2584-48-7Relevant articles and documents
Design of a Chemical Probe for the Bromodomain and Plant Homeodomain Finger-Containing (BRPF) Family of Proteins
Igoe, Niall,Bayle, Elliott D.,Tallant, Cynthia,Fedorov, Oleg,Meier, Julia C.,Savitsky, Pavel,Rogers, Catherine,Morias, Yannick,Scholze, Sarah,Boyd, Helen,Cunoosamy, Danen,Andrews, David M.,Cheasty, Anne,Brennan, Paul E.,Müller, Susanne,Knapp, Stefan,Fish, Paul V.
supporting information, p. 6998 - 7011 (2017/09/07)
The bromodomain and plant homeodomain finger-containing (BRPF) family are scaffolding proteins important for the recruitment of histone acetyltransferases of the MYST family to chromatin. Here, we describe NI-57 (16) as new pan-BRPF chemical probe of the bromodomain (BRD) of the BRPFs. Inhibitor 16 preferentially bound the BRD of BRPF1 and BRPF2 over BRPF3, whereas binding to BRD9 was weaker. Compound 16 has excellent selectivity over nonclass IV BRD proteins. Target engagement of BRPF1B and BRPF2 with 16 was demonstrated in nanoBRET and FRAP assays. The binding of 16 to BRPF1B was rationalized through an X-ray cocrystal structure determination, which showed a flipped binding orientation when compared to previous structures. We report studies that show 16 has functional activity in cellular assays by modulation of the phenotype at low micromolar concentrations in both cancer and inflammatory models. Pharmacokinetic data for 16 was generated in mouse with single dose administration showing favorable oral bioavailability.
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.
Synthesis of 2-oxindoles via 'transition-metal-free' intramolecular dehydrogenative coupling (IDC) of sp2 C-H and sp3 C-H bonds
Kumar, Nivesh,Ghosh, Santanu,Bhunia, Subhajit,Bisai, Alakesh
supporting information, p. 1153 - 1169 (2016/07/06)
The synthesis of a variety of 2-oxindoles bearing an all-carbon quaternary center at the pseudo benzylic position has been achieved via a 'transition-metal-free' intramolecular dehydrogenative coupling (IDC). The construction of 2-oxindole moieties was carried out through formation of carbon-carbon bonds using KOt-Bu-catalyzed one pot C-alkylation of β-N-arylamido esters with alkyl halides followed by a dehydrogenative coupling. Experimental evidences indicated toward a radical-mediated path for this reaction.
QUINOLONES AS INHIBITORS OF CLASS IV BROMODOMAIN PROTEINS
-
Page/Page column 68, (2016/03/19)
The present invention provides compounds of formula (I) as described herein and pharmaceutically acceptable salts, hydrates and solvates thereof for use in medicine, for example in the treatment of acute myeloid leukaemia:
An efficient green protocol for the preparation of acetoacetamides and application of the methodology to a one-pot synthesis of Biginelli dihydropyrimidines. Expansion of dihydropyrimidine topological chemical space
Gama, Fernando H. S.,De Souza, Rodrigo O. M. A.,Garden, Simon J.
, p. 70915 - 70928 (2015/09/08)
The present study describes the preparation of N-aryl-(15) and N-alkyl-(17) acetoacetamides, in good to excellent yields, using both conventional and microwave heating, by reaction of amine derivatives (14 and 16) with 2,2,6-trimethyl-4H-1,3-dioxin-4-one (TMD, 12) in aqueous medium. The acetoacetamides were used to prepare novel Biginelli dihydropyrimidine derivatives. The introduction of the amino acid derivatives potentially allows for the exploration of new structural complexity and topologically diversifies the chemical space occupied by this versatile chemical scaffold.
Organocatalytic enantio- and diastereoselective conjugate addition to nitroolefins: When ketoamides surpass ketoesters
Du, Haiying,Rodriguez, Jean,Bugaut, Xavier,Constantieux, Thierry
supporting information, p. 8458 - 8466 (2014/07/08)
Our findings on the bifunctional squaramide-catalyzed enantioselective conjugate addition of ketoamides to nitroolefins are disclosed. It appears that simple acyclic methylene ketoamides, unlike the extensively studied ketoesters, afford the products in excellent diastereoselectivities, and maintain high yields and enantioselectivities. Moreover, competition and kinetic studies were conducted to rationalize the observed reactivity and selectivity. The high level of diastereocontrol, along with the amenability of the amide group to postfunctionalization, dramatically increase the synthetic usefulness of the transformation.
One-pot synthesis of 3-hydroxyquinolin-2(1 H)-ones from N-phenylacetoacetamide via PhI(OCOCF3)2-mediated α-hydroxylation and H2SO4-promoted intramolecular cyclization
Yuan, Yucheng,Yang, Rui,Zhang-Negrerie, Daisy,Wang, Junwei,Du, Yunfei,Zhao, Kang
, p. 5385 - 5392 (2013/07/26)
A clean, one-pot synthesis of the biologically important 3-hydroxyquinolin-2(1H)-one compounds has been realized from the readily available N-phenylacetoacetamide derivatives through a PhI(OCOCF 3)2-mediated α-hydroxylation and a H 2SO4-promoted intramolecular condensation. The hydroxyl group in the generated α-hydroxylated intermediate can be well tolerated in the second H2SO4-promoted cyclization step.
Synthesis of oxindoles via visible light photoredox catalysis
Ju, Xuhui,Liang, Yan,Jia, Pingjing,Li, Weifei,Yu, Wei
scheme or table, p. 498 - 501 (2012/01/15)
2-Electron-withdrawing-group-substituted 2-bromoanilides can be converted to the corresponding 3,3-disubstituted oxindoles with high efficiency under visible light irradiation by using fac-Ir(ppy)3 as the photoredox catalyst. This protocol is suitable for the synthesis of oxindoles with chloro and bromo atoms attached to the phenyl ring.
Ruthenium-catalyzed intramolecular cyclization of diazo-β-ketoanilides for the synthesis of 3-alkylideneoxindoles
Chan, Wai-Wing,Kwong, Tsz-Lung,Yu, Wing-Yiu
experimental part, p. 3749 - 3755 (2012/06/01)
With [Ru(p-cymene)Cl2]2 as catalyst, diazo-β-ketoanilides would undergo intramolecular carbenoid arene C-H bond functionalization to afford 3-alkylideneoxindoles in up to 92% yields. The reaction occurs under mild conditions and exhibits excellent chemoselectivity. The lack of primary KIE (kH/kD ～ 1) suggests that the reaction should not proceed by rate-limiting C-H bond cleavage; a mechanism involving cyclopropanation of the arene is proposed.
Synthesis of 3-alkoxy/aryloxy - Lactams using diazoacetate esters as ketene precursors under photoirradiation
Qi, Hengzhen,Yang, Zhanhui,Xu, Jiaxi
experimental part, p. 723 - 730 (2011/04/24)
3-Alkoxy/aryloxy - lactams are synthesized in satisfactory to good yields from the reaction of imines and alkyl/aryl di-azoacetates under photoirradiation conditions. Typically, trans - lactams are obtained as the major products from linear imines using the current method. By contrast, the corresponding thermal reaction of imines and alkoxy/aryloxyacetyl chlorides, or their equivalents, in the presence of triethylamine affords cis - lactams as the major or exclusive products. The formation of trans - lactams from linear imines is attributed to isomerization of the imines from their trans-isomers into syn-isomers under UV irradiation. The reported method represents a metal-free and neutral approach for the synthesis of 3-alkoxy/aryloxy - lactams. Georg Thieme Verlag Stuttgart New York.
