5317-89-5Relevant academic research and scientific papers
Process development of a novel anti-inflammatory agent. The regiospecific bromination of 4′-acetylmethanesulfonanilide
Zanka, Atsuhiko,Kubota, Ariyoshi,Hirabayashi, Satoshi,Nakamura, Hitoshi
, p. 71 - 77 (1998)
An efficient, practical synthesis of a novel antiinflammatory agent (FK3311, 1) which is acceptable environmentally and could be used for pilot plant manufacture is described. Regiospecific bromination of 4′-acetylmethanesulfonanilide, allowing selective side chain or nuclear halogenation, also has been investigated. Development efforts focused on the optimized Ullmann coupling reaction conditions and the isolation and purification of 1 to give satisfactory quality product (99.8% purity) according to the new and concise synthetic route.
Synthesis, biological evaluation and molecular docking of new sulfonamide-based indolinone derivatives as multitargeted kinase inhibitors against leukemia
El-Hussieny, Marwa,El-Sayed, Naglaa F.,Fouad, Marwa A.,Ewies, Ewies F.
, (2021/10/20)
Series of novel sulfonamide-based 3-indolinones 3a-m and 4a-f were designed, synthesized and then their cytotoxic activity was evaluated against a panel of sixty cancer cell lines. This screening indicated that 4-(2-(5-fluoro-2-oxoindolin-3-ylidene)acetyl)phenyl benzenesulfonate (4f) possessed promising cytotoxicity against CCRF-CEM and SR leukemia cell lines with IC50 values 6.84 and 2.97 μM, respectively. Further investigation of the leukemic cytotoxicity of compound 4f was carried out by performing PDGFRα, VEGFR2, Aurora A/B and FLT3 enzyme assays and CCRF-CEM and SR cell cycle analysis. These investigations showed that compound 4f exhibited pronounced dual inhibition of both kinases PDGFRα and Aurora A with potency of 24.15 and 11.83 nM, respectively. The in vitro results were supported by molecular docking studies in order to explore its binding affinity and its key amino acids interactions. This work represents compound 4f as a promising anticancer agent against leukemia.
COUP-TFII RECEPTOR INHIBITORS AND METHODS USING SAME
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Page/Page column 40, (2019/12/04)
The invention relates in one aspect to the identification of compounds that inhibit COUP-TFII activity. In certain embodiments, the compounds of the invention have submicromolar activity against COUP-TFII. In other embodiments, the compounds of the invention have no measurable effect on COUP-TFII-negative cells. In yet other embodiments, the compounds of the invention inhibiting prostate tumor growth in a subject without significant effect on the subject's body weight.
Discovery and structure-activity relationship of novel 4-hydroxy-thiazolidine-2-thione derivatives as tumor cell specific pyruvate kinase M2 activators
Li, Ridong,Ning, Xianling,Zhou, Shuo,Lin, Zhiqiang,Wu, Xingyu,Chen, Hong,Bai, Xinyu,Wang, Xin,Ge, Zemei,Li, Runtao,Yin, Yuxin
, p. 48 - 65 (2017/11/23)
Pyruvate kinase M2 isoform (PKM2) is a crucial protein responsible for aerobic glycolysis of cancer cells. Activation of PKM2 may alter aberrant metabolism in cancer cells. In this study, we discovered a 4-hydroxy-thiazolidine-2-thione compound 2 as a novel PKM2 activator from a random screening of an in-house compound library. Then a series of novel 4-hydroxy-thiazolidine-2-thione derivatives were designed and synthesized for screening as potent PKM2 activators. Among these, some compounds showed higher PKM2 activation activity than lead compound 2 and also exhibited significant anti-proliferative activities on human cancer cell lines at nanomolar concentration. The compound 5w was identified as the most potent antitumor agent, which showed excellent anti-proliferative effects with IC50 values from 0.46 μM to 0.81 μM against H1299, HCT116, Hela and PC3 cell lines. 5w also showed less cytotoxicity in non-tumor cell line HELF compared with cancer cells. In addition, Preliminary pharmacological studies revealed that 5w arrests the cell cycle at the G2/M phase in HCT116 cell line. The best PKM2 activation by compound 5t was rationalized through docking studies.
Cascade Michael-Aldol reaction: Efficient annulation of sulfonamide chalcones into novel cyclohexenones under solvent-free conditions
Agrawal, Nikita R.,Bahekar, Sandeep P.,Agrawal, Abhijeet R.,Sarode, Prashant B.,Chandak, Hemant S.
, p. 227 - 245 (2016/07/06)
A simple, convenient and efficient synthesis of novel sulfonamide cyclohexenones from differently substituted sulfonamide chalcones has been developed. Syntheses of cyclohexenones have been achieved via cascade Michael-Aldol reaction under solvent free condition. This process features mild and solvent-free synthesis of the titled compounds with high yields (18 examples, up to 95% yield). The synthesized scaffold is a promising intermediate for the further transformation into various heterocyclic compounds.
Photochemistry of N-Arylsulfonimides: An Easily Available Class of Nonionic Photoacid Generators (PAGs)
Torti, Edoardo,Protti, Stefano,Merli, Daniele,Dondi, Daniele,Fagnoni, Maurizio
supporting information, p. 16998 - 17005 (2016/11/16)
The photochemical behavior of differently substituted N-arylsulfonimides was investigated. Homolysis of the S?N bond took place as the exclusive path from the singlet state to afford both N-arylsulfonamides and photo-Fries adducts, the amount of which depended on reaction conditions and aromatic substituents. Sulfinic and sulfonic acids were released upon irradiation under deaerated and oxygenated conditions, respectively. The nature of the excited states and intermediates involved were proved by laser flash photolysis and EPR experiments. These results highlighted the potential of such compounds as nonionic photoacid generators able to photorelease up to two equivalents of a strong acid for each mole of substrate.
Palladium-Catalyzed, Ring-Forming Aromatic C-H Alkylations with Unactivated Alkyl Halides
Venning, Alexander R. O.,Bohan, Patrick T.,Alexanian, Erik J.
supporting information, p. 3731 - 3734 (2015/04/14)
A catalytic C-H alkylation using unactivated alkyl halides and a variety of arenes and heteroarenes is described. This ring-forming process is successful with a variety of unactivated primary and secondary alkyl halides, including those with β-hydrogens. In contrast to standard polar or radical cyclizations of aromatic systems, electronic activation of the substrate is not required. The mild, catalytic reaction conditions are highly functional group tolerant and facilitate access to a diverse range of synthetically and medicinally important carbocyclic and heterocyclic systems.
Design, synthesis and structure-activity relationship studies of novel and diverse cyclooxygenase-2 inhibitors as anti-inflammatory drugs
Hayashi, Shigeo,Ueno, Naomi,Murase, Akio,Takada, Junji
, p. 846 - 867 (2015/02/19)
Because of the pivotal role of cyclooxygenase (COX) in the inflammatory processes, non-steroidal anti-inflammatory drugs (NSAIDs) that suppress COX activities have been used clinically for the treatment of inflammatory diseases/syndromes; however, traditional NSAIDs exhibit serious side-effects such as gastrointestinal damage and hyper sensitivity owing to their COX-1 inhibition. Also, COX-2 inhibition-derived suppressive or preventive effects against initiation/proliferation/invasion/motility/recurrence/metastasis of various cancers/tumours such as colon, gastric, skin, lung, liver, pancreas, breast, prostate, cervical and ovarian cancers are significant. In this study, design, synthesis and structure-activity relationship (SAR) of various novel {2-[(2-, 3- and/or 4-substituted)-benzoyl, (bicyclic heterocycloalkanophenyl)carbonyl or cycloalkanecarbonyl]-(5- or 6-substituted)-1H-indol-3-yl}acetic acid analogues were investigated to seek and identify various chemotypes of potent and selective COX-2 inhibitors for the treatment of inflammatory diseases, resulting in the discovery of orally potent agents in the peripheral-inflammation model rats. The SARs and physicochemical properties for the analogues are described as significant findings. For graphical abstract: see Supplementary Material. (www.informahealthcare.com/enz)
α-Methylated simplified resiniferatoxin (sRTX) thiourea analogues as potent and stereospecific TRPV1 antagonists
Kim, Ho Shin,Jin, Mi-Kyoung,Kang, Sang-Uk,Lim, Ju-Ok,Tran, Phuong-Thao,Hoang, Van-Hai,Ann, Jihyae,Ha, Tae-Hwan,Pearce, Larry V.,Pavlyukovets, Vladimir A.,Blumberg, Peter M.,Lee, Jeewoo
, p. 2685 - 2688 (2014/06/09)
A series of α-methylated analogues of the potent sRTX thiourea antagonists were investigated as rTRPV1 ligands in order to examine the effect of α-methylation on receptor activity. The SAR analysis indicated that activity was stereospecific with the (R)-configuration of the newly formed chiral center providing high binding affinity and potent antagonism while the configuration of the C-region was not significant.
Synthesis, anti-inflammatory and antioxidant activity of ring-a-monosubstituted chalcone derivatives
Iqbal, Hiba,Prabhakar, Visakh,Sangith, Atul,Chandrika, Baby,Balasubramanian, Ranganathan
, p. 4383 - 4394 (2015/04/22)
A library of ring-A-monosubstituted chalcone derivatives (4a-4i, 5a and 5b) was designed and synthesised. The structures as well as the identities of these compounds were established on the basis of spectral (1H NMR, 13C NMR, FT-IR and Mass) and elemental (C, H, N) analyses. All the derivatives were evaluated for their anti-inflammatory and antioxidant activities in vitro using the inhibition of protein denaturation and 2,2-diphenyl-1-picrylhydrazyl radical scavenging assays, respectively. The results indicated a promising anti-inflammatory activity for most of the synthesised compounds with many derivatives showing activities similar to or greater than that of the standard. The sulphonamide-substituted chalcones 4h, 4i, 5a and 5b were found to be the most active derivatives across the concentration range tested. However, all the derivatives exhibited rather mild antioxidant activity compared to the ascorbic acid standard. Interestingly, it was observed that the unsubstituted parent chalcone was one of the optimal compounds with only the trifluoromethyl analogue 4a showing better activity as an antioxidant. The two regioisomeric aminochalcones and 4′-cyanochalcone 4b also seemed to possess decent antioxidant potential.
