120157-95-1Relevant articles and documents
Structure-Based Design of Potent and Orally Active Isoindolinone Inhibitors of MDM2-p53 Protein-Protein Interaction
Chessari, Gianni,Hardcastle, Ian R.,Ahn, Jong Sook,Anil, Burcu,Anscombe, Elizabeth,Bawn, Ruth H.,Bevan, Luke D.,Blackburn, Timothy J.,Buck, Ildiko,Cano, Celine,Carbain, Benoit,Castro, Juan,Cons, Ben,Cully, Sarah J.,Endicott, Jane A.,Fazal, Lynsey,Golding, Bernard T.,Griffin, Roger J.,Haggerty, Karen,Harnor, Suzannah J.,Hearn, Keisha,Hobson, Stephen,Holvey, Rhian S.,Howard, Steven,Jennings, Claire E.,Johnson, Christopher N.,Lunec, John,Miller, Duncan C.,Newell, David R.,Noble, Martin E. M.,Reeks, Judith,Revill, Charlotte H.,Riedinger, Christiane,St. Denis, Jeffrey D.,Tamanini, Emiliano,Thomas, Huw,Thompson, Neil T.,Vinkovi?, Mladen,Wedge, Stephen R.,Williams, Pamela A.,Wilsher, Nicola E.,Zhang, Bian,Zhao, Yan
supporting information, p. 4071 - 4088 (2021/05/04)
Inhibition of murine double minute 2 (MDM2)-p53 protein-protein interaction with small molecules has been shown to reactivate p53 and inhibit tumor growth. Here, we describe rational, structure-guided, design of novel isoindolinone-based MDM2 inhibitors. MDM2 X-ray crystallography, quantum mechanics ligand-based design, and metabolite identification all contributed toward the discovery of potent in vitro and in vivo inhibitors of the MDM2-p53 interaction with representative compounds inducing cytostasis in an SJSA-1 osteosarcoma xenograft model following once-daily oral administration.
Thiamine hydrochloride as a recyclable organocatalyst for the efficient and chemoselective N-tert-butyloxycarbonylation of amines
Ingale, Ajit P.,Garad, Dnyaneshwar N.,Ukale, Dattatraya,Thorat, Nitin M.,Shinde, Sandeep V.
supporting information, p. 3791 - 3804 (2021/11/04)
Thiamin hydrochloride promoted highly efficient and ecofriendly approach has been described for the chemoselective N-tert-butyloxycarbonylation of amines under solvent-free conditions at ambient temperature. The demonstrated approach has been applicable for the N-Boc protection of variety of aliphatic, aryl, heteroaryl amines. The chemoselective protection of amino group occurs in chiral amines and amino alcohol without racemization in high yield. Thiamin hydrochloride is stable, economical, easy to handle and environmentally friendly.
Highly efficient chemoselective N-tert butoxycarbonylation of aliphatic/aromatic/heterocyclic amines using diphenylglycoluril as organocatalyst
Awasthi, Amardeep,Mukherjee, Anagh,Singh, Mandeep,Rathee, Garima,Vanka, Kumar,Chandra, Ramesh
, (2020/05/14)
An efficient approach for the Chemoselective N-tert-butoxycarbonylation of a variety of amines using diphenylglycoluril as organocatalyst has been described. For the first time, a plausible mechanism for the N-tert-butoxycarbonylation has been proposed using density functional theory (DFT) calculations supported by NMR studies. The reusability of the organocatalyst and observation of the desired N-Boc protected amines being formed without the formation of side products like urea, oxazolidinone, isocyanate, and N, N-di-Boc derivatives makes the present protocol desirable.
Sustainable and chemoselective N-Boc protection of amines in biodegradable deep eutectic solvent
Azizi, Najmedin,Shirdel, Fatemeh
, p. 1069 - 1074 (2017/05/12)
Abstract: A green and practical approach for the chemoselective N-tert-butyloxycarbonylation of structurally diverse amines with di-tert-butyl dicarbonate (Boc2O) is described. Selective N-Boc protection was achieved in excellent yields in urea-choline chloride deep eutectic solvent (DES) as the most promising environmentally benign and cost-effective solvent under mild reaction condition. DES can protect various aromatic and aliphatic amines using Boc2O in good to excellent yields in short reaction times without any side products. Graphical abstract: [Figure not available: see fulltext.].
ISOINDOLINONE INHIBITORS OF THE MDM2-P53 INTERACTION HAVING ANTICANCER ACTIVITY
-
Page/Page column 156; 157, (2017/05/07)
The invention provides a compound of formula (I): (I) or tautomer or a solvate or a pharmaceutically acceptable salt thereof, wherein the various substituents are as defined in the claims. Also provided are pharmaceutical compositions containing the compounds of formula (I), processes for making the compounds and the medical uses of the compounds.
Efficient chemoselective hydrogenation of organic azides catalyzed by palladium nanoparticles with alkyne-derived homogeneous supports
Arai, Noriyoshi,Onodera, Nozomi,Ohkuma, Takeshi
supporting information, p. 4183 - 4186 (2016/08/24)
Catalytic chemoselective hydrogenation of organic azides using palladium nanoparticles stabilized by alkyne derivatives was studied. A broad range of aromatic and aliphatic azides were smoothly reduced to the corresponding amines in excellent yields with a quite small amount of the catalyst. Hydrogenation of 3-phenylpropylazide gave 3-phenylpropylamine almost quantitatively with a substrate-to-palladium molar ratio (S/Pd) of 12,900 under 8?atm of H2. The reaction under 1?atm of H2also proceeded smoothly with an S/Pd of 1000. Several reduction-sensitive functional groups, such as carbonyl, halide, benzylic OH, and aliphatic nitro were well tolerated under the reaction conditions.
One-pot synthesis of α-amino acids from CO2 using a bismetal reagent with Si-B bond
Mita, Tsuyoshi,Chen, Jianyang,Sugawara, Masumi,Sato, Yoshihiro
, p. 6202 - 6205 (2013/02/23)
In the presence of 1.1 equiv of PhMe2Si-Bpin, 5 equiv of CsF, and 20 mol % of TsOH·H2O, precursors of N-Boc-imines can be converted into the corresponding α-aryl or α-alkenyl glycine derivatives under gaseous CO2 in moderate-to-high yields with a single operation. α-Isobutenyl glycine thus obtained can be further derivatized into various types of α-amino acids including N-Boc-leucine, serine, and glycine derivatives in short steps.
Synthesis of arylglycine and mandelic acid derivatives through carboxylations of α-amido and α-acetoxy stannanes with carbon dioxide
Mita, Tsuyoshi,Sugawara, Masumi,Hasegawa, Hiroyuki,Sato, Yoshihiro
experimental part, p. 2159 - 2168 (2012/06/01)
Incorporation reactions of carbon dioxide (CO2) with N-Boc-α-amido and α-acetoxy stannanes were developed using CsF as a mild tin activator. Monoprotected α-amido stannanes could be used, and the corresponding arylglycine derivatives were obtained in moderate-to-high yields under 1 MPa (10 atm) of CO2 pressure. α-Acetoxy stannanes also underwent carboxylation to afford mandelic acid derivatives in excellent yields under ambient CO2 pressure. Both transformations enabled the synthesis of α-tertiary and α-quaternary carboxylic acid derivatives. In addition, the chirality of (S)-N-tert-butylsulfonyl-α- amido stannanes was transferred with up to 90% inversion of configuration at 100 °C.
One-pot synthesis of α-amino acids from imines through CO2 incorporation: An alternative method for strecker synthesis
Mita, Tsuyoshi,Chen, Jianyang,Sugawara, Masumi,Sato, Yoshihiro
supporting information; experimental part, p. 1393 - 1396 (2011/04/22)
Itas a gas: A novel one-pot process for the synthesis of α-amino acids from imine equivalents using CO2 gas as a carbon source has been developed. This reaction was made possible by the reagent combination of TMSSnBu3 and CsF (see scheme). Three successive reactions (imine formation, stannylation, and carboxylation) proceeded in the same flask under these conditions to give products in up to 79 % yield. Boc=tert-butoxycarbonyl, TMS=trimethylsilyl.
Thioglycoluril as a highly efficient, recyclable and novel organocatalyst for N-Boc protection of amines
Khaksar, Samad,Vahdat, Seyed Mohammad,Tajbakhsh, Mahmood,Jahani, Fatemeh,Heydari, Akbar
experimental part, p. 6388 - 6391 (2011/01/03)
A simple and efficient protocol for the chemoselective mono-N-Boc protection of various structurally diverse amines with di-tert-butyl dicarbonate using thioglycoluril as the catalyst is described. The catalyst can be readily separated from the reaction products by simple filtration and recovered for reuse. No competitive side reactions, such as formation of isocyanate, urea, oxazolidinone, and N,N-di-Boc derivatives were observed.
