136159-65-4Relevant academic research and scientific papers
The structural requirements of histone deacetylase inhibitors: C4-modified SAHA analogs display dual HDAC6/HDAC8 selectivity
Negmeldin, Ahmed T.,Knoff, Joseph R.,Pflum, Mary Kay H.
, p. 1790 - 1806 (2018)
Histone deacetylase (HDAC) enzymes govern the post-translational acetylation state of lysine residues on protein substrates, leading to regulatory changes in cell function. Due to their role in cancers, HDAC proteins have emerged as promising targets for
Dual Activation of Unsaturated Amides with Schwartz's Reagent: A Diastereoselective Access to Cyclopentanols and N,O-Dimethylcyclopentylhydroxylamines.
Coelho, Aurélien,Souvenir Zafindrajaona, Mahasoa-Salina,Vallée, Alexis,Behr, Jean-Bernard,Vasse, Jean-Luc
supporting information, (2021/12/06)
The diastereoselective access to cyclopentanols and N,O-dimethylcyclopentylhydroxylamines from 4-pentenoic acid-derived Weinreb amides is described. Based on the concomitant generation of both the nucleophilic and the electrophilic poles by hydrozirconati
TARGETED PLASMA PROTEIN DEGRADATION
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Page/Page column 127-129, (2021/08/14)
The present invention is directed to the bifunctional compounds and the use of such bifunctional compounds to lower plasma levels of extracellular target molecules by lysosomal degradation. Such bifunctional compounds have a cell surface receptor ligand covalently linked to a ligand that is capable of binding to an extracellular target molecule (such as a ligand for a growth factor, a cytokine, a chemokine, a hormone, a neurotransmitter, a capsid, a soluble receptor, an extracellular secreted protein, an antibody, a lipoprotein, an exosome, a virus, a cell, or a plasma membrane protein), where the cell surface receptor is associated with receptor mediated endocytosis, including asialoglycoprotein receptor (ASGPR) mediated lysosomal degradation and mannose-6-phosphate (M6PR) mediated lysosomal degradation. Pharmaceutical compositions comprising such bifunctional compounds and methods of treating a disease or disorder mediated by an extracellular molecule using such bifunctional compounds are also provided herein.
Nickel-Catalyzed Alkyl-Alkyl Cross-Electrophile Coupling Reaction of 1,3-Dimesylates for the Synthesis of Alkylcyclopropanes
Chen, Pan-Pan,Hong, Xin,Jarvo, Elizabeth R.,McGinnis, Tristan M.,Sanford, Amberly B.,Thane, Taylor A.
, (2020/03/23)
Cross-electrophile coupling reactions of two Csp3-X bonds remain challenging. Herein we report an intramolecular nickel-catalyzed cross-electrophile coupling reaction of 1,3-diol derivatives. Notably, this transformation is utilized to synthesize a range of mono- and 1,2-disubstituted alkylcyclopropanes, including those derived from terpenes, steroids, and aldol products. Additionally, enantioenriched cyclopropanes are synthesized from the products of proline-catalyzed and Evans aldol reactions. A procedure for direct transformation of 1,3-diols to cyclopropanes is also described. Calculations and experimental data are consistent with a nickel-catalyzed mechanism that begins with stereoablative oxidative addition at the secondary center.
CYCLIC TETRAMER COMPOUNDS AS PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9) INHIBITORS FOR THE TREATMENT OF METABOLIC DISORDERS
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Paragraph 0624-0625, (2020/06/16)
The disclosure relates to inhibitors of PCSK9 useful in the treatment of cholesterol lipid metabolism, and other diseases in which PCSK9 plays a role, having the Formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, N-oxide, or tautomer thereof, wherein R1, R1, R1, R1, R1, R1, R1, R1, R1, X1, X2, and X3 are described herein.
CYCLIC PENTAMER COMPOUNDS AS PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9) INHIBITORS FOR THE TREATMENT OF METABOLIC DISORDER
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Page/Page column 309-310, (2020/06/19)
The disclosure relates to inhibitors of PCSK9 useful in the treatment of cholesterol lipid metabolism, and other diseases in which PCSK9 plays a role, having the Formula (I):, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, N-oxide, or tautomer thereof, wherein X1, R1, R2, R3, R4, R5, R6, R6', R7, R7', R8, R9, R9', R10, R11, R12, and n are described herein.
Dess-Martin periodinane oxidative rearrangement for preparation of α-keto thioesters
Sanichar, Randy,Carroll, Ciaran,Kimmis, Ryan,Reiz, Bela,Vederas, John C.
supporting information, p. 593 - 597 (2018/02/09)
A Dess-Martin Periodinane (DMP) mediated oxidative rearrangement reaction was uncovered. The reaction proceeds via oxidation of a β-hydroxy thioester to a β-keto thioester, followed by an α-hydroxylation and then further oxidation to form a vicinal thioester tricarbonyl. This product then rearranges, extruding CO2, to form an α-keto product. The mechanism of the rearrangement was elucidated using 13C labelling and analysis of the intermediates as well as the products of the reaction. This efficient process allows for easy preparation of α-keto thioesters which are potential intermediates in the synthesis of pharmaceutically important heterocyclic scaffolds such as quinoxalinones.
Diastereoselective Electrophilic Trifluoromethylthiolation of Chiral Oxazolidinones: Access to Enantiopure α-SCF3 Alcohols
Chachignon, Hélène,Kondrashov, Evgeniy V.,Cahard, Dominique
, p. 965 - 971 (2018/01/27)
Lithium imide enolates featuring Evans’ chiral oxazolidinone auxiliary were involved in diastereoselective α-trifluoromethylthiolation with electrophilic SCF3 donors. Diastereopure products were isolated and converted to enantiopure α-SCF3 alcohols without racemisation. (Figure presented.).
Structural requirements of histone deacetylase inhibitors: C4-modified saha analogs display dual HDAC6/HDAC8 selectivity
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Paragraph 0106; 0108, (2018/03/25)
A compound having formula I for histone deacetylase inhibition is provided: or a pharmaceutically acceptable salt or hydrate thereof wherein R is alkyl, C6-18 aryl, C5-18 heteroaryl, C8-22 alkylaryl, C8-22 alkyl
Diazaphospholene Precatalysts for Imine and Conjugate Reductions
Adams, Matt R.,Tien, Chieh-Hung,Huchenski, Blake S. N.,Ferguson, Michael J.,Speed, Alexander W. H.
supporting information, p. 6268 - 6271 (2017/05/19)
The first examples of 1,3,2-diazaphospholene-catalyzed imine reduction and conjugate reduction reactions are reported. This approach employs readily synthesized alkoxydiazaphospholene precatalysts that can be handled in open air. Reduction of substrates containing Lewis basic functionality, isolated unsaturation, and protic functional groups was accomplished. The synthetic utility of this approach is demonstrated by the synthesis of the important antiparkinson medicine rasagiline and the natural product zingerone.
