- Toward Angiogenesis Inhibitors Based on the Conjugation of Organometallic Platinum(II) Complexes to RGD Peptides
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A novel conjugate between a cyclometalated platinum(II) complex with dual antiangiogenic and antitumor activity and a cyclic peptide containing the RGD sequence (-Arg-Gly-Asp-) has been synthesized by combining solid- and solution-phase methodologies. Although peptide conjugation rendered a non-cytotoxic compound in all tested tumor cell lines (± αVβ3 and αVβ5 integrin receptors), the antiangiogenic activity of the Pt-c(RGDfK) conjugate in human umbilical vein endothelial cells at sub-cytotoxic concentrations opens the way to the design of a novel class of angiogenesis inhibitors through conjugation of metallodrugs with high antiangiogenic activity to cyclic RGD-containing peptides or peptidomimetic analogues.
- Zamora, Ana,Gandioso, Albert,Massaguer, Anna,Buenestado, Silvia,Calvis, Carme,Hernández, Jose Luis,Mitjans, Francesc,Rodríguez, Venancio,Ruiz, José,Marchán, Vicente
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- DIAZANAPHTHALEN-3-YL CARBOXAMIDES AND PREPARATION AND USE THEREOF
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Diazanaphthalene compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of a diazanaphthalene compound or analogs thereof, in the treatment of disorders characterized by the activa
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Paragraph 0949; 0952
(2019/05/15)
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- Combination of 4-anilinoquinazoline, arylurea and tertiary amine moiety to discover novel anticancer agents
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In present study, 4-anilinoquinazolines scaffold, arylurea and tertiary amine moiety were combined to design, synthesize gefitinib analogs and discover novel anticancer agents. A series of 4-anilinoquinazoline derivatives (1, 2, 3 and 4) bearing arylurea and tertiary amine moiety at its 6-position were synthesized. Their antiproliferative activities in vitro were evaluated via MTT assay against A431 cell and A549 cell. The SAR of the title compounds was discussed. The compounds 2d, 2i and 2j with potent antiproliferative activities were evaluated their inhibitory activity against EGFR-TK. Compound 2j displayed potent inhibitory activity against EGFR-TK. In addition, compound 2j, at 50 mg/kg, can completely inhibit cancer growth in established nude mouse A549 xenograft model in vivo. These results suggest that the 4-anilinoquinazoline derivatives bearing diarylurea and tertiary amino moiety at its 6-position can serve as anticancer agents and EGFR inhibitors.
- Zuo, Sai-Jie,Zhang, Sai,Mao, Shuai,Xie, Xiao-Xiao,Xiao, Xue,Xin, Min-Hnag,Xuan, Wei,He, Yuan-Yuan,Cao, Yong-Xiao,Zhang, San-Qi
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p. 179 - 190
(2015/12/31)
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- Design, synthesis and evaluation of novel HDAC inhibitors as potential antitumor agents
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Phenyl imidazolidin-2-one was introduced as the linker for novel HDAC inhibitors. A focused library of 20 compounds was designed and synthesized, among which eight compounds showed equivalent or higher potencies against HDAC1 as compared to vorinostat. In vitro antitumor activity assays in HCT-116, PC-3 and HL-60 cancer cells revealed six compounds with potent antitumor activities, and compound 1o showed 6- to 9-fold higher potencies compared to vorinostat. In an HCT-116 nude mice xenograft model, compound 1o displayed significant antitumor activity in both continuous and intermittent dosing schedules.
- Cheng, Jianjun,Qin, Jihong,Guo, Sihua,Qiu, Hangdeng,Zhong, Yun
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p. 4768 - 4772
(2015/01/09)
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- RENIN INHIBITORS
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Disclosed are compounds of Formula (I) wherein the R, R1, R2, R3, X, Y, A, Q, E, and G are defined herein. These compounds bind to aspartic proteases to inhibit their activity and are useful in the treatment or amelioration of diseases associated with aspartic protease activity. Also disclosed are methods of use of the compounds of Formula I for ameliorating or treating aspartic protease related disorders in a subject in need thereof.
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Page/Page column 142
(2008/12/04)
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- Protease inhibitors
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The present invention provides compounds of formula (I) which inhibit proteases, including cathepsin K, pharmaceutical compositions of such compounds, and methods for treating diseases of excessive bone loss or cartilage or matrix degradation, including osteoporosis; gingival disease including gingivitis and periodontitis; arthritis, more specifically, osteoarthritis and rheumatoid arthritis; Paget's disease; hypercalcemia or malignancy; and metabolic bone disease therewith.
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