- Effective C5-Arylation of Peptide-Integrated Oxazoles: Almazole D
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An efficient functionalization approach of oxazoles by using Pd-catalyzed cross-coupling reactions is reported. Oxazolone formation and subsequent sulfamoylation in situ are facilitated by employing N,N-diethylsulfamoyl imidazolium triflate. Cross-couplings provide both oxazole-arenes and oxazole-heteroarenes and were compatible with sensitive and epimerization-prone substrates, as exemplified by the total synthesis of the natural product almazole D. (Figure presented.).
- Oberheide, Ansgar,Arndt, Hans-Dieter
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supporting information
p. 1132 - 1136
(2020/12/22)
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- Phenyl and Diaryl Ureas with Thiazolo[5,4-d]pyrimidine Scaffold as Angiogenesis Inhibitors: Design, Synthesis and Biological Evaluation
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Angiogenesis is crucial for tumor growth and inhibition of angiogenesis has been regarded as a promising approach for cancer therapy. Vascular endothelial growth factor receptor-2 (VEGFR-2) is an important factor in angiogenesis. In this work, a novel series of thiazolo[5,4-d]pyrimidine derivatives inhibiting angiogenesis were rationally designed and synthesized. Their inhibitory activities against human umbilical vein endothelial cells (HUVEC) were investigated in vitro. 1-(4-Fluorophenyl)-3-{4-[(5-methyl-2-phenyl[1,3]thiazolo[5,4-d]pyrimidin-7-yl)amino]phenyl}urea (19b) and 1-(3-Fluorophenyl)-3-{4-[(5-methyl-2-phenyl[1,3]thiazolo[5,4-d]pyrimidin-7-yl)amino]phenyl}urea (19g) exhibited the most potent inhibitory effect on HUVEC proliferation (IC50=12.8 and 5.3 μm, respectively). Compound 19g could inhibit the migration of human umbilical vein endothelial cells. These results support the further investigation of these compounds as potent anticancer agents.
- Xue, Wen-Jun,Deng, Ya-Hui,Yan, Zhong-Hui,Liu, Ji-Ping,Liu, Yu,Sun, Li-Ping
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- Transformation of Racemic Azlactones into Enantioenriched Dihydropyrroles and Lactones Enabled by Hydrogen-Bond Organocatalysis
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Azlactones, a potent building block for the synthesis of complex molecules, have been explored in an organocatalytic Mannich reaction with protected imines. In this study, azlactones containing a propargyl substituent were employed for the first time in organocatalysis so far. The catalytically active species responsible for high enantioselectivity with substrate containing such a small linear substituent is assembled in situ from a bifunctional thiourea, prone to dimerization, and an organic acid, as evidenced by DOSY NMR. The resulting α,β-diamino acid derivatives were subjected to further derivatization: as an example, gold-catalyzed intramolecular hydroamination of alkynes gave chiral spirocyclic dihydropyrrole. Alternatively, related squaramide catalyst enabled a Mannich reaction of azlactones with N-aryl or alkyl glyoxylate imines. Reduction of these adducts gave access to 2,3-diaminobutyrolactones or 2,3-diamino-1,4-diol with a tertiary and a quaternary stereocenter.
- ?abka, Matej,Kocian, Adrián,Bilka, Stanislav,Andrej?ák, Samuel,?ebesta, Radovan
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p. 6077 - 6087
(2019/09/12)
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- Exploring the 7-oxo-thiazolo[5,4-d]pyrimidine core for the design of new human adenosine A3 receptor antagonists. Synthesis, molecular modeling studies and pharmacological evaluation
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A new series of 5-methyl-thiazolo[5,4-d]pyrimidine-7-ones bearing different substituents at position 2 (aryl, heteroaryl and arylamino groups) was synthesized and evaluated in radioligand binding assays to determine their affinities at the human (h) A1, A2A, and A3 adenosine receptors (ARs). Efficacy at the hA2B and antagonism of selected ligands at the hA3 were also assessed through cAMP experiments. Some of the new derivatives exhibited good to high hA3AR affinity and selectivity versus all the other AR subtypes. Compound 2-(4-chlorophenyl)-5-methyl-thiazolo[5,4-d]pyrimidine-7-one 4 was found to be the most potent and selective ligand of the series (Ki hA3 Combining double low line 18 nM). Molecular docking studies of the reported derivatives were carried out to depict their hypothetical binding mode in our hA3 receptor model.
- Varano, Flavia,Catarzi, Daniela,Squarcialupi, Lucia,Betti, Marco,Vincenzi, Fabrizio,Ravani, Annalisa,Varani, Katia,Dal Ben, Diego,Thomas, Ajiroghene,Volpini, Rosaria,Colotta, Vittoria
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p. 105 - 121
(2015/04/22)
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- Synthesis of new ligands for targeting the S1P1 receptor
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Sphingosine-1-phosphate (S1P) influences various fundamental biological processes by interacting with a family of five G protein-coupled receptors (S1P1-5). FTY720, a sphingosine analogue, which was approved for treatment of relapsing forms of multiple sclerosis, is phosphorylated in vivo and acts as an agonist of four of the five S1P receptor subtypes. Starting from these lead structures we developed new agonists for the S1P1 receptor. The biological activity was tested in vivo and promising ligands were fluorinated at different positions to identify candidates for positron emission tomography (PET) imaging after [18F]-labelling. The radioligands shall enable the imaging of S1P1 receptor expression in vivo and thus may serve as novel imaging markers of S1P-related diseases.
- Schilson, Stefanie S.,Keul, Petra,Shaikh, Rizwan S.,Sch?fers, Michael,Levkau, Bodo,Haufe, Günter
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supporting information
p. 1011 - 1026
(2015/03/04)
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- Phenylpropenamide derivatives: Anti-hepatitis B virus activity of the Z isomer, SAR and the search for novel analogs
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Phenylpropenamides have been reported to be a class of non-nucleoside inhibitors of the hepatitis B virus (HBV). This class of compounds was explored with the objective of developing potent anti-HBV agents, with a novel mechanism of action, that could be combined with nucleos(t)ide analogs currently used to treat HBV infection. To accomplish this objective a series of substituted arylpropenamide derivatives were prepared and the E and Z geometrical isomers were separated. The structural identity of each of the E and Z isomers was determined by single crystal X-ray crystallography. Contrary to previous reports, the activity of this class of molecules resides in the Z isomer. Further structure-activity relationship studies around the active Z isomer identified compounds that displayed potent antiviral activity against HBV with EC90 value of approximately 0.5 μM in vitro. Attempts to develop ring constrained analogs did not lead to active HBV inhibitors.
- Wang, Peiyuan,Naduthambi, Devan,Mosley, Ralph T.,Niu, Congrong,Furman, Phillip A.,Otto, Michael J.,Sofia, Michael J.
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scheme or table
p. 4642 - 4647
(2011/09/12)
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- Structure-activity relationships of heteroaromatic esters as human rhinovirus 3C protease inhibitors
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Human rhinovirus 3C protease (HRV 3Cpro) is known to be a promising target for development of therapeutic agents against the common cold because of the importance of the protease in viral replication as well as its expression in a large number of serotypes. To explore non-peptidic inhibitors of HRV 3Cpro, a series of novel heteroaromatic esters was synthesized and evaluated for inhibitory activity against HRV 3Cpro, to determine the structure-activity relationships. The most potent inhibitor, 7, with a 5-bromopyridinyl group, had an IC50 value of 80 nM. In addition, the binding mode of a novel analog, 19, with the 4-hydroxyquinolinone moiety, was explored by molecular docking, suggesting a new interaction in the S1 pocket.
- Im, Isak,Lee, Eui Seung,Choi, Soo Jeong,Lee, Ju-Yeon,Kim, Yong-Chul
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scheme or table
p. 3632 - 3636
(2010/03/24)
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- Convenient preparation of substituted 5-aminooxazoles via a microwave-assisted Cornforth rearrangement
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The preparation of oxazole-4-carboxamides and their subsequent thermal rearrangement to 5-aminooxazole-4-carboxylates is optimized in a high-speed microwave-assisted procedure. The reaction sequence is effective with a variety of substituted oxazoles, and produces products in good yield and high purity.
- Nolt, M. Brad,Smiley, Mark A.,Varga, Sandor L.,McClain, Ray T.,Wolkenberg, Scott E.,Lindsley, Craig W.
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p. 4698 - 4704
(2007/10/03)
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- Organocatalyzed route to enantioenriched pipecolic esters: decarboxylation of an aminomalonate hemiester
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Enantioenriched pipecolic esters were prepared in good yields in the decarboxylation, at room temperature, of N-protected piperidinohemimalonates catalyzed by cinchona alkaloids. Enantiomeric excesses as high as 72% were obtained when using 9-epi-cinchonine and the N-benzoyl substituted piperidinohemimalonate. A detailed study of the different reaction parameters revealed that the selectivity of this noncovalent organocatalyzed reaction is strongly dependent on the solvent, toluene or carbon tetrachloride being the best ones. The whole process based on the malonic acid synthesis was successfully tested on a 10 mmolar scale and established a practical alternative to the asymmetric protonation of lithium enolates.
- Seitz, Thomas,Baudoux, Jér?me,Bekolo, Henri,Cahard, Dominique,Plaquevent, Jean-Christophe,Lasne, Marie-Claire,Rouden, Jacques
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p. 6155 - 6165
(2007/10/03)
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- FIVE-MEMBERED HETEROCYCLIC DERIVATIVE
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The present invention relates to a compound represented by formula (I): a salt of the compound, or a solvate of the compound or the salt; a drug containing any of the compounds, the salts, and the solvates; a preventive and/or therapeutic agent for an ischemic disease containing any of the compounds, the salts, and the solvates; and a platelet coagulation inhibitor containing any of the compounds, the salts, and the solvates. The compound of the present invention is useful as a strong platelet coagulation inhibitor without inhibiting COX-1 or COX-2.
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Page/Page column 40-41
(2010/11/08)
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- 4-hydroxy-2-quinolones. 31. 3-amino-1R-2-oxo-4-hydroxyquinolines and their acyl derivatives
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An alternative method has been developed for preparing and studying the antioxidant activity of 3-acylamino-2-oxo-4-hydroxyquinolones. Results are presented from an investigation of the antithyroid and antimicrobial action of the intermediate 2-oxo-3-(1-pyridinio)quinolin-4-olates and the 3-amino-2-oxo-4-hydroxyquinolines. 1997 Plenum Publishing Corporation.
- Ukrainets,Taran,Sidorenko,Gorokhova,Ogirenko,Turov,Filimonova
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p. 960 - 970
(2007/10/03)
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