- Design, synthesis and anticancer evaluation of 3-methyl-1H-indazole derivatives as novel selective bromodomain-containing protein 4 inhibitors
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Bromodomain-containing Protein 4 (BRD4), an ‘epigenetic reader’, regulates chromatin structure and gene expression via recognizing and binding acetylated lysine in histones. BRD4 has become a therapeutic target for cancers because it promotes the expression of the tumor genes, such as c-Myc, NF-κB, and Bcl-2. In this study, a new series of 3-methyl-1H-indazole derivatives were designed via virtual screening and structure-based optimization. All compounds were synthesized and evaluated for their inhibitory activities to BRD4-BD1 and their antiproliferative effects in cancer cell lines. Among them, several compounds (such as 9d, 9u and 9w) exhibited strong BRD4-BD1 affinities and inhibition activities, and potently suppressed MV4;11 cancer cell line proliferation. Among them, compound 9d showed excellent selectivity for BRD4 and effectively suppressed c-Myc, the downstream protein of BRD4. This study provided new lead compounds for further biological evaluation on BRD4.
- Dong, Ru,Zhang, Cheng,Wang, Chao,Zhou, Xin,Li, Wen,Zhang, Jin-Yang,Wang, Min,Xu, Yong,Sun, Li-Ping
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- An Environmentally Benign, Catalyst-Free N?C Bond Cleavage/Formation of Primary, Secondary, and Tertiary Unactivated Amides
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Herein, we report an operationally simple, cheap, and catalyst-free method for the transamidation of a diverse range of unactivated amides furnishing the desired products in excellent yields. This protocol is environmentally friendly and operates under extremely mild conditions without using any promoter or additives. Significantly, this strategy has been implied in the chemoselective synthesis of a pharmaceutical molecule, paracetamol, on a gram-scale with excellent yield. We anticipate that this universally applicable strategy will be of great interest in drug discovery, biochemistry, and organic synthesis.
- Kumar, Vishal,Dhawan, Sanjeev,Girase, Pankaj Sanjay,Singh, Parvesh,Karpoormath, Rajshekhar
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p. 5627 - 5639
(2021/11/11)
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- HCl-mediated transamidation of unactivated formamides using aromatic amines in aqueous media
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We report transamidation protocol to synthesize a range of secondary and tertiary amides from weakly nucleophilic aromatic and hetero-aryl amines with low reactive formamide derivatives, utilizing hydrochloric acid as catalyst. This current acid mediated strategy is beneficial because it eliminates the need for a metal catalyst, promoter or additives in the reaction, simplifies isolation and purification. Notably, this approach conventionally used to synthesize molecules on gram scales with excellent yields and a high tolerance for functional groups.
- Dhawan, Sanjeev,Girase, Pankaj Sanjay,Kumar, Vishal,Karpoormath, Rajshekhar
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p. 3729 - 3739
(2021/10/14)
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- Method of N-formylating amines with a phosphonic anhydride
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A method for N-formylating an amine that includes reacting the amine and a formamide compound in the presence of a phosphonic anhydride to form an N-formylated amine. The phosphonic anhydride is present in an amount of 5-100 mol % relative to a total number of moles of the amine, and the reacting is performed for 1-24 hours at a temperature of 45-100° C.
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Page/Page column 21; 22; 25; 26; 29
(2018/02/28)
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- Rational design and synthesis of 1,5-disubstituted tetrazoles as potent inhibitors of the MDM2-p53 interaction
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Using the computational pharmacophore-based ANCHOR.QUERY platform a new scaffold was discovered. Potent compounds evolved inhibiting the protein-protein interaction p53-MDM2. An extensive SAR study was performed based on our four-point pharmacophore model
- Surmiak, Ewa,Neochoritis, Constantinos G.,Musielak, Bogdan,Twarda-Clapa, Aleksandra,Kurpiewska, Katarzyna,Dubin, Grzegorz,Camacho, Carlos,Holak, Tad A.,D?mling, Alexander
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p. 384 - 407
(2016/12/22)
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- Synthesis method of anti-tumor medicine afatinib
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The invention discloses a synthesis method of an anti-tumor medicine afatinib and belongs to the technical field of pharmaceutical chemistry. The method takes 2-nitryl-5-bromophenol as a raw material and obtains the afatinib through a five-step chemical reaction. The raw material of a synthesis route is easy to obtain, a process route is shortened, the operation is simple and the yield of products is high; and industrial production is easy to realize.
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Paragraph 0041; 0042; 0043; 0044
(2017/05/13)
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- Survey reactivity of some N-aryl formamides with pentafluoropyridine
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Chemo selectivity of some N-aryl formamides with pentafluoropyridine under basic conditions in dry THF was investigated. The aromatic nucleophilic substitution of pentafluoropyridine with enol-imines derived from N-aryl formamides occurs at the 4-position of pyridine ring by both oxygen and nitrogen site of enol-imines depending on the nature of the aromatic ring substituent; with electron releasing group, nucleophilic attack was accomplished by oxygen atom and with an electron withdrawing group, the reaction of N-aryl formamide anions with pentafluoropyridine proceeded via nitrogen site.
- Ranjbar-Karimi, Reza,Poorfreidoni, Alireza,Masoodi, Hamid Reza
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p. 222 - 226
(2015/11/03)
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- AMINONITRILES AS KYNURENINE PATHWAY INHIBITORS
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The present application provides novel kynurenine pathway inhibitors and pharmaceutically acceptable salts and prodrugs thereof. Also provided are methods for preparing these compounds. These compounds are useful in regulating the kynurenine pathway and the activity of indoleamine 2,3-dioxygenase and/or tryptophan 2,3-dioxygenase by administering a therapeutically effective amount of one or more of the compounds of formula (I) to a patient. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the kynurenine pathway. A variety of conditions can be treated using these compounds and include diseases which are characterized by immunosuppression, abnormal cellular proliferation and/or inflammation. In one embodiment, the disease is cancer. In another embodiment, the disease is a viral infection. In a further embodiment, the disease is depression.
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Page/Page column 80
(2014/09/29)
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- Organic reactions in water: A practical and convenient method for the N-formylation of amines in water
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A simple, efficient, scaleable process has been developed for the N-formylation amines in water. Treatment of amines with triethyl orthoformate in water at reflux under neutral conditions without any additives gives the corresponding N-formyl derivatives in good yields. Georg Thieme Verlag Stuttgart - New York.
- Kaboudin, Babak,Khodamorady, Minoo
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experimental part
p. 2905 - 2907
(2011/02/26)
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- Formylation without catalyst and solvent at 80 °C
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A simple and efficient protocol for N-formylation of aliphatic and heterocyclic amines has been described with formic acid in the absence of catalyst and solvent.
- Rahman, Matiur,Kundu, Dhiman,Hajra, Alakananda,Majee, Adinath
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experimental part
p. 2896 - 2899
(2010/06/14)
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- Facile N-formylation of amines using Lewis acids as novel catalysts
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Alky, aryl, and heteroaryl amines were found to react efficiently with formic acid under Lewis acid catalysis giving N-formyl derivatives in high yields. A study of ZnCl2-catalyzed N-formylation of a variety of amines using formic acid as formylating agent is described.
- Chandra Shekhar,Ravi Kumar,Sathaiah,Luke Paul,Sridhar, Madabhushi,Shanthan Rao
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experimental part
p. 7099 - 7101
(2010/03/03)
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- A convenient procedure for the formylation of amines and alcohols using cyanomethyl formate
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A simple metyod for the direct formylation of amines using cyanomethyl formate is described. The formylation succeeds in moderate to high yields under mild and neutral conditions. Thus, formamides 2a-f, 2i-m are obtained at room temperature. A chemoselective N-formylation is achieved in the case of ethanolamine. The formylation of nitroanilines and the O-formylation of alcohols only succeeds in the presence of a catalytic amount of imidazole leading to 2g,h and 3a-e, respectively.
- Deutsch,Niclas
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p. 1561 - 1568
(2007/10/02)
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