71193-36-7Relevant academic research and scientific papers
Cu-Catalyzed Site-Selective Benzylic Chlorination Enabling Net C–H Coupling with Oxidatively Sensitive Nucleophiles
Lopez, Marco A.,Buss, Joshua A.,Stahl, Shannon S.
supporting information, p. 597 - 601 (2022/01/20)
Site-selective chlorination of benzylic C–H bonds is achieved using a CuICl/bis(oxazoline) catalyst with N-fluorobenzenesulfonimide as the oxidant and KCl as a chloride source. This method exhibits higher benzylic selectivity, relative to estab
Design, synthesis and analgesic/anti-inflammatory evaluation of novel diarylthiazole and diarylimidazole derivatives towards selective COX-1 inhibitors with better gastric profile
Abdelazeem, Ahmed H.,El-Saadi, Mohammed T.,Safi El-Din, Asmaa G.,Omar, Hany A.,El-Moghazy, Samir M.
, p. 665 - 676 (2016/12/30)
The inhibition of gastric cyclooxygenase 1 (COX-1) enzyme was believed to be the major cause of non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastric ulcer. Recent studies disproved this belief and showed that the gastric tissues vulnerability is not solely connected to COX-1 inhibition. This work aimed at exploring and rationalizing the differential analgesic and anti-inflammatory activities of novel selective COX-1 inhibitors with improved gastric profile. Two novel series of 4,5-diarylthiazole and diarylimidazole were designed, synthesized in analogy to selective COX-1 inhibitors (mofezolac and FR122047) which lack gastric damaging effects. The new compounds were evaluated in vitro for their COXs inhibitory activity and in vivo for their anti-inflammatory and analgesic potentials. Four compounds; diphenylthiazole glycine derivatives (15a, 15b) and diphenylimidazolo acetic acid derivatives (19a, 19b), which possess carboxylic acid group exhibited significant activity and selectivity against COX-1 over COX-2. Of these compounds, (4,5-bis(4-methoxyphenyl)thiazol-2-yl)glycine 15b was the most potent compound against COX-1 with an inhibitory half maximal concentration (IC50) of 0.32 μM and a selectivity index (COX-2 IC50/COX-1 IC50) of 28.84. Furthermore, an ulcerogenicity study was performed where the tested compounds demonstrated a significant gastric tolerance. Interestingly, the most selective COX-1 inhibitor showed higher analgesic activity in vivo as expected compared to their moderate anti-inflammatory activity. This study underscores the need for further design and development of novel analgesic agents with low tendency to cause gastric damage based on improving their COX-1 affinity and selectivity profile.
Design and synthesis of imidazo[2,1-b]thiazole-chalcone conjugates: Microtubule-destabilizing agents
Kamal, Ahmed,Balakrishna, Moku,Nayak, V. Lakshma,Shaik, Thokhir Basha,Faazil, Shaikh,Nimbarte, Vijaykumar D.
, p. 2766 - 2780 (2015/02/02)
A series of chalcone conjugates featuring the imidazo[2,1- b]thiazole scaffold was designed, synthesized, and evaluated for their cytotoxic activity against five human cancer cell lines (MCF-7, A549, HeLa, DU-145 and HT-29). These new hybrid molecules have shown promising cytotoxic activity with IC50 values ranging from 0.64 to 30.9 mm. Among them, (E)-3-(6-(4- fluorophenyl)-2,3-bis(4-methoxyphenyl)imidazo[2,1-b]thiazol-5- yl)-1-(pyridin-2-yl)prop-2-en-1-one (11 x) showed potent antiproliferative activity with IC50 values ranging from 0.64 to 1.44 mm in all tested cell lines. To investigate the mechanism of action, the detailed biological aspects of this promising conjugate (11x) were carried out on the A549 lung cancer cell line. The tubulin polymerization assay and immunofluoresence analysis results suggest that this conjugate effectively inhibits microtubule assembly in A549 cells. Flow cytometric analysis revealed that this conjugate induces cell-cycle arrest in the G2/M phase and leads to apoptotic cell death. This was further confirmed by Hoechst staining, activation of caspase-3, DNA fragmentation analysis, and Annexin V-FITC assay. Moreover, molecular docking studies indicated that this conjugate (11 x) interacts and binds efficiently with the tubulin protein.
Utilization of natural sunlight and air in the aerobic oxidation of benzyl halides
Su, Yijin,Zhang, Liangren,Jiao, Ning
supporting information; body text, p. 2168 - 2171 (2011/06/21)
Chemical equations presented. A novel, efficient oxidation of α-aryl halogen derivatives to the corresponding α-aryl carbonyl compounds at room temperature has been disclosed. Natural sunlight and air are successfully utilized in this approach through the combination of photocatalysis and organocatalysis. A plausible mechanism was proposed on the basis of the mechanistic studies.
The use of bromotrichloromethane in chlorination reactions
Newman, Stephen G.,Bryan, Christopher S.,Perez, Didier,Lautens, Mark
supporting information; experimental part, p. 342 - 346 (2011/03/18)
Carbon tetrachloride is no longer used as a common solvent due to its toxicity and harmful environmental impact. The synthesis of gem-dichloroalkenes from aldehydes by using triphenylphosphine typically requires carbon tetrachloride as a solvent. We report that stoichiometric bromotrichloromethane in acetonitrile can be used in place of solvent quantities of carbon tetrachloride in this transformation. Similarly, bromotrichloromethane in dichloromethane can be used for the room-temperature Appel reaction of benzyl alcohols to form benzyl chlorides, which is commonly carried out in refluxing carbon tetrachloride. Georg Thieme Verlag Stuttgart New York.
Generation of iminyl copper species from α-azido carbonyl compounds and their catalytic C-C bond cleavage under an oxygen atmosphere
Chiba, Shunsuke,Zhang, Line,Ang, Gim Yean,Hui, Benjamin Wei-Qiang
supporting information; experimental part, p. 2052 - 2055 (2010/07/04)
Figure presented A copper-catalyzed reaction of α-azidocarbonyl compounds under an oxygen atmosphere is reported where nitriles are formed via C-C bond cleavage of a transient iminyl copper intermediate. The transformation is carried out by a sequence of denitrogenative formation of iminyl copper species from α-azidocarbonyl compounds and their C-C bond cleavage, where molecular oxygen (1 atm) is a prerequisite to achieve the catalytic process and one of the oxygen atoms of O2 was found to be incorporated into the β-carbon fragment as a carboxylic acid.
Synthesis and biological evaluation of analogues of the anti-tumor alkaloid naamidine A
Aberle, Nicholas,Catimel, Jenny,Nice, Edouard C.,Watson, Keith G.
, p. 3741 - 3744 (2008/02/12)
A small series of derivatives of the alkaloid naamidine A was synthesized and tested in vitro for their ability to inhibit mitogenesis in BaF/ERX cells. Replacement of the imidazole core with a thiazole was found to have only a minor effect on potency, and the 4-methoxybenzyl substituent of the natural product was shown to be unnecessary for activity.
Antiplatelet Agents Based on Cyclooxygenase Inhibition without Ulcerogenesis. Evaluation and Synthesis of 4,5-Bis(4-methoxyphenyl)-2-substituted-thiazoles
Tanaka, Akito,Sakai, Hiroyoshi,Motoyama, Yukio,Ishikawa, Takatoshi,Takasugi, Hisashi
, p. 1189 - 1199 (2007/10/02)
The syntheses, biological evaluations, and structure-activity relationships of a series of 4,5-bis(4-methoxyphenyl)-2-substituted-thiazoles as potent antiplatelet agents with vasodilatory activity are described. 2-Guanidino-4,5-bis(4-methoxyphenyl)thiazole (3), designed from two parent compounds (itazigrel and timegadine), showed inhibitory activity of malondialdehyde (MDA, IC50 = 31 μM) production which is formed from the cyclooxygenase (CO)-catalyzed oxygenation of arachidonic acid in the synthesis of prostanoids in platelets, with vasodilatory activity (ED50 = 2.0 μM). Further structure-activity relationship studies on 3 culminated in the preparation of 4,5-bis(4-methoxyphenyl)-2-thiazole (10a, FR122047) which exhibited potent inhibitory activity on MDA synthesis in vitro (IC50 = 0.088 μM) and platelet aggregation in guinea pigs ex vivo (100percent inhibition even 6 h after 1.0 mg/kg administration) with vasodilatory activity in vitro (ED50 = 6.2 μM). Moreover, 10a demonstrated no ulcerogenesis effect in rats even at 100 mg/kg dosage (safety margin in rats is more than 70 while that of aspirin is only 1.2) in spite of its potent CO inhibition (IC50 = 0.43 μM), while the use of aspirin, a CO inhibitor and the most popular thromboembolic drug, is restricted by the side effect. Pharmacokinetic studies on 10a have revealed that 10a is detectable in platelet-rich plasma but not in platelet-poor plasma 1 day after oral administration, which indicates that 10a tends to be localized in platelets. This property could be responsible for its low toxicity and reduction of side effects in clinical studies.
"STRUCTURE-REACTIVITY-SELECTIVITY" RELATIONSHIP IN SN2 PROCESSES. REACTION OF 4,4'-SUBSTITUTED α-CHLORODEOXYBENZOINS WITH SODIUM THIOPHENOLATES
Karavan, V. S.,Simonov, D. A.
, p. 145 - 148 (2007/10/02)
In the SN2 reactions of α-chlorodeoxybenzoins X'C6H4CHClCOC6H4X with YC6H4SNa in methanol there is no unambiguous relationship at all between the reactivity of the substrate and its selectivity toward the nucleophile (ρY).At the same
