
Despite the increasing incidence of hepatocellular carcinoma (HCC) worldwide, current pharmacological treatments are still unsatisfactory. We have previously shown that lysophosphatidic acid receptor 6 (LPAR6) supports HCC growth and that 9-xanthenylacetic acid (XAA) acts as an LPAR6 antagonist inhibiting HCC growth without toxicity. Here, we synthesized four novel XAA derivatives, (±)-2-(9H-xanthen-9-yl)propanoic acid (compound 4 – MC9), (±)-2-(9H-xanthen-9-yl)butanoic acid (compound 5 – MC6), (±)-2-(9H-xanthen-9-yl)hexanoic acid (compound 7 – MC11), and (±)-2-(9H-xanthen-9-yl)octanoic acid (compound 8 – MC12, sodium salt) by introducing alkyl groups of increasing length at the acetic α-carbon atom. Two of these compounds were characterized by X-ray powder diffraction and quantum mechanical calculations, while molecular docking simulations suggested their enantioselectivity for LPAR6. Biological data showed anti-HCC activity for all XAA derivatives, with the maximum effect observed for MC11. Our findings support the view that increasing the length of the alkyl group improves the inhibitory action of XAA and that enantioselectivity can be exploited for designing novel and more effective XAA-based LPAR6 antagonists.
- Gnocchi, Davide,Cavalluzzi, Maria M.,Mangiatordi, Giuseppe F.,Rizzi, Rosanna,Tortorella, Cosimo,Spennacchio, Mauro,Lentini, Giovanni,Altomare, Angela,Sabbà, Carlo,Mazzocca, Antonio
-
p. 2121 - 2129
(2021/06/07)
-
- Synthesis of protected α-amino acids: Via decarboxylation amination from malonate derivatives
-
A general and efficient strategy for the synthesis of protected α-amino acids is reported. The method uses malonate derivatives as the starting materials and Cs2CO3 as a base at 60 degrees, giving α-amino acid derivatives in moderate yields by releasing CO2. This methodology shows broad substrate scope (primary and secondary acids), excellent functional group tolerance and high efficiency to give the desired products under mild reaction conditions. It also allows the construction of β and γ-amino acids and other unnatural products.
- Dai, Qipu,Fu, Hui,Hu, Changwen,Li, Peihe,Li, Xiaoying,Wang, Zheng
-
p. 4439 - 4446
(2020/10/20)
-
- Synthesis of specific deuterated derivatives of the long chained stratum corneum lipids [EOS] and [EOP] and characterization using neutron scattering
-
The synthesis of specific deuterated derivatives of the long chained ceramides [EOS] and [EOP] is described. The structural differences with respect to the natural compounds are founded in the substitution of the 2 double bonds containing linoleic acid by a palmitic acid branched with a methyl group in 10-position. The specific deuteration is introduced both in the branched and in the terminal methyl group, which was realized by common methods of successive deuteration of carboxylic groups in 3 steps. These modified fatty acids resp. the corresponding ceramides [EOS] and [EOP] were prepared for neutron scattering investigations. First results of these investigations were presented in this manuscript showing that the deuterated compounds could be detected in the stratum corneum lipid model membranes. The deuterated ceramides [EOS] and [EOP] are valuable tools to investigate the influence of these long chained ceramide species on the nanostructure of stratum corneum lipid model membranes.
- Sonnenberger, Stefan,Eichner, Adina,Schmitt, Thomas,Hau?, Thomas,Lange, Stefan,Langner, Andreas,Neubert, Reinhard H.H.,Dobner, Bodo
-
p. 316 - 330
(2017/06/08)
-
- Reductive bromine atom-transfer reaction
-
Atom-transfer radical (ATR) reactions of alkenes with R-X usually give products having new C-C and C-X bonds at the adjacent carbons. However, when the reaction was carried out under irradiation using a low-pressure Hg lamp, addition/reduction products were obtained in good yield. Hydrogen bromide, formed by H-abstraction of a bromine radical from alkenes, is likely to play a key role in the reductive ATR reaction.
- Sumino, Shuhei,Fusano, Akira,Ryu, Ilhyong
-
supporting information
p. 2826 - 2829
(2013/07/19)
-
- Pyrimidine Non-Classical Cannabinoid Compounds and Related Methods of Use
-
Disclosed are compounds of the formula I: wherein R1, R2, V, W, X, Y and Z can be as defined herein. The compounds can be used in the treatment of disorders mediated by the cannabinoid receptors.
- -
-
Page/Page column 8
(2009/12/05)
-
- Pyridine Non-Classical Cannabinoid Compounds and Related Methods of Use
-
wherein R1, R2, V, W, X, Y and Z can be as defined herein. The compounds can be used in the treatment of disorders mediated by the cannabinoid receptors.
- -
-
Page/Page column 6
(2009/12/05)
-
- Synthesis of 3-alkyl(aryl)thietanes
-
A preparative procedure for the synthesis of thietanes bearing alkyl substituents in the β-position was developed. Using this procedure, 3-substituted thietanes can be obtained in four steps with an ultimate yield of > 50%. 3-R-thietanes (where R = CH3, C4H9, C5H11, C6H13, C6H 5) and the corresponding sulfoxides and sulfones were synthesized and examined. The feasibility of preparation of gem-3,3-substituted thietanes was exemplified by the synthesis of 3,3-dihexylthietane.
- Shevchenko,Volynskii
-
body text
p. 123 - 128
(2010/02/28)
-
- Structure-retention relationship in a series of chiral 1,4-disubstituted piperazine derivatives on carbohydrate chiral stationary phases
-
New racemic 1,4-disubstituted piperazines chemically named ethyl 2-[(4-pyrimidin-2yl-piperazine-1yl)carbonyl]C3-C5-alkanoates 1-7 were synthesized. The compounds were resolved into enantiomers on cellulose tris(4-methylbenzoate) and amylose tris(3,5-dimethylphenylcarbamate) stationary phases using hexane/propan-2-ol mobile phases. The optimum separation conditions for the compounds were obtained on cellulose tris(4-methylbenzoate) with 5% of 2-propanol in hexane. The relationship between structural and chromatographic parameters is discussed.
- Chilmonczyk, Zdzislaw,Sienicki, Lukasz,Lozowicka, Bozena,Lisowska-Kuzmicz, Malgorzata,Jonczyk, Anna,Aboul-Enein, Hassan Y.
-
p. 439 - 443
(2007/10/03)
-
- Solution parallel synthesis of cyclic guanidines
-
An efficient method for the solution phase synthesis of cyclic guanidines is presented. A variety of 2-substituted monoprotected propanediamines react with a set of 5-substituted 2-methylthio-3,4,5,6- tetrahydropyrimidines under Rathke conditions for the construction of a potential library of 81 cyclic guanidines.
- Marmillon, Christelle,Bompart, Jacques,Calas, Michèle,Escale, Roger,Bonnet, Pierre-Antoine
-
p. 1317 - 1328
(2007/10/03)
-
- The synthesis and electro-optic properties of liquid crystalline 2- (2,3-difluorobiphenyl-4'-yl)-1,3-dioxanes
-
Fifty-six novel alkyl and/or alkoxy disubstituted 2-(2,3- difluorobiphenyl-4'-yl)-1,3-dioxanes (DFBPD) were prepared. Smectic C and nematic mesophases were exhibited by most of the alkyl-alkoxy homologues. Conversely, most of the dialkyl compounds exhibited smectic C, smectic A and nematic phases. The birefringence (Δn), dielectric anisotropy (Δε), spontaneous polarisation and response times of two ferroelectric mixtures formulated from the dioxanyl systems were determined. The birefringence results were compared with eight other groups of mixtures where the materials were based on different core systems. The overall electro-optic properties of the DFBPDs were found to be comparable to the best of the eight most commonly used materials in ferroelectric display devices.
- Dong, Chu Chuan,Styring, Peter,Goodby, John W.,Chan, Lawrence K. M.
-
p. 1669 - 1677
(2007/10/03)
-
- Electrochemical Reduction of 1,6-Dihalohexanes at Carbon Cathodes in Dimethylformamide
-
Cyclic voltammograms for the reduction of 1,6-dibromo-, 1,6-diiodo-, 1-bromo-6-chloro-, and 1-chloro-6-iodohexane at glassy carbon electrodes in dimethylformamide containing tetramethylammonium perchlorate exhibit single irreversible waves that correspond to the reductive cleavage of carbon-bromine or carbon-iodine bonds.When large-scale controlled-potential electrolyses of either 1,6-dibromo- or 1,6-diiodohexane are performed at reticulated vitreous carbon, the principal products are n-hexane (30-45percent), 1-hexene (28-34percent), 1,5-hexadiene (6-16percent), and cyclohexane (7percent), with n-dodecane being another significant species obtained from 1,6-diiodohexane.Because a carbon-chlorine bond is not directly reducible, 1-bromo-6-chloro- and 1-chloro-5-iodohexane give rise mainly to 1-chlorohexane (47-64percent), 6-chloro-1-hexene (20-33percent), and 1,12-dichlorododecane (2-25percent).From these product distributions, and with the aid of experiments done in the presence of deuterium-labeled reagents, we conclude that the electrolytic reduction of 1,6-diiodo- and 1-chloro-6-iodohexane involves both radical and carbanion intermediates, whereas only carbanionic pathways are important for electrolyses of 1,6-dibromo- and 1-bromo-6-chlorohexane.
- Mubarak, Mohammad S.,Peters, Dennis G.
-
p. 681 - 685
(2007/10/02)
-
- Synthesis and Liquid Crystal Properties of Dimethylene Linked Compounds Incorporating the Cyclobutane or Spiroheptane Rings
-
The preparation of sixteen dimethylene linked compounds is described heptane ring>, and a comparison is made between the transition temperatures of these compounds and those of the corresponding esters.This comparison once again highlights the fact that the cyclobutane ring should be regarded, in terms of its ability to promote nematic thermal stability, as a "chain stiffener rather than as a ring system.A comparison is also made of the nematic thermal stabilities of the trans-cyclobutane and the spiroheptane systems and of the trans-cyclohexane and the spiroundecane systems.
- Chan, L. K. M.,Gemmell, P. A.,Gray, G. W.,Lacey, D.,Toyne, K. J.
-
p. 229 - 246
(2007/10/02)
-
- Synthesis and liquid crystal properties of compounds incorporating cyclobutane, spiroheptane and dispirodecane rings
-
A number of esters of structure (I) incorporating the cyclobutane, spiroheptane, or dispirodecane rings has been prepared using a diethyl malonate synthesis.Strict comparison of the liquid crystal behaviour amongst the three classes containing a terminal cyano-substituent was not possible because both the cyclobutanes and dispirodecanes are mixtures of cis- and trans-isomers; the spiroheptanes are racemic systems.Using preparative hplc, it was however possible to isolate the pure cis- and trans-isomers of two of the cyano-substituted cyclobutane esters (I; R = alkyl, -X- = --, Y = CN).From the physical data and the results for the corresponding spiroheptane esters, conclusions regarding the effects of these ring systems on liquid crystal behaviour were obtained.The pure cis- and trans-isomers of the cyclobutane ester (I, R = C3H7, -X- = --, Y = CN) have been assessed for the trends in both order parameter and viscosity with temperature; the results support the idea that idea that the trans-cyclobutane ring adopts a more planar conformation at higher temperatures.Keywords: cyclobutane- and related spiro-systems, cis-/trans-isomerism, order parameter, briefringence, viscosity, structure/property relations.
- Chain, L. K. M.,Gemmel, P. A.,Gray, G. W.,Lacey, D.,Toyne, K. J.
-
p. 113 - 140
(2007/10/02)
-
- LIQUID CRYSTAL MATERIALS WITH SULFUR ATOMS INCORPORATED IN THE PRINCIPAL STRUCTURE: 1. NEW LIQUID CRYSTAL COMPOUNDS WITH 1,3-DITHIANE RING.
-
2-(p-Substituted phenyl)-5-alkyl-1,3-dithianes, new liquid crystals, were synthesized by the thioacetalization of the corresponding aldehydes and dithiols. These compounds have characteristic supercooling states, exhibit monotropic liquid crystal phases even in the case of long terminal alkyl substituents. The mesomorphic characteristics of these compounds were different from those of the corresponding 1,3-dioxanes, this must originate in the difference in the molecular width caused by the difference in the atomic volume between sulfur and oxygen.
- Haramoto,Nobe,Kamogawa
-
p. 1966 - 1969
(2007/10/02)
-
- 170. Asymmetric Palladium-Assisted Alkylation of Alkenes
-
Palladium-promoted alkylation of alkenes using chiral sulfoxide-containing carbanions and chiral lithiated oxazolines results in asymmetric induction (AI) ranging from 3-5 percent (1,5 induction), 20-40 percent (1,3 induction) to 44-52 percent (1,4 induction).No general trend allowing predictions of results was found.With 1-hexene, attack at C(1) is almost exclusive but propene gives a mixture of attack at C(1) and C(2).The use of a chiral ligand together with malonate anion also leads to some asymmetric induction (ca. 20 percent).
- Solladie-Cavallo, Arlette,Haesslein, Jean-Luc
-
p. 1760 - 1773
(2007/10/02)
-
- Model compounds for biodegradation studies on hydrocarbon-type dielectric fluids
-
The hydrocarbons 7-methylpentadecane (1, n = 0) and 7-methyl-9-n-hexyl heptadecane (1, n = 1) have been synthesized.These compounds are suitable as model compounds for biodegradation studies on mixtures of oligomers of 1-octene and related compounds which have been proposed as dielectric fluids for the replacement of PCB's.The synthesis confirms the feasibility of isotope labelling for such biodegradation studies.
- Baarschers, Willem Hendrik,Li, Maria Angela
-
p. 1784 - 1787
(2007/10/02)
-
- ASYMMETRIC PALLADIUM-ASSISTED ALKYLATION OF OLEFINS
-
Palladium-promoted alkylation of some alkenes using chiral sulfoxide-containing carbanion as nucleophiles or using optically active N,N-dimethyl-α-phenylethylamine as ligand together with a non-chiral stabilized carbanion as nucleophile results in an asymmetric induction of 10-40percent.
- Solladie-Cavallo, A.,Haesslein, J. L.,Baeckvall, Jan-E.
-
p. 939 - 942
(2007/10/02)
-
- Reactions of N-Substituted Pyridinium Cations with Carbanions: 5,6,8,9-Tetrahydro-7-phenylbisbenzoacridine, a Superior Leaving Group
-
N-Substituents are transferred from pyridinium cations to malonate, cyanoacetate , and acetoacetate carbanions: for alkyl substituents the pentacyclic derivatives (4) attain the required activity.
- Katritzky, Alan R.,Thind, Sukhpal S.
-
p. 661 - 663
(2007/10/02)
-