- Preparation method 3 - phenoxybromopropane or analogue thereof
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The invention discloses a preparation method of 3 -phenoxybromopropane or an analogue thereof, wherein 3 - phenoxybromopropane and an allyl compound thereof are obtained through substitution reaction and addition reaction so as to avoid the inconvenience of using gaseous hydrogen bromide, 2nd-step addition reaction is realized by using the brominated salt and the acid in situ, and the process is simple in operation. The condition is easy to control, the atom economy is good, the aspect of environmental impact is low pollution, zero emission accords with the current green chemical synthesis direction, and the cost is economic.
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Paragraph 0084-0086
(2021/11/26)
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- Novel compound, polymer prepared therefrom, and organic light emitting device comprising the polymer
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The present invention relates to a novel compound, a copolymer prepared therefrom, and an organic light emitting device comprising the copolymer.COPYRIGHT KIPO 2020
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Paragraph 0185-0189
(2020/07/28)
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- POLYCYCLIC COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF RAPIDLY ACCELERATED FIBROSARCOMA POLYPEPTIDES
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The present disclosure relates to bifunctional compounds, ULM— L—PTM, which find utility as modulators of Rapidly Accelerated Fibrosarcoma (RAF, such as c-RAF, A- RAF and/or B-RAF; the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein RAF, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein, or the constitutive activation of the target protein, are treated or prevented with compounds and compositions of the present disclosure.
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Paragraph 1462; 1463
(2020/03/29)
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- Twist-bend nematic liquid crystals based on thioether linkage
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We developed twist-bend nematogens based on cyanobiphenyl dimers with thioether or sulfur linkage, as opposed to the commonly used methylene and ether linkages. Based on the smaller bond angle of thioether C-S-C than methylene C-CH2-C and ether
- Arakawa, Yuki,Komatsu, Kenta,Tsuji, Hideto
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supporting information
p. 6786 - 6793
(2019/05/10)
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- Discovery of Carboline Derivatives as Potent Antifungal Agents for the Treatment of Cryptococcal Meningitis
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Clinical treatment of cryptococcal meningitis (CM) remains a significant challenge because of the lack of effective and safe drug therapies. Developing novel CM therapeutic agents with novel chemical scaffolds and new modes of action is of great importanc
- Tu, Jie,Li, Zhuang,Jiang, Yanjuan,Ji, Changjin,Han, Guiyan,Wang, Yan,Liu, Na,Sheng, Chunquan
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p. 2376 - 2389
(2019/03/07)
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- Compound with spiro structure, preparation method and application thereof
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The invention discloses a compound with a spiro structure, a preparation method and application thereof. The compound with a spiro structure shown as formula I, formula II or formula III or pharmaceutically acceptable salts thereof have excellent hDHFR inhibitory activity, antitumor activity and antibacterial activity.
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Paragraph 0089; 0090; 0091
(2018/08/04)
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- Design, synthesis, docking studies and biological evaluation of novel dihydro-1,3,5-triazines as human DHFR inhibitors
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A novel series of dihydro-1,3,5-triazine derivatives bearing a heteroatom spiro-ring were designed and synthesized on the basis of molecular flexible docking work, and their biological activities were evaluated. Compounds A2, A5, B1 and B3 showed potent human dihydrofolate reductase (hDHFR) inhibitory activity with IC50values of 7.46 nM, 3.72 nM, 6.46 nM, 4.08 nM, versus reference drug methotrexate (MTX). From the molecular docking result we concluded that the conformation space generated by deformation of the flexible residue Phe31 is favorable for the binding of the spiro-ring, and inserting heteroatom into spiro ring might increase the binding affinity. There were 24 compounds with broadspectrum antiproliferative activity against several tumor cell lines (HCT116, A549, HL-60, HepG2 and MDA-MB-231) with IC50values ranging from 0.79 to 0.001 μM. The antitumor activity in?vivo of compound A2 was determined in a human alveolar basal epithelial cell line A549 xenograft model. This study offered novel anticancer agents with high inhibitory activity that target hDHFR and have a binding mode of the novel molecular scaffold with hDHFR. This provides potent support for further development of novel hDHFR inhibitors.
- Zhou, Xiaotian,Lin, Kuaile,Ma, Xiang,Chui, Wai-Keung,Zhou, Weicheng
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p. 1279 - 1288
(2016/11/29)
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- Catalytic Access to Alkyl Bromides, Chlorides and Iodides via Visible Light-Promoted Decarboxylative Halogenation
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Herein is reported the catalytic, visible light-promoted, decarboxylative halogenation (bromination, chlorination, and iodination) of aliphatic carboxylic acids. This operationally-simple reaction tolerates a range of functional groups, proceeds at room temperature, and is redox neutral. By employing an iridium photocatalyst in concert with a halogen atom source, the use of stoichiometric metals such as silver, mercury, thallium, and lead can be circumvented. This reaction grants access to valuable synthetic building blocks from the large pool of cheap, readily available carboxylic acids.
- Candish, Lisa,Standley, Eric A.,Gómez-Suárez, Adrián,Mukherjee, Satobhisha,Glorius, Frank
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p. 9971 - 9974
(2016/07/19)
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- Toward the discovery of dual HCMV-VZV inhibitors: Synthesis, structure activity relationship analysis, and cytotoxicity studies of long chained 2-uracil-3-yl-N-(4-phenoxyphenyl)acetamides
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The need for novel therapeutic options to fight herpesvirus infections still persists. Herein we report the design, synthesis and antiviral evaluation of a new family of non-nucleoside antivirals, derived from 1-[ω-(4-bromophenoxy)alkyl]uracil derivatives - previously reported inhibitors of human cytomegalovirus (HCMV). Introduction of the N-(4-phenoxyphenyl)acetamide side chain at N3 increased their potency and widened activity spectrum. The most active compounds in the series exhibit submicromolar activity against different viral strains of HCMV and varicella zoster virus (VZV) replication in HEL cell cultures. Inactivity against other DNA and RNA viruses, including herpes simplex virus 1/2, points to a novel mechanism of antiviral action.
- Babkov, Denis A.,Khandazhinskaya, Anastasia L.,Chizhov, Alexander O.,Andrei, Graciela,Snoeck, Robert,Seley-Radtke, Katherine L.,Novikov, Mikhail S.
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p. 7035 - 7044
(2015/11/11)
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- Design and synthesis of guanylthiourea derivatives as potential inhibitors of Plasmodium falciparum dihydrofolate reductase enzyme
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A new class of compounds based on S-benzylated guanylthiourea has been designed as potential PfDHFR inhibitors using computer aided methods (molecular electrostatic potential, molecular docking). Several compounds in this class have been synthesized start
- Adane, Legesse,Bhagat, Shweta,Arfeen, Minhajul,Bhatia, Sonam,Sirawaraporn, Rachada,Sirawaraporn, Worachart,Chakraborti, Asit K.,Bharatam, Prasad V.
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supporting information
p. 613 - 617
(2014/01/23)
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- Novel Carboline Derivatives as Potent Antifungal Lead Compounds: Design, Synthesis, and Biological Evaluation
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A series of novel antifungal carboline derivatives was designed and synthesized, which showed broad-spectrum antifungal activity. Particularly, compound C38 showed comparable in vitro antifungal activity to fluconazole without toxicity to human embryonic lung cells. It also exhibited good fungicidal activity against both fluconazole-sensitive and -resistant Candida albicans cells and had potent inhibition activity against Candida albicans biofilm formation and hyphal growth. Moreover, C38 showed good synergistic antifungal activity in combination with fluconazole (FLC) against FLC-resistant Candida species. Preliminary mechanism studies revealed that C38 might act by inhibiting the synthesis of fungal cell wall.
- Wang, Shengzheng,Wang, Yan,Liu, Wei,Liu, Na,Zhang, Yongqiang,Dong, Guoqiang,Liu, Yang,Li, Zhengang,He, Xiaomeng,Miao, Zhenyuan,Yao, Jianzhong,Li, Jian,Zhang, Wannian,Sheng, Chunquan
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p. 506 - 511
(2014/06/09)
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- Design, synthesis and structure-activity relationships of new triazole derivatives containing N-substituted phenoxypropylamino side chains
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The incidence of invasive fungal infections and resistance to antifungal agents is increasing dramatically. It is highly desirable to develop novel azoles with improved biological profiles. The structure-activity relationship (SAR) of the N-substitutions was investigated in this study. In vitro antifungal activities revealed that sterically large groups were not favored for the N-substitutions. The removal of the N-substitutions had little effect on the antifungal activity. Two compounds with free amine group (i.e. 9a and 10a) showed excellent activity with broad antifungal spectrum. The SAR results were supported by molecular docking and the N-substitutions were found to be important for the conformation of the side chains. The SAR and binding mode of the azoles are useful for further lead optimization.
- Wang, Shengzheng,Jin, Gang,Wang, Wenya,Zhu, Lingjian,Zhang, Yongqiang,Dong, Guoqiang,Liu, Yang,Zhuang, Chunlin,Miao, Zhenyuan,Yao, Jianzhong,Zhang, Wannian,Sheng, Chunquan
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experimental part
p. 292 - 299
(2012/08/07)
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- Synthesis and biological evaluation of vinyl ether-containing azole derivatives as inhibitors of Trichophyton rubrum
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In an attempt to search for many target compounds with excellent activities, a series of vinyl ether-containing azole derivatives were designed, synthesized, and evaluated as antifungal agents. Results of preliminary antifungal tests against Trichophyton rubrum in vitro indicated that most of the synthesized compounds showed excellent activities. In comparison with fluconazole, itraconazole, voriconazole, omoconazole and amphotericin B, several compounds (such as 7d, 7g and 7h) exhibited more potent inhibitory activities, suggesting that they were promising leads for the development of novel antifungal agents.
- Wang, Lulu,Yang, Wenge,Wang, Kai,Zhu, Jing,Shen, Fei,Hu, Yonghong
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scheme or table
p. 4887 - 4890
(2012/08/07)
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- N-LINKED HYDROXAMIC ACID DERIVATIVES USEFUL AS ANTIBACTERIAL AGENTS
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The present invention is directed to a new class of hydroxamic acid derivatives, their use as LpxC inhibitors, and more specifically their use to treat bacterial infections. Formula (I).
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Page/Page column 40
(2011/07/07)
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- The synthesis and preliminary pharmacological evaluation of a series of substituted 4-phenoxypropyl analogues of the atypical antipsychotic clozapine
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Herein we report the synthesis, characterization, and preliminary pharmacological activity of a new series of substituted 4′-phenoxypropyl tricyclic analogues of clozapine as potential antipsychotic agents for the treatment of schizophrenia. The lead comp
- Capuano, Ben,Crosby, Ian T.,McRobb, Fiona M.,Podloucka, Anna,Taylor, David A.,Vom, Amelia,Yuriev, Elizabeth
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experimental part
p. 116 - 124
(2010/05/18)
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- Synthesis and biological evaluation of a new series of berberine derivatives as dual inhibitors of acetylcholinesterase and butyrylcholinesterase
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A series of novel berberine derivatives were designed, synthesized, and biologically evaluated as inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Among these derivatives, compound 48a, berberine linked with 3-methylpyridi
- Huang, Ling,Luo, Zonghua,He, Feng,Lu, Jing,Li, Xingshu
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experimental part
p. 4475 - 4484
(2010/08/22)
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- New azoles with potent antifungal activity: Design, synthesis and molecular docking
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In response to the urgent need for novel antifungal agents with improved activity and broader spectrum, computer modeling was used to rational design novel antifungal azoles. On the basis of the active site of lanosterol 14α-demethylase from Candida albicans (CACYP51), a series of new azoles with substituted-phenoxypropyl piperazine side chains were rational designed and synthesized. In vitro antifungal activity assay indicates that the new azoles show good activity against most of the tested pathogenic fungi. Interestingly, the designed compounds are also active against an azole-resistant clinical strain. Compared to fluconazole and itraconazole, several compounds (such as 12i, 12j and 12n) show higher antifungal activity and broader spectrum, which are promising leads for the development of novel antifungal agents.
- Che, Xiaoying,Sheng, Chunquan,Wang, Wenya,Cao, Yongbing,Xu, Yulan,Ji, Haitao,Dong, Guoqiang,Miao, Zhenyuan,Yao, Jianzhong,Zhang, Wannian
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scheme or table
p. 4218 - 4226
(2009/12/09)
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- Synthesis and preliminary evaluation of novel analogues of quindolines as potential stabilisers of telomeric G-quadruplex DNA
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Telomeric DNA is a potential selective target for cancer therapy since the tumour-associated enzyme telomerase regulates telomere maintenance in most cancer cells. The 3′ single-stranded ends of telomeric DNA can be folded into quadruplex structures by appropriate small molecules. We describe the preparation of a new class of 2,7-disubstituted 10H-indolo[3,2-b]quinolines with enhanced selectivity for the stabilisation of quadruplex DNA compared to duplex DNA, and also the preparation of a key intermediate for the synthesis of trisubstituted quindolines.
- Le Sann, Christine,Huddleston, Jonathan,Mann, John
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p. 12903 - 12911
(2008/03/27)
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- Synthesis and Pharmacological Evaluation of 1-Oxo-2-(3-piperidyl)-1,2,3,4-tetrahydroisoquinolines and Related Analogues as a New Class of Specific Bradycardic Agents Possessing If Channel Inhibitory Activity
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A series of 1-oxo-2-(3-piperidyl)-1,2,3,4-tetrahydroisoquinolines and related analogues were prepared and evaluated for their bradycardic activities in isolated right atrium and in anesthetized rats. (± )-6,7-Dimethoxy-2-{1- [3-(3,4-methylenedioxyphenoxy)propyl]-3-piperidyl}-1,2,3, 4-tetrahydroisoquinoline (4) was chosen as a lead, and structural modifications were performed on the tetrahydroisoquinoline ring and the terminal aromatic ring. The modifications on the tetrahydroisoquinoline ring revealed that the 1-oxo-1,2,3,4-tetrahydroisoquinoline ring system was optimum structure for both in vitro potency and in vivo efficacy. Furthermore, methoxy, ethoxy, and methoxycarbonyl groups were identified as preferable substituents on the terminal aromatic ring. One of the 1-oxo-1,2,3,4-tetrahydroisoquinoline derivatives, (R)-10a, was further evaluated for its bradycardic activity and inhibitory activity against If currents. Compound (R)-10a demonstrated potent bradycardic activity in rats with minimal influence on blood pressure after oral administration. The compound also showed inhibition of If currents (IC50 = 0.32 μM) in guinea pig pacemaker cells.
- Kubota, Hideki,Kakefuda, Akio,Watanabe, Toshihiro,Ishii, Noe,Wada, Koichi,Masuda, Noriyuki,Sakamoto, Shuichi,Tsukamoto, Shin-ichi
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p. 4728 - 4740
(2007/10/03)
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- Phenoxypropoxybiguanides, prodrugs of DHFR-inhibiting diaminotriazine antimalarials
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A total of 34 analogues of the biguanide PS-15 (5s), a prodrug of the diaminotriazine WR-99210 (8s), have been prepared. Several of them, such as 5b (PS-33) and 5m (PS-26), maintain or exceed the in vivo activity of PS-15 while not requiring the use of highly regulated starting materials. The putative diaminotriazine metabolites of these new analogues (compounds 8) have also been prepared and shown to maintain the activity against resistant P. falciparum strains. The structure-activity relationships of biguanides 5 and putative metabolites 8 are discussed.
- Jensen,Ager,Bliss,Canfield,Kotecka,Rieckmann,Terpinski,Jacobus
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p. 3925 - 3931
(2007/10/03)
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- Preparation of a new class of cleavable surfactants based on the silicon-carbon bond
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The ability of silicon to direct electrophiles to the ipso-position is used in developing a new class of cleavable amphiphiles containing an acid labile silicon-carbon (aromatic) bond. The synthesis of these amphiphiles is carried out in four steps to yie
- Noronha, Glenn,Nguyen, Khanhlinh T.
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p. 4935 - 4938
(2007/10/03)
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- BIS(ARYLOXY)ALKANES AS INHIBITORS OF PHOSPHOLIPASE A2 ENZYMES
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Compounds having the formula I: STR1 are inhibitors of the PLA 2 s enzymes. These compounds are useful as anti-allergic, anti-asthmatic, they are also useful in treating various inflammatory diseases such as rheumatoid arthritis, osteoarthritis, bursitis,
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