2235-46-3Relevant articles and documents
Design, synthesis, and molecular docking study of new monastrol analogues as kinesin spindle protein inhibitors
El-Hamamsy, Mervat H.,Sharafeldin, Nabaweya A.,El-Moselhy, Tarek F.,Tawfik, Haytham O.
, (2020/06/03)
Lung, colorectal, and breast cancers are the top three types of cancer by incidence and are responsible for one-third of the cancer incidence and mortality. A series of 18 3,4-dihydropyrimidine analogues bearing a 1,2-methylenedioxybenzene component at position 4 with diverse side chains at positions 5 and 6 was designed and synthesized as inhibitors of the Eg5 kinesin enzyme. Target compounds were screened for their anticancer activity according to the NCI-USA protocol toward a panel of 60 cancer cell lines. Compounds 12a and 12b displayed the best antiproliferation activity against many cell lines. Interestingly, compound 12a displayed lethal effects against non-small-cell lung cancer NCI-H522 cells (?42.26%) and MDA-MB-468 breast cancer cells (?1.10%) at a single-dose assay concentration of 10?5 M. Compounds 11c, 11d, 11g, 12a–d, 13, 15, and 18a were assayed against the kinesin enzyme, with IC50 values ranging from 1.2 to 18.71 μM, which were more potent compared with monastrol (IC50 = 20 μM). Cell cycle analysis of NCI-H522 cells treated with compound 12a showed cell cycle arrest at the G2/M phase. Furthermore, the expression levels of active caspase-3 and -9 were measured. A molecular docking study was performed for some demonstrative compounds as well as monastrol docked into the allosteric binding site of the kinesin spindle protein.
NEW ANALOGS AS ANDROGEN RECEPTOR AND GLUCOCORTICOID RECEPTOR MODULATORS
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Paragraph 0194; 0196, (2019/05/16)
The present invention relates to novel dihydropyridine derivatives of formula (I): as modulators of nuclear receptors selected from androgen receptor and glucocorticoid receptor, to processes for their preparation, to pharmaceutical compositions comprising said compounds and to the use of said for manufacturing a medicament for the treatment of pathological conditions or diseases that can improve by modulation of androgen receptor and/or glucocorticoid receptor, selected from cancer, metastasizing cancers, benign prostate hyperplasia, polycystic ovary syndrome (PCOS), hair loss, hirsutism, acne, hypogonadism, muscle wasting diseases, cachexia, Cushing's syndrome, anti-psychotic drug induced weight gain, obesity, post-traumatic stress disorder and alcoholism.
Intermolecular acetoxyaminoalkylation of α-diazo amides with (diacetoxyiodo)benzene and amines
D?ben, Nadine,Yan, Hong,Kischkewitz, Marvin,Mao, Jincheng,Studer, Armido
supporting information, p. 7933 - 7936 (2019/01/04)
Multicomponent reactions of diazo compounds have attracted much attention in recent years. Such transformations are generally conducted by applying transition metal catalysis and involve the corresponding metal carbenes as key intermediates. In this letter, a metal-free three-component intermolecular acetoxyaminoalkylation of α-diazo amides with tertiary aryl amines and (diacetoxyiodo)benzene is presented.
O -Iodoxybenzoic Acid (IBX)-Iodine Mediated One-Pot Deacylative Sulfonylation of 1,3-Dicarbonyl Compounds: A Synthesis of β-Carbonyl Sulfones
Katrun, Praewpan,Songsichan, Teerawat,Soorukram, Darunee,Pohmakotr, Manat,Reutrakul, Vichai,Kuhakarn, Chutima
supporting information, p. 1109 - 1121 (2017/02/24)
A combination of o-iodoxybenzoic acid (IBX) and a catalytic amount of iodine is found to promote a facile one-pot deacylative sulfonylation reaction of 1,3-dicarbonyl compounds with sodium sulfinates to yield β-carbonyl sulfones. The present method provides the target products bearing a wide variety of functional groups in one step and in good yields.
Novel 5-oxo-hexahydroquinoline derivatives: Design, synthesis, in vitro P-glycoprotein-mediated multidrug resistance reversal profile and molecular dynamics simulation study
Shahraki, Omolbanin,Edraki, Najmeh,Khoshneviszadeh, Mehdi,Zargari, Farshid,Ranjbar, Sara,Saso, Luciano,Firuzi, Omidreza,Miri, Ramin
, p. 407 - 418 (2017/02/26)
Overexpression of the efflux pump P-glycoprotein (P-gp) is one of the important mechanisms of multidrug resistance (MDR) in many tumor cells. In this study, 26 novel 5-oxo-hexahydroquinoline derivatives containing different nitrophenyl moieties at C4 and various carboxamide substituents at C3 were designed, synthesized and evaluated for their ability to inhibit P-gp by measuring the amount of rhodamine 123 (Rh123) accumulation in uterine sarcoma cells that overexpress P-gp (MES-SA/Dx5) using flow cytometry. The effect of compounds with highest MDR reversal activities was further evaluated by measuring the alterations of MES-SA/Dx5 cells’ sensitivity to doxorubicin (DXR) using MTT assay. The results of both biological assays indicated that compounds bearing 2-nitrophenyl at C4 position and compounds with 4-chlorophenyl carboxamide at C3 demonstrated the highest activities in resistant cells, while they were devoid of any effect in parental nonresistant MES-SA cells. One of the active derivatives, 5c, significantly increased intracellular Rh123 at 100 μM, and it also significantly reduced the IC50 of DXR by 70.1% and 88.7% at 10 and 25 μM, respectively, in MES-SA/Dx5 cells. The toxicity of synthesized compounds against HEK293 as a noncancer cell line was also investigated. All tested derivatives except for 2c compound showed no cytotoxicity. A molecular dynamics simulation study was also performed to investigate the possible binding site of 5c in complex with human P-gp, which showed that this compound formed 11 average H-bonds with Ser909, Thr911, Arg547, Arg543 and Ser474 residues of P-gp. A good agreement was found between the results of the computational and experimental studies. The findings of this study show that some 5-oxo-hexahydroquinoline derivatives could serve as promising candidates for the discovery of new agents for P-gp-mediated MDR reversal.
α-Crotyl-α-difluoroboranyloxy-amides: Structure and Reactivity of Isolable Intermediates in Stereospecific α-Ketol Rearrangements
Rossbach, Jan,Harms, Klaus,Koert, Ulrich
supporting information, p. 3122 - 3125 (2015/06/30)
The stereospecific BF3-mediated α-ketol rearrangement of β-hydroxy-α-ketoamides yields isolable 2-difluoroboranyloxy-3-keto-amides. X-ray and NMR analysis reveal a carbonyl coordination of the boron by the amide not the ketone. The boron complexes are air-stable solids, can be purified by silica gel chromatography, and exhibit novel reactivity in bromination and superior stereoselectivity in dipolar cycloaddition reactions.
Regio- and diastereoselective crotylboration of vic-tricarbonyl compounds
Rossbach, Jan,Baumeister, Julia,Harms, Klaus,Koert, Ulrich
supporting information, p. 662 - 665 (2013/03/13)
Crotylboration of vic-diketoamides and vic-diketo esters was achieved with high diastereoselectivity and complementary regioselectivity. Whereas (E)-crotylboration of α,β-diketoamides resulted in high yields (91-99 %) of β-crotylated products obtained as a single diastereomer (anti), Lewis acid promoted crotylboration of α,β-diketo esters yielded the α-crotylated species with the anti product as main diastereomer. (E)-Crotylboration of α,β-diketoamides resulted in high yields (91-99 %) of β-crotylated products obtained as a single diastereomer (anti). Lewis acid promoted crotylboration of α,β-diketo esters yielded the α-crotylated species with the anti product as main diastereomer. Copyright
Ru-catalyzed asymmetric hydrogenation of 3-oxoglutaric acid derivatives via solvent-assisted pinpoint recognition of carbonyls in close chemical propinquity
Li, Wanfang,Ma, Xin,Fan, Weizheng,Tao, Xiaoming,Li, Xiaoming,Xie, Xiaomin,Zhang, Zhaoguo
supporting information; experimental part, p. 3876 - 3879 (2011/10/01)
Upon comparison of hydrogenation rates of various β-ketocarboxylic acid derivatives, β-ketoamides were found to be hydrogenated slightly faster than β-ketoesters in EtOH in the presence of [RuCl(benzene)(S)- SunPhos]Cl at 70 °C with 20 bar of hydrogen. In THF these differences were so sharpened that β-ketoamides were hydrogenated even faster than in EtOH while the esters were extremely slow. Based on these findings, a series of 3-oxoglutaric acid derived with ester and amide moieties on the two ends were hydrogenated to 3-hydroxyl products with high enantioselectivities.
Regioselective access to substituted oxindoles via rhodium-catalyzed carbene C-H insertion
Gauthier, Delphine,Dodd, Robert H.,Dauban, Philippe
experimental part, p. 8542 - 8555 (2009/12/24)
Rhodium-catalyzed decomposition of diazoamides followed by insertion of the resulting carbenes into an aromatic C-H bond gives access to substituted oxindoles. The reaction takes place with aromatic rings substituted by either electron-donating or -withdrawing groups at ortho, meta or para positions and the regioselectivity can be controlled by a substitution α to the diazo functionality. In the presence of an ester, the reaction leads to the formation of 2-silyloxyindole-3-carboxylates in 40-85% yields and regioselectivities up to 80% are observed in the case of meta-substituted substrates. This selectivity mainly relies on steric factors and use of a more bulky N,N-diethylamide then affords 2-silyloxyindole-3-carboxamides in 42-91% yields with complete regioselectivity.
Dihydropyrazolopyrimidine Inhibitors of KV1.5 (IKur)
Vaccaro, Wayne,Huynh, Tram,Lloyd, John,Atwal, Karnail,Finlay, Heather J.,Levesque, Paul,Conder, Mary Lee,Jenkins-West, Tonya,Shi, Hong,Sun, Lucy
experimental part, p. 6381 - 6385 (2009/09/06)
A series of dihydropyrazolopyrimidine inhibitors of KV1.5 (IKur) have been identified. The synthesis, structure-activity relationships and selectivity against several other ion channels are described.
