501-89-3Relevant articles and documents
Substituent contributions to the transport of substituted p-toluic acids across lipid bilayer membranes
Xiang,Anderson
, p. 1511 - 1518 (1994)
The fluxes of p-toluic acid and seven α-methylene-substituted analogs have been determined as a function of pH across planar egg lecithin/decane bilayers to construct a set of well-isolated polar functional group contributions to the free energy of transfer from water to the bilayer transport barrier domain. Nonlinear regression analyses of flux-pH profiles using a model which accounts for unstirred layer effects yielded membrane permeability coefficients (P(RX)) that varied from 1.1 cm/s for p-toluic acid to 4.1 x 10-5 cm/s for the α-carbamoyl-p-toluic acid. Bulk organic solvent/water partition coefficients (K(RX)) were obtained for the same set of permeants using four solvent systems to identify a bulk solvent which closely resembles the chemical nature of the bilayer barrier microenvironment for these permeants. The slopes of plots of log P(RX) vs log K(RX) were 0.85, 0.91, 0.99, and 2.4, respectively, for hexadecane/water, hexadecane/water, 1,9-decadiene/water, and octanol/water with the best model solvent being that which yielded a slope closest to unity. A significant deviation in the slope from 1, as observed in the correlation with octanol/water partition coefficients, reveals that this relatively polar, hydrogen-bonding solvent is a poor model solvent for describing the barrier microenvironment for these permeants. Thus, the polar interfacial regions occupied by phospholipid head groups are not the barrier domain for the transport of the series examined in this study. The incremental group contributions to the free energy of transfer to the barrier domain (cal/mol) for the functional groups, Cl, OCH3, CN, OH, COOH, and CONH2, were found to be 325, 687, 2170, 3860, 5170, and 6060, respectively. Except for Cl, these group contributions are generally 500-1200 cal/mol smaller than those for transfer between water and hexadecane, resembling most closely the values obtained for transfer from water to 1,9-decadiene.
Pd(OH)2/C, a Practical and Efficient Catalyst for the Carboxylation of Benzylic Bromides with Carbon Monoxide
Wakuluk-Machado, Anne-Marie,Dewez, Damien F.,Baguia, Hajar,Imbratta, Miguel,Echeverria, Pierre-Georges,Evano, Gwilherm
, p. 713 - 723 (2020/02/04)
A simple, efficient, cheap, and broadly applicable system for the carboxylation of benzylic bromides with carbon monoxide and water is reported. Upon simple reaction with only 2.5 wt % of Pearlman's catalyst and 10 mol % of tetrabutylammonium bromide in tetrahydrofuran at 110 °C for 4 h, a range of benzylic bromides can be smoothly converted to the corresponding arylacetic acids in good to excellent yields after simple extraction and acid-base wash. The reaction was found to be broadly applicable, scalable, and could be successfully extended to the use of ex situ-generated carbon monoxide and applied to the synthesis of the nonsteroidal anti-inflammatory drug diclofenac.
Spiroindoline-Capped Selective HDAC6 Inhibitors: Design, Synthesis, Structural Analysis, and Biological Evaluation
Saraswati, A. Prasanth,Relitti, Nicola,Brindisi, Margherita,Osko, Jeremy D.,Chemi, Giulia,Federico, Stefano,Grillo, Alessandro,Brogi, Simone,McCabe, Niamh H.,Turkington, Richard C.,Ibrahim, Ola,O'Sullivan, Jeffrey,Lamponi, Stefania,Ghanim, Magda,Kelly, Vincent P.,Zisterer, Daniela,Amet, Rebecca,Hannon Barroeta, Patricia,Vanni, Francesca,Ulivieri, Cristina,Herp, Daniel,Sarno, Federica,Di Costanzo, Antonella,Saccoccia, Fulvio,Ruberti, Giovina,Jung, Manfred,Altucci, Lucia,Gemma, Sandra,Butini, Stefania,Christianson, David W.,Campiani, Giuseppe
, p. 2268 - 2276 (2020/12/17)
Histone deacetylase inhibitors (HDACi) have emerged as promising therapeutics for the treatment of neurodegeneration, cancer, and rare disorders. Herein, we report the development of a series of spiroindoline-based HDAC6 isoform-selective inhibitors based on the X-ray crystal studies of the hit 6a. We identified compound 6j as the most potent and selective hHDAC6 inhibitor of the series. Biological investigation of compounds 6b, 6h, and 6j demonstrated their antiproliferative activity against several cancer cell lines. Western blotting studies indicated that they were able to increase tubulin acetylation, without significant variation in histone acetylation state, and induced PARP cleavage indicating their apoptotic potential at the molecular level. 6j induced HDAC6-dependent pSTAT3 inhibition.
Synthetic method of fatty acid containing nitrogen heterocycle
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Paragraph 0042, (2018/07/30)
The invention discloses a synthetic method of fatty acid containing nitrogen heterocycle. The synthetic method comprises the following steps: (S1) adding a heterocyclic compound with substitution of chloromethyl groups, a catalyst and a solvent DMF into a reaction kettle; (S2) introducing carbon dioxide to lead the pressure in the kettle to be 2-4MPa, adjusting and reacting for 10-16 hours at thetemperature of 40-50 DEG C; (S3) adding diluted hydrochloric acid into the reaction kettle to carry out acidification, using ethyl acetate for extraction, combining organic phases, carrying out rotaryevaporation to remove liquid, and further carrying out vacuum drying, thus obtaining the fatty acid containing nitrogen heterocycle. The synthetic method disclosed by the invention has the beneficialeffects that a one-pot method is adopted, the raw materials are easy to obtain, price is low, aftertreatment of products is also simpler, the universality for a substrate is also very high, and the promotion and application are easy.
AMIDE-LINKED EP4 AGONIST-BISPHOSPHONATE COMPOUNDS AND USES THEREOF
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Paragraph 00127-00128, (2017/01/31)
The present invention relates to EP4 agonist-bisphosphonate conjugates or related compounds and uses thereof. Said conjugates or related compounds may be used to provide delivery of an EP4 agonist or related compound to a desired site of action, such as a bone. Bisphosphonate moieties, linked to the EP4 agonists via amide linkers, have been implicated in the inhibition of bone resorption and bone targeting.
Isoflavone amide type derivative, preparation method and medical application thereof
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Paragraph 0015; 0056; 0057; 0058, (2016/10/10)
The invention relates to the field of medicinal chemistry, and relates to an isoflavone amide type derivative, a preparation method and a medical application thereof, in particular to an isoflavone amide type derivative with the general formula (I), a preparation method thereof, medicine compositions including the isoflavone amide type derivative and a medical application thereof, especially an application of the isoflavone amide type derivative as a medicine for preventing or curing hyperlipemia, obesity or type II diabetes. The general formula (I) is shown in the description.
SELECTIVE HDAC6 INHIBITORS
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, (2015/07/15)
The present invention provides hydroxamic acids of the formula described herein, that have activity toward inhibiting histone deacetylases, and in particular HDAC6. Also contemplated are pharmaceutical compositions and methods of use of an effective amount of the hydroxamic acid compounds provided, for treating a disease in a subject. In certain embodiments, the subject is afflicted with cancer, neurodegenerative disease, or HIV infection.
TRISUBSTITUTED HETEROCYCLIC DERIVATIVES AS ROR GAMMA MODULATORS
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Page/Page column 39; 40, (2014/09/03)
The present invention provides trisubstituted heterocyclic derivatives of formula (I), which may be therapeutically useful, more particularly as RORγ modulators; (I) in which R1, R2, R3, Ra, X, L, m and ring A have the meanings given in the specification, and pharmaceutically acceptable salts thereof that are useful in the treatment and prevention of diseases or disorder, in particular their use in diseases or disorder where there is an advantage in modulating RORγ receptor. The present invention also provides preparation of the compounds and pharmaceutical formulations comprising at least one of the trisubstituted heterocyclic derivatives of formula (I) together with a pharmaceutically acceptable carrier, diluent or excipient therefor.
CHROMONE INHIBITORS OF S-NITROSOGLUTATHIONE REDUCTASE
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, (2011/09/15)
The present invention is directed to inhibitors of S-nitrosoglutathione reductase (GSNOR), pharmaceutical compositions comprising such GSNOR inhibitors, and methods of making and using the same.
Discovery of hydrolytic catalysts in a peptidocalixarene library by binding assay with a transition state analogue for the hydrolysis
Hioki, Hideaki,Nishimoto, Ryosuke,Kawaguchi, Kota,Kubo, Miwa,Harada, Kenichi,Fukuyama, Yoshiyasu
supporting information; experimental part, p. 7194 - 7196 (2010/03/25)
Hydrolytic catalysts were found in a peptidocalixarene library by binding assay with a transition state analogue for the hydrolysis. The rate of the reaction can be specifically enhanced up to 50-fold in the presence of the discovered catalyst. The Royal
