228557-26-4Relevant academic research and scientific papers
Discovery of (S)-4-isobutyloxazolidin-2-one as a novel leucyl-tRNA synthetase (LRS)-targeted mTORC1 inhibitor
Yoon, Suyoung,Kim, Jong Hyun,Yoon, Ina,Kim, Changhoon,Kim, Sung-Eun,Koh, Yura,Jeong, Seung Jae,Lee, Jiyoun,Kim, Sunghoon,Lee, Jeewoo
, p. 3038 - 3041 (2016)
A series of leucinol analogs were investigated as leucyl-tRNA synthetase-targeted mTORC1 inhibitors. Among them, compound 5, (S)-4-isobutyloxazolidin-2-one, showed the most potent inhibition on the mTORC1 pathway in a concentration-dependent manner. Compound 5 inhibited downstream phosphorylation of mTORC1 by blocking leucine-sensing ability of LRS, without affecting the catalytic activity of LRS. In addition, compound 5 exhibited cytotoxicity against rapamycin-resistant colon cancer cells, suggesting that LRS has the potential to serve as a novel therapeutic target.
TREATMENT OF RB-NEGATIVE TUMORS USING TOPOISOMERASE INHIBITORS IN COMBINATION WITH CYCLIN DEPENDENT KINASE 4/6 INHIBITORS
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Page/Page column 102, (2016/06/01)
This invention is in the area of improved therapeutic combinations for and methods of treating selected retinoblastoma (Rb)-negative cancers and Rb-negative abnormal cellular proliferative disorders using particular topoisomerase inhibitors and specific c
Parallel synthesis of an oligomeric imidazole-4, 5-dicarboxamide library
Xu, Zhigang,DiCesare, John C.,Baures, Paul W.
supporting information; experimental part, p. 248 - 254 (2010/08/19)
A library of oligomeric compounds was synthesized based on the imidazole-4, 5-dicarboxylic acid scaffold along with amino acid esters and chiral diamines derived from amino acids. The final compounds incorporate nonpolar amino acids (Leu, Phe, Trp), polar amino acids (Ser, Asp, Arg), and neutral amino acids (Gly, Ala), and were designed to be useful in screening for inhibitors of protein-protein interactions. Many of the protected and deprotected oligomers show evidence of conformational isomers persistent at room temperature in aqueous solution. A total of 317 final oligomers, out of 441 targeted compounds, were obtained in high analytical purity and of sufficient quantity to submit them for high-throughput screening as part of the NIH Roadmap.
Synthesis of thioureido-linked peptidomimetics, glycosylated amino acids, and neoglycoconjugates using bis(benzotriazolyl)methanethione as thioacylating agent
Sureshbabu, Vommina V.,Chennakrishnareddy, Gundala,Hemantha, Hosahalli P.
body text, p. 715 - 720 (2010/06/14)
A practical synthesis of thiourea-linked peptidomimetics, glycosylated amino acids, and neoglycoconjugates is described employing bis(benzotriazolyl) methanethione as thiocarbonylating reagent. The entire protocol is mild, efficient, high-yielding, and free from hazardous reagents. All the intermediates and products have been isolated and fully characterized by 1H NMR, 13C NMR, and mass spectrometry. Georg Thieme Verlag Stuttgart ? New York.
N-urethane-protected amino alkyl isothiocyanates: Synthesis, isolation, characterization, and application to the synthesis of thioureidopeptides
Sureshbabu, Vommina V.,Naik, Shankar A.,Hemantha,Narendra,Das, Ushati,Guru Row, Tayur N.
supporting information; experimental part, p. 5260 - 5266 (2009/12/06)
(Chemical Equation Presented) Synthetically useful N-Fmoc amino-alkyl isothiocyanates have been described, starting from protected amino acids. These compounds have been synthesized in excellent yields by thiocarbonylation of the monoprotected 1,2-diamines with CS2/TEA/p-TsCl, isolated as stable solids, and completely characterized. The procedure has been extended to the synthesis of amino alkyl isothiocyanates from Boc- and Z-protected amino acids as well. The utility of these isothiocyanates for peptidomimetics synthesis has been demonstrated by employing them in the preparation of a series of dithioureidopeptide esters. Boc-Gly-OH and Boc-Phe-OH derived isothiocyanates 9a and 9c have been obtained as single crystals and their structures solved through X-ray diffraction. They belong to the orthorhombic crystal system, and have a single molecule in the asymmetric unit (Z′ = 1). 9a crystallizes in the centrosymmetric space group Pbca, while 9c crystallizes in the noncentrosymmetric space group P212121.
A simple approach for the synthesis of new classes of dithiocarbamate-linked peptidomimetics
Hemantha, Hosahalli P.,Sureshbabu, Vommina V.
body text, p. 7062 - 7066 (2010/03/01)
An efficient protocol for the synthesis of a new series of dithiocarbamate-linked peptidomimetics is described. The in situ generated dithiocarbamic acid intermediate formed by the reaction of an amino acid ester and carbon disulfide in the presence of triethylamine was treated with N-protected amino alkyl iodide to afford title compounds 3a-g in good to moderate yields. The synthesis of N-Fmoc-protected tripeptidomimetics 4a-e containing two dithiocarbamate linkages is also described. The protocol was further extended to synthesize N,N′-orthogonally protected dithiocarbamate-linked dipeptidomimetics 7a-c as well. The mild reaction conditions and non-toxic reagents are the advantages of the present method.
New pyrrole-based amino acids for the synthesis of peptidomimetic constrained scaffolds
Alongi, Maddalena,Minetto, Giacomo,Taddei, Maurizio
, p. 7069 - 7072 (2007/10/03)
A new family of pyrrole-based amino acids have been prepared through the microwave assisted Paal-Knorr reaction of 1-4 ketoesters derived from the corresponding β-ketoester with a functional homologation. The carboxylic group is located in position 3 of the pyrrole, whereas the amino group, protected with the Cbz moiety, is present on the side chain in positions 1 or 2. These compounds were used to prepare constrained oligopeptides.
A novel, simple, chemoseleetive and practical protocol for the reduction of azides using In/NH4Cl
Reddy, G. Vidyasagar,Rao, G. Venkat,Iyengar
, p. 3937 - 3938 (2007/10/03)
A simple, mild and efficient method for the reduction of azides to amines using In/NH4Cl is described.
