35600-34-1Relevant articles and documents
Mechanistic investigation and DFT calculation of the new reaction between S-methylisothiosemicarbazide and methyl acetoacetate
Markovic, Violeta,Markovic, Svetlana,Janicijevic, Ana,Rodic, Marko V.,Leovac, Vukadin M.,Todorovic, Nina,Trifunovic, Snezana,Joksovic, Milan D.
, p. 2127 - 2136 (2013)
A study on the synthesis and mechanistical aspects of formation of 3-methyl-5-oxo-3-pyrazolin-1-carboxamide (MOPC) starting from S-methylisothiosemicarbazide hydrogen iodide and methyl acetoacetate was performed. In the alkaline aqueous solution, the intermediate methyl acetoacetate S-methylisothiosemicarbazone undergoes substitution of CH 3S- anion by hydroxide anion, cyclization, carbanion formation, and elimination of methanol, thus yielding corresponding Na-enolate salt of pyrazol-5-one derivative. The structure of the compound obtained after protonation of the formed enolate salt was determined by means of spectroscopic techniques and single-crystal X-ray diffraction analysis. The mechanism of conversion of methyl acetoacetate S-methylisothiosemicarbazone into MOPC was investigated by means of the B3LYP functional, and it was found that the reaction is thermodynamically controlled.
Structure-activity relationships of lipopolysaccharide sequestration in guanylhydrazone-bearing lipopolyamines
Wu, Wenyan,Sil, Diptesh,Szostak, Michal L.,Malladi, Subbalakshmi S.,Warshakoon, Hemamali J.,Kimbrell, Matthew R.,Cromer, Jens R.,David, Sunil A.
, p. 709 - 715 (2009)
The toxicity of Gram-negative bacterial endotoxin (lipopolysaccharide, LPS) resides in its structurally highly conserved glycolipid component called lipid A. Our major goal has been to develop small-molecules that would sequester LPS by binding to the lipid A moiety, so that it could be useful for the prophylaxis or adjunctive therapy of Gram-negative sepsis. We had previously identified in rapid-throughput screens several guanylhydrazones as potent LPS binders. We were desirous of examining if the presence of the guanylhydrazone (rather than an amine) functionality would afford greater LPS sequestration potency. In evaluating a congeneric set of guanylhydrazone analogues, we find that C16 alkyl substitution is optimal in the N-alkylguanylhydrazone series; a homospermine analogue with the terminal amine N-alkylated with a C16 chain with the other terminus of the molecule bearing an unsubstituted guanylhydrazone moiety is marginally more active, suggesting very slight, if any, steric effects. Neither C16 analogue is significantly more active than the N-C16-alkyl or N-C16-acyl compounds that we had characterized earlier, indicating that basicity of the phosphate-recognizing cationic group, is not a determinant of LPS sequestration activity.
Selenium-containing heterocycles from isoselenocyanates: Synthesis of 5-amino-2,4-dihydro-3H-1,2,4-triazole-3-selones
Sommen, Geoffroy L.,Linden, Anthony,Heimgartner, Heinz
, p. 641 - 651 (2007)
The reaction of S-methylisothiosemicarbazide hydroiodide (=S-methyl hydrazinecarboximido-thioate hydroiodide; 1), prepared from thiosemicarbazide by treatment with MeI in EtOH, and aryl isoselenocyanates 5 in CH 2Cl2 affords 3H-1,2,4-triazole-3-selone derivatives 7 in good yield (Scheme 2, Table 10). During attempted crystallization, these products undergo an oxidative dimerization to give the corresponding bis(4H-1,2,4-triazol-3-yl) diselenides 11 (Scheme 3). The structure of 11a was established by X-ray crystallography.
TRIAZOLE-PYRIDINYL SUBSTITUTED AZACYCLOHEXYL ACETIC ACID COMPOUNDS AS LPA RECEPTOR ANTAGONISTS
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Paragraph 0465, (2022/02/28)
This application relates to novel substituted azacyclohexyl acetic acid compounds, their manufacture, pharmaceutical compositions comprising them, and their use as medicaments for treating a disease associated with dysregulation of lysophosphatidic acid receptors (LPA).
Synthesis and antioxidant activities of new nickel(II) complexes derived from 4-benzy-loxysalicylidene-S-methyl/propyl thiosemicarbazones
Eglence-Bakir, Songül
, p. 835 - 844 (2021/07/26)
Six nickel(II) complexes of the N2O2chelating thiosemicarbazones were synthesized using N1-4-benzyloxysalicylidene-S-methyl/propyl thiosemicarbazone and methoxy-substitute-salicylaldehydes in the presence of Ni(II) ion by template reaction. The structures of thiosemicarbazones and nickel(II) complexes were characterized by elemental analysis, UV-Vis, IR, and 1H-NMR spectroscopies. The structure of the N1-4-benzyloxysalicylidene-S-propyl thiosemicarbazone (2) was determined by X-ray single-crystal diffraction method. The total antioxidant capacities of synthesized compounds were evaluated by using cupric reducing antioxidant capacity (CUPRAC) method. The thiosemicarbazones exhibited more potent antioxidant capacity than Ni(II) complexes. Trolox equivalent antioxidant capacity (TEAC) of 1c was found highest in tested nickel(II) complexes. In addition, antioxidant activities of tested compounds were evaluated by using the hydroxyl radical, DPPH radical, and ABTS radical scavenging abilities of these compounds.
S-alkylated thiosemicarbazone derivatives: Synthesis, crystal structure determination, antimicrobial activity evaluation and molecular docking studies
?zkul, Ceren,ülküseven, Bahri,?ahin, Onur,Gündüz, Miyase G?zde,Kaya, Bü?ra,Rekha, Estharla Madhu,Sriram, Dharmarajan
, (2021/07/01)
Increasing antimicrobial resistance is one of the most serious threats to human health worldwide. Therefore, there is an urgent need for the discovery of novel antimicrobial agents. Herein, we presented the synthesis of ten thiosemicarbazone derivatives (T1-T10) obtained by the reaction of S-alkylthiosemicarbazide with various dicarbonyl derivatives. The compounds were characterized by IR, 1H NMR, ESI-MS and X-ray crystallography. Reaction with the dicarbonyl compound bearing the 4-fluorobenzoyl group unexpectedly gave a pyrazole derivative (T8) containing the entire S-methylthiosemicarbazone backbone. We extensively screened these derivatives for their antimicrobial activities against Mycobacterium tuberculosis and various bacterial and Candida strains. Additionally, the biofilm inhibition capacity of T8 was evaluated on Staphylococcus epidermidis and Pseudomonas aeruginosa biofilm positive strains. To find out the potential mechanism of anti-biofilm activity against PAO1, the docking studies of T8 were carried out into the binding site of LasR, which is the main regulator of bacterial cell-to-cell communication system known as quorum sensing.
New M(II) (M=Mn, Co, Ni, Cu, Zn, Pd) coordinative compounds with 2-formylpyridine S-methyl-isothiosemicarbazide
Danac, Ramona,Pui, Aurel,Corja, Ion,Amarandi, Roxana-Maria,Ciobanu, Catalina Ionica,Apostu, Mircea-Odin,Palamarciuc, Oleg
, (2020/02/03)
The synthesis and structure of the new organic proligand 2-formylpyridine S-methyl-isothiosemicarbazone in a bi-protonated form (HL.2HCl) and its coordination compounds with Mn(II) - [Mn(HL)·Cl2], Co(III) - [CoL2]·ClO4, Ni(II) - [Ni(HL)2]·2ClO4, Cu(II) - [Cu(HL)Cl2]·(H2O), Zn(II) - [Zn(HL)2]·2(ClO4)·(H2O) and Pd(II) - [Pd(HL)·Cl]·Cl are reported. According to the X-ray investigation, the ligand has the molecular form of HL in the case of Mn(II), Cu(II), Zn(II) and Pd(II) compounds, and the deprotonated form L? in case of the Co(III) complex. The ligand coordinates to the metal ions via a N,N,N set of donors atoms in case of Zn(II), Cu(II) and Co(III). For Mn(II), the ligand coordinates via N,N donor atoms, whereas in the case of Pd(II) metal ions, the coordination sphere is N,N,S. This latter coordination mode (via S(CH3)) has been previously reported in case of salicylaldehyde S-alkyl-isothiosemicarbazones.
Comparison of non-covalent interactions and spectral properties in 1-methyl-3-methylthio-5-phenyl-1,2,4-triazinium mono- and tetraiodide crystals
Yushina, Irina D.,Rudakov, Boris V.,Stash, Adam I.,Bartashevich, Ekaterina V.
, p. 1981 - 1991 (2019/07/17)
The reaction of 1-methyl-3-methylthio-5-phenyl-1,2,4-triazinium (MTPT) iodide with diiodine in a solution leads to monoiodide crystal structure that in excess of iodine gives the unusual tetraiodide anion with two central iodine atoms in disorder. The bonding within the anion has been characterized as I–…I2…I–; the existence of the bound iodine molecule inside has been proven by the characteristic band in experimental and calculated Raman spectra. Non-covalent interactions of MTPT in considered crystal structures are different. Monoiodide anion as a strong electron donor allows the formation of the S…I chalcogen bonds that are absent in tetraiodide structure. The features of halogen bonds within the I4 2– anion are?also performed.
Synthetic Route Design of AZD4635, an A2AR Antagonist
Littleson, Mairi M.,Campbell, Andrew D.,Clarke, Adam,Dow, Mark,Ensor, Gareth,Evans, Matthew C.,Herring, Adam,Jackson, Bethany A.,Jackson, Lucinda V.,Karlsson, Staffan,Klauber, David J.,Legg, Danny H.,Leslie, Kevin W.,Morav?ík, ?tefan,Parsons, Chris D.,Ronson, Thomas O.,Meadows, Rebecca E.
, p. 1407 - 1419 (2019/08/12)
The AstraZeneca approach to synthetic Route Design is exemplified through our AZD4635 chemical development program. The identification of possible new route concepts is presented, as well as their subsequent prioritization for practical exploration based on project objectives. Selected ideas were tested to demonstrate proof of concept for the bond formation strategy and, where successful, were fed into a decision tool based on key SELECTion principles.
1,3,4-Thiadiazole Compounds and Their Use in Treating Cancer
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Paragraph 0296; 0297, (2017/06/30)
A compound of Formula (I): or a pharmaceutically acceptable salt thereof, where: Q can be 1,2,4-triazin-3-yl, pyridazin-3-yl, 6-methylpyridazin-3-yl, or 6-fluoropyridazin-3-yl; R1 can be hydrogen, methoxy, trifluoromethoxy, oxetan-3-yl, 3-fluoroazetidin-1-yl, 3-methoxyazetidin-1-yl, or 3,3-difluoroazetidin-1-yl; R2 can be hydrogen or fluoro; R3 can be hydrogen or methoxy; and R4 can be methoxy, ethoxy, or methoxymethyl; provided that when R1 is hydrogen, methoxy or trifluoromethoxy, then R3 is not hydrogen, and/or R4 is methoxymethyl. The compound of formula (I) can inhibit glutaminase, e.g., GLS1.
