- Practical Decagram-Scale Synthesis of a Lamellarin Analogue and Deprotection of Lamellarin Isopropyl Ethers
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Modular syntheses of naturally occurring lamellarin ε (5) and the synthetic analogue dehydrolamellarin J (6), both of them promising lead candidates for anticancer activity, were accomplished in high overall yields. Key steps in these routes are a late-st
- Klintworth, Robin,de Koning, Charles B.,Michael, Joseph P.
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- 2-Benzopyrilium Salts. 30. Synthesis and Properties of 2-Benzopyrilium Salts with the 2,6-Di-t-butylphenyl Substituent in Position 3
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We achieved the synthesis of 2-benzopyrilium salts with a 2,6-di-t-butylphenyl substituent in position 3 by acylation of 3,5-di-t-butyl-4-hydroxy-3',4'-dimethoxydesoxybenzoin.We carried out a comparison of the concurrent deprotonation of 1-methylene and h
- Shcherbakova, I. V.,Ukhin, L. Yu.,Komissarov, V. N.,Kuznetsov, E. V.,Polyakov, A. V.,et al.
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- Oxidative route to pyrroloisoquinoline-2,3-dione
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We herein report an efficient constructive method for synthesis of structurally important Pyrroloisoquinoline-2,3-dione from dihydroisoquinoline through oxidative cyclisation. Process is optimised to give best efficiency at gram scale and laborious purification techniques such as column chromatography or recrystallisation were avoided in all steps further featuring uniqueness of this method as compared to the available literature.
- Kadam, Hari K.,Tilve, Santosh G.
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- Synthesis of ortho-arylated/benzylated arylacetamide derivatives: Pd(OAc)2-catalyzed bidentate ligand-aided arylation and benzylation of the γ-C[sbnd]H bond of arylacetamides
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In this paper, we report the Pd(OAc)2/AgOAc, bidentate ligand-directed C[sbnd]H functionalization of the sp2γ-C[sbnd]H bond of arylacetamides. While, the bidentate ligand-directed site selective functionalization of the β-C[sbnd]H bond of aromatic carboxylic acid derivatives is well known, we herein, report our attempts on the Pd(II)-catalyzed, bidentate ligand-directed arylation, benzylation, alkylation, acetoxylation and hydroxylation of the sp2γ-C[sbnd]H bond of the arylacetamide systems. The arylation and benzylation of arylacetamides were successful; however, the alkylation and acetoxylation/hydroxylation of arylacetamides were not successful. Various ligands were screened to substantiate the need for the bidentate ligand in the arylation/benzylation of arylacetamides, and 8-aminoquinoline was found to be the best bidentate ligand. Several substituted aryl-/heteroaryl iodides, 4-nitrobenzyl bromide and arylacetamide substrates were used to examine their reactivity pattern and accomplish the substrate scope/generality. In general, the bidentate ligand 8-aminoquinoline-directed arylation of arylacetamides gave the corresponding ortho-diarylated arylacetamides and benzylation of arylacetamides gave the corresponding ortho-mono benzylated arylacetamides as the predominant compounds. Overall, this method has led to the synthesis of new ortho-substituted arylacetamides in good to high yields.
- Bisht, Narendra,Babu, Srinivasarao Arulananda
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- Structure-based optimization of non-peptidic Cathepsin D inhibitors
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We discovered a novel series of non-peptidic acylguanidine inhibitors of Cathepsin D as target for osteoarthritis. The initial HTS-hits were optimized by structure-based design using CatD X-ray structures resulting in single digit nanomolar potency in the
- Gr?dler, Ulrich,Czodrowski, Paul,Tsaklakidis, Christos,Klein, Markus,Werkmann, Daniela,Lindemann, Sven,Maskos, Klaus,Leuthner, Birgitta
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- A convergent and enantioselective synthesis of (+)-amurensinine via selective C-H and C-C bond insertion reactions
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A convergent and enantioselective synthesis of the natural product amurensinine is described. The synthetic strategy takes advantage of mild and selective C-H and C-C bond insertion reactions, in addition to the palladium-catalyzed aerobic oxidative kinet
- Tambar, Uttam K.,Ebner, David C.,Stoltz, Brian M.
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- Lewis Acid and Fluoroalcohol Mediated Nucleophilic Addition to the C2 Position of Indoles
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Indole readily undergoes nucleophilic substitution at the C3 site, and many indole derivatives have been functionalized using this property. Indole also forms indolium, which allows electrophilic addition in acidic conditions, but current examples have been limited to intramolecular reactions. C2 site-selective nucleophilic addition to indole derivatives using fluoroalcohol and a Lewis acid was developed.
- Morimoto, Naoki,Morioku, Kumika,Suzuki, Hideyuki,Takeuchi, Yasuo,Nishina, Yuta
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- Bioinspired Design Provides High-Strength Benzoxazine Structural Adhesives
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A synthetic strategy to incorporate catechol functional groups into benzoxazine thermoset monomers was developed, leading to a family of bioinspired small-molecule resins and main-chain polybenzoxazines derived from biologically available phenols. Lap-she
- Higginson, Cody J.,Malollari, Katerina G.,Xu, Yunqi,Kelleghan, Andrew V.,Ricapito, Nicole G.,Messersmith, Phillip B.
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- A Simple and Efficient Synthesis of Fused Benzo[ b ]thiophene Derivatives
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A new approach to the synthesis of fused benzothiophene derivatives was developed based on iodine-promoted photocyclization of 4,5-diaryl-substituted thiophenes obtained in three steps from commercially available compounds. Comparative analysis showed that photochemical cyclization is a more efficient method for the preparation of fused benzo[ b ]thiophene derivatives, compared to oxidative coupling of 4,5-diaryl-substituted thiophenes in the presence of iron(III) chloride and palladium-catalyzed intramolecular arylation. This new approach provides an efficient synthesis of functionally substituted naphtho[2,1- b:3,4- b ′]dithiophenes, phenanthro[9,10- b ]thiophenes, benzo[1,2- b:3,4- b ′:6,5- b ′′]trithiophenes, as well as new fused heterocycles containing a pyridine ring and/or a carbazole moiety.
- Ulyankin, Evgeny B.,Kostyuchenko, Anastasia S.,Chernenko, Sergey A.,Bystrushkin, Mikhail O.,Samsonenko, Anna L.,Shatsauskas, Anton L.,Fisyuk, Alexander S.
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p. 2422 - 2434
(2021/04/21)
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- Design, synthesis, biological evaluation and silico prediction of novel sinomenine derivatives
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Sinomenine is a morphinan alkaloid with a variety of biological activities. Its derivatives have shown significant cytotoxic activity against different cancer cell lines in many studies. In this study, two series of sinomenine derivatives were designed and synthesized by modifying the active positions C1 and C4 on the A ring of sinomenine. Twenty‐three compounds were synthesized and characterized by spectroscopy (IR,1H‐NMR,13C‐NMR, and HRMS). They were further evaluated for their cytotoxic activity against five cancer cell lines, MCF‐7, Hela, HepG2, SW480 and A549, and a normal cell line, Hek293, using MTT and CCK8 methods. The chlorine‐containing compounds exhibited significant cytotoxic activity compared to the nucleus structure of sinomenine. Furthermore, we searched for cancer‐related core targets and verified their interaction with derivatives through molecular docking. The chlorine‐containing compounds 5g, 5i, 5j, 6a, 6d, 6e, and 6g exhibited the best against four core targets AKT1, EGFR, HARS and KARS. The molecular docking results were consistent with the cytotoxic results. Overall, results indicate that chlorine‐containing derivatives might be a promising lead for the development of new anticancer agents.
- Cui, Dongmei,Gao, Mingjie,Li, Jinjie,Li, Shoujie,Nian, Xin,Zhang, Chen,Zhang, Liyu,Zhao, Changqi
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- Complex Polyheterocycles and the Stereochemical Reassignment of Pileamartine A via Aza-Heck Triggered Aryl C-H Functionalization Cascades
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Structurally complex benzo- and spiro-fused N-polyheterocycles can be accessed via intramolecular Pd(0)-catalyzed alkene 1,2-aminoarylation reactions. The method uses N-(pentafluorobenzoyloxy)carbamates as the initiating motif, and this allows aza-Heck-type alkene amino-palladation in advance of C-H palladation of the aromatic component. The chemistry is showcased in the first total synthesis of the complex alkaloid (+)-pileamartine A, which has resulted in the reassignment of its absolute stereochemistry.
- Bower, John F.,Caiger, Lewis,García-Cárceles, Javier,Hazelden, Ian R.,Jones, Benjamin T.,Langer, Thomas,Lewis, Richard J.
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supporting information
p. 15593 - 15598
(2021/10/12)
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- N-monoarylacetothioureas as potent urease inhibitors: synthesis, SAR, and biological evaluation
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A urease inhibitor with good in vivo profile is considered as an alternative agent for treating infections caused by urease-producing bacteria such as Helicobacter pylori. Here, we report a series of N-monosubstituted thioureas, which act as effective urease inhibitors with very low cytotoxicity. One compound (b19) was evaluated in detail and shows promising features for further development as an agent to treat H. pylori caused diseases. Excellent values for the inhibition of b19 against both extracted urease and urease in intact cell were observed, which shows IC50 values of 0.16 ± 0.05 and 3.86 ± 0.10 μM, being 170- and 44-fold more potent than the clinically used drug AHA, respectively. Docking simulations suggested that the monosubstituted thiourea moiety penetrates urea binding site. In addition, b19 is a rapid and reversible urease inhibitor, and displays nM affinity to urease with very slow dissociation (koff=1.60 × 10?3 s?1) from the catalytic domain.
- Fang, Hai-Lian,He, Jie-Ling,Li, Wei-Yi,Liu, Shan-Shan,Ni, Wei-Wei,Pan, Xing-Ming,Xiao, Zhu-Ping,Ye, Ya-Xi,Yi, Juan,Zhou, Mi,Zhou, Tian-Li,Zhu, Hai-Liang
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p. 404 - 413
(2020/01/03)
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- Demethylative Lactonization Provides a Shortcut to High-Yielding Syntheses of Lamellarins
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Modular gram-scale syntheses of the trimethyl ethers of lamellarins G (6) and D (7) were achieved from readily accessible precursors in the highest overall yields reported to date (6, six steps, 82%; 7, seven steps, 86%). A novel demethylative lactonizati
- De Koning, Charles B.,Klintworth, Robin,Michael, Joseph P.
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- Synthesis of indolo[2,1-a]isoquinolines by CF3COOH-induced cyclization
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Indolo[2,1-a]isoquinoline alkaloids and related compounds have been known to have interesting biological activities, such as antileukemic and antitumor activities. We found that 1-(3,4-dimethoxyphenethyl)indole gave 2,3-dimethoxyindolo[2,1-a]isoquinoline
- Wada, Yasuhiro,Kurono, Nobuhito,Senboku, Hisanori,Orito, Kazuhiko
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p. 3703 - 3708
(2020/08/25)
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- Palladium-Catalyzed Distal C?H Selenylation of 2-Aryl Acetamides with Diselenides and Selenyl Chlorides
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A convenient and effective method of palladium-catalyzed C?H selenylation of the 2-aryl acetamides assisted with removable 8-aminoquinoline with readily available diselenides and selenyl chlorides has been developed. This selenylation reaction is scalable and tolerates a wide range of functional groups, providing a straightforward way of the preparing unsymmetrical diaryl selenides and dibenzoselene-pinone. Preliminary mechanistic studies indicated that a single-electron transfer type mechanism and facile C?H metalation are operative. (Figure presented.).
- Gu, Linghui,He, Meicui,Ma, Wenbo,Tan, Yuqiang,Wang, Yang,Wang, Yuchi,Zhang, Chunran
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supporting information
p. 5708 - 5715
(2020/12/01)
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- Preparation of Organic Nitrates from Aryldiazoacetates and Fe(NO3)3·9H2O
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A thermal protocol is reported for the formal insertion of nitric acid into aryldiazoacetates using Fe(NO3)3·9H2O. This strategy is mild and high yielding and allows the preparation of a large variety of members of an unprecedented family of organic nitrates. The nitrate group can be also readily transformed into other functional groups and heterocyclic moieties and can possibly allow new biological explorations of untapped potential associated with their NO-releasing ability.
- Thurow, Samuel,Fernandes, Alessandra A. G.,Quevedo-Acosta, Yovanny,De Oliveira, Matheus F.,De Oliveira, Marcelo G.,Jurberg, Igor D.
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supporting information
p. 6909 - 6913
(2019/09/12)
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- Directed Remote Lateral Metalation: Highly Substituted 2-Naphthols and BINOLs by In Situ Generation of a Directing Group
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A general synthesis of highly substituted 2-naphthols based on a new carbanionic reaction sequence is demonstrated. The reaction exploits the dual nature of lithium bases consisting of consecutive ring opening of readily available coumarins with either LiNEt2 or LiNiPr2 into Z-cinnamamides, thus generating a directing group in situ and allowing, by conformational freedom, a lateral directed remote metalation for ring closure to give the aryl 2-naphthols in good to excellent yields. These transformations can be combined to provide a more efficient one-pot process. Mechanistic insight into the remote lateral metalation step, demonstrating the requirement of Z-cinnamamide, is described. Application of this methodology to the synthesis of highly substituted 3,3′-diaryl BINOL ligands is also reported.
- Patel, Jignesh J.,Laars, Marju,Gan, Wei,Board, Johnathan,Kitching, Matthew O.,Snieckus, Victor
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supporting information
p. 9425 - 9429
(2018/07/29)
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- Development of catalytic deacylative alkylations (DaA) of 3-acyl-2-oxindoles: total synthesis of meso-chimonanthine and related alkaloids
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We present an effective deacylative alkylation strategy for the construction of a variety of 2-oxindoles bearing an all-carbon quaternary center at the pseudobenzylic position. A wide variety of products with quaternary centers could be accessed by employing simple Pd(0) catalysis under mild reaction conditions. Importantly, the same strategy works equally well for the dimeric 2-oxindole system, furnishing products with a vicinal quaternary center in favour of meso-isomer as the major product. Eventual application to the total syntheses of meso-chimonanthine and meso-folicanthine very well demonstrates the synthetic potential of this strategy.
- Kumar, Nivesh,Das, Mrinal Kanti,Ghosh, Santanu,Bisai, Alakesh
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supporting information
p. 2170 - 2173
(2017/02/19)
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- First Synthesis of (R)- and (S)-1,2,3,4-Tetrahydroisoquinoline-3-phosphonic Acid (TicP) Using a Pictet-Spengler Reaction
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We report here a practical and efficient synthesis of diethyl 1,2,3,4-tetrahydroisoquinoline-3-phosphonate derivatives. The target compounds were prepared in good yield using a Pictet-Spengler reaction involving α-amino phosphonates that were easily obtai
- Viveros-Ceballos, José Luis,Ordó?ez, Mario,Sayago, Francisco J.,Jiménez, Ana I.,Cativiela, Carlos
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p. 2711 - 2719
(2016/06/08)
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- Hybrids of coumarin-indole: Design, synthesis and biological evaluation in Triton WR-1339 and high-fat diet induced hyperlipidemic rat models
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In this study, a series of coumarin-indole hybrids have been synthesized and evaluated for their lipid lowering activity. Preliminary biological screening of the synthesized compounds was undertaken in an in vitro model of the HMG-CoA reductase enzyme, an
- Sashidhara, Koneni V.,Rao, K. Bhaskara,Sonkar, Ravi,Modukuri, Ram K.,Chhonker, Yashpal S.,Kushwaha, Pragati,Chandasana, Hardik,Khanna,Bhatta, Rabi S.,Bhatia, Gitika,Suthar, Manish Kumar,Saxena, Jitendra Kumar,Kumar, Vikash,Siddiqi, Mohammad Imran
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p. 1858 - 1869
(2016/09/28)
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- ACYLGUANIDINES FOR TREATING OSTEOARTHRITIS
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The present invention relates to compounds of the formula (I) and in particular to medicaments comprising at least one compound of the formula I for use in the treatment and/or prophylaxis of physiological and/or pathophysiological conditions in the trigg
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Paragraph 0234; 0235
(2015/12/30)
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- Pd(OAc)2-catalyzed lactonization of arylacetamides involving oxidation of C-H bonds
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The reaction of arylacetamides that contain a quinolin-8-ylmethylamine as the directing group with PhI(OAc)2, in the presence of Pd(OAc)2 as the catalyst, results in lactonization to give γ-lactones, the formation of which involves activation of the ortho C-H bonds, with concomitant cleavage of the directing group.
- Uemura, Takeshi,Igarashi, Takuya,Noguchi, Moe,Shibata, Kaname,Chatani, Naoto
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supporting information
p. 621 - 623
(2015/05/20)
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- Synthesis, crystal structure, anti-inflammatory and anti-hyperglycemic activities of novel 3,4-disubstituted 1,2,4-triazol-5(4H)-one derivatives
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A new series of 3,4-disubstituted 1,2,4-triazol-5(4H)-one 5a-r, bearing various methoxyphenyl, fluorophenyl, tolyl and phenyl groups, was synthesized by the dehydrocyclization of hydrazinecarboxamides 4a-r by refluxing in a 2 N sodium hydroxide solution. Hydrazinecarboxamides 4a-r was synthesized via the condensation of the corresponding aralkanoic acid hydrazides, 3a-g, with fluoro-, tolyl- and methoxyphenylisocyanates. The newly synthesized compounds (5ar) were characterized by IR, 1H NMR and 13C NMR analyses. The structure of one compound 5a was determined by single crystal X-ray diffraction analysis. All of the synthesized compounds were screened for their anti-inflammatory and anti-diabetic (α-glucosidase and α-amylase inhibition) activity to identify new drugs that might be useful in preventing damage related to diabetes and inflammation. Compounds 5j, 5k and 5m decrease the expression of type II collagen in a dose dependent manner; similarly 5l decrease the COX-2 expression of rabbit articular chondrocytes in a dose dependent manner possessing potent anti-inflammatory potential while some of derivatives including 5c, 5e, 5g and 5h cause inflammation. Meanwhile, excellent α-glucosidase and moderate α-amylase inhibitory profiles against carbohydrate modulating enzymes were demonstrated by compounds 5b, 5f, 5k and 5q compared to the reference standard acarbose, and compounds 5g, 5h, 5i, 5j, 5l and 5o exhibited moderate to low enzyme inhibition potential among the series.
- Saleem, Muhammad,Yu, Seon-Mi,Rafiq, Muhammad,Kim, Song-Ja,Seo, Sung-Yum,Lee, Ki Hwan
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p. 810 - 823
(2015/04/14)
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- Efficient and Practical Syntheses of Enantiomerically Pure (S)-(-)-Norcryptostyline I, (S)-(-)-Norcryptostyline II, (R)-(+)-Salsolidine and (S)-(-)-Norlaudanosine via a Resolution-Racemization Method
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Four racemic tetrahydroisoquinolines (RS)-(±)-1-4 were prepared from homoveratrylamine via amidation, Bischler-Napieralski reaction and the subsequent reduction. The enantiomerically pure tetrahydroisoquinolines (S)- (-)-norcryptostyline I [(S)-(-)-1], (S)-(-)-norcryptostyline II [(S)-(-)-2], (R)-(+)-salsolidine [(R)-(+)-3] and (S)-(-)-norlaudanosine [(S)-(-)-4] were then obtained in 45%, 40%, 41% and 38% yields, respectively, via resolution of the racemic compounds (RS)-(±)-1-4 with half equivalent of chiral acids. In addition, the enantiomerically enriched compounds (R)-(+)-1, (R)-(+)-2, (S)-(-)-3 and (R)-(+)-4 from the mother liquors were efficiently racemized via a one-pot redox method in almost quantitative yields.
- Zhu, Ruiheng,Xu, Zhangli,Ding, Wei,Liu, Shiling,Shi, Xiaoxin,Lu, Xia
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p. 1039 - 1048
(2016/02/18)
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- An optimized RAD51 inhibitor that disrupts homologous recombination without requiring michael acceptor reactivity
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Homologous recombination (HR) is an essential process in cells that provides repair of DNA double-strand breaks and lesions that block DNA replication. RAD51 is an evolutionarily conserved protein that is central to HR. Overexpression of RAD51 protein is
- Budke, Brian,Kalin, Jay H.,Pawlowski, Michal,Zelivianskaia, Anna S.,Wu, Megan,Kozikowski, Alan P.,Connell, Philip P.
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p. 254 - 263
(2013/02/23)
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- Metal-free aerobic oxidation of benzazole derivatives
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2-Benzyl benzothiazoles and benzimidazoles are easily oxidized under air and basic conditions to give the corresponding ketones in good yields. The use of palladium acetate as a catalyst has little effect and even gives, in some cases, much lower yields.
- Dos Santos, Aurelie,El Kaim, Laurent,Grimaud, Laurence
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supporting information
p. 3282 - 3287
(2013/06/05)
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- Restraining the flexibility of the central linker in terameprocol results in constrained analogs with improved growth inhibitory activity
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The semi-synthetic lignan terameprocol inhibits the transcription of several inflammatory and oncogenic genes and has been evaluated for its anti-cancer properties. Here we investigated the effect of restricting the flexibility of the carbon linker connecting the terminal rings of terameprocol on its growth inhibitory activity. Conformational restriction was explored by introducing unsaturation, inserting polar entities with limited flexibility and cyclization of the connecting linker. Twenty three compounds were synthesized and evaluated on a panel of malignant human cells. The most promising compounds were those with non-polar linkers, as seen in butadiene 1a and the cyclized benzylideneindane analog 7. Both compounds were more potent than terameprocol on pancreatic BxPC-3 cells with GI50 values of 3.4 and 8.1 μM, respectively. Selected isomers of 1a (E,E) and 7 (Z) adopted low energy bent conformations that mimicked the low energy conformer of terameprocol. It is tempting to propose that conformational similarity to terameprocol may have contributed to their good activity. The scaffolds of 1a and 7 should be further investigated for their anticancer potential.
- Ho, Sherman Si Han,Go, Mei Lin
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supporting information
p. 6127 - 6133
(2013/11/06)
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- Cis-tetrahydro-spiro(cyclohexane-1,1'-pyrido[3,4-b]indole)-4-amine Compounds
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Cis-tetrahydro-spiro(cyclohexane-1,1′-pyrido[3,4-b]indole)-4-amine compounds which act on the nociceptin/ORL-1 receptor system as well as on the μ-opioid receptor system and which are distinguished in particular by selective effectiveness in the treatment of chronic pain, such as inflammatory pain, visceral pain, tumour pain, and neuropathic pain, without at the same time developing pronounced effectiveness against acute, nociceptive pain.
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(2012/02/06)
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- Asymmetric hydrogenation of α- Or β-acyloxy α,β- unsaturated phosphonates catalyzed by a Rh(i) complex of monodentate phosphoramidite
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The Rh(i) complex of a monodentate phosphoramidite bearing a primary amine moiety (DpenPhos) has been disclosed to be highly efficient for the asymmetric hydrogenation of a variety of α- or β-acyloxy α,β- unsaturated phosphonates, providing the corresponding biologically important chiral α- or β-hydroxy phosphonic acid derivatives with excellent enantioselectivities (90->99% ee).
- Zhang, Jinzhu,Dong, Kaiwu,Wang, Zheng,Ding, Kuiling
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supporting information; scheme or table
p. 1598 - 1601
(2012/03/22)
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- Stereoselective construction of the tetracyclic core of Cryptotrione
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An efficient stereoselective approach to the tetracyclic core of Cryptotrione, involving an asymmetric Michael addition, ring-closing metathesis, and subsequent cyclopropanation, is described.
- Chen, Song,Rong, Chao,Feng, Pengju,Li, Songlei,Shi, Yian
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supporting information; experimental part
p. 5518 - 5520
(2012/08/08)
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- Design, synthesis, and biological evaluation of novel deguelin-based heat shock protein 90 (HSP90) inhibitors targeting proliferation and angiogenesis
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Deguelin exhibits potent apoptotic and antiangiogenic activities in a variety of transformed cells and cancer cells. Deguelin also exhibits potent tumor suppressive effects in xenograft tumor models for many human cancers. Our initial studies confirmed that deguelin disrupts ATP binding to HSP90 and consequently induces destabilization of its client proteins such as HIF-1α. Interestingly, a fluorescence probe assay revealed that deguelin and its analogues do not compete with ATP binding to the N-terminus of HSP90, unlike most HSP90 inhibitors. To determine the key parts of deguelin that contribute to its potent HSP90 inhibition, as well as its antiproliferative and antiangiogenic activities, we have established a structure-activity relationship (SAR) of deguelin. In the course of these studies, we identified a series of novel and potent HSP90 inhibitors. In particular, analogues 54 and 69, the B- and C-ring-truncated compounds, exhibited excellent antiproliferative activities with IC50 of 140 and 490 nM in the H1299 cell line, respectively, and antiangiogenic activities in zebrafish embryos in a dose dependent manner (0.25-1.25 μM).
- Chang, Dong-Jo,An, Hongchan,Kim, Kyoung-Suk,Kim, Hyun Ho,Jung, Jinkyung,Lee, Jung Min,Kim, Nam-Jung,Han, Young Taek,Yun, Hwayoung,Lee, Sujin,Lee, Geumwoo,Lee, Seungbeom,Lee, Ju Sung,Cha, Jong-Ho,Park, Ji-Hyeon,Park, Ji Won,Lee, Su-Chan,Kim, Sang Geon,Kim, Jeong Hun,Lee, Ho-Young,Kim, Kyu-Won,Suh, Young-Ger
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p. 10863 - 10884
(2013/03/13)
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- Hexaphenylbenzene-based polymers of intrinsic microporosity
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Microporous polymers derived from the 1,2- and 1,4-regioisomers of di(3′,4′-dihydroxyphenyl)tetraphenylbenzene have very different properties with the former being composed predominantly of cyclic oligomers whereas the latter is of high molar mass suitable for the formation of robust solvent-cast films of high gas permeability.
- Short, Rhys,Carta, Mariolino,Bezzu, C. Grazia,Fritsch, Detlev,Kariuki, Benson M.,McKeown, Neil B.
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supporting information; experimental part
p. 6822 - 6824
(2011/08/08)
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- Synthesis, spasmolytic activity and structure-activity relationship study of a series of polypharmacological thiobenzanilides
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Recently we presented a series of benzanilide derivatives with a selective spasmolytic effect on terminal ileum preparations of the guinea pig. In this report we demonstrate a further development of these compounds. The exchange of the amide oxygen agains
- Brunhofer, Gerda,Studenik, Christian,Ecker, Gerhard F.,Erker, Thomas
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experimental part
p. 37 - 44
(2012/03/08)
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- Enantioselective syntheses and X-ray structures of (S)- and (R)-N-norlaudanidine: trace opium constituents
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The enantioselective synthesis of each of the enantiomers of N-norlaudanidine, a minor Papaver somniferum opium benzyltetrahydoisoquinoline alkaloid is described. This was achieved using a chiral auxiliary-mediated Bischler-Napieralski cyclization-sodium borohydride reduction strategy. The X-ray crystal structures of each of these secondary amines are reported.
- Zein, Ahmed L.,Dakhil, Otman O.,Dawe, Louise N.,Georghiou, Paris E.
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scheme or table
p. 177 - 180
(2010/03/04)
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- Perylenequinone natural products: Enantioselective synthesis of the oxidized pentacyclic core
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(Chemical Equation Presented) An enantioselective approach to the perylenequinone core found in the mold perylenequinone natural products is outlined. Specifically, the first asymmetric syntheses of helical chiral perylenequinones absent any additional st
- Mulrooney, Carol A.,Morgan, Barbara J.,Li, Xiaolin,Kozlowski, Marisa C.
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supporting information; experimental part
p. 16 - 29
(2010/04/26)
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- Synthesis and biological activity of some 1,3-dihydro-2H-3-benzazepin-2- ones with a piperazine moiety as bradycardic agents
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A series of 1,3-dihydro-2H-3-benzazepin-2-ones with a piperazine moiety were designed and synthesized by treating the common intermediate of 1,3-dihydro-7,8-dimethoxy-3-[3-(1-piperazinyl)-propyl]-2H-3-benzazepin-2-ones with a variety of N-aryl-2-chloroacetamides and acyl chlorides. Their structures have been characterized by 1H-NMR, MS, and elemental analysis. The title compounds were evaluated for their bradycardic activity in vitro. Most of the synthesized compounds exhibited some vasorelaxant activity and heart-rate-reducing activity with bradycardic potency.
- Liang, Hong-Yu,Zhang, Deng-Qing,Yue, Yun,Shi, Zhe,Zhao, Sheng-Yin
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scheme or table
p. 114 - 119
(2010/06/13)
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- PROCESS FOR PREPARATION OF IVABRADINE
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The present invention describes a new process for optical resolution of [N-[[3,4- dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl]-N-methylamine] which is an intermediate in the preparation of ivabradine.
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Page/Page column 16-17
(2010/07/09)
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- Enantioselective total synthesis and X-ray structures of the tetrahydroprotoberberine alkaloids (-)-(S)-tetrahydropalmatrubine and (-)-(S)-corytenchine
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Enantioselective total syntheses and X-ray structures of both (S)-tetrahydropalmatrubine (2) and (S)-corytenchine (3) are reported for the first time. They were both derived from (S)-N-norlaudanidine, a benzyltetrahydroisoquinoline that was synthesized with high (>95% ee) enantioselectivity using a chiral auxiliary-assisted Bischler-Napieralski cyclization/reduction approach.
- Zein, Ahmed L.,Dawe, Louise N.,Georghiou, Paris E.
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scheme or table
p. 1427 - 1430
(2010/10/21)
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- Synthesis, characterization and cardioprotective activity of some novel benzotriazole and pyrazole derivatives
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A series of N-(1-(1H-benzo[d]) [1,2,3]triazol-1-yl)-2,2-dimethyl propyl)-2-(substituted phenyl) acetamide derivatives and methyl 5-((4- (2,5-disubstituted phenyl) furan-2 carboxylate derivatives are prepared from different substituted aryl carboxylic acids, phenyl acetic acid and cinnamic acid, respectively. All the synthesized compounds are investigated for cardioprotective activity by ischemia reperfusion method, while all the compounds show significant activity.
- Gudaparthi, Vijayalakshmi,Bharathi,Panda, Jagadeesh
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experimental part
p. 5323 - 5330
(2012/07/28)
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- Efficient syntheses of crispine A and harmicine by Rh-catalyzed cyclohydrocarbonylation
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The first examples of Rh-catalyzed cyclohydrocarbonylation-bicyclization of N-allylic amides of arylacetic acids are reported. This novel carbonylative bicyclization process was successfully applied to the rapid syntheses of crispine A and its analogues (
- Chiou, Wen-Hua,Lin, Gau-Hong,Hsu, Che-Cheng,Chaterpaul, Stephen J.,Ojima, Iwao
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supporting information; experimental part
p. 2659 - 2662
(2009/10/02)
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- A new synthetic approach towards isoquinobenzazepinone and isoindolinobenzazepinone using acid-mediated cyclisation and Heck reaction
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Six-membered ring cyclisation of N-ethylbenzazepinone, prepared from the condensation of benzazepinone with phenethyl iodide under basic conditions, smoothly provided the corresponding product, isoquino[1,2-b][3]benzazepinone, under acid-mediated conditions. On the other hand, the attempted direct five-membered ring cyclisation using the acid-mediated conditions failed to give the 7,5 fused ring isoindolinobenzazepinone from N-benzylbenzazepinone, but the 7,6 fused ring product was instead obtained. However, five-membered ring cyclisation of N-benzylbenzazepinone could be effected efficiently by employing the Heck reaction followed by catalytic hydrogenation to furnish the desired isoindolinobenzazepinone.
- Phakhodee, Wong,Ploypradith, Poonsakdi,Sahakitpichan, Poolsak,Ruchirawat, Somsak
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experimental part
p. 351 - 356
(2009/04/06)
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- Process for the synthesis of 7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one, and application in the synthesis of ivabradine and addition salts thereof with a pharmaceutically acceptable acid
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Process for the synthesis of the compound of formula (I): Application in the synthesis of ivabradine, addition salts thereof with a pharmaceutically acceptable acid and hydrates thereof.
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Page/Page column 4
(2009/12/28)
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- An investigation into the electrophilic cyclisation of N-acyl-pyrrolidinium ions: A facile synthesis of Pyrrolo-tetrahydroisoquinolones and Pyrrolo-benzazepinones
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The triflic acid-mediated cyclisation of N-arylmethyl- and N-arylethyl-acylpyrrolidinium ions gave moderate to good yields of pyrrolo-tetrahydroisoquinolones and pyrrolo-benzazepinones respectively. Electron-donating R substituents enhanced the rate of reaction and gave higher yields than electron-withdrawing substituents. Substituents on the methyl or ethyl chain in general enhanced the reaction, unless sterically encumbered. The equivalent acylpiperidinium ions cyclised much slower and in lower yield.
- King, Frank D.,Aliev, Abil E.,Caddick, Stephen,Copley, Royston C. B.
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experimental part
p. 3561 - 3571
(2010/01/06)
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- Discovery and biological evaluation of novel cyanoguanidine P2X7 antagonists with analgesic activity in a rat model of neuropathic pain
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We disclose the design of a novel series of cyanoguanidines that are potent (IC50 ? 10-100 nM) and selective (≥100-fold) P2X7 receptor antagonists against the other P2 receptor subtypes such as the P2Y2, P2X4, and P2X3. We also found that these P2X7 antagonists effectively reduced nociception in a rat model of neuropathic pain (Chung model). Particularly, analogue 53 proved to be effective in the Chung model, with an ED50 of 38 μmol/kg after intraperitoneal administration. In addition compound 53 exhibited antiallodynic effects following oral administration and maintained its efficacy following repeated administration in the Chung model. These results suggest an important role of P2X7 receptors in neuropathic pain and therefore a potential use of P2X7 antagonists as novel therapeutic tools for the treatment of this type of pain.
- Perez-Medrano, Arturo,Donnelly-Roberts, Diana L.,Honore, Prisca,Hsieh, Gin C.,Namovic, Marian T.,Peddi, Sridhar,Shuai, Qi,Wang, Ying,Faltynek, Connie R.,Jarvis, Michael F.,Carroll, William A.
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experimental part
p. 3366 - 3376
(2010/04/03)
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- Orthogonal synthesis of indolines and isoquinolines via aryne annulation
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Described in this report is the development of two unique methodologies exploiting the reactivity of arynes. Reaction of N-carbamoyl-functionalized enamine derivatives with benzyne affords substituted indolines. An orthogonal reactivity is uncovered when related enamine derivatives are modified as amides, such that isoquinolines are formed as the product of condensation with benzyne. This latter transformation is applied to a concise total synthesis of the opiate alkaloid papaverine. Copyright
- Gilmore, Christopher D.,Allan, Kevin M.,Stoltz, Brian M.
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p. 1558 - 1559
(2008/09/17)
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- Investigation of the acid-mediated cyclisation of amide acetal for the synthesis of benzazepinone
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On treatment with acids, the open-chained amide acetals (1) gave the 7,7 membered ring fused benzazepinones (4) via the bis-cyclisation.
- Phakhodee, Wong,Sahakitpichan, Poolsak,Deechongkit, Songpon,Ruchirawat, Somsak
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experimental part
p. 1963 - 1970
(2009/04/06)
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- Pd-catalyzed enantioselective aerobic oxidation of secondary alcohols: Applications to the total synthesis of alkaloids
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Enantioselective syntheses of the alkaloids (-)-aurantioclavine, (+)-amurensinine, (-)-lobeline, and (-)- and (+)-sedamine are described. The syntheses demonstrate the effectiveness of the Pd-catalyzed asymmetric oxidation of secondary alcohols in diverse contexts and the ability of this methodology to set the absolute configuration of multiple stereocenters in a single operation. The utility of an aryne C-C insertion reaction in accessing complex polycyclic frameworks is also described.
- Krishnan, Shyam,Bagdanoff, Jeffrey T.,Ebner, David C.,Ramtohul, Yeeman K.,Tambar, Uttam K.,Stoltz, Brian M.
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supporting information; experimental part
p. 13745 - 13754
(2009/02/06)
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- Heteroaryl β-tetralin ureas as novel antagonists of human TRPV1
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We report on a series of α-substituted-β-tetralin-derived and related phenethyl-based isoquinolinyl and hydroxynaphthyl ureas as potent antagonists of the human TRPV1 receptor. The synthesis and Structure-activity relationships (SAR) of the series are described.
- Jetter, Michele C.,Youngman, Mark A.,McNally, James J.,McDonnell, Mark E.,Zhang, Sui-Po,Dubin, Adrienne E.,Nasser, Nadia,Codd, Ellen E.,Flores, Christopher M.,Dax, Scott L.
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p. 6160 - 6163
(2008/03/18)
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- Efficient synthesis of a new structural phenanthro[9,10,3′,4′] indolizidine starting from pyrrole
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(Chemical Equation Presented) A new structural phenanthroindolizidine, 2,3,6,7-tetramethoxyphenanthro[9,10,3′,4′]indolizidine, has been synthesized efficiently from pyrrole. An important feature of this synthesis is that intramolecular oxidative coupling
- Wang, Kailiang,Wang, Qingmin,Huang, Runqiu
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p. 8416 - 8421
(2008/03/12)
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- Synthesis and in vitro evaluation of iodinated derivatives of piperazine as a new ligand for sigma receptor imaging by single photon emission computed tomography
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A new series of radioiodinated analogues of 1-[2-(3,4-dimethoxyphenyl) ethyl]-4-(3-phenylpropyl)piperazine (SA4503) was synthesized and evaluated as a potential brain sigma-1 receptor imaging ligands by single photon emission computed tomography (SPECT).
- Hirata, Masahiko,Mori, Tetsuya,Soga, Seigo,Umeda, Takuya,Ohmomo, Yoshiro
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p. 470 - 475
(2007/10/03)
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- 2-ACYLAMINOTHIAZOLE DERIVATIVES
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The Invention relates to compounds of the formula I, wherein the variables are as defined in the claims, for use as a medicament. The compounds are A2A-receptor legends and are useful in the treatment of neurological and psychiatric disorders where an A2A-receptor is implicated.
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Page/Page column 37-38
(2008/06/13)
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