- Application of naftifine analogue in control of agricultural plant diseases
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The invention discloses application of any compound of naftifine analogues H-01 to H-22 in control of agricultural plant fungal diseases. Biological activity tests indicate that the derivatives show certain inhibitory activity on the six plant diseases, i
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Paragraph 0011-0015
(2020/07/21)
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- Design, synthesis, and biological evaluation of a series of resorcinol-based N-benzyl benzamide derivatives as potent Hsp90 inhibitors
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Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that is responsible for the stabilization and maturation of many oncogenic proteins. Therefore, Hsp90 has emerged as an attractive target in the field of cancer chemotherapy. In this study, we report the design, synthesis, and biological evaluation of a series of Hsp90 inhibitors. In particular, compound 30f shows a significant Hsp90α inhibitory activity with IC50 value of 5.3 nM and an excellent growth inhibition with GI50 value of 0.42 μM against non-small cell lung cancer cells, H1975. Compound 30f effectively reduces the expression levels of Hsp90 client proteins including Her2, EGFR, Met, Akt, and c-Raf. Consequently, compound 30f promotes substantial cleavages of PARP, Caspase 3, and Caspase 8, indicating that 30f induces cancer cell death via apoptotic pathway. Moreover, cytochrome P450 assay indicates that compound 30f has weak inhibitory effect on the activities of five major P450 isoforms (IC50 > 5 μM for 1A2, 2C9, 2C19, 2D6, and 3A), suggesting that clinical interactions between 30f and the substrate drugs of the five major P450 isoforms are not expected. Compound 30f also inhibits the tumor growth in a mouse xenograft model bearing subcutaneous H1975 without noticeable abnormal behavior and body weight changes. The immunostaining and western immunoblot analysis of EGFR, Met, Akt in xenograft tissue sections of tumor further demonstrate a good agreement with the in vitro results.
- Park, Sun You,Oh, Yong Jin,Lho, Yunmee,Jeong, Ju Hui,Liu, Kwang-Hyeon,Song, Jaeyoung,Kim, Soong-Hyun,Ha, Eunyoung,Seo, Young Ho
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p. 390 - 401
(2017/12/07)
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- SUBSTITUTED PIPERAZINE DERIVATIVES
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The present invention relates to substituted piperazine derivatives (herein referred to as compounds or compounds of formula (1)) or stereoisomers, or pharmaceutically acceptable salts thereof and their use as tachykinin receptor antagonists. Such antagon
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- Substituted alkyldiamine derivatives
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The present invention relates to novel substituted alkyldiamine derivatives and pharmaceutically acceptable salts thereof which are useful tachykinin antagonists. Such antagonists are useful in the treatment of tachykinin-mediated diseases and conditions including asthma, cough, and bronchitis.
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- Folate Antagonists. 18. Synthesis and Antimalarial Effects of N6-(Arylmethyl)-N6-methyl-2,4,6-pteridinetriamines and Related N6,N6-Disubstituted 2,4,6-Pteridinetriamines
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N6-(Arylmethyl)-N6-methyl-2,4,6-pteridinetriamines (1-5) and related N6-substituted 2,4,6-pteridinetriamines (16-20) were obtained by the condensation of 6-chloro-2,4-pteridinediamine with methylarylmethanamine and other selected secondary amines.The requisite N-methylarylmethanamines (21-32) were prepared by the hydrogenation over Pt/C of the corresponding arylcarboxaldehyde in the presence of methanamine.Several of the N6-(arylmethyl)-N6-methyl-2,4,6-pteridinetriamines exhibited exceptional suppressive antimalarial activity against a drug-sensitive line of Plasmodium berghei in mice.N6-Methyl-N6-(1-naphthalenylmethyl)-2,4,6-pteridinetriamine (9), the most active of those compounds, was also shown to be curative at 3.16 mg/kg in a single oral dose against P. cynomolgi in the rhesus monkey.This compound was also shown to be effective against a chloroquine-resistant line of P. berghei in the mouse but showed cross-resistance to a pyrimethamine-resistant strain.Most of the 2,4,6-pteridinetriamines showed strong antibacterial action against Streptococcus faecalis and Staphylococcus aureus.
- Elslager, Edward F.,Johnson, Judith L.,Werbel, Leslie M.
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p. 140 - 145
(2007/10/02)
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