33125-05-2Relevant articles and documents
Stille coupling of stereochemically defined α- sulfonamidoorganostannanes
Kells, Kevin W.,Chong, J. Michael
, p. 15666 - 15667 (2004)
Addition of tributylstannylmetallics to (R)-tert-butanesulfonimine derivatives of arylaldehydes provides α-sulfinamidostannanes with high (>98% de) diastereoselectivities. Oxidation of these compounds with m-CPBA gives α-sulfonamidostannanes which undergo Pd/Cu-catalyzed Stille-type couplings with benzoyl chloride. Best yields are achieved using the electron-rich tris(2,4,6-trimethoxyphenyl)phosphine as the ligand. Inversion of configuration at the benzylic carbon is observed. Copyright
Synthesis ofN-Boc-α-amino Acids from Carbon Dioxide by Electrochemical Carboxylation ofN-Boc-α-aminosulfones
Senboku, Hisanori,Minemura, Yoshihito,Suzuki, Yuto,Matsuno, Hidetoshi,Takakuwa, Mayu
, p. 16077 - 16083 (2021/10/12)
Electrochemical reduction ofN-Boc-α-aminosulfones in DMF using an undivided cell equipped with a Pt plate cathode and an Mg rod anode under atmospheric pressure of bubbling carbon dioxide through the solution under constant current conditions resulted in a reductive C-S bond cleavage with elimination of benzenesulfinate ion generating the corresponding anion species followed by fixation of carbon dioxide to give the correspondingN-Boc-α-amino acids in moderate to good yields.
Discovery of M3Antagonist-PDE4 Inhibitor Dual Pharmacology Molecules for the Treatment of Chronic Obstructive Pulmonary Disease
Armani, Elisabetta,Rizzi, Andrea,Capaldi, Carmelida,De Fanti, Renato,Delcanale, Maurizio,Villetti, Gino,Marchini, Gessica,Pisano, Anna Rita,Pitozzi, Vanessa,Pittelli, Maria Gloria,Trevisani, Marcello,Salvadori, Michela,Cenacchi, Valentina,Puccini, Paola,Amadei, Francesco,Pappani, Alice,Civelli, Maurizio,Patacchini, Riccardo,Baker-Glenn, Charles A.G.,Van De Po?l, Hervé,Blackaby, Wesley P.,Nash, Kevin,Amari, Gabriele
supporting information, p. 9100 - 9119 (2021/07/19)
In this paper, we report the discovery of dual M3 antagonist-PDE4 inhibitor (MAPI) compounds for the inhaled treatment of pulmonary diseases. The identification of dual compounds was enabled by the intuition that the fusion of a PDE4 scaffold derived from our CHF-6001 series with a muscarinic scaffold through a common linking ring could generate compounds active versus both the transmembrane M3 receptor and the intracellular PDE4 enzyme. Two chemical series characterized by two different muscarinic scaffolds were investigated. SAR optimization was aimed at obtaining M3 nanomolar affinity coupled with nanomolar PDE4 inhibition, which translated into anti-bronchospastic efficacy ex vivo (inhibition of rat trachea contraction) and into anti-inflammatory efficacy in vitro (inhibition of TNFα release). Among the best compounds, compound 92a achieved the goal of demonstrating in vivo efficacy and duration of action in both the bronchoconstriction and inflammation assays in rat after intratracheal administration.
Anti-amyotrophic lateral sclerosis effect of thiourea homologues compound
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Paragraph 0007-0008, (2020/12/30)
The invention relates to an anti-amyotrophic lateral sclerosis effect of a thiourea homologues compound, and belongs to the technical field of motor neuron disease treatment. The technical problem tobe solved by the invention is that the thiourea homologues compound has the effect of resisting amyotrophic lateral sclerosis. The structure of the compound is shown as the description, and the compound has the effect of resisting amyotrophic lateral sclerosis.
Synthesis, characterization and antimicrobial activity of some novel 1-substituted benzimidazole derivatives
Astley, Demet,Isik, Erkut,Yasa, Ihsan,Yuksekdanaci, Seda
, p. 1372 - 1379 (2020/10/06)
Background: Benzimidazole derivatives are an important class of heterocyclic compounds in organic chemistry as they are related to a wide range of biological properties, including antimicrobial activity. Methods: A series of 1-naphthoyl and benzoyl benzimidazole derivatives were synthesised, identified and screened for their antimicrobial activities against a number of different test organisms such as Escherichia coli, Pseudomonas aureginosa, Klebsiella pneumoniae, Staphylococcus aureus, En-terococcus faecalis, Bacillus cereus, Salmonella typhimurium, Candida albicans (yeast). Results and Discussion: Benzimidazole derivatives (3a-d) were synthesised by using 4 different aminoacids. L-methionine, L-isoleucine, D-Phenylysine and L-Phenylamine as starting materials in the study. Experimental studies involve the use of benzimidazole derivatives (3a-d) of the selected amino acids to synthesize the benzoyl and naphthoyl derivatives of benzimidazole (4a-d, 5a-c). The structures of the synthesized compounds were confirmed by spectroscopic analyses (FTIR,1H-NMR,13C-NMR) and elemental analysis. Conclusion: In this study, only one compound (5a) showed a low MIC value against the eukaryotic microorganism C. albicans. The other six compounds showed higher antimicrobial activities against the prokaryotes C. albicans which is a normal flora in the mouth but is one of the organisms that cause infections leading to the weakening of the human immune system. Compound 5a is a can-didate for future alternative antimicrobial drugs against C. albicans infections. In addition, compound 5a has a potential to be used as an inhibitor against P. aureginosa for the treatment of cyst-ic fibrosis.
ALLOSTERIC EGFR INHIBITORS AND METHODS OF USE THEREOF
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Page/Page column 62-63; 90, (2021/01/22)
The disclosure relates to compounds that act as an allosteric inhibitors of epidermal growth factor receptor (EGFR); pharmaceutical compositions comprising the compounds; and methods of treating or preventing kinase-mediated disorders, including cancer and other proliferation diseases.
A new type of L-Tertiary leucine-derived ligand: Synthesis and application in Cu(II)-catalyzed asymmetric Henry reactions
Cai, Zedong,Lan, Ting,Ma, Pengfei,Zhang, Jingfang,Yang, Qingqing,He, Wei
, (2019/08/08)
A new series of Schiff bases derived from amino acids were developed as chiral ligands for Cu(II)-catalyzed asymmetric Henry reactions. The optimum ligand 7d exhibited outstanding catalytic efficiency in the Cu(II)-catalyzed asymmetric Henry additions of four nitroalkanes to different kinds of aldehydes to produce 76 desired adducts in high yields (up to 96%) with excellent enantioselectivities, up to 99% enantiomeric excess (ee).
Small-Molecule Activator of UNC-51-Like Kinase 1 (ULK1) That Induces Cytoprotective Autophagy for Parkinson's Disease Treatment
Ouyang, Liang,Zhang, Lan,Zhang, Shouyue,Yao, Dahong,Zhao, Yuqian,Wang, Guan,Fu, Leilei,Lei, Peng,Liu, Bo
supporting information, p. 2776 - 2792 (2018/04/23)
UNC-51-like kinase 1 (ULK1), the yeast Atg1 ortholog, is the sole serine-threonine kinase and initiating enzyme in autophagy, which may be regarded as a target in Parkinson's disease (PD). Herein, we discovered a small molecule 33i (BL-918) as a potent activator of ULK1 by structure-based drug design. Subsequently, some key amino acid residues (Arg18, Lys50, Asn86, and Tyr89) were found to be crucial to the binding pocket between ULK1 and 33i by site-directed mutagenesis. Moreover, we found that 33i induced autophagy via the ULK complex in SH-SY5Y cells. Intriguingly, this activator displayed a cytoprotective effect on MPP+-treated SH-SY5Y cells, as well as protected against MPTP-induced motor dysfunction and loss of dopaminergic neurons by targeting ULK1-modulated autophagy in mouse models of PD. Together, these results demonstrate the therapeutic potential to target ULK1, and 33i, the novel activator of ULK1, may serve as a candidate drug for future PD treatment.
Synthesis of Tripeptide Derivatives with Three Stereogenic Centers and Chiral Recognition Probed by Tetraaza Macrocyclic Chiral Solvating Agents Derived from d -Phenylalanine and (1 S,2 S)-(+)-1,2-Diaminocyclohexane via 1H NMR Spectroscopy
Feng, Lei,Gao, Guangpeng,Zhao, Hongmei,Zheng, Li,Wang, Yu,Stavropoulos, Pericles,Ai, Lin,Zhang, Jiaxin
, p. 13874 - 13887 (2018/11/23)
Enantiomers of a series of tripeptide derivatives with three stereogenic centers (±)-G1-G9 have been prepared from d- and l-α-amino acids as guests for chiral recognition by 1H NMR spectroscopy. In the meantime, a family of tetraaza macrocyclic chiral solvating agents (TAMCSAs) 1a-1d has been synthesized from d-phenylalanine and (1S,2S)-(+)-1,2-diaminocyclohexane. Discrimination of enantiomers of (±)-G1-G9 was carried out in the presence of TAMCSAs 1a-1d by 1H NMR spectroscopy. The results indicate that enantiomers of (±)-G1-G9 can be effectively discriminated in the presence of TAMCSAs 1a-1d by 1H NMR signals of multiple protons exhibiting nonequivalent chemical shifts (ΔΔδ) up to 0.616 ppm. Furthermore, enantiomers of (±)-G1-G9 were easily assigned by comparing 1H NMR signals of the split corresponding protons with those attributed to a single enantiomer. Different optical purities (ee up to 90%) of G1 were clearly observed and calculated in the presence of TAMCSAs 1a-1d, respectively. Intermolecular hydrogen bonding interactions were demonstrated through theoretical calculations of enantiomers of (±)-G1 with TAMCSA 1a by means of the hybrid functional theory with the standard basis sets of 3-21G of the Gaussian 03 program.
Dynamic Kinetic Resolution of N-Protected Amino Acid Esters via Phase-Transfer Catalytic Base Hydrolysis
Yamamoto, Eiji,Wakafuji, Kodai,Furutachi, Yuho,Kobayashi, Kaoru,Kamachi, Takashi,Tokunaga, Makoto
, p. 5708 - 5713 (2018/05/30)
Asymmetric base hydrolysis of α-chiral esters with synthetic small-molecule catalysts is described. Quaternary ammonium salts derived from quinine were used as chiral phase-transfer catalysts to promote the base hydrolysis of N-protected amino acid hexafluoroisopropyl esters in a CHCl3/NaOH (aq) via dynamic kinetic resolution, providing the corresponding products in moderate to good yields (up to 99%) with up to 96:4 er. Experimental and computational mechanistic studies using DFT calculation and pseudotransition state (pseudo-TS) conformational search afforded a TS model accounting for the origin of the stereoselectivity. The model suggested π-stacking and H-bonding interactions play essential roles in stabilizing the TS structures.
