38749-68-7Relevant academic research and scientific papers
Synthesis and structure-activity relationship studies of n-monosubstituted aroylthioureas as urease inhibitors
Dawalamu,Fang, Hai-Lian,Fu, Zi-Juan,Li, Fang,Li, Ke,Li, Wei-Yi,Liu, Li,Ni, Wei-Wei,Ouyang, Hui,Xiao, Zhu-Ping,Ye, Ya-Xi,Zhu, Hai-Liang,Zhu, Wen-Yan,Zou, Xia
, p. 1046 - 1059 (2021/11/30)
Background: Thiourea is a classical urease inhibitor which is usually used as a positive control, and many N,N'-disubstituted thioureas have been determined as urease inhibitors. However, due to steric hindrance, N,N'-disubstituted thiourea motif could not bind urease as thiourea. On the contrary, N-monosubstituted thiourea with a tiny thiourea motif could theoretically bind into the active pocket as thiourea. Objective: A series of N-monosubstituted aroylthioureas were designed and synthesized for evaluation as urease inhibitors. Methods: Urease inhibition was determined by the indophenol method and IC50 values were calculated using computerized linear regression analysis of quantal log dose-probit functions. The kinetic parameters were estimated via surface plasmon resonance (SPR) and by nonlinear regression analysis based on the mixed type inhibition model derived from Michaelis-Menten kinetics. Results: Compounds b2, b11, and b19 reversibly inhibited urease with a mixed mechanism, and showed excellent potency against both cell-free urease and urease in the intact cell, with IC50 values being 90-to 450-fold and 5-to 50-fold lower than the positive control acetohydroxamic acid, respectively. The most potent compound b11 showed an IC50 value of 0.060 ± 0.004μM against cell-free urease, which bound to urea binding site with a very low KD value (0.420±0.003nM) and a very long residence time (6.7 min). Compound b11 was also demonstrated to have very low cytotoxicity to mammalian cells. Conclusion: The results revealed that N-monosubstituted aroylthioureas bound to the active site of urease as expected, and represent a new class of urease inhibitors for the development of potential therapeutics against infections caused by urease-containing pathogens.
Identification of novel thiourea-stilbene-triazine conjugates as persuasive lymphoid tyrosine phosphatase inhibitors
Batool, Iram,Jabeen, Farukh,Saeed, Aamer,Shabir, Ghulam,Vellore, Nadeem Ahmed
, p. 3400 - 3411 (2020/08/19)
A library of novel thiourea-based symmetrical stilbene-triazines (5a-i) was synthesized in an effort to develop new protein tyrosine phosphatase LYP inhibitors. The versatile nature of 2,4,6-trichloro-1,3,5-triazine allows considerable scope for derivatization and hence exploration of structure activity relationships. A convenient and versatile three-step synthetic approach involved the successive replacement of the two chloro groups of 2,4,6-trichloro-1,3,5-triazine by a variety of substituents for structural modification. The newly synthesized derivatives were subjected to tyrosine phosphatase LYP inhibition studies. The results for the in vitro bioassays were promising with the identification of compound 5k and 5l having a 4-methyl and 4-methoxy substituent on phenyl ring, as the lead and selective candidate for LYP inhibition with an IC50 value of 2.1 ± 0.05 μM and 28 ± 3.3 μM, respectively. Moreover, docking studies were carried out to determine the possible interaction sites of thiourea-based stilbene-triazine compounds with Lymphoid Tyrosine Phosphatase. Results of docking computations further ascertained the inhibitory potential of compound 5k and 5l. The results indicated that the compound 5k may serve as a structural model for the design of most potent LYP inhibitors.
Chalcone-Thiazole Hybrids: Rational Design, Synthesis, and Lead Identification against 5-Lipoxygenase
Doble, Mukesh,Manju, S. L.,Sinha, Shweta
, (2019/10/08)
A hybrid pharmacophore approach is used to design and synthesize novel chalcone-thiazole hybrid molecules. Herein, thiazole has been hybridized with chalcone to obtain a new class of 5-LOX inhibitors. In vitro biological evaluation showed that most of the compounds were better 5-LOX inhibitors than the positive control, Zileuton (IC50 = 1.05 ± 0.03 μM). The best compounds in the series, namely, 4k, 4n, and 4v (4k: IC50 = 0.07 ± 0.02 μM, 4n: IC50 = 0.08 ± 0.05 μM, 4v: 0.12 ± 0.04 μM) are found to be 10 times more active than previously reported 2-amino thiazole (2m: IC50 = 0.9 ± 0.1 μM) by us. Further, 4k has redox (noncompetitive) while 4n and 4v act through a competitive inhibition mechanism. SAR indicated that the presence of methoxy/methyl either in the vicinity of chalcone or both thiazole and chalcone contributed to the synergistic inhibitory effect.
4′-Methyl-4,5′-bithiazole-based correctors of defective ΔF508-CFTR cellular processing
Yoo, Choong Leol,Yu, Gui Jun,Yang, Baoxue,Robins, Lori I.,Verkman,Kurth, Mark J.
, p. 2610 - 2614 (2008/12/21)
The synthesis and ΔF508-CFTR corrector activity of a 148-member methylbithiazole-based library are reported. Synthetic routes were devised and optimized to generate methylbithiazole analogs in four steps. Corrector potency and efficacy were assayed using epithelial cells expressing human ΔF508-CFTR. These structure-activity data establish that the bithiazole substructure plays a critical function; eight novel methylbithiazole correctors were identified with low micromolar potencies.
A facile synthesis of substituted N-benzoylthiourea
Xu, Xiaoyong,Zhongli,Yang, Zhengyu,Chen, Gang,Qian, Xuhong
, p. 2585 - 2592 (2007/10/03)
One pot reaction of benzoyl isothiocyanate and Tris(hydroxymethyl)aminomethane (Tris) at room temperature with polyethylene glycol-400 (PEG-400) as solid-liquid phase-transfer catalyst produced substituted N-benzoylthioureas with high yield. A reasonable pathway for their formation has been suggested.
One Pot Synthesis of 4-Arylbenzoxazolo-s-triazine-2-thiones
Sambaiah, T.,Reddy, K. Kondal
, p. 693 - 701 (2007/10/02)
The reaction of 2-aminobenzoxazoles (1a-b) with aroyl isothiocyanates in acetone gave 4-arylbenzoxazolo-s-triazine-2-thiones (3a-g), aroylthioureas (5a-e) and 2-benzoxazolones (6a-b).A reasonable pathway for the formation of 3, 5 and 6 from 1 has been suggested.
