118992-89-5Relevant academic research and scientific papers
Cyanopivaloyl Ester in the Automated Solid-Phase Synthesis of Oligorhamnans
Geert Volbeda, Anne,Van Mechelen, Jeanine,Meeuwenoord, Nico,Overkleeft, Herman S.,Van Der Marel, Gijsbert A.,Codée, Jeroen D. C.
, p. 12992 - 13002 (2017)
The development of effective protecting group chemistry is an important driving force behind the progress in the synthesis of complex oligosaccharides. Automated solid-phase synthesis is an attractive technique for the rapid assembly of oligosaccharides, built up of repetitive elements. The fact that (harsh) reagents are used in excess in multiple reaction cycles makes this technique extra demanding on the protecting groups used. Here, the synthesis of a set of oligorhamnan fragments is reported using the cyanopivaloyl (PIVCN) ester to ensure effective neighboring group participation during the glycosylation events. The PIVCN group combines the favorable characteristics of the parent pivaloyl (PIV) ester, stability, minimal migratory aptitude, minimal orthoester formation, while it can be cleaved under mild conditions. We show that the remote CN group in the PIVCN renders the PIVCN carbonyl more electropositive and thus susceptible to nucleophilic cleavage. This feature is built upon in the automated solid-phase assembly of the oligorhamnan fragments. Where the use of a PIV-protected building block failed because of incomplete cleavage, PIVCN-protected synthons performed well and allowed the generation of oligorhamnans, up to 16 monosaccharides in length.
Hybrids of 4-hydroxy derivatives of goniothalamin and piplartine bearing a diester or a 1,2,3-triazole linker as antiproliferative agents
Grigolo, Thiago A.,Braga, Carolyne B.,Ornelas, Catia,Russowsky, Dennis,Ferreira-Silva, Guilherme A.,Ionta, Marisa,Pilli, Ronaldo A.
supporting information, (2021/09/14)
A library of nine hybrids of 4-hydroxygoniothalamin (2), 4-hydroxypiplartine (4), monastrol (5) and oxo-monastrol (6) was prepared via a modular synthetic route with a diester or a 1,2,3-triazole as linkers. The compounds were assayed against a panel of h
THERAPEUTIC AGENTS AND CONJUGATES THEREOF
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Paragraph 00605-00607, (2021/09/11)
The present disclosure provides a class of conjugates of general formula (X), a class of TLR9 agonist derivatives, such as formula (I), (XX), and (XXI), certain diastereomers of STING agonists, a class of STING agonist derivatives, such as formula (XXVIV), a class of heterocyclic compounds of general formula (II), a class of heterocyclic compounds of general formula (III), as defined herein. A1, A2, T, Z1, Z2, Z3, b1, and b2, in formula (X) are defined herein. The conjugate provides unique properties that are based upon the properties of the therapeutic agents that are part of the conjugate. Also provided are methods of synthesis and use of compounds.
Discovery of CRBN E3 Ligase Modulator CC-92480 for the Treatment of Relapsed and Refractory Multiple Myeloma
Hansen, Joshua D.,Correa, Matthew,Nagy, Mark A.,Alexander, Matt,Plantevin, Veronique,Grant, Virginia,Whitefield, Brandon,Huang, Dehua,Kercher, Timothy,Harris, Roy,Narla, Rama Krishna,Leisten, Jim,Tang, Yang,Moghaddam, Mehran,Ebinger, Katalin,Piccotti, Joseph,Havens, Courtney G.,Cathers, Brian,Carmichael, James,Daniel, Thomas,Vessey, Rupert,Hamann, Lawrence G.,Leftheris, Katerina,Mendy, Derek,Baculi, Frans,Lebrun, Laurie A.,Khambatta, Gody,Lopez-Girona, Antonia
, p. 6648 - 6676 (2020/09/11)
Many patients with multiple myeloma (MM) initially respond to treatment with modern combination regimens including immunomodulatory agents (lenalidomide and pomalidomide) and proteasome inhibitors. However, some patients lack an initial response to therapy (i.e., are refractory), and although the mean survival of MM patients has more than doubled in recent years, most patients will eventually relapse. To address this need, we explored the potential of novel cereblon E3 ligase modulators (CELMoDs) for the treatment of patients with relapsed or refractory multiple myeloma (RRMM). We found that optimization beyond potency of degradation, including degradation efficiency and kinetics, could provide efficacy in a lenalidomide-resistant setting. Guided by both phenotypic and protein degradation data, we describe a series of CELMoDs for the treatment of RRMM, culminating in the discovery of CC-92480, a novel protein degrader and the first CELMoD to enter clinical development that was specifically designed for efficient and rapid protein degradation kinetics.
CYCLIC-AMP RESPONSE ELEMENT BINDING PROTEIN (CBP) AND/OR ADENOVIRAL E1A BINDING PROTEIN OF 300 KDA (P300) DEGRADATION COMPOUNDS AND METHODS OF USE
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Page/Page column 170, (2020/09/12)
Bivalent compounds composition comprises one or more of the bivalent compounds. The bivalent compound comprises a cyclic-AMP response element binding protein (CBP) and/or adenoviral E1A binding protein of 300kDa (P300) ligand (CBP/P300 ligand) conjugated
Silica-coated Fe3O4 magnetic nanoparticles-supported sulfonic acid as a highly active and reusable catalyst in chemoselective deprotection of tert-butyldimethylsilyl (TBDMS) ethers
Hossein Javadi, Sayed,Zareyee, Daryoush,Monfared, Azam,Didehban, Khadijeh,Mirshokraee, Sayed Ahmmad
supporting information, p. 7 - 12 (2019/11/03)
Anchored propyl sulfonic acid on the surface of silica-coated magnetic nanoparticles (Fe3O4@SiO2@PrSO3H) was successfully employed in the deprotection of TBDMS ethers. The prepared magnetically separable nanocatalyst exhibited efficient catalytic activity with high conversion and selectivity in cleavage of TBDMS ethers. TBDMS ethers are efficiently cleaved to the corresponding hydroxyl compounds in methanol solution containing 2 mol% magnetic nano-catalysts. Good to excellent yields of products, simple work-up and product separation, selective cleavage of TBDMS ethers in the presence of TBDPS ethers, easy recycling of the catalyst with external magnet with no loss in its activity (7 reaction cycles) are important features of this new protocol.
Compounds and Their Use in Treating Cancer
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Paragraph 0686; 0687, (2019/07/10)
The specification generally relates to compounds of Formula (I): and pharmaceutically acceptable salts and prodrugs thereof, where R1, R4, R5, R6, R7, Linker, X, Y, A, G, D and E have any of the meanings defined herein. This specification also relates to the use of such compounds and pharmaceutically acceptable salts and prodrugs thereof in methods of treatment of the human or animal body, for example in prevention or treatment of cancer. This specification also relates to processes and intermediate compounds involved in the preparation of such compounds and to pharmaceutical compositions containing them.
Hafnium Triflate as a Highly Potent Catalyst for Regio- and Chemoselective Deprotection of Silyl Ethers
Zheng, Xiu-An,Kong, Rui,Huang, Hua-Shan,Wei, Jing-Ying,Chen, Ji-Zong,Gong, Shan-Shan,Sun, Qi
, p. 944 - 953 (2019/02/10)
As a Group IVB transition metal Lewis acid, hafnium triflate [Hf(OTf) 4 ] exhibited exceptionally high potency in desilylations. Since the amounts of Hf(OTf) 4 required for the deprotection of 1°, 2°, 3° alkyl and aryl tert -butyldimethylsilyl (TBS) ethers are significantly different, ranging from 0.05 mol% to 3 mol%, regioselective deprotection of TBS could be easily implemented. Moreover, chemoselective cleavage of different silyl ethers or removal of TBS in the presence of most hydroxyl protecting groups was also accomplished. NMR analyses of silyl products from TBS deprotection indicated that Hf(OTf) 4 -catalyzed desilylation may proceed via different mechanisms, depending on the solvent used.
Hafnium trifluoromethanesulfonate catalyzed silyl ether protecting group removing method
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Paragraph 0013; 0014, (2019/01/21)
The invention provides a hafnium trifluoromethanesulfonate catalyzed silyl ether protecting group removing method. Various silyl ether protecting groups of nearly 50 kinds of substrates can be efficiently removed in 0.5-16 hours at room temperature by taking 0.02mol%-0.3mol% hafnium trifluoromethanesulfonate as a catalyst, a silyl ether protected hydroxyl compound as a substrate and conventional AR methanol as a solvent. 42 kinds of silyl ether protecting group removing products can be obtained at high yield by performing conventional slica column chromatography purification on a crude product. By regulating the use amount of the catalyst, the Hf(OTf)4 catalyst can realize regioselective removal of 1-degree, 2-degree and 3-degree alkyl TBS and aryl TBS protective groups. Moreover, in a proper equivalent scope, the Hf(OTf)4 catalyst can also realize 1) chemoselective removal of different kinds of silica-based protective groups; and 2) chemoselective removal of 1-degree TBS protective groups under the condition of not affecting a majority of common hydroxyl protective groups.
Mild and selective deprotection of tert -butyl(dimethyl)silyl ethers with catalytic amounts of sodium tetrachloroaurate(III) dihydrate
Zhang, Qi,Kang, Xiuqin,Long, Lei,Zhu, Lijuan,Chai, Yonghai
, p. 55 - 64 (2015/02/02)
A simple and mild method for the removal of tert-butyl(dimethyl)silyl (TBS) protecting groups with catalytic amounts of sodium tetrachloroaurate(III) dihydrate is described. The procedure permits selective deprotection of aliphatic TBS ethers in good to excellent yields in the presence of aromatic TBS ethers, aliphatic triisopropylsilyl ethers, aliphatic tert-butyl(diphenyl)silyl ethers, or sterically hindered aliphatic TBS ethers. Additionally, TBS ethers can also be transformed into 4-methoxybenzyl ethers or methyl ethers in one pot by using larger quantities of the catalyst and a higher reaction temperature.
