6939-63-5Relevant academic research and scientific papers
Design, Synthesis, and Insecticidal Activity of Novel Doramectin Derivatives Containing Acylurea and Acylthiourea Based on Hydrogen Bonding
Bai, Ping,Cheng, Yao,Lu, Xiaoxia,Yang, Jian,Zhang, Qi,Zheng, Cheng
, p. 5806 - 5815 (2020/06/19)
Our recent investigation on the insecticidal activities of several doramectin derivatives preliminarily revealed that the presence of hydrogen bonds at the C4″ position of the molecule with target protein γ-aminobutyric acid (GABA) receptor was crucial for retaining high insecticidal activity. As a continuation of our research work on the development of new insecticides, two series of novel acylurea and acylthiourea doramectin derivatives were designed and synthesized. The bioassay results indicated that the newly synthesized compounds (5o, 5t, and 6t) exhibited higher insecticidal activity against diamondback moth, oriental armyworm, and corn borer than the control compounds doramectin, commercial avermectins, chlorbenzuron, and lead compound 3g in our laboratory. Specifically, compound 5t was identified as the most promising insecticide against diamondback moth, with a final mortality rate of 80.00% at the low concentration of 12.50 mg/L, showing approximately 7.75-fold higher potency than the parent doramectin (LC50 value of 48.1547 mg/L), 6.52-fold higher potency than commercial avermectins (LC50 value of 40.5507 mg/L), and 3.98-fold higher potency than compound 3g (LC50 value of 24.7742 mg/L). Additionally, molecular docking simulations revealed that compound 5t (2.17, 2.20, 2.56, and 2.83 ?) displayed stronger hydrogen-bond action in binding with the GABA receptor, better than that of compound 5o (1.64 and 2.15 ?) and compound 6t (2.20 and 2.31 ?) at the C4″ position. This work demonstrated that these compounds containing hydrogen-bond groups might contribute to the improvement of insecticidal activity and supply certain hints toward structure optimization design for the development of new insecticides.
Biological evaluation of halogenated thioureas as cholinesterases inhibitors against alzheimer's disease & molecular modeling studies
Iqbal, Jamshed,Zaib, Sumera,Saeed, Aamer,Muddassar, Muhammad
, p. 488 - 494 (2015/06/22)
Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition is thought to be an encouraging approach towards the therapy of Alzheimer's disease (AD). The current paper targets to give a concise information of mono and dihalo- substituted thioureas similarity with anti-AD potential. The present results represent evaluation of cholinesterase inhibitory potential for halogenated thioureas derivatives. Compound 1t was constituted to be highly potent inhibitor with Ki value 0.12 ± 0.05 μM against AChE, while 1b was most the active inhibitor for BChE with Ki value of 0.03 ± 0.001 μM. Molecular docking simulations were performed using the homology models of both cholinesterases in order to explore the plausible binding modes of synthesized compounds.
Acylthiourea, acylurea, and acylguanidine derivatives with potent Hedgehog inhibiting activity
Solinas, Antonio,Faure, Hélène,Roudaut, Hermine,Traiffort, Elisabeth,Schoenfelder, Angèle,Mann, André,Manetti, Fabrizio,Taddei, Maurizio,Ruat, Martial
, p. 1559 - 1571 (2012/04/17)
The Smoothened (Smo) receptor is the major transducer of the Hedgehog (Hh) signaling pathway. On the basis of the structure of the acylthiourea Smo antagonist (MRT-10), a number of different series of analogous compounds were prepared by ligand-based structural optimization. The acylthioureas, originally identified as actives, were converted into the corresponding acylureas or acylguanidines. In each series, similar structural trends delivered potent compounds with IC50 values in the nanomolar range with respect to the inhibition of the Hh signaling pathway in various cell-based assays and of BODIPY-cyclopamine binding to human Smo. The similarity of their biological activities, in spite of discrete structural differences, may reveal the existence of hydrogen-bonding interactions between the ligands and the receptor pocket. Biological potency of compounds 61, 72, and 86 (MRT-83) were comparable to those of the clinical candidate GDC-0449. These findings suggest that these original molecules will help delineate Smo and Hh functions and can be developed as potential anticancer agents.
New substituted thiazol-2-ylidene-benzamides and their reaction with 1-Aza-2-azoniaallene salts. Synthesis and anti-HIV activity
Saeed, Aamer,Al-Masoudi, Najim A.,Ahmed, Amjed A.,Pannecouque, Christophe
body text, p. 512 - 520 (2011/07/08)
Aseries of N-(3-(substituted-aikyl- or halophenyl)-4-methylthiazol-2(3H)- ylidene)-substituted alkyl- or halo-benzamides 21-40 were prepared by base-catalyzed cyclization of the corresponding 1-(substituted-alkyl- or halo-benzoyl)-3-(substituted-halophenyl)thioureas 1-20. Substituted pyrazolo[4,3-d]thiazol-5(6aH)-ylidene)benzamides 45a-d were synthesized by cycloaddition of compound 45 with the reactive cumulene intermediates 42a -d. All compounds were evaluated for their antiviral activity against the replication of HIV-1 and HIV-2 in MT-4. Compounds 35 and 39 showed an IC 50 of 2.02 μgmL-1 and 0.40 μgmL-1 against the HIV-2 strain ROD with CC50 of ≥ 104.00 μgmL-1 and > 125.00 μgmL-1, respectively, resulting in a selectivity index of ≥ 52 and > 313. Based on the chemical structure of compounds 35 and 39, these molecules can be proposed to act as NNRTIs. However, it is exceptional to observe an antiretroviral activity that is limited to HIV-2.
Synthesis, characterization of some new 1-aroyl-3-(4-aminosulfonylphenyl) thioureas and crystal structure of 1-(3,4,5-trimethoxybenzoyl)- 3-(4-aminosulfonylphenyl)thiourea
Saeed, Aamer,Mumtaz, Amara,Ishida
experimental part, p. 45 - 54 (2012/01/06)
A small library of novel 1-aroyl-3-(4-aminosulfonylphenyl)thiourea derivatives was synthesized by the reaction of sulfanilamide with substituted aroyl isothiocyanates in dry acetonitrile. The scope of the reaction was indicated by the synthesis of 1-undecanoyl-3-(4-aminosulfonylphenyl)thiourea, an acyl derivative involving alkanoyl isothiocyanate. All the compounds have been characterized by analytical and spectroscopic methods and in one case by single-crystal X-ray diffraction data.
Synthesis, characterization, crystal structures, and antibacterial activity of some new 1-(3,4,5-trimethoxybenzoyl)-3-aryl thioureas
Saeed, Aamer,Khera, Rasheed Ahmad,Abbas, Naeem,Latif, Muhammad,Sajid, Imran,Floerke, Ulrich
experimental part, p. 335 - 345 (2010/11/03)
Synthesis of some novel 1-(3,4,5-trimethoxy)benzoyl-3-arylthiourea derivatives (1a-o) was accomplished in 2 steps. The synthetic route involves the reaction of 1-(3,4,5-trimethoxy)benzoyl chloride with potassium thiocyanate in 1:1 molar ratio in acetone t
Synthesis, characterization and antimicrobial activity of some new 1-(fluorobenzoyl)-3-(fluorophenyl)thioureas
Saeed, Aamer,Shaheen, Uzma,Hameed,Naqvi, S.Z. Haider
experimental part, p. 1028 - 1034 (2010/04/28)
Synthesis of a variety of new 1-(isomeric fluorobenzoyl)-3-(isomeric fluorophenyl)thioureas (1a-t) was accomplished in two steps. The synthetic route involves the reaction of equimolar quantities of isomeric fluorobenzoyl chlorides with potassium thiocyanate in anhydrous acetone to afford the corresponding isothiocyantes in situ, followed by treatment with equimolar quantities of isomeric fluoroanilines. All of the synthesized compounds (1a-t) were screened for their in vitro antibacterial activity using Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis) and Gram-negative bacteria (Escherichia coli, Pseudomonas aureginosa). The minimum inhibitory concentration (MIC) was also determined for the most active compounds. In vitro antifungal activity was also determined against the five fungal species (Rhizopus oryzae, Aspergillus tereus, Fusarium oxysporum, Aspergillus niger, Aspergillus fumigatus). In general, the antifungal activity of compounds was better than their antibacterial activity.
BENZIMIDAZOLE DERIVATIVES AND THEIR USE AS GNRH ANTAGONISTS
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Page/Page column 33, (2008/06/13)
A subject of the present application is new benzimidazole derivatives of formula in which A, Y, R1, R2, R3 and R4 represent different variable groups. These products have an antagonist activity of GnRH (Gonadotropin-Releasing Hormone). The invention also relates to pharmaceutical compositions containing said products and their use for the preparation of a medicament.
Novel derivatives of benzimidazole and imidazo-pyridine and their use as medicaments
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Page/Page column 12-14, (2008/06/13)
A compound of the formula wherein the substituents are as defined in the specification and pharmaceutical salts thereof having a good affinity for sub-types of melanocortin receptors making them useful for treating diseases in which such receptors are included such as pain, inflammatory conditions, etc.
