6965-59-9Relevant articles and documents
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.
Quinazolinediones and quinazolinethiones by intramolecular ester amidation
Ahmed, Ejaz,Manwar, Muhammad Ramzan,Sharif, Ahsan,Mukhtar-Ul-Hassan,Ahmed, Neman,Malik, Abdul,Mahmood, Zaid,Munawar, Munawar Ali
experimental part, p. 417 - 420 (2012/04/04)
A new synthetic route was devised for synthesis of Quinazoline-2,4(1H,3H)- dione 5 in which salicylic acid 1 was treated with urea 2 to afford urea arylated ortho-urahydroxy benzoic acid 4. Ortho-urahydroxy benzoic acid 4 is the intermediate moiety which upon cyclization corroborated the cyclic formation of 2, 4-quinazolinedione 5. To form the quinazoline derivative 2, 3-dihydro-2-thioxoquinazolin-4(1H)-one 5a thiourea 3 is used in place of urea 2. Thiourahydroxy benzoic acid 4a is another intermediate compound formed by reacting salicylic acid 1 with thiourea 3. Thiourahydroxy benzoic acid 4a upon interamolecular ester amidation gave final product 2, 3-dihydro-2- thioxoquinazolin-4(1H)-one 5a. This new method replaces the isocyanates and cyanides usage for the formation of quinazolinediones because the incorporation of isocyanates and cyanides is extremely poisonous and cause fatal diseases and immediate death upon contact.
