33267-45-7Relevant academic research and scientific papers
Potent antiproliferative activity of bradykinin B2 receptor selective agonist FR-190997 and analogue structures thereof: A paradox resolved?
Rassias, Gerasimos,Leonardi, Sofia,Rigopoulou, Dionisia,Vachlioti, Eleanna,Afratis, Konstantinos,Piperigkou, Zoi,Koutsakis, Christos,Karamanos, Nikos K.,Gavras, Haralambos,Papaioannou, Dionissios
supporting information, (2020/11/12)
Βradykinin stimulation of B2 receptor is known to activate the oncogenic ERK pathway and overexpression of bradykinin receptors B1 and B2 has been reported to occur in glioma, colorectal and cervical cancers. B1R and B2R antagonists have been shown to reverse tumor proliferation and invasion. Paradoxically, B1R and B2R agonism has also been reported to elicit antiproliferative benefits. In order to complement the data accumulated to date with the natural substrate bradykinin and peptidic B2R antagonists, we decided to examine for the first time the response elicited by B2R stimulation in breast cancer lines with a non-peptidic small molecule B2R agonist. We synthesized and assessed the highly selective and potent B2R partial agonist FR-190997 in MCF-7 and MDA-MBA-231 breast cancer lines and found it possessed significant antiproliferative activity (IC50 2.14 and 0.08 μΜ, respectively). The modular nature of FR-190997 allowed us to conduct a focused SAR study and discover compound 10 which exhibits subnanomolar antiproliferative activity (IC 50 0.06 nΜ) in the TNBC MDA-MBA-231 cell line. This performance surpasses, in most cases by several orders of magnitude, those of established anticancer agents and FDA-approved breast cancer drugs. In line with the established literature we suggest that this remarkable activity precipitates from a dual mode of action involving agonist-induced receptor internalization/degradation combined with sequestration of functional intracellular B2 receptors and inhibition of the associated endosomal signaling. The latter mode may be realized by appropriate ligands regardless of B2R agonist/antagonist designation which only relates to membrane residing GCPRs. Under this prism the controversy over the antiproliferative effects of B2 agonists and antagonists is potentially neutralized.
Vanadium(IV) acetylacetonate catalyzed stereoselective synthesis of β-enaminoesters and β-enaminones
Laskar, Rajibul A.,Begum, Naznin A.,Hedayetullah Mir, Mohammad,Ali, Shahzad,Khan, Abu T.
, p. 436 - 440 (2013/02/23)
An efficient and stereoselective procedure has been described for the synthesis of a series of β-enaminoesters and β-enaminones by vanadium(IV) acetylacetonate [VO(acac)2] catalyzed reaction of β-ketoesters and 1,3-diketones with both aliphatic and aromatic amines. X-ray crystallographic studies of some representative compounds corroborate two types of structural geometry formed by inter-molecular as well as intra-molecular hydrogen bonds.
B2O3/Al2O3 as a new, highly efficient and reusable heterogeneous catalyst for the selective synthesis of β-enamino ketones and esters under solvent-free conditions
Chen, Jiu-Xi,Zhang, Chang-Fu,Gao, Wen-Xia,Jin, Hui-Le,Ding, Jin-Chang,Wu, Hua-Yue
experimental part, p. 1552 - 1556 (2010/11/16)
Boron oxide adsorbed on alumina (B2O3/Al 2O3) has been found to be a new and highly efficient heterogeneous catalyst for the synthesis of β-enamino ketones and esters by the enamination of various primary and secondary amines with β-dicarbonyl compounds under solvent-free conditions. The important features of this methodology are broad substrate scope, high yield, no requirement of metal catalysts, high regio-and chemoselectivity and environmental friendliness. In addition, the catalyst could be recovered easily after the reactions and reused without evident loss of reactivity.
Solvent-free synthesis of β-enamino compounds promoted by Ferric(III) ammonium nitrate
Murthy,Venu,Govindh,Diwakar,Nagalakshmi,Singh
experimental part, p. 3047 - 3053 (2010/11/04)
A variety of β-enamino esters and β-enaminones can be synthesized by the reaction of 1,3-dicarbonyl compounds and various primary amines in the presence of catalytic amount of ferric(III) ammonium nitrate at room temperature. This method is simple, requires short reaction times, high yield and the reaction proceeds under solvent-free conditions.
Synthesis and antiproliferative evaluations of certain 2-phenylvinylquinoline (2-styrylquinoline) and 2-furanylvinylquinoline derivatives
Chang, Feng-Shuo,Chen, Weichung,Wang, Chihuei,Tzeng, Cherng-Chyi,Chen, Yeh-Long
experimental part, p. 124 - 133 (2010/04/06)
The present study describes the synthesis of 2-phenylvinylquinoline (styrylquinoline) and 2-furanylvinylquinoline derivatives and evaluation for their antiproliferative activities. (E)-2-Styrylquinolin-8-ol (14a) was inactive against a 3-cell line panel consisting of MCF-7 (Breast), NCI-H460 (Lung), and SF-268 (CNS). Replacement of the phenyl ring with 5-nitrofuran-2-yl group significantly enhanced antiproliferative activity in which (E)-2-(2-(5-nitrofuran-2-yl)vinyl)quinolin-8-ol (14i) and its 4-substituted derivatives 15-19 exhibited strong inhibitory effects against the growth of all three cancer cells. These compounds were further evaluated for their IC50 against the growth of MCF-7, LNCaP, and PC3. Results indicated that a hydrogen bond donating oxime derivative 19a was more active than its hydrogen bond accepting methyloxime derivative 19b. For the inhibition of LNCaP, the potency decreased in an order 14i > 19a > 19b > 15 > 18 > 16. Compound 14i is the most active with an IC50 value of 0.35 and 0.14 μM, respectively, against the growth of LNCaP and PC3 cancer cells. Therefore, compound 14i was evaluated by flow cytometric analysis for its effects on cell cycle distributions. Results indicated that 14i effectively induced cell cycle arrest at S phase for both cell lines, which consequently trigger late apoptosis for both LNCaP and PC3 cells.
Microwave-assisted solvent-free synthesis of 4-methyl-2-hydroxy- And 2-methyl-4-hydroxyquinolines
Nadaraj,Selvi, S. Thamarai
, p. 1203 - 1207 (2008/09/18)
Rapid and efficient microwave-assisted synthesis of 4-methyl-2-hydroxy- and 2-methyl-4-hydroxyquinolines from anilines and ethyl acetoacetate under different conditions is described.
Efficient synthetic method for β-Enamino esters catalyzed by Yb(OTf)3 under solvent-free conditions
Varala, Ravi,Nuvula, Sreelatha,Adapa, Srinivas R.
, p. 921 - 924 (2007/10/03)
A wide range of ?-enamino esters have been synthesized in moderate to excellent yields by reacting 1,3-dicarbonyl compounds with amines in the presence of catalytic amounts of Yb(OTf)3 (2 mol%). The reaction proceeds smoothly at ambient temperature under solvent-free conditions. The catalyst can be recovered and reused. CSIRO 2006.
A New Series of Highly Potent Non-Peptide Bradykinin B2 Receptor Antagonists Incorporating the 4-Heteroarylquinoline Framework. Improvement of Aqueous Solubility and New Insights into Species Difference
Sawada, Yuki,Kayakiri, Hiroshi,Abe, Yoshito,Imai, Keisuke,Mizutani, Tsuyoshi,Inamura, Noriaki,Asano, Masayuki,Aramori, Ichiro,Hatori, Chie,Katayama, Akira,Oku, Teruo,Tanaka, Hirokazu
, p. 1617 - 1630 (2007/10/03)
Introduction of nitrogen-containing heteroaromatic groups at the 4-position of the quinoline moiety of our non-peptide B2 receptor antagonists resulted in enhancing binding affinities for the human B 2 receptor and reducing binding affinities for the guinea pig one, providing new structural insights into species difference. A CoMFA study focused on the diversity of the quinoline moiety afforded correlative and predictive QSAR models of binding for the human B2 receptor but not for the guinea pig one. A series of 4-(1-imidazolyl)quinoline derivatives could be dissolved in a 5% aqueous solution of citric acid up to a concentration of 10 mg/mL. A representative compound 48a inhibited the specific binding of [ 3H]BK to the cloned human B2 receptor expressed in Chinese hamster ovary cells with an IC50 value of 0.26 nM and significantly inhibited BK-induced bronchoconstriction in guinea pigs even at 1 μg/kg by intravenous administration.
Reversible inhibitors of the gastric (H+/K+)-ATPase. 4. Identification of an inhibitor with an intermediate duration of action
Leach,Brown,Ife,Keeling,Parsons,Theobald,Wiggall
, p. 2748 - 2762 (2007/10/03)
3-Acyl-4-(arylamino)quinolines were previously identified as gastric (H+/K+)-ATPase inhibitors, and clinical efficacy has been demonstrated for compound 3 (SK and F 96067). In the present study the further structure- activity relatio
