- New supramolecular ferrocene incorporated N,N'-disubstituted thioureas: Synthesis, characterization, DNA binding, and antioxidant studies
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Ferrocene incorporated N,N'-disubstituted thioureas (S1-S6) were synthesized by allowing 4-ferrocenyl-3-methylaniline to react with freshly prepared aliphatic isothiocyanates and were characterized by using different analytical techniques. Based on single
- Hussain, Shabeeb,Badshah, Amin,Lal, Bhajan,Hussain, Raja Azadar,Ali, Shafqat,Tahir, Muhammad Nawaz,Altaf, Ataf Ali
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- Synthesis, characterization, antimicrobial, antioxidant and computational evaluation of N-acyl-morpholine-4-carbothioamides
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Abstract: The present research paper reports the convenient synthesis, successful characterization, in vitro antibacterial, antifungal, antioxidant potency and biocompatibility of N-acyl-morpholine-4-carbothioamides (5a–5j). The biocompatible derivatives were found to be highly active against the tested bacterial and fungal strains. Moreover, some of the screened N-acyl-morpholine-4-carbothioamides exhibited excellent antioxidant potential. Docking simulation provided additional information about possibilities of their inhibitory potential against RNA. It has been predicted by in silico investigation of the binding pattern that compounds 5a and 5j can serve as the potential surrogate for design of novel and potent antibacterial agents. The results for the in vitro bioassays were promising with the identification of compounds 5a and 5j as the lead and selective candidate for RNA inhibition. Results of the docking computations further ascertained the inhibitory potential of compound 5a. Based on the in silico studies, it can be suggested that compounds 5a and 5j can serve as a structural model for the design of antibacterial agents with better inhibitory potential. Graphic abstract: Binding mode of compound 5j inside the active site of RNA in 3D space. 5j displayed highest antibacterial potential than the reference drug ampicillin with ZOI 10.50?mm against Staphylococcus aureus. 5j also displayed highest antifungal potential than the reference drug amphotericin B with ZOI 18.20?mm against Fusarium solani.[Figure not available: see fulltext.].
- Aziz, Hamid,Saeed, Aamer,Khan, Muhammad Aslam,Afridi, Shakeeb,Jabeen, Farukh
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p. 763 - 776
(2020/03/04)
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- 3-Aminobenzenesulfonamides incorporating acylthiourea moieties selectively inhibit the tumor-associated carbonic anhydrase isoform IX over the off-target isoforms I, II and IV
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We describe the synthesis of a series of novel 1-aroyl/acyl-3-(3-aminosulfonylphenyl) thioureas (4a–k) acting as human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors. Reaction of alkyl/aryl isothiocyanates with 3-aminobenzenesulfonamide afforded a series of the title compounds incorporating a variety of short as well as highly lipophilic long tails. The newly synthesized sulfonamides were evaluated against 4 physiologically relevant CA isoforms (hCA I, II, IV, and IX). Several compounds showed interesting inhibitory activity. The tumor-associated hCA IX was the most sensitive isoform to inhibition with these compounds, with KIs in the range of 21.5–44.0 nM and selectivity ratios over the major cytosolic isoform hCA II in the range of 3.35–37.3. The sulfonamides incorporating the phenylacetylthioureido and pentadecanoylthioureido moieties were the most hCA IX-selective inhibitors detected in this work, making them of interest for further investigations.
- Fattah, Tanzeela Abdul,Bua, Silvia,Saeed, Aamer,Shabir, Ghulam,Supuran, Claudiu T.
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p. 123 - 128
(2018/10/20)
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- Phosphine-free direct conversion of carboxylic acids into acyl isothiocyanates using various electrophilic halogenation reagents
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In this study, the efficiency of some electrophilic halogen reagents including 2,4,6-trichloro-1,3,5-triazine, 2,4,4,6-tetrabromo-2,5-cyclohexadienone, 2-chloro-1-methylpyridinium iodide, N-bromosuccinimide, trichloroisocyanuric acid, and 1,3-dibromo-5,5-
- Khaje-Kolaki, Aslan,Mokhtari, Babak
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p. 805 - 808
(2018/09/26)
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- A novel serine racemase inhibitor suppresses neuronal over-activation in vivo
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Serine racemase (SRR) is an enzyme that produces D-serine from L-serine. D-Serine acts as an endogenous coagonist of NMDA-type glutamate receptors (NMDARs), which regulate many physiological functions. Over-activation of NMDARs induces excitotoxicity, which is observed in many neurodegenerative disorders and epilepsy states. In our previous works on the generation of SRR gene knockout (Srr-KO) mice and its protective effects against NMDA- and Aβ peptide-induced neurodegeneration, we hypothesized that the regulation of NMDARs’ over-activation by inhibition of SRR activity is one such therapeutic strategy to combat these disease states. In the previous study, we performed in silico screening to identify four compounds with inhibitory activities against recombinant SRR. Here, we synthesized 21 derivatives of candidate 1, one of four hit compounds, and performed screening by in vitro evaluations. The derivative 13J showed a significantly lower IC50 value in vitro, and suppressed neuronal over-activation in vivo.
- Mori, Hisashi,Wada, Ryogo,Takahara, Satoyuki,Horino, Yoshikazu,Izumi, Hironori,Ishimoto, Tetsuya,Yoshida, Tomoyuki,Mizuguchi, Mineyuki,Obita, Takayuki,Gouda, Hiroaki,Hirono, Shuichi,Toyooka, Naoki
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p. 3736 - 3745
(2017/06/13)
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- Identification of acylthiourea derivatives as potent Plk1 PBD inhibitors
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Thiourea derivatives have drawn much attention for their latent capacities of biological activities. In this study, we designed acylthiourea compounds as polo-like kinase 1 (Plk1) polo-box domain (PBD) inhibitors. A series of acylthiourea derivatives without pan assay interference structure (PAINS) were synthesized. Four compounds with halogen substituents exhibited binding affinities to Plk1 PBD in low micromole range. The most potent compound (3v) showed selectivity over other subtypes of Plk PBDs and inhibited the kinase activity of full-length Plk1.
- Yun, Taikangxiang,Qin, Tan,Liu, Ying,Lai, Luhua
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p. 229 - 236
(2016/09/09)
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- Direct and facile synthesis of acyl isothiocyanates from carboxylic acids using trichloroisocyanuric acid/triphenylphosphine system
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A mild, efficient, and practical method for one-step synthesis of alkanoyl and aroyl isothiocyanates from carboxylic acids using a safe and inexpensive mixed reagent, trichloroisocyanuric acid/triphenyl-phosphine is described at room temperature. Availability of the reagents and easy workup of the reaction make this method attractive for organic chemists.
- Entezari, Najmeh,Akhlaghinia, Batool,Rouhi-Saadabad, Hamed
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p. 201 - 206
(2015/02/05)
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- PYRIDONE/HYDROXYPYRIDINE 11-BETA HYDROXYSTEROID DEHYDROGENASE TYPE I INHIBITORS
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Novel compounds are provided which are 11-beta-hydroxysteroid dehydrogenase type I inhibitors. 11-beta-hydroxysteroid dehydrogenase type I inhibitors are useful in treating, preventing, or slowing the progression of diseases requiring 11-beta-hydroxysteroid dehydrogenase type I inhibitor therapy. These novel compounds have the structure: enantiomers, diastereomers, solvates, salts, tautomers or prodrugs thereof wherein, A, W, X, Y and R1 are defined herein.
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Paragraph 0346; 0347
(2014/05/20)
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- SERINE RACEMASE INHIBITOR
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A novel serine racemase inhibitor exhibits sufficient activity and specificity. The serine racemase inhibitor includes one or more compounds selected from compounds respectively represented by the following general formulas [MM_1], [DR_1], [DR'_1], [LW_1], and [ED_1] as an active ingredient.
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Paragraph 0164 - 0166
(2014/12/12)
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- Discovery of N-(4-sulfamoylphenyl)thioureas as Trypanosoma brucei leucyl-tRNA synthetase inhibitors
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Human African trypanosomiasis (HAT) is one of the most neglected diseases in the tropic regions, which is fatal if not treated in time. There is an urgent need for new therapeutics, especially those in new chemical classes. Leucyl-tRNA synthetase (LeuRS) has been paid much attention as a recently clinically validated antimicrobial target. Our group has previously reported T. brucei LeuRS (TbLeuRS) inhibitors, including benzoxaboroles targeting the editing site and pyrrolinones targeting the synthetic site. Here we report the discovery of N-(4-sulfamoylphenyl)thioureas as a new class of TbLeuRS inhibitors. The R1 and R2 groups, reminiscent of the leucyl and adenyl regions of aa-AMP and aa-AMS, were optimized to result in a significant 13-fold increase of inhibitory activity (compound 19, IC 50 = 13.7 μM). Aided by ligand-protein docking, the 1,3-substitution at the central phenyl ring was predicted and proved to give significantly improved activity (59, IC50 = 1.1 μM). This work provided a new scaffold for the exploration of novel inhibitors against TbLeuRS, which may become potential therapeutics for the treatment of HAT.
- Zhang, Fenglong,Du, Jin,Wang, Qing,Hu, Qinghua,Zhang, Jiong,Ding, Dazhong,Zhao, Yaxue,Yang, Fei,Wang, Enduo,Zhou, Huchen
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p. 5310 - 5324
(2013/08/23)
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- ACYLTHIOUREA COMPOUND OR SALT THEREOF, AND USE THEREOF
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To provide an antitumor agent which exhibits excellent c-Met inhibitory effect and mitigates side effects by virtue of selectively affecting to tumor cells in which c-Met is specifically expressed. The invention provides an acylthiourea compound represent
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Page/Page column 9
(2011/02/26)
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- One-pot synthesis and crystal structure of N-acyl-N′-[1-(2,6- dichloro-4-trifluoromethyl)phenyl-3-cyano-1H-pyrazol-5-yl]thioureas
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Nine novel thiourea derivatives containing pyrazole rings have been prepared in good yields by the reaction of 5-amino-3-cyano-1-(2,6-dichloro-4- trifluoromethylphenyl)pyrazole with acylisothiocyanates, which were generated in situ by potassium thiocyanate and different acyl chlorides in one pot. N-Benzoyl-N′-[1-(2,6-dichloro-4-trifluoromethyl)phenyl-3-cyano-1H-pyrazol- 5-yl]thiourea was characterised by a single crystal X-ray diffraction study.
- Zhang, Xiaohong,He, Hui,Xu, Mei,Zhong, Ping
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experimental part
p. 323 - 325
(2011/10/02)
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- Synthesis, characterization of some new 1-aroyl-3-(4-aminosulfonylphenyl) thioureas and crystal structure of 1-(3,4,5-trimethoxybenzoyl)- 3-(4-aminosulfonylphenyl)thiourea
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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.
- Saeed, Aamer,Mumtaz, Amara,Ishida
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experimental part
p. 45 - 54
(2012/01/06)
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- FUSED HETEROCYCLIC DERIVATIVES AND USE THEREOF
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The present invention provides a fused heterocyclic derivative having a strong kinase inhibitory activity and use thereof. The present invention relates to a compound represented by the formula wherein each symbol is as defined in the present specificatio
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Page/Page column 227-228
(2010/01/29)
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- PYRIDONE/HYDROXYPYRIDINE 11-BETA HYDROXYSTEROID DEHYDROGENASE TYPE I INHIBITORS
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Novel compounds are provided which are 11-beta-hydroxysteroid dehydrogenase type I inhibitors. 11-beta-hydroxysteroid dehydrogenase type I inhibitors are useful in treating, preventing, or slowing the progression of diseases requiring 11-beta-hydroxysteroid dehydrogenase type I inhibitor therapy. These novel compounds have the structure formula (I) enantiomers, diastereomers, solvates, salts, tautomers or prodrugs thereof wherein, A, W, X, Y and R1 are defined herein.
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Page/Page column 72-73
(2008/06/13)
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- BIS-ARYL KINASE INHIBITORS AND METHOD
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Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
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Page/Page column 54-55
(2010/11/25)
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- Identification of potent and selective inhibitors of PDGF receptor autophosphorylation
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We report the structure-activity relationship of quinoline and quinazoline derivatives, which include urea, thiourea, urethane, and acylthiourea groups, as inhibitors of the platelet-derived growth factor (PDGF) receptor autophosphorylation. Our previous studies showed that the quinoline and quinazoline derivatives including urea, thiourea, and carbamate groups were highly potent compounds as the PDGF receptor autophosphorylation inhibitor, but these compounds did not exhibit receptor selectivity between the PDGF receptor and the c-kit receptor. As a result of further synthesis and biological evaluation, we have found that the quinoline and quinazoline-acylthiourea derivatives showed not only good inhibitory activity for the PDGF receptor but also receptor selectivity between the PDGF receptor and the c-kit receptor. Furthermore N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2- methylbenzoyl)thiourea exhibited potent oral efficacy in in vivo assay using the rat carotid balloon injury model. Therefore, the quinoline and quinazoline-acylthiourea derivatives may be expected to have potential as therapeutic agents for the treatment of restenosis.
- Furuta, Takayuki,Sakai, Teruyuki,Senga, Terufumi,Osawa, Tatsushi,Kubo, Kazuo,Shimizu, Toshiyuki,Suzuki, Rika,Yoshino, Tetsuya,Endo, Megumi,Miwa, Atsushi
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p. 2186 - 2192
(2007/10/03)
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- Efficient synthesis of 1-(5′-acylamino-1′,3′,4′- thiadiazol-2′-yl)-4-acyl-thiosemicarbazides
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Acyl chlorides reacted with ammonium thiocyanate and carbonic dihydrazide under phase-transfer catalysis to first afford 2,2′- bis(acylaminothiocarbonyl)-carbonic dihydrazides, which further cyclized in the presence of glacial acetic acid to efficiently give 1-(5′-acylamino- 1′,3′,4′-thiadiazol-2′-yl)-4-acyl-thiosemicarbazides in high yield. Copyright Taylor & Francis Group, LLC.
- Li, Zheng,Yang, Jing-Ya,Wang, Xi-Cun
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p. 2355 - 2362
(2007/10/03)
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- C-MET MODULATORS AND METHODS OF USE
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The present invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. More specifically, the invention provides quinazolines and quinolines which inhibit, regulate and/or modulate kinase receptor, particularly c-Met, KDR, c-Kit, flt-3 and flt-4, signal transduction pathways related to the changes in cellular activities as mentioned above, compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. The present invention also provides methods for making compounds as mentioned above, and compositions which contain these compounds.
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Page/Page column 185
(2008/06/13)
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- Processes and intermediates useful for preparing fused heterocyclic kinase inhibitors
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The present invention is directed to intermediates that are useful for preparing pyrrolotriazines, and processes for preparing such intermediates.
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Page/Page column 16
(2008/06/13)
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- Conversion of Alcohols, Thiols, Carboxylic Acids, Trimethylsilyl Ethers, and Carboxylates to Thiocyanates with Triphenylphosphine/ Diethylazodicarboxylate/NH4SCN
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A novel and highly selective method is described using triphenylphosphine/ diethylazodicarboxylate (DEAD)/NH4SCN for the conversion of alcohols, thiols, carboxylic acids, silyl ethers, and silyl carboxylates to their corresponding thiocyanates.
- Iranpoor, Nasser,Firouzabadi, Habib,Akhlaghinia, Batool,Azadi, Roya
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- Reaction of stable trialkylsilyl esters with Ph3P(SCN)2: A novel method for the preparation of acyl and aroyl isothiocyanates under neutral condition
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An efficient, mild and novel method is described for one-pot conversion of stable triisopropylsilyl- and tert-butyldimethylsilyl carboxylates to their corresponding acyl- or aroyl isothiocyanates using in-situ generation of Ph3P(SCN)2 at room temperature under neutral condition. This method has also been applied for the high yield preparation of 2-thioxo-3,4-dihydro-2H-1,3-benzoxazine-4-one, which has fungicidal and bactericidal activities.
- Iranpoor,Firouzabadi,Shaterian
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p. 3653 - 3657
(2007/10/03)
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- Synthesis of benzoyl-N-phenylthioureas under microwave irradiation and phase transfer catalysis conditions
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A simple, rapid and efficient method for the synthesis of benzoyl-N-phenylthioureas under microwave irradiation is reported. The effect of microwave irradiation power, times and phase transfer catalyst on the reaction is investigated.
- Bai, Lin,Li, Shengying,Wang, Jin-Xian,Chen, Mingkai
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p. 127 - 132
(2007/10/03)
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- Phase transfer catalytic synthesis of phenylacetyl arylthioureas under microwave irradiation conditions
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A simple, rapid, and efficient method for the synthesis of phenylacetyl arylthioureas under microwave irradiation is reported. The effects of microwave irradiation power, times, and solvent on the reaction are investigated.
- Bai, Lin,Li, Kanglan,Li, Shengying,Wang, Jin-Xian
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p. 1001 - 1007
(2007/10/03)
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- A Convenient Synthesis of Tertiary Isothiocyanates and Acyl Isothiocyanates Using Phosphoryl Isothiocyanate.
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Phosphoryl iosthiocyanate, PO(NCS)3, reacts readily with tertiary alcohols and carboxylic acids, giving the respective tertiary isothiocyanates and acyl isothiocyanates in good yields and purity.
- Kniezo, Ladislav,Bernat, Juraj
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p. 509 - 513
(2007/10/02)
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