- Discovery of 2-aryl-8-hydroxy (or methoxy)-isoquinolin-1(2H)-ones as novel EGFR inhibitor by scaffold hopping
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2-Aryl-8-hydroxy (or methoxy)-isoquinolin-1(2H)-one has been proposed as a novel scaffold of EGFR inhibitor based on scaffold hoping. In the present study, a series of 2-aryl-8-hydroxy (or methoxy)-isoquinolin-1(2H)-one derivatives were synthesized. Their antiproliferative activities in vitro were evaluated via MTT assay against two human cancer cell lines, including A431 and A549. The SAR of the title compounds was preliminarily discussed. The compounds with ideal inhibition were evaluated through ELISA-based EGFR-TK assay. Compound 6c showed the best activity against A431 and EGFR tyrosine kinase. These findings suggest that title compounds are EGFR inhibitors with novel structures.
- Kang, Bo-Rui,Shan, Ai-Lin,Li, Yi-Ping,Xu, Jing,Lu, She-Min,Zhang, San-Qi
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- Synthesis and antitumor activity evaluation of 2-arylisoquinoline-1,3(2H, 4H)-diones in vitro and in vivo
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Six 2-(2-acylaminobenzothiazol-6-yl)isoquinoline-1,3(2H,4H)-diones (1a-1f) and five 2-arylisoquinoline-1,3(2H,4H)-diones (1g-1k) were synthesized by refluxing homophthalic anhydrides with 2-acylaminobenzothiazolyl-6-amine or substituted aniline in glacial acetic acid. The cytotoxic activities of 1a-1k were evaluated via MTT method against A431, A549, and PC3. Compound 1b relatively displayed a higher cytotoxic activity than the others. The antitumor effect of 1b were evaluated in established nude mice PANC-1 xenograft model. The results suggest that compound 1b could potentially inhibit tumor growth.
- Kang, Bo-Rui,Wang, Juan,Li, Huan,Li, Yan,Mei, Qi-Bing,Zhang, San-Qi
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p. 1340 - 1349
(2014/03/21)
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- Total synthesis of viridicatumtoxin B and analogues thereof: Strategy evolution, structural revision, and biological evaluation
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The details of the total synthesis of viridicatumtoxin B (1) are described. Initial synthetic strategies toward this intriguing tetracycline antibiotic resulted in the development of key alkylation and Lewis acid-mediated spirocyclization reactions to form the hindered EF spirojunction, as well as Michael-Dieckmann reactions to set the A and C rings. The use of an aromatic A-ring substrate, however, was found to be unsuitable for the introduction of the requisite hydroxyl groups at carbons 4a and 12a. Applying these previous tactics, we developed stepwise approaches to oxidize carbons 12a and 4a based on enol- and enolate-based oxidations, respectively, the latter of which was accomplished after systematic investigations that revealed critical reactivity patterns. The herein described synthetic strategy resulted in the total synthesis of viridicatumtoxin B (1), which, in turn, formed the basis for the revision of its originally assigned structure. The developed chemistry facilitated the synthesis of a series of viridicatumtoxin analogues, which were evaluated against Gram-positive and Gram-negative bacterial strains, including drug-resistant pathogens, revealing the first structure-activity relationships within this structural type.
- Nicolaou,Hale, Christopher R. H.,Nilewski, Christian,Ioannidou, Heraklidia A.,Elmarrouni, Abdelatif,Nilewski, Lizanne G.,Beabout, Kathryn,Wang, Tim T.,Shamoo, Yousif
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p. 12137 - 12160
(2014/11/08)
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- TREATMENT OF DISEASES BY EPIGENETIC REGULATION
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The present disclosure provides non-naturally occurring polyphenol compounds that inhibit the bromodomain and extra terminal domain (BET) proteins. The disclosed compositions and methods can be used for treatment and prevention of cancer, including NUT midline carcinoma, Burkitt's Lymphoma, Acute Myelogenous Leukemia, and Multiple Myeloma; autoimmune or inflammatory diseases or conditions, and sepsis.
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Paragraph 0471
(2013/11/05)
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- COMPOUNDS FOR THE PREVENTION AND TREATMENT OF CARDIOVASCULAR DISEASES
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The present disclosure relates to compounds, which are useful for regulating the expression of apolipoprotein A-I (ApoA-I), and their use for treatment and prevention of cardiovascular disease and related disease states, including cholesterol- or lipid-related disorders, such as, for example, atherosclerosis.
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Page/Page column 32-33
(2008/12/07)
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- PHARMACEUTICAL COMPOSITIONS FOR THE PREVENTION AND TREATMENT OF COMPLEX DISEASES AND THEIR DELIVERY BY INSERTABLE MEDICAL DEVICES
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The present invention relates to polyphenol-like compounds that are useful for inhibiting VCAM-1 expression, MCP-1 expression and/or SMC proliferation in a mammal. The disclosed compounds are useful for regulating markers of inflammatory conditions, including vascular inflammation, and for treatment and prevention of inflammatory and cardiovascular diseases and related disease states.
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Page/Page column 105-106
(2008/06/13)
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- Total Synthesis of Premithramycinone H and Related Anthrapyran Antibiotics
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Two approaches are described for the preparation of 2-(1',3'-dioxoalkyl)-substituted 1-hydroxyanthraquinones 10a-d and 20a-c, which were cyclized in a biomimetic-type reaction to the anthra[1,2-b]pyran skeletons 11a-d and 21a-c of the heydamcin- or pluram
- Krohn, Karsten,Vitz, Juergen
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p. 209 - 219
(2007/10/03)
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- An anionic polycondensation strategy for the synthesis of dibenzoxanthenones: Progress toward the synthesis of hypoxyxylerone
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An anionic polycondensation has been used as the key step in a highly convergent strategy for the preparation of hypoxyxylerone derivatives.
- Chevenier, Emmanuel,Lucatelli, Christophe,Pandya, Urvish,Wang, Wei,Gimbert, Yves,Greene, Andrew E.
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p. 2693 - 2696
(2007/10/03)
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- An efficient synthesis of 3,5-dimethoxyhomophthalic acid, a key intermediate for synthesis of natural isocoumarins
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3,5-Dimethoxyhomophthalic acid was prepared efficiently in three steps, from 3,5-dimethoxybenzyl bromide via rhodium-catalyzed direct carbonylation to 3,5-dimethoxyphenylacetic acid followed by successive o-formylation and oxidation. Isocoumarins related
- Saeed, Aamer,Rama, Nasim H.,Arfan
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p. 519 - 522
(2007/10/03)
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- Formal synthesis of angiogenesis inhibitor NM-3
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We report the formal synthesis of angiogenesis inhibitor NM-3 (1) in six steps from either of the 2,4-dimethoxyhalobenzenes 13a,b or 3,5-dimethoxychlorobenzene (13c). The first key reaction is the regiospecific alkylation/rearrangement between the aryne derived from 13a-c with sodium diethylmalonate in THF to produce diester 11, which after hydrolysis and cyclization affords homophthalic anhydride 3. The second is the reaction of anhydride 3 with either ethyl 2-methylmalonate (28a), in the presence of 1,1′-carbonyldiimidazole, or ethyl-2-methylmalonyl chloride (28b) under basic conditions to afford key isocoumarin 27. The conversion of 27 constitutes a formal synthesis of NM-3.
- Bauta, William E.,Lovett, Dennis P.,Cantrell Jr., William R.,Burke, Brian D.
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p. 5967 - 5973
(2007/10/03)
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- Process for the manufacture of hypoxyxylerone derivatives
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The present invention relates to the total synthesis of hypoxyxylerone derivatives (formula I) and their biological activities. R1-R5 are as described in the description.
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- Synthesis and cytotoxic activity of tetracenomycin d and of saintopin analogues
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Regiospecific synthesis of title compounds is based either on cycloaddition of ketene acetals derived from Hagemann's ester or of homophthalic anhydrides. Thus, tetracenomycin D and 3,8-di-O-methyl saintopin have been prepared in few steps. New derivatives of 10-deoxysaintorpin have been also obtained. Evaluation of their cytotoxicity against L1210 leukemia cells are reported. Copyright
- Martin, Philippe,Rodier, Stephane,Mondon, Martine,Renoux, Brigitte,Pfeiffer, Bruno,Renard, Pierre,Pierre, Alain,Gesson, Jean-Pierre
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p. 253 - 260
(2007/10/03)
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- Synthesis of homophthalates from allenic diesters: Conversion into viocristin and analogues, and application to 6-methylpretetramid
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Oxy-substituted homophthalic anhydrides have been synthesized by cycloaddition of di- and tri-oxy butadienes to the allenic diester (1). By base-catalysed cycloaddition to appropriate benzoquinones they have afforded new syntheses of viocristin (19), isov
- Caliskan, Ece,Cameron, Donald W.,Griffiths, Peter G.
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p. 1013 - 1020
(2007/10/03)
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- Biosyntheses of Antibiotic A26771B by Penicillium turbatum and Dehydrocurvularin by Alternaria cinerariae: Comparison of Stereochemistry of Polyketide and Fatty Acid Enoyl Thiol Ester Reductases
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The biosyntheses of reduced polyketides and fatty acids were compared by use of stable isotope labeling and NMR spectroscopy.Incorporations of sodium -, -, -, -, -, and acetates i
- Arai, Kunizo,Rawlings, Bernard J.,Yoshizawa, Yuko,Vederas, John C.
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p. 3391 - 3399
(2007/10/02)
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- SYNTHETIC STUDIES ON NOGALAMYCIN CONGENERS ; SYNTHESES AND ANTITUMOR ACTIVITY OF VARIOUS NOGALAMYCIN CONGENERS
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Various structural types of nogalamycin congeners and their partial structures, which had been previously synthesized in the course of our synthetic studies on the total syntheses or were originally produced by employing the explored synthetic scheme, were subjected to in vitro cytotoxicity and in vivo antitumor activity assay against P388 murine leukemia.These studies obviously disclosed novel aspects of the structure-activity relationships of nogalamycin congeners.
- Matsuda, Fuyuhiko,Kawasaki, Motoji,Ohsaki, Masako,Yamada, Kaoru,Terashima, Shiro
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p. 5745 - 5760
(2007/10/02)
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- Syntheses and Cytotoxicity of Various 7-Methoxynogarene Derivatives
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The title compounds were prepared employing the regioselective cycloaddition of the (+)-naphthoquinone derivative, the CDEF-ring system of nogalamycin, with various homophthalic anhydrides.Among the 7-metoxylnogarene derivatives obtained, 7-methoxy- and 9
- Matsuda, Fuyuhiko,Kawasaki, Motoji,Ohsaki, Masako,Yamada, Kaoru,Terashima, Shiro
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p. 653 - 656
(2007/10/02)
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- A BIOMIMETIC SYNTHESIS OF POLICYCLIC QUINONES
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Various polycyclic quinones were synthesized by the intramolecular condensation of polyketides followed by the air-oxidation.
- Yamaguchi, Masahiko,Hasebe, Koichi,Uchida, Minoru,Irie, Akemi,Minami, Toru
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p. 2017 - 2020
(2007/10/02)
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- Synthesis of Chlorinated Isocoumarin Derivatives
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Syhtheses of 5-chloro-, 7-chloro-, and 5,7-dichloro-isocoumarin derivatives, including the fungal metabolites 5-chloro-3,4-dihydro-8-hydroxy-6-methoxy-3-methylisocoumarin (3), 7-chloro-3,4-dihydro-8-hydroxy-6-methoxy-3-methylisocoumarin (2), and 5,7-dichl
- Henderson, Graeme B.,Hill, Robert A.
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p. 1111 - 1116
(2007/10/02)
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- Convenient Preparation of Homophthalic Acids
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Preparation of homophthalic acids by peroxide oxidation of indan-1-one-2-glyoxalates is reported. Orientation of acetylation of methyl 3,5-dimethoxyphenylacetate has been established.
- Bhakta, C.,Mukherjee, Sanat K.
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p. 637 - 639
(2007/10/02)
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