- Design and synthesis of benzoacridines as estrogenic and anti-estrogenic agents
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Estrogens play undisputedly important physiological roles, but lifetime exposure to estrogens has also been linked to the development of breast cancer. Moreover, imbalanced estrogen levels have been associated with various symptoms such as osteoporosis and menopausal disorders. For the improvement of such estrogen imbalances, estrogenic reagents with regulatory properties have shown promising potential. Herein, we report the construction of a 12-arylbenzoacridine library via a diversity-oriented strategy that furnished non-toxic estrogenic and anti-estrogenic agents. Derivatives with a hydroxy group at the molecular edge exhibit potent binding affinity to the estrogen receptor α (ERα) and ERβ (IC50 μM), while binding to the estrogen-related receptor γ (ERRγ), i.e., an orphan nuclear receptor on which estrogens often trigger unfavorable events, was not observed. These findings offer valuable insights into 12-arylbenzoacridines as a novel platform for the development of selective estrogen-receptor modulators (SERMs).
- Torikai, Kohei,Koga, Rintaro,Liu, Xiaohui,Umehara, Kaoru,Kitano, Tatsuya,Watanabe, Kenji,Oishi, Tohru,Noguchi, Hiroshi,Shimohigashi, Yasuyuki
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- Synthesis and Properties of Ligands Based on Benzoquinoline
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The preparation of 3-amino-2-naphthaldehyde is described.Ammonolysis of 3-hydroxy-2-naphthoic acid affords the corresponding amino acid which can be esterified and then reduced with LAH.Protection of the amino group, MnO2 oxidation of the primary alcohol to an aldehyde, and deprotection gave the amino aldehyde which is an excellent Friedlaender synthon for benzoquinolines.Dimethylene-bridged analogues of 2,2'-bipyridine and 2,2';6,2''-terpyridine were prepared as well as orthocyclophanes derived from tetracyclo4,11.05,9>undecane-2,7-dione (TCU-2,7-dione).The absorption and emission spectra of these species are consistent with the parent benzoquinoline where bathochromic shifts result from increased delocalization.The TCU derivative evidences exciplex formation so that its benzoquinoline emission is almost completely quenched and an exciplex emission appears at 525 nm.Electrochemical analysis indicates that both reduction and UV absorption involve the same ?* orbital.
- Taffarel, Emmanuelle,Chirayil, Sarah,Thummel, Randolph P.
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- Synthesis of unsymmetrical troeger's bases bearing groups sensitive to reduction
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An efficient approach for the synthesis of unsymmetrically substituted Troeger's base derivatives is reported. This approach is based on the N-alkylation of an arylamine by tert-butyl [2-(bromomethyl)aryl]carbamate to give the corresponding diamine, which
- Havlik, Martin,Dolensky, Bohumil,Jakubek, Milan,Kral, Vladimir
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- Tuned Classical Thermal Aromatization Furnishing an Estrogenic Benzoacridine
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The diversity-oriented doubling strategy, which generates two 12-arylbenzoacridines from a single triarylmethanol precursor was developed to construct a library of drug candidates for the identification of biologically active compounds. Exploration of this 12-arylbenzoacridine library furnished a 4′-OH derivative as an estrogenic compound.
- Koga, Rintaro,Oishi, Tohru,Torikai, Kohei
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- Cationic Iridium-Catalyzed Asymmetric Decarbonylative Aryl Addition of Aromatic Aldehydes to Bicyclic Alkenes
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We report an unprecedented catalytic protocol for the enantioselective decarbonylative transformation of aryl aldehydes. In this process, the decarbonylation of aldehydes catalyzed by chiral iridium complexes enabled the formation of asymmetric C?C bonds
- Nonami, Reina,Morimoto, Yusei,Kanemoto, Kazuya,Yamamoto, Yasunori,Shirai, Tomohiko
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supporting information
(2022/02/05)
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- Metal-Free C-C/C-N/C-C Bond Formation Cascade for the Synthesis of (Trifluoromethyl)sulfonylated Cyclopenta[ b]indolines
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A bis(triflyl)ethylation [triflyl = (trifluoromethyl)sulfonyl] inserted into a sequential cyclization cascade resulted in the direct formation of gem-bis(triflyl)ated cyclopenta[b]indolines from anilide-derived allenols and alkenols. This catalyst- and irradiation-free sequence facilitated the efficient preparation of functionalized tricyclic indoline cores bearing two contiguous stereocenters. The formed cyclopenta[b]indolines can be easily transformed into a wide variety of triflylated indolines, including the tetracycle ring system found in polyveoline.
- Lázaro-Milla, Carlos,Yanai, Hikaru,Almendros, Pedro
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supporting information
p. 2921 - 2926
(2021/05/05)
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- A Convenient Formal [4+2] Heterocylization Route to Bis(triflyl)tetrahydroquinolines
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We report the sustainable and efficient synthesis of a new type of quinoline derivatives bearing one or two SO2CF3 groups. The protocol is metal-, catalyst- and irradiation-free, involves the use of readily available and stable precursors, and avoids the formation of side products. Also, the mild conditions of the process allow the tolerance of a wide range of functional groups.
- Lázaro-Milla, Carlos,Almendros, Pedro
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supporting information
p. 13534 - 13538
(2021/08/13)
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- Biocatalytic reduction of α,β-unsaturated carboxylic acids to allylic alcohols
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We have developed robust in vivo and in vitro biocatalytic systems that enable reduction of α,β-unsaturated carboxylic acids to allylic alcohols and their saturated analogues. These compounds are prevalent scaffolds in many industrial chemicals and pharmaceuticals. A substrate profiling study of a carboxylic acid reductase (CAR) investigating unexplored substrate space, such as benzo-fused (hetero)aromatic carboxylic acids and α,β-unsaturated carboxylic acids, revealed broad substrate tolerance and provided information on the reactivity patterns of these substrates. E. coli cells expressing a heterologous CAR were employed as a multi-step hydrogenation catalyst to convert a variety of α,β-unsaturated carboxylic acids to the corresponding saturated primary alcohols, affording up to >99percent conversion. This was supported by the broad substrate scope of E. coli endogenous alcohol dehydrogenase (ADH), as well as the unexpected CC bond reducing activity of E. coli cells. In addition, a broad range of benzofused (hetero)aromatic carboxylic acids were converted to the corresponding primary alcohols by the recombinant E. coli cells. An alternative one-pot in vitro two-enzyme system, consisting of CAR and glucose dehydrogenase (GDH), demonstrates promiscuous carbonyl reductase activity of GDH towards a wide range of unsaturated aldehydes. Hence, coupling CAR with a GDH-driven NADP(H) recycling system provides access to a variety of (hetero)aromatic primary alcohols and allylic alcohols from the parent carboxylates, in up to >99percent conversion. To demonstrate the applicability of these systems in preparative synthesis, we performed 100 mg scale biotransformations for the preparation of indole-3-aldehyde and 3-(naphthalen-1-yl)propan-1-ol using the whole-cell system, and cinnamyl alcohol using the in vitro system, affording up to 85percent isolated yield.
- Aleku, Godwin A.,Leys, David,Roberts, George W.
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supporting information
p. 3927 - 3939
(2020/07/09)
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- Phosphine-Catalyzed Reaction between 2-Aminobenzaldehydes and Dialkyl Acetylenedicarboxylates: Synthesis of 1,2-Dihydroquinoline Derivatives and Toward the Development of an Olefination Reaction
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A series of 1,2-dihydroquinolines were synthesized in good to excellent yields by reacting 2-aminobenzaldehyde derivatives and dialkyl acetylenedicarboxylates with catalytic amounts of phosphine. This reaction was rendered catalytic by the selective in situ phosphine oxide reduction with the use of phenylsilane. Furthermore, with the same starting materials and with an additional role of the reducing agent, a new olefination reaction was discovered. Hydrogen/deuterium (H/D) exchange experiments revealed the possible mechanism of this reaction.
- Han, Xu,Saleh, Nidal,Retailleau, Pascal,Voituriez, Arnaud
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supporting information
p. 4584 - 4588
(2018/08/09)
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- Pd-Catalyzed Three-Component Domino Reaction of Vinyl Benzoxazinanones for Regioselective and Stereoselective Synthesis of Allylic Sulfone-Containing Amino Acid Derivatives
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A Pd-catalyzed, highly regioselective and stereoselective three-component domino allylic substitution/N-H carbene insertion reaction under mild conditions is described. This reaction demonstrates a wide substrate scope and satisfactory functional group tolerance, providing a broad range of allylic sulfone-containing amino acid derivatives. Moreover, DBU mediates highly diastereoselective cross-dehydrogenative coupling annulation of allylic sulfones without using peroxides or any metal oxidants. This developed protocol affords 7-membered ring heterocyclic compounds incorporating both sulfone-containing amino acid esters and one quaternary carbon center. Mechanistic studies indicate that an unusual umpolung of glycine occurred in this annulation.
- Hao, Jiping,Xu, Yi,Xu, Zhongliang,Zhang, Zhiqiang,Yang, Weibo
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supporting information
p. 7888 - 7892
(2019/01/04)
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- Asymmetric synthesis of isoquinolinonaphthyridines catalyzed by a chiral Br?nsted acid
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A catalytic asymmetric method for the synthesis of chiral isoquinolinonaphthyridines has been developed. A chiral disulfonimide catalyzes a redox cyclization reaction between 2-methyl-3-aldehydeazaarenes and 1,2,3,4-tetrahydroisoquinolines to deliver a range of isoquinolinonaphthyridines with good to high yields (up to 91%) and up to 92:8 er.
- Li, Jianjun,Fu, Yiwei,Qin, Cong,Yu, Yang,Li, Hao,Wang, Wei
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supporting information
p. 6474 - 6477
(2017/08/16)
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- Amphoteric 2-(sulfonylamino)benzaldehydes, secondary amines and isocyanides in the multicomponent synthesis of elusive N-alkyl-2,3-diaminoindoles
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A novel interrupted Ugi reaction between ortho-sulfonylaminated aryl aldehydes, secondary amines, and isocyanides affords in good to high yields N-alkyl-2,3-diaminoindoles, providing access to a so far unexplored area of the indole chemical space. With only one single chemical operation, this novel reaction affords a broad gamma of substituted 2,3-diaminoindoles with five points of diversity. The success of this novel multicomponent transformation lies in presence of the amphoteric sulfonylamino group, which sequentially acts as a Br?nsted acids and as a nucleophile the lack of need for additional catalysts and the high atom economy, with the loss of only one molecule of water, renders this approach a very effective one.
- Giustiniano, Mariateresa,Pelliccia, Sveva,Sangaletti, Luca,Meneghetti, Fiorella,Amato, Jussara,Novellino, Ettore,Tron, Gian Cesare
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supporting information
p. 4264 - 4268
(2017/10/11)
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- A kind of metal complex and in the organic electroluminescent device in the application
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The invention relates to a novel metal complex and application thereof in an organic luminescent device. The structural general formula of the metal iridium complex for near infrared luminescence is LnIrX(3-n), wherein X is selected from acetylacetone, dibenzoylmethane, dipivaloylmethane or picolinic acid; n is selected from 1, 2 or 3; L is selected from the following structural formula L1, L2 or L3; R1-R9 are independently selected from H, C1-10 alkyl, C1-10 alkoxy, C1-10 alkylamino, carbazolyl, F, trifluoromethyl and C5-18 aryl respectively; and Ar represents C5-18 aryl and C5-18 heterocyclic aryl. The metal complex has the advantages of short luminescence life and high luminescence efficiency; and an organic luminescent device prepared from the luminescent material has the characteristic of high luminescence efficiency under high current density. The structural formula L1, the structural formula L2 and the structural formula L3 are shown in the specification.
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Paragraph 0066; 0068
(2016/11/17)
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- Sunlight-Driven Forging of Amide/Ester Bonds from Three Independent Components: An Approach to Carbamates
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A photoredox catalytic route to carbamates enabled by visible irradiation (or simply sunlight) has been developed. This process leads to a novel approach to the construction of heterocyclic rings wherein the amide or ester motifs of carbamates were assembled from three isolated components. Large-scale experiments were realized by employing continuous flow techniques, and reuse of photocatalyst demonstrated the green and sustainable aspects of this method.
- Zhao, Yating,Huang, Binbin,Yang, Chao,Chen, Qingqing,Xia, Wujiong
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supporting information
p. 5572 - 5575
(2016/11/17)
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- GLUCOSYLCERAMIDE SYNTHASE INHIBITORS FOR THE TREATMENT OF DISEASES
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Described herein are compounds of Formula I, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or conditions associated with the enzyme
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Paragraph 000248
(2016/09/26)
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- Cycloadditions with Bromo-Substituted Morita-Baylis-Hillman Adducts of Isatins and N-(ortho-Chloromethyl)aryl Amides
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Efficient construction of a challenging aza-spirocycloheptane oxindole scaffold is reported through an unprecedented [4 + 3] cycloaddition reaction with bromo-substituted Morita-Baylis-Hillman adducts of isatins and N-(ortho-chloromethyl)aryl amides. Both reactive intermediates, the allylic phosphonium ylides and aza-o-quinone methides, were in situ generated, chemoselectively facilitated by a Lewis base and Bronsted base, respectively.
- Zhan, Gu,Shi, Ming-Lin,He, Qing,Du, Wei,Chen, Ying-Chun
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supporting information
p. 4750 - 4753
(2015/10/12)
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- Near-infrared-emitting iridium(III) complexes as phosphorescent dyes for live cell imaging
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The three near-infrared-emitting cationic iridium(III) complexes [Ir(pbq-g)2(NaN)]+PF 6- (pbq-g = phenylbenzo[g]quinoline; N aN = bipyridine (1), 1,10-phenanthroline (2), 4,7-diphenyl-1,10-phenanthroline (3)) have been demonstrated as phosphorescent dyes in live cell imaging. These complexes with different ancillary ligands show similar near-infrared (NIR) emission with λmax,peak at 698 nm and λmax,shoulder at 760 nm in CH2Cl2 solutions, with a moderate quantum yield of around 3%. However, these complexes behave quite differently as NIR dyes for live cell imaging. Complexes 1 and 2 exhibit exclusive staining in the cytoplasm with good cell membrane permeability under excitation at 488 nm, while 3 gives almost no cell uptake, as further determined by flow cytometry. Although the lipophilicities of these complexes follow the order 1 a key role in the design of NIR-emitting iridium(III) complexes for practical applications in bioimaging.
- Zhang, Guoliang,Zhang, Huiyuan,Gao, Yuan,Tao, Ran,Xin, Lijun,Yi, Junyang,Li, Fuyou,Liu, Wanli,Qiao, Juan
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- A method for the synthesis of substituted quinolines via electrophilic cyclization of 1-azido-2-(2-propynyl)benzene
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(Chemical Equation Presented) A new and efficient strategy for the synthesis of substituted quinolines via electrophilic cyclization is developed. The intramolecular cyclization of 1-azido-2-(2-propynyl)benzene 1 proceeds smoothly in the presence of electrophilic reagents (I2, Br 2 , ICl, NBS, NIS, and HNTf2) in CH3NO 2 at room temperature or in the presence of catalytic amounts of AuCl3/AgNTf2 in THF at 100 °C to afford the corresponding quinolines 2 in good to high yields. In the case of the electrophilic reagents, E of 2 is either I, Br, orH, depending on the reagent type, while E of 2 is H in the case of the electrophilic catalyst. 2010 American Chemical Society.
- Huo, Zhibao,Gridnev, Ilya D.,Yamamoto, Yoshinori
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supporting information; experimental part
p. 1266 - 1270
(2010/04/29)
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- CHOLESTERYL ESTER TRANSFER PROTEIN INHIBITORS
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Compounds of Formula (I), including pharmaceutically acceptable salts of the compounds, are CETP inhibitors, and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis. In the compounds of Formula (I), A1 is a cyclic group, and B is a cyclic group which is attached to the heterocyclic ring directly or through a methylene group.
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- CETP INHIBITORS
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Compounds having the structure of Formula (I), including pharmaceutically acceptable salts of the compounds, are CETP inhibitors and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis. In the compounds of Formula (I), B is a cyclic group other than phenyl, and B has a cyclic substituent at a position that is ortho to the position at which B is connected to the remainder of the structure of Formula (I). The 5-membered ring of Formula (I) has a second cyclic substituent in addition to B.
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Page/Page column 48
(2008/06/13)
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- Intramolecular addition of benzylic radicals onto ketenimines. Synthesis of 2-alkylindoles
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The inter- and intramolecular addition of free radicals onto ketenimines is studied. All the attempts to add intermolecularly several silicon, oxygen or carbon centered radicals to N-(4-methylphenyl)-C,C-diphenyl ketenimine were unsuccessful. In contrast, the intramolecular addition of benzylic radicals, generated from xanthates, onto the central carbon of a ketenimine function with its N atom linked to the ortho position of the aromatic ring occurred under a variety of reaction conditions. These intramolecular cyclizations provide a novel radical-mediated synthesis of 2-alkylindoles.
- Alajarin, Mateo,Vidal, Angel,Ortin, Maria-Mar
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p. 4282 - 4292
(2007/10/03)
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