- Platinum(II) Complexes of Functionalized Malonato Ligands: Unequivocal Synthesis, Interaction with a Tetradeoxyribonucleotide and Deoxyribonucleic Acid
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The unequivocal syntheses of four cis-> complexes has been achieved, avoiding any interaction between the pendant carboxyl group and the platinum.The complexes have been characterized by elemental analysis, 13C NMR and FAB mass spectroscopy.Their interaction with a tetradeoxyribonucleotide d(T-G-G-T) (G = guanosine, T = ribosylthymine) and DNA (in vitro) has been investigated to show that they form adducts of the type 7,N7'>> as do the known therapeutically activeplatinum complexes.However, the presence of the free carbonyl function increases significantly the reactivity with respect to that of the non-functionalized malonato complexes >.
- Laurent, Jean-Pierre,Morvan, Bernard
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Read Online
- PROTAC-mediated crosstalk between E3 ligases
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Small-molecule heterobifunctional degraders can effectively control protein levels and are useful research tools. We assembled proteolysis targeting chimeras (PROTACs) from a cereblon (CRBN) and a von-Hippel-Lindau (VHL) ligase ligand and demonstrated a PROTAC-induced heterodimerization of the two E3 ligases leading to unidirectional and efficient degradation of CRBN.
- Steinebach, Christian,Kehm, Hannes,Lindner, Stefanie,Vu, Lan Phuong,K?pff, Simon,López Mármol, álvaro,Weiler, Corinna,Wagner, Karl G.,Reichenzeller, Michaela,Kr?nke, Jan,Gütschow, Michael
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supporting information
p. 1821 - 1824
(2019/02/12)
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- Discovery of ERD-308 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Estrogen Receptor (ER)
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The estrogen receptor (ER) is a validated target for the treatment of estrogen receptor-positive (ER+) breast cancer. Here, we describe the design, synthesis, and extensive structure-activity relationship (SAR) studies of small-molecule ERα degraders base
- Hu, Jiantao,Hu, Biao,Wang, Mingliang,Xu, Fuming,Miao, Bukeyan,Yang, Chao-Yie,Wang, Mi,Liu, Zhaomin,Hayes, Daniel F.,Chinnaswamy, Krishnapriya,Delproposto, James,Stuckey, Jeanne,Wang, Shaomeng
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p. 1420 - 1442
(2019/01/30)
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- COMPOUNDS AND COMPOSITIONS FOR INTRACELLULAR DELIVERY OF AGENTS
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The disclosure features amino lipids and compositions involving the same. Nanoparticle compositions include an amino lipid as well as additional lipids such as phospholipids, structural lipids, PEG lipids, or a combination thereof. Nanoparticle compositions further including therapeutic and/or prophylactic agents such as RNA are useful in the delivery of therapeutic and/or prophylactic agents to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.
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Paragraph 001036
(2019/01/08)
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- Tri-Orthogonal Scaffolds for the Solid-Phase Synthesis of Peptides
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Multi-orthogonal scaffolds can be useful for the attachment of several different compounds to the same central skeleton. Such compounds can find applications in the development of protein mimics because of their potential to mimic several distant epitopes
- Pícha, Jan,Fabre, Benjamin,Budě?ínsky, Milo?,Hajduch, Jan,Abdellaoui, Mehdi,Jirá?ek, Ji?í
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supporting information
p. 5180 - 5192
(2018/08/01)
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- INHIBITORS OF HEPATITIS C VIRUS POLYMERASE
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The present invention provides, among other things, compounds represented by the general Formula I: (I) and pharmaceutically acceptable salts thereof, wherein L and A (and further substituents) are as defined in classes and subclasses herein and compositions (e.g., pharmaceutical compositions) comprising such compounds, which compounds are useful as inhibitors of hepatitis C virus polymerase, and thus are useful, for example, as medicaments for the treatment of HCV infection.
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Paragraph 670; 671
(2016/10/11)
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- OLIGONUCLEOTIDE-LIGAND CONJUGATES AND PROCESS FOR THEIR PREPARATION
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The present invention relates to ligand conjugates of oligonucleotides (e.g., iRNA agents) and methods for their preparation. The ligands are derived primarily from monosaccharides These conjugates are useful for the in vivo delivery of oligonucleotides.
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Page/Page column 182; 183
(2015/02/02)
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- Heterovalent inhibitors targeting N-end Rule Pathway and its use
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An alkali-soluble polymer resin compound of formula 1 a including N-end Rule pathway inhibitors disclosure the composition. According to type 1 and type 2 herein each compounds recognizing substrate UBR box and a ClpS box a mammal having two tolerance N-e
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Paragraph 0145; 0146
(2016/10/10)
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- The development of a new class of inhibitors for betaine-homocysteine S-methyltransferase
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Betaine-homocysteine S-methyltransferase (BHMT) is an important zinc-dependent methyltransferase that uses betaine as the methyl donor for the remethylation of homocysteine to form methionine. In the liver, BHMT performs to half of the homocysteine remethylation. In this study, we systematically investigated the tolerance of the enzyme for modifications at the "homocysteine" part of the previously reported potent inhibitor (R,S)-5-(3-amino-3-carboxy-propylsulfanyl)-pentanoic acid (1). In the new compounds, which are S-alkylated homocysteine derivatives, we replaced the carboxylic group in the "homocysteine" part of inhibitor 1 with different isosteric moieties (tetrazole and oxadiazolone); we suppressed the carboxylic negative charge by amidations; we enhanced acidity by replacing the carboxylate with phosphonic or phosphinic acids; and we introduced pyrrolidine steric constraints. Some of these compounds display high affinity toward human BHMT and may be useful for further pharmacological studies of this enzyme. Although none of the new compounds were more potent inhibitors than the reference inhibitor 1, this study helped to completely defi ne the structural requirements of the active site of BHMT and revealed the remarkable selectivity of the enzyme for homocysteine.
- Pi?ha, Jan,Vaňek, Václav,Budě??sińsky, Milo?,Mlad?ková, Jana,Garrow, Timothy A.,Ji??acek, Ji??i
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p. 256 - 275
(2013/10/01)
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- DIURETICS
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A compound having the structure (I) wherein R is selected from the group consisting of 1) and 2), or a pharmaceutically acceptable salt thereof, and methods of using the compounds for treating hypertension.
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Page/Page column 27-28
(2011/05/11)
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- A PROCESS FOR PREPARING TETRAHYDROQUINOLINE DERIVATIVES
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The present invention is to provide a process for preparing optically active tetrahydroquinoline derivatives which can be used for the treatment and/or prevention of diseases such as arteriosclerotic diseases, dyslipidemia and the like, and a process for preparing synthetic intermediates thereof. Specifically, (2R,4S)-2-ethyl-6-trifluoromethyl-1,2,3,4-tetrahydroquinolin-4-ylamine or a salt thereof is prepared with fewer steps without using an optical resolution, and the optically active tetrahydroquinoline derivatives are obtained from the amine compound.
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Page/Page column 50
(2008/06/13)
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- A new photocleavable linker in solid-phase chemistry for ether cleavage
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(equation presented) We have designed a new linker (1) for the solid-phase synthesis that cleaves ether bonds photolytically. the linker was prepared in nine steps and anchored to the support via an amide bond. Photocleavage is a two-step process in which
- Glatthar, Ralf,Giese, Bernd
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p. 2315 - 2317
(2007/10/03)
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- Pd-mediated C-C and C-S bond formation on solid support: A scope and limitations study
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The scope and limitations of Pd(0)-mediated coupling reactions between aromatic halides linked to a polystyrene resin and boronic acid derivatives (Suzuki coupling), aromatic and vinylic tin compounds (Stille coupling), as well as thiols are reported. For all reactions, conditions were optimized and evaluated with various reagents. In many cases, upon cleavage from the solid support, products were obtained in excellent yields. In most cases, the optimized reaction conditions are superior to those previously reported in the literature.
- Wendeborn, Sebastian,Berteina, Sabine,Brill, Wolfgang K.-D.,De Mesmaeker, Alain
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p. 671 - 675
(2007/10/03)
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- Application of radical chemistry to solid support synthesis
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Radical cyclization of aryl iodides bound to polystyrene is described together with the trapping of the resulting radical, prior to its reduction, by allyltributyl tin.
- Berteina, Sabine,De Mesmaeker, Alain
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p. 5759 - 5762
(2007/10/03)
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