- Kolbe-Schmitt type reaction under ambient conditions mediated by an organic base
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The combined use of an organic base for resorcinols realized a Kolbe-Schmitt type reaction under ambient conditions. When resorcinols (3-hydroxyphenol derivatives) were treated with DBU under a carbon dioxide atmosphere, nucleophilic addition to carbon dioxide proceeded to afford the corresponding salicylic acid derivatives in high yields.
- Sadamitsu, Yuta,Okumura, Akira,Saito, Kodai,Yamada, Tohru
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supporting information
p. 9837 - 9840
(2019/08/20)
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- HSP90B N-TERMINAL ISOFORM-SELECTIVE INHIBITORS
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The present technology provides compounds according to Formula (I) as well as compositions including such compounds useful for the treatment of cancers such as non-small cell lung cancer, bladder cancer, or colon cancer.
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Paragraph 0137-0138
(2018/08/03)
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- Phenyl 1, 2 - isoxazole or phenyl 1, 2 - pyrazole compound and use thereof (by machine translation)
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The invention discloses the following formula of phenyl 1, 2 - different oxazole or 1, 2 - pyrazole compounds with use. Through the biological activity tests show that, the compound inhibiting heat shock protein 90 activity. Therefore, the invention phenyl 1, 2 - different oxazole or 1, 2 - pyrazole compounds can be used as a heat shock protein 90 inhibitor for the treatment of cancer. (by machine translation)
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Paragraph 0254; 0255; 0257; 0258; 0259
(2017/01/19)
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- Identification of a new series of potent diphenol HSP90 inhibitors by fragment merging and structure-based optimization
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Heat shock protein 90 (HSP90) is a molecular chaperone to fold and maintain the proper conformation of many signaling proteins, especially some oncogenic proteins and mutated unstable proteins. Inhibition of HSP90 was recognized as an effective approach to simultaneously suppress several aberrant signaling pathways, and therefore it was considered as a novel target for cancer therapy. Here, by integrating several techniques including the fragment-based drug discovery method, fragment merging, computer aided inhibitor optimization, and structure-based drug design, we were able to identify a series of HSP90 inhibitors. Among them, inhibitors 13, 32, 36 and 40 can inhibit HSP90 with IC50 about 20-40 nM, which is at least 200-fold more potent than initial fragments in the protein binding assay. These new HSP90 inhibitors not only explore interactions with an under-studied subpocket, also offer new chemotypes for the development of novel HSP90 inhibitors as anticancer drugs.
- Ren, Jing,Li, Jian,Wang, Yueqin,Chen, Wuyan,Shen, Aijun,Liu, Hongchun,Chen, Danqi,Cao, Danyan,Li, Yanlian,Zhang, Naixia,Xu, Yechun,Geng, Meiyu,He, Jianhua,Xiong, Bing,Shen, Jingkang
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supporting information
p. 2525 - 2529
(2014/05/20)
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- Simple and improved regioselective brominations of aromatic compounds using N-benzyl-N,N-dimethylanilinium peroxodisulfate in the presence of potassium bromide under mild reactions conditions
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A simple, efficient, and mild method for the selective bromination of some activated aromatic compounds using N-benzyl-N,N-dimethylanilinium peroxodisulfate in the presence of potassium bromide in non-aqueous solution is reported. The results obtained revealed good to excellent selectivity between the ortho and para positions of phenols and methoxyarenes.
- Ghasemnejad-Bosra, Hassan,Ramzanian-Lehmali, Farhad,Jafari, Somaye
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experimental part
p. 685 - 692
(2012/01/16)
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- Targeting mycobacterium protein tyrosine phosphatase B for antituberculosis agents
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Protein tyrosine phosphatases are often exploited and subverted by pathogenic bacteria to cause human diseases. The tyrosine phosphatase mPTPB from Mycobacterium tuberculosis is an essential virulence factor that is secreted by the bacterium into the cytoplasm of macrophages, where it mediates mycobacterial survival in the host. Consequently, there is considerable interest in understanding the mechanism by which mPTPB evades the host immune responses, and in developing potent and selective mPTPB inhibitors as unique antituberculosis (antiTB) agents. We uncovered that mPTPB subverts the innate immune responses by blocking the ERK1/2 and p38 mediated IL-6 production and promoting host cell survival by activating the Akt pathway. We identified a potent and selective mPTPB inhibitor I-A09 with highly efficacious cellular activity, from a combinatorial library of bidentate benzofuran salicylic acid derivatives assembled by click chemistry. We demonstrated that inhibition of mPTPB with I-A09 in macrophages reverses the altered host immune responses induced by the bacterial phosphatase and prevents TB growth in host cells. The results provide the necessary proof-of-principle data to support the notion that specific inhibitors of the mPTPB may serve as effective antiTB therapeutics.
- Zhou, Bo,He, Yantao,Zhang, Xian,Xu, Jie,Luo, Yong,Wang, Yuehong,Franzblau, Scott G.,Yang, Zhenyun,Chan, Rebecca J.,Liu, Yan,Zheng, Jianyu,Zhang, Zhong-Yin
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scheme or table
p. 4573 - 4578
(2010/10/03)
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- Derivatives of salicylic acid as inhibitors of YopH in yersinia pestis
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Yersinia pestis causes diseases ranging from gastrointestinal syndromes to bubonic plague and could be misused as a biological weapon. As its protein tyrosine phosphatase YopH has already been demonstrated as a potential drug target, we have developed two series of forty salicylic acid derivatives and found sixteen to have micromolar inhibitory activity. We designed these ligands to have two chemical moieties connected by a flexible hydrocarbon linker to target two pockets in the active site of the protein to achieve binding affinity and selectivity. One moiety possessed the salicylic acid core intending to target the phosphotyrosine-binding pocket. The other moiety contained different chemical fragments meant to target a nearby secondary pocket. The two series of compounds differed by having hydrocarbon linkers with different lengths. Before experimental co-crystal structures are available, we have performed molecular docking to predict how these compounds might bind to the protein and to generate structural models for performing binding affinity calculation to aid future optimization of these series of compounds.
- Huang, Zunnan,He, Yantao,Zhang, Xian,Gunawan, Andrea,Wu, Li,Zhang, Zhong-Yin,Wong, Chung F.
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scheme or table
p. 85 - 99
(2011/03/19)
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- TRIAZOLE DERIVATIVE AS AN HSP 90 INHIBITOR
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5-[4-(2-Methylphenyl)-3-hydroxy-4H-1,2,4-triazol-5-yl]-2,4-dihydroxy-N-methyl-N-butylbenzamide is an HSP90 inhibitor and can be used for the preparation of a medicament for the treatment of diseases in which the inhibition, regulation and/or modulation of HSP90 plays a role.
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Page/Page column 14-15
(2010/05/13)
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- 1,3-DIHYDROISOINDOLE DERIVATIVES
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Novel 1,3-dihydroisoindole derivatives of the formula (I), in which R1-R3 have the meanings indicated in claim 1, areHSP90 inhibitors and can be used for the preparation of a medicament for the treatment of diseases in which the inhibition, regulation and/or modulation of HSP90 plays a role.
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Page/Page column 17
(2010/12/29)
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- Bromination of some aromatic compounds with potassium bromide in the presence of benzyltriphenylphosphonium peroxodisulfate
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A simple, efficient, and mild method for selective bromination of some activated aromatic compounds using potassium bromide in the presence of benzyltriphenylphosphonium peroxodisulfate in nonaqueous solution is reported. The results obtained revealed good to excellent selectivity between ortho and para positions of phenols and methoxyarenes. Copyright Taylor & Francis Group, LLC.
- Tajik, Hassan,Mohammadpoor-Baltork, Iraj,Albadi, Jalal
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p. 323 - 328
(2007/10/03)
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- Design, synthesis, and structure - Activity relationships for chimeric inhibitors of Hsp90
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(Chemical Equation Presented) Inhibition of the 90 kDa heat shock protein (Hsp90) family of molecular chaperones represents a promising new chemotherapeutic approach toward the treatment of several cancers. Previous studies have demonstrated that the natural products, radicicol and geldanamycin, are potent inhibitors of the Hsp90 N-terminal ATP binding site. The cocrystal structures of these molecules bound to Hsp90 have been determined, and through molecular modeling and superimposition of these ligands, hybrids of radicicol and geldanamycin have been designed. A series of macrocylic chimeras of radicicol and geldanamycin and the corresponding seco-agents have been prepared and evaluated for both antiproliferative activity and their ability to induce Hsp90-dependent client protein degradation.
- Shen, Gang,Wang, Mingwen,Welch, Timothy R.,Blagg, Brian S. J.
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p. 7618 - 7631
(2007/10/03)
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- Total synthesis of seco-lateriflorone
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A convergent strategy toward the synthesis of lateriflorone (5) is described. Our approach is based on biosynthetic considerations and draws on a sequence of prenylation, oxygenation and Claisen reactions for the construction of chromenequinone 6, and a tandem Claisen/Diels-Alder reaction cascade for the synthesis of caged tricycle 7. Union of fragments 6 and 7 led to the synthesis of seco-lateriflorone (49).
- Tisdale, Eric J.,Vong, Binh G.,Li, Hongmei,Kim, Sun Hee,Chowdhury, Chinmay,Theodorakis, Emmanuel A.
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p. 6873 - 6887
(2007/10/03)
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- Regioselective synthesis of the tricyclic core of lateriflorone
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(Matrix presented) An efficient synthetic approach to the tricyclic core 8 of lateriflorone is described. Essential to the synthesis was the implementation of a biomimetic tandem Claisen/Diels-Alder reaction that produced the desired tricyclic scaffold as a single isomer. A rationalization of the excellent regio and stereoselectivity of this transformation is also proposed.
- Tisdale, Eric J.,Li, Hongmei,Vong, Binh G.,Kim, Sun Hee,Theodorakis, Emmanuel A.
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p. 1491 - 1494
(2007/10/03)
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