29682-15-3Relevant articles and documents
SYNTHETIC RETINOIDS FOR USE IN RAR ACTIVATION
-
Page/Page column 18-19, (2020/09/27)
The present invention relates to compounds of formula I: in which A1-A7 and R1 to R5 are defined herein, for use in the treatment of a condition or disease which is alleviated by the activation of retinoic acid receptors (RAR). The invention also relates to pharmaceutical compounds comprising such compounds, and related methods of treatment. In an aspect, the invention relates to a method of screening compounds for therapeutic potential in the treatment of a condition or disease which is alleviated by the activation of retinoic acid receptors (RAR). Aspects of the invention relate to novel compounds of formula I in which at least one of A1 to A3 is N or at least one of A4 is CR12 or A5 is CR13 in which R12/R13 is halogen.
CARBOXAMIDES AS MODULATORS OF SODIUM CHANNELS
-
Paragraph 00559, (2020/07/25)
Compounds, and pharmaceutically acceptable salts thereof, useful as inhibitors of sodium channels are provided. Also provided are pharmaceutical compositions comprising the compounds or pharmaceutically acceptable salts and methods of using the compounds, pharmaceutically acceptable salts, and pharmaceutical compositions in the treatment of various disorders, including pain.
A biocatalytic method for the chemoselective aerobic oxidation of aldehydes to carboxylic acids
Knaus, Tanja,Tseliou, Vasilis,Humphreys, Luke D.,Scrutton, Nigel S.,Mutti, Francesco G.
, p. 3931 - 3943 (2018/09/11)
Herein, we present a study on the oxidation of aldehydes to carboxylic acids using three recombinant aldehyde dehydrogenases (ALDHs). The ALDHs were used in purified form with a nicotinamide oxidase (NOx), which recycles the catalytic NAD+ at the expense of dioxygen (air at atmospheric pressure). The reaction was studied also with lyophilised whole cell as well as resting cell biocatalysts for more convenient practical application. The optimised biocatalytic oxidation runs in phosphate buffer at pH 8.5 and at 40 °C. From a set of sixty-one aliphatic, aryl-Aliphatic, benzylic, hetero-Aromatic and bicyclic aldehydes, fifty were converted with elevated yield (up to >99%). The exceptions were a few ortho-substituted benzaldehydes, bicyclic heteroaromatic aldehydes and 2-phenylpropanal. In all cases, the expected carboxylic acid was shown to be the only product (>99% chemoselectivity). Other oxidisable functionalities within the same molecule (e.g. hydroxyl, alkene, and heteroaromatic nitrogen or sulphur atoms) remained untouched. The reaction was scaled for the oxidation of 5-(hydroxymethyl)furfural (2 g), a bio-based starting material, to afford 5-(hydroxymethyl)furoic acid in 61% isolated yield. The new biocatalytic method avoids the use of toxic or unsafe oxidants, strong acids or bases, or undesired solvents. It shows applicability across a wide range of substrates, and retains perfect chemoselectivity. Alternative oxidisable groups were not converted, and other classical side-reactions (e.g. halogenation of unsaturated functionalities, Dakin-Type oxidation) did not occur. In comparison to other established enzymatic methods such as the use of oxidases (where the concomitant oxidation of alcohols and aldehydes is common), ALDHs offer greatly improved selectivity.
HETEROCYCLIC INTEGRIN AGONISTS
-
Paragraph 0246; 0247, (2018/07/29)
The present invention provides polycyclic oxothioxoimidazolidines, dioxoimidazolines, oxothioxooxazolidines, dioxooxazolidines, and related compounds, which are useful as integrin agonists. Methods for the treatment of integrin-mediated diseases such as cancer are also described.
Design, synthesis and evaluation of antiproliferative activity of melanoma-targeted histone deacetylase inhibitors
Raji, Idris,Ahluwalia, Kabir,Oyelere, Adegboyega K.
supporting information, p. 744 - 749 (2017/02/18)
The clinical validation of histone deacetylase inhibition as a cancer therapeutic modality has stimulated interest in the development of new generation of potent and tumor selective histone deacetylase inhibitors (HDACi). With the goal of selective delivery of the HDACi to melanoma cells, we incorporated the benzamide, a high affinity melanin-binding template, into the design of HDACi to generate a new series of compounds 10a-b and 11a-b which display high potency towards HDAC1 and HDAC6. However, these compounds have attenuated antiproliferative activities relative to the untargeted HDACi. An alternative strategy furnished compound 14, a prodrug bearing the benzamide template linked via a labile bond to a hydroxamate-based HDACi. This pro-drug compound showed promising antiproliferative activity and warrant further study.
Fusaric acid and analogues as Gram-negative bacterial quorum sensing inhibitors
Tung, Truong Thanh,Jakobsen, Tim Holm,Dao, Trong Tuan,Fuglsang, Anja Thoe,Givskov, Michael,Christensen, S?ren Br?gger,Nielsen, John
, p. 1011 - 1020 (2016/12/30)
Taking advantage of microwave-assisted synthesis, efficient and expedite procedures for preparation of a library of fusaric acid and 39 analogues are reported. The fusaric acid analogues were tested in cell-based screening assays for inhibition of the las and rhl quorum sensing system in Pseudomonas aeruginosa and the lux quorum sensing system in Vibrio fischeri. Eight of the 40 compounds in the library including fusaric acid inhibited lux quorum sensing and one compound inhibited activity of the las quorum sensing system. To our delight, none of the compounds showed growth inhibitory effects in the tested concentration ranges.
Structure–Activity Relationship of Propargylamine-Based HDAC Inhibitors
Wünsch, Matthias,Senger, Johanna,Schultheisz, Philipp,Schwarzbich, Sabrina,Schmidtkunz, Karin,Michalek, Carmela,Kla?, Michaela,Goskowitz, Stefanie,Borchert, Philipp,Praetorius, Lucas,Sippl, Wolfgang,Jung, Manfred,Sewald, Norbert
supporting information, p. 2044 - 2053 (2017/12/07)
As histone deacetylases (HDACs) play an important role in the treatment of cancer, their selective inhibition has been the subject of various studies. These continuous investigations have given rise to a large collection of pan- and selective HDAC inhibitors, containing diverse US Food and Drug Administration (FDA)-approved representatives. In previous studies, a class of alkyne-based HDAC inhibitors was presented. We modified this scaffold in two previously neglected regions and compared their cytotoxicity and affinity toward HDAC1, HDAC6, and HDAC8. We were able to show that R-configured propargylamines contribute to increased selectivity for HDAC6. Docking studies on available HDAC crystal structures were carried out to rationalize the observed selectivity of the compounds. Substitution of the aromatic portion by a thiophene derivative results in high affinity and low cytotoxicity, indicating an improved drug tolerance.
CYCLOPROPYL FUSED THIAZIN-2-AMINE COMPOUNDS AS BETA-SECRETASE INHIBITORS AND METHODS OF USE
-
Page/Page column 330, (2016/04/20)
The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula (I): wherein variables A4, A5, A6, A8, and each of Ra, Rb, R1, R2, R3 and R7 of Formula (I), independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and 15 deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimers Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formulas (II) and (III), and sub-formula embodiments thereof, intermediates and methods for preparing compounds of the invention.
PYRAZOLYL-SUBSTITUTED PYRIDONE COMPOUNDS AS SERINE PROTEASE INHIBITORS
-
Paragraph 00379-00380, (2016/04/09)
There are provided inter alia pyrazolyl-substituted pyridone compounds, which exhibit biological activity, e.g., inhibitory action, against serine proteases, including thrombin and various kallikreins. There are additionally provided pharmaceutical compositions. There are additionally provided methods of treating and preventing certain diseases or disorders, which disease or disorder is amenable to treatment or prevention by the inhibition of serine proteases, including thrombin and various kallikreins.
A thiophene and pyrimidine derivatives, its preparation process and its use in medicine
-
Paragraph 0135-0137, (2016/12/01)
The invention discloses thiophene miazines derivates as well as a preparation method and a medical application thereof. The thiophene miazines derivates are compounds with a general formula I, a general formula II or a general formula III, wherein in the general formulae, Ar is any one of phenyl, halogen-substituted phenyl, C1-6 alkyl-substituted phenyl, biphenylyl, halogen-substituted biphenylyl, naphthyl, pyridyl, thienyl, halogen-substituted thienyl, C1-3 alkyl-substituted thienyl, furyl, halogen-substituted furyl and C1-3 alkyl-substituted furyl, A, D and E are respectively carbon atoms or nitrogen atoms but are not carbon atoms at the same time, and R is R1-NH-. The thiophene miazines derivates provided by the invention can be used for obviously restraining the activity of an EGFR (Epidermal Growth Factor Receptor) and the activity of A431 cells, are expected to be developed as a tyrosine kinase inhibitor, and are extensive in application prospect and medicinal value.
