53588-95-7Relevant academic research and scientific papers
A kind of IDO inhibitor and use thereof
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Paragraph 0731-0735, (2019/07/11)
The embodiment of the invention provides general formula (I) compound or its pharmaceutically acceptable salts, stereoisomers, a tautomeric form each other, polymorphs, solvate, prodrug, metabolite or isotope derivatives, wherein the substituents R1
Fast and pH-Independent Elimination of trans-Cyclooctene by Using Aminoethyl-Functionalized Tetrazines
Sarris, Alexi J. C.,Hansen, Thomas,de Geus, Mark A. R.,Maurits, Elmer,Doelman, Ward,Overkleeft, Herman S.,Codée, Jeroen D. C.,Filippov, Dmitri V.,van Kasteren, Sander I.
supporting information, p. 18075 - 18081 (2018/11/23)
The inverse-electron-demand Diels–Alder/pyridazine elimination tandem reaction, in which the allylic substituent on trans-cyclooctene is eliminated following reaction with tetrazines, is gaining interest as a versatile bioorthogonal process. One potential shortcoming of such currently used reactions is their propensity to proceed faster and more efficiently at lower pH, a feature caused by the nature of the tetrazines used. Here, we present aminoethyl-substituted tetrazines as the first pH-independent reagents showing invariably fast elimination kinetics at all biologically relevant pH values.
Synthesis of novel amide and urea derivatives of thiazol-2-ethylamines and their activity against Trypanosoma brucei rhodesiense
Patrick, Donald A.,Wenzler, Tanja,Yang, Sihyung,Weiser, Patrick T.,Wang, Michael Zhuo,Brun, Reto,Tidwell, Richard R.
, p. 2451 - 2465 (2016/05/19)
2-(2-Benzamido)ethyl-4-phenylthiazole (1) was one of 1035 molecules (grouped into 115 distinct scaffolds) found to be inhibitory to Trypanosoma brucei, the pathogen causing human African trypanosomiasis, at concentrations below 3.6 μM and non-toxic to mammalian (Huh7) cells in a phenotypic high-throughput screen of a 700,000 compound library performed by the Genomics Institute of the Novartis Research Foundation (GNF). Compound 1 and 72 analogues were synthesized in this lab by one of two general pathways. These plus 10 commercially available analogues were tested against T. brucei rhodesiense STIB900 and L6 rat myoblast cells (for cytotoxicity) in vitro. Forty-four derivatives were more potent than 1, including eight with IC50 values below 100 nM. The most potent and most selective for the parasite was the urea analogue 2-(2-piperidin-1-ylamido)ethyl-4-(3-fluorophenyl)thiazole (70, IC50 = 9 nM, SI > 18,000). None of 33 compounds tested were able to cure mice infected with the parasite; however, seven compounds caused temporary reductions of parasitemia (≥97%) but with subsequent relapses. The lack of in vivo efficacy was at least partially due to their poor metabolic stability, as demonstrated by the short half-lives of 15 analogues against mouse and human liver microsomes.
Synthesis and structural characterization of monomeric and dimeric peptide nucleic acids prepared by using microwave-promoted multicomponent reactions
Ovadia, Reuben,Lebrun, Aurélien,Barvik, Ivan,Vasseur, Jean-Jacques,Baraguey, Carine,Alvarez, Karine
, p. 11052 - 11071 (2015/11/25)
A solution phase synthesis of peptide nucleic acid monomers and dimers was developed by using microwave-promoted Ugi multicomponent reactions. A mixture of a functionalized amine, a carboxymethyl nucleobase, paraformaldehyde and an isocyanide as building blocks generates PNA monomers which are then partially deprotected and used in a second Ugi 4CC reaction, leading to PNA dimers. Conformational rotamers were identified by using NMR and MD simulations.
A multifaceted secondary structure mimic based on piperidine-piperidinones
Xin, Dongyue,Perez, Lisa M.,Ioerger, Thomas R.,Burgess, Kevin
supporting information, p. 3594 - 3598 (2014/04/17)
Minimalist secondary structure mimics are typically made to resemble one interface in a protein-protein interaction (PPI), and thus perturb it. We recently proposed suitable chemotypes can be matched with interface regions directly, without regard for secondary structures. Here we describe a modular synthesis of a new chemotype 1, simulation of its solution-state conformational ensemble, and correlation of that with ideal secondary structures and real interface regions in PPIs. Scaffold 1 presents amino acid side-chains that are quite separated from each other, in orientations that closely resemble ideal sheet or helical structures, similar non-ideal structures at PPI interfaces, and regions of other PPI interfaces where the mimic conformation does not resemble any secondary structure. 68 different PPIs where conformations of 1 matched well were identified. A new method is also presented to determine the relevance of a minimalist mimic crystal structure to its solution conformations. Thus dld-1-faf crystallized in a conformation that is estimated to be 0.91 kcal-mol-1 above the minimum energy solution state. Do we know, when designing a new peptidomimetic scaffold like the one shown, how it can resemble secondary structures? Design and modular synthesis of this elongated mimic is reported, and the structure is related to ideal and real structures at PPI interfaces.
New thiadiazole derivatives
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Page/Page column 49, (2011/04/25)
The present invention relates to thiadiazole derivatives of formula (I), to processes for their preparation and to pharmaceutical compositions containing them. These compounds are potent agonists of S1P1 receptors and thus, they are useful in the treatment, prevention or suppression of diseases and disorders known to be susceptible to improvement by sphingosine-1-phosphate receptors agonists (S1P1), such as autoimmune diseases, chronic immune and inflammatory diseases, transplant rejection, malignant neoplastic diseases, angiogenic-related disorders, pain, neurological diseases, viral and infectious diseases.
NEW THIADIAZOLE DERIVATIVES
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Page/Page column 71, (2011/04/24)
The present invention relates to thiadiazole derivatives of formula (I), to processes for their preparation and to pharmaceutical compositions containing them. These compounds are potent agonists of S1P1 receptors and thus, they are useful In the treatment, prevention or suppression of diseases and disorders known to be susceptible to improvement by sphingosine-1-phosphate receptors agonists (S1P1), such as autoimmune diseases, chronic immune and inflammatory diseases, transplant rejection, malignant neoplastic diseases, angiogenic-related disorders, pain, neurological diseases, viral and infectious diseases.
Synthesis of (2R,3R,4S)-N-Boc-2,4-diarylpyrrolidine-3-carboxamides
Jayachandra Reddy,Somasekhara Reddy
experimental part, p. 5165 - 5174 (2012/07/28)
A synthesis of (2R,3R,4S)-N-boc-2,4-diarylpyrrolidine-3-carboxylic amides (i-vii) via HATU, BOP and Mukaiyama mediated coupling of (2R,3R,4S)-1-(tert- butoxycarbonyl)-4-(benzo[d][1,3]dioxol-6-yl)-2-(4-methoxyphenyl) pyrrolidine-3-carboxylic acid (13) with amine (a1-g1) has been developed. Under HATU coupling conditions, the products were achieved in good yields comparatively than BOP and Mukaiyama reagent. The structures of compounds i-vii were elucidated on the basis of spectral and chemical studies.
FUSED BICYCLIC COMPOUNDS AS INHIBITORS FOR PI3 KINASE
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Page/Page column 111, (2010/09/18)
The invention relates to compounds of formula (I) for the regulation of phosphoinositides 3-kinases activity and related diseases.
IBX/TBAB-mediated oxidation of primary amines to nitriles
Drouet, Fleur,Fontaine, Patrice,Masson, Geraldine,Zhu, Jieping
experimental part, p. 1370 - 1374 (2010/01/13)
The combination of o-iodoxybenzoic acid (IBX) and tetrabutylammonium bromide (TBAB) efficiently oxidizes primary amines to the corresponding nitriles in good to excellent yield under mild conditions. The reaction is racemization-free when applied to a chiral lysine derivative. Georg Thieme Verlag Stuttgart.
