4822-44-0Relevant academic research and scientific papers
Facile synthesis of spiro thiazolidinone via cyclic ketones, amines and thioglycolic acid by MCM-41-Schiff base-CuSO4·5H2O
Hui, Yonghai,Zhang, Yongfei,Luo, Yongyue,Li, Jianpeng,Wang, Yun,Gao, Tianming,Xia, Jialiang,Wang, Sheng,Zhang, Shiqi
, p. 521 - 532 (2020/10/19)
Mesoporous MCM-41-supported Schiff base and CuSO4?5H2O (MCM-41@Schiff base-CuSO4?5H2O) catalyzed one-pot three-component condensation of cyclic ketones, amines and thioglycolic acid in toluene. And a series of corresponding spiro thiazolidinone derivatives were obtained in high yields (up to 97%). The synthesized catalyst was characterized via FT-IR, XRD, SEM, TEM and EDS and can be easily recovered by centrifugation and reused at 10 times without any change in catalytic activity. Moreover, the scale-up experiment also demonstrated the practicability of the catalytic system on the condensation. The possible mechanisms pave the way to investigation on the reactions of other cyclic ketones with thioglycolic acid.
N-Aryl mercaptoacetamides as potential multi-target inhibitors of metallo-β-lactamases (MBLs) and the virulence factor LasB fromPseudomonas aeruginosa
Brunst, Steffen,Ducho, Christian,Frank, Denia,Hirsch, Anna K. H.,Kramer, Jan S.,Proschak, Ewgenij,Rotter, Marco,Voos, Katrin,Weizel, Lilia,Wichelhaus, Thomas A.,Yahiaoui, Samir,Haupenthal, J?rg
supporting information, p. 1698 - 1708 (2021/11/23)
Increasing antimicrobial resistance is evolving to be one of the major threats to public health. To reduce the selection pressure and thus to avoid a fast development of resistance, novel approaches aim to target bacterial virulence instead of growth. Another strategy is to restore the activity of antibiotics already in clinical use. This can be achieved by the inhibition of resistance factors such as metallo-β-lactamases (MBLs). Since MBLs can cleave almost all β-lactam antibiotics, including the “last resort” carbapenems, their inhibition is of utmost importance. Here, we report on the synthesis andin vitroevaluation ofN-aryl mercaptoacetamides as inhibitors of both clinically relevant MBLs and the virulence factor LasB fromPseudomonas aeruginosa. All testedN-aryl mercaptoacetamides showed low micromolar to submicromolar activities on the tested enzymes IMP-7, NDM-1 and VIM-1. The two most promising compounds were further examined in NDM-1 expressingKlebsiella pneumoniaeisolates, where they restored the full activity of imipenem. Together with their LasB-inhibitory activity in the micromolar range, this class of compounds can now serve as a starting point for a multi-target inhibitor approach against both bacterial resistance and virulence, which is unprecedented in antibacterial drug discovery.
Discovery of cyanopyridine scaffold as novel indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors through virtual screening and preliminary hit optimisation
Xu, Xi,Ren, Jie,Ma, Yinghe,Liu, Hongting,Rong, Quanjin,Feng, Yifan,Wang, Yameng,Cheng, Yu,Ge, Ruijia,Li, Zhiyu,Bian, Jinlei
, p. 250 - 263 (2019/01/10)
With the aim of discovering novel IDO1 inhibitors, a combined similarity search and molecular docking approach was employed to the discovery of 32 hit compounds. Testing the screened hit compounds has led to several novel submicromolar inhibitors. Especially for compounds LVS-019 with cyanopyridine scaffold, showed good IDO1 inhibitory activity. To discover more compounds with similar structures to LVS-019, a shape-based model was then generated on the basis of it and the second-round virtual screening was carried out leading to 23 derivatives. Molecular docking studies suggested a possible binding mode of LVS-019, which provides a good starting point for the development of cyanopyridine scaffold compounds as potent IDO1 inhibitor. To improve potency of these hits, we further designed and synthesised another 14 derivatives of LVS-019. Among these compounds, LBJ-10 showed improved potency compared to the hits and displayed comparable potency to the control GDC-0919 analogue. LBJ-10 can serve as ideal leads for further modifications as IDO1 inhibitors for cancer treatment.
Ambient temperature synthesis of spiro[indoline-3,2′-thiazolidinones] by a DBSA-catalyzed sequential reaction in water
Preetam, Amreeta,Nath, Mahendra
, p. 1502 - 1506 (2016/03/12)
An energy-efficient eco-friendly methodology for the synthesis of a series of pharmacologically important spiro[indoline-3,2′-thiazolidinones] has been developed by the reaction of primary amines with various isatin derivatives and thioglycolic acid in the presence of p-dodecylbenzenesulfonic acid (DBSA) as an efficient Br?nsted acid surfactant combined catalyst in aqueous medium at 25 °C. This synthetic protocol demonstrates several advantages such as operational simplicity, energy-efficiency, good to excellent isolated yields, and the use of a preferred green solvent system for the preparation of desired products.
Synthesis and cytotoxicity of thieno[2,3-b]pyridine and furo[2,3-b]pyridine derivatives
Hung, Joy M.,Arabshahi, Homayon J.,Leung, Euphemia,Reynisson, Jóhannes,Barker, David
, p. 420 - 437 (2015/02/19)
Forty seven thieno[2,3-b]pyridines-2-carboxamides, furo[2,3-b]pyridines-2-carboxamides and tetrahydrothieno[2,3-b]quinolones-2-carboxamides derivatives were synthesized and tested for their antiproliferative activity against the NCI-60 cell lines. The 5-keto-tetrahydrothieno[2,3-b]quinolones-2-carboxamides (series 17) were found to have the greatest activity, with the compound containing a 3-methoxyphenylcarboxamide (compound 17d) being the most active, with GI50values in the low nanomolar range against a range of cell lines, in particular the melanoma cell line MDA-MD-435 (GI50- 23 nM) and the breast cancer cell line MDA-MB-468 (GI50- 46 nM). Molecular modelling of series 17 against phosphoinositide specific-phospholipase C reveals that the side chains of the amino acids His356, Glu341, Arg549 and Lys438 are involved in hydrogen bonding with the ligands as well as a lipophilic pocket is occupied by the phenyl carboxamide moiety.
Synthesis of biologically important n-heteroaryl-2-(heteroarylthio) acetamides
Krishnaraj, Thulasiraman,Muthusubramanian, Shanmugam
, p. 1012 - 1019 (2014/08/05)
The synthesis of compounds having triazole and selena/thiadiazole rings connected by a chain having sulfur and nitrogen in the link has been described. The resultant N-heteroaryl-2-(heteroarylthio)acetamide may be biologically important as related compounds found application in the inhibition of HIV 1 replications.
Supported protic acid-catalyzed synthesis of 2,3-disubstituted thiazolidin-4-ones: Enhancement of the catalytic potential of protic acid by adsorption on solid supports
Kumar, Dinesh,Sonawane, Mukesh,Pujala, Brahmam,Jain, Varun K.,Bhagat, Srikant,Chakraborti, Asit K.
, p. 2872 - 2884 (2013/10/08)
The catalytic potential of various protic acids has been assessed for the one pot tandem condensation-cyclisation reaction involving an aldehyde, an amine, and thioglycolic acid to form 2,3-disubstituted thiazolidin-4-ones. The catalytic potential of the various protic acids that follows the order TfOH > HClO4 > H2SO4 ～ p-TsOH > MsOH ～ HBF4 > TFA ～ AcOH is improved significantly by adsorption on solid supports, in particular using silica gel (230-400 mesh size), with the resulting relative catalytic potential following the order HClO 4-SiO2 > TfOH-SiO2 ? H2SO 4-SiO2 > p-TsOH-SiO2 > MsOH-SiO 2 ～ HBF4-SiO2 > TFA-SiO2 ～ HOAc-SiO2. The better catalytic potential of HClO 4-SiO2 as compared to that of Tf-SiO2, although TfOH is a stronger protic acid than HClO4, can be rationalised through a transition state model depicting the interaction of the individual protic acid with SiO2. The catalytic efficiency of HClO4 adsorbed on various solid supports was in the order HClO4-SiO 2 ? HClO4-K10 > HClO4-KSF > HClO 4-TiO2 ～ HClO4-Al2O3. The catalytic system HClO4-SiO2 is compatible with different variations of aldehydes (aryl/heteroaryl/alkyl/cycloalkyl) and the amines (aryl/heteroaryl/arylalkyl/alkyl/cycloalkyl) affording the desired 2,3-disubstituted thiazolidin-4-ones in 70-87% yields (43 examples). The electronic and the steric factors associated with the aldehydes and the amines provide a handle for selective thiazolidinone formation and were found to be dependent on the extent of imine formation. No significant amount of thiazolidinone formation took place during the reaction of the preformed amide (synthesised from the amine and thioglycolic acid) with benzaldehyde suggesting that the reaction proceeds through the initial reversible imine formation followed by cyclocondensation of the preformed imine with thioglycolic acid, the reversible imine formation being the determining step to control selectivity of thiazolidinone formation in competitive environments. The feasibility of a large scale reaction and catalyst recycling/reuse is demonstrated.
Metal complexes of a new class of polydentate Mannich bases: Synthesis and spectroscopic characterisation
Al-Jeboori, Mohamad J.,Al-Jebouri, Fahad A.,Al-Azzawi, Muayed A.R.
experimental part, p. 163 - 170 (2012/02/02)
A new class of polydentate Mannich bases featuring an N2S 2 donor system, bis((2-mercapto-N-phenylacetamido)methyl)phosphinic acid H3L1 and bis((2-mercapto-N-propylacetamido)methyl) phosphinic acid H3L2, has been synthesised from condensation of phosphinic acid and paraformaldehyde with 2- mercaptophenylacetamide W1 and 2-mercaptopropylacetamide W2, respectively. Monomeric complexes of these ligands, of general formula K2[Cr III(Ln)Cl2], K3[M′ II(Ln)Cl2] and K[M(Ln)] (M′ = Mn(II) or Fe(II); M = Co(II), Ni(II), Cu(II), Zn(II), Cd(II) or Hg(II); n = 1, 2) are reported. The structures of new ligands, mode of bonding and overall geometry of the complexes were determined through IR, UV-Vis, NMR, and mass spectral studies, magnetic moment measurements, elemental analysis, metal content, and conductance. These studies revealed octahedral geometries for the Cr(III), Mn(II) and Fe(II) complexes, square planar for Ni(II) and Cu(II) complexes and tetrahedral for the Co(II), Zn(II), Cd(II) and Hg(II) complexes. Complex formation studies via molar ratio in DMF solution were consistent to those found in the solid complexes with a ratio of (M:L) as (1:1).
Monolayer assemblies of a de novo designed 4-α-helix bundle carboprotein and its sulfur anchor fragment on Au(111) surfaces addressed by voltammetry and in situ scanning tunneling microscopy
Brask, Jesper,Wackerbarth, Hainer,Jensen, Knud J.,Zhang, Jingdong,Chorkendorff, Ib,Ulstrup, Jens
, p. 94 - 104 (2007/10/03)
Mapping and control of proteins and oligonucleotides on metallic and nonmetallic surfaces are important in many respects. Electrochmical techniques based on single-crystal electrodes and scanning probe microscopies directly in aqueous solution (in situ SPM) have recently opened perspectives for such mapping at a resolution that approaches the single-molecule level. De novo design of model proteins has evolved in parallel and holds promise for testing and controlling protein folding and for new tailored protein structural motifs. In this report we combine these two strategies. We present a scheme for the synthesis of a new 4-α-helix bundle carboprotein built on a galactopyranoside derivative with a thiol anchor aglycon suitable for surface immobilization on gold. The carboprotein with thiol anchor in monomeric and dimeric (disulfide) form, the thiol anchor alone, and a sulfur-free 4-α-helix bundle carboprotein without thiol anchor have been prepared and investigated for comparison. Cyclic and differential pulse voltammetry (DPV) of the proteins show desorption peaks around -750 mV (SCE), whereas the thiol anchor desorption peak is at -685 mV. The peaks are by far the highest for thiol monomeric 4-α-helix bundle carboprotein and the thiol anchor. This pattern is supported by capacitance data. The DPV and capacitance data for the thiolated 4-α-helix bundle carboproteins and the thiol anchor hold a strong Faradaic reductive desorption component as supported by X-ray photoelectron spectroscopy. The desorption peak of the sulfur-free 4-α-helix bundle carboprotein, however, also points to a capacitive component. In situ scanning tunneling microscopy (in situ STM) of the thiol anchor discloses an adlayer with small domains and single molecules ordered in pin-striped supramolecular structures. In situ STM of thiolated 4-α-helix bundle carboprotein monomer shows a dense monolayer in a broad potential range on the positive side of the desorption potential. The coverage decreases close to this potential and single-molecule structures become apparent. The in situ STM contrast is also strengthened, indicative of a new redox-based tunneling mechanism. The data overall suggest that single-molecule mapping of natural and synthetic proteins on well-characterized surfaces by electrochemistry and in situ STM is within reach.
Designer ligands. Part 2. Synthesis of novel, dithiadicarboxamide ligands
Hagemann, Justin P.,Kaye, Perry T.
, p. 303 - 310 (2007/10/03)
Novel, sulfur-containing diamide ligands have been synthesised, and preliminary complexation studies indicate their selectivity for palladium (II) over copper (II), nickel (II) and cobalt (II).
