- Bis(vinylsulfonyl)piperazines as efficient linkers for highly homogeneous antibody-drug conjugates
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Disulfide re-bridging strategy has demonstrated significant advantages in the construction of homogeneous antibody drug conjugates (ADCs). However, a major issue that disulfide scrambling at the hinge region of antibody leads to the formation of “half-antibody” has appeared for many re-bridging linkers. We present bis(vinylsulfonyl)piperazines (BVP) as efficient linkers to selectively re-bridge disulfides at the antigen-binding fragment (Fab) regions and produce highly homogeneous conjugates with a loading of two drugs without disulfide scrambling. We also found that optically active (S)-configuration linkers led to more sufficient conjugation compared with (R)-configuration. The BVP-linked ADCs demonstrated superior efficacy and antigen-selectivity in vitro cytotoxicity.
- Huang, Rong,Sheng, Yao,Wei, Ding,Yu, Jianghui,Chen, Hongli,Jiang, Biao
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- Method for synthesizing monoamine-protected piperazine-(R/S)2-formate
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The invention discloses a method for synthesizing monoamine-protected piperazine-(R/S)2-formate, wherein the method comprises the steps: by using 2-piperazinecarboxylate as a raw material, protecting1,4-site amines by using different protective groups, and salifying by using different chiral amines, resolving to obtain a single chiral compound; and finally, using pyridine or DMAP and other pyridine analogues as an alkali, reacting oxalyl chloride, triphosgene, phosgene, thionyl chloride and other similar acyl chlorides in anhydrous tetrahydrofuran, 2-methyl tetrahydrofuran or toluene and other solvents, and finally adding methanol, ethanol, isopropanol, benzyl alcohol and other alcohol reagents to generate the target product capable of removing carboxylic acid ortho-amino protecting groups in a positioned manner and esterifying carboxylic acid. Amino groups on piperazine are separately protected through simple three-step reaction, chiral resolution is performed by utilizing the characteristics of acid, finally, protonated intermediates are formed through organic alkali and carboxylic acid, anhydride is formed by the protonated intermediates and ortho-amino groups, formic acid esterification is performed by utilizing alcohol to replace ring opening, and a final product is obtained.
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Page/Page column 0024-0025
(2021/02/06)
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- HETEROCYCLIC COMPOUNDS FOR THE TREATMENT OF ABNORMAL CELLULAR PROLIFERATION
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This invention is in the area of heterocyclic-based compounds for the treatment of disorders involving abnormal cellular proliferation, including but not limited to tumors and cancers.
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Page/Page column 151
(2019/07/20)
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- AZAQUINAZOLINE INHIBITORS OF ATYPICAL PROTEIN KINASE C
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The present invention provides a compound of formula (I) or a salt thereof, wherein R7, R8, R9, G, and X are as defined herein. A compound of formula (I) and its salts have a PKC inhibitory activity, and may be used to treat proliferative disorders.
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- Human Adam-10 Inhibitors
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Magnesium salts/complexes of compounds useful for inhibiting the ADAM-IO protein and methods of making and purifying them are provided. Further provided are compositions comprising magnesium salts/complexes of the compounds in combination with a pharmaceutically acceptable carrier. The compounds well as such compositions comprising them are useful for the treatment of cancer, arthritis, diseases related to angiogenesis, such as renal diseases, heart diseases, such as heart failure, atherosclerosis, and stroke, inflammation, ulcer, infertility, scleroderma, endometriosis, mesothelioma, and diabetes. In addition, methods of treating forms of cancer, arthritis, and diseases related to angiogenesis in which ADAM-10 plays a critical role are provided.
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Page/Page column 20-21
(2011/01/12)
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- PIPERAZINES AS ANTI-OBESITY AGENTS
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The present invention relates to new compounds of formula (I), to pharmaceutical compositions comprising these compounds, to processes for their preparation, and to the use of these compounds as leptin receptor modulator mimetics in the preparation of medicaments against conditions associated with weight gain, type 2 diabetes and dyslipidemias.
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Page/Page column 27
(2009/07/17)
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- NOVEL INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
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Novel compounds and pharmaceutical compositions are disclosed which are inhibitors of the enzyme, farnesyl-protein transferase. Also disclosed is a method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells. The method comprises administering the novel aminooxyamide compound to a biological system. In particular, the method inhibits the abnormal growth of cells in a mammal such as a human.
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Page/Page column 83
(2010/02/12)
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- FARNESYL PROTEIN TRANSFERASE INHIBITORS
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Disclosed are compounds of formula (1.0), wherein R represents a cyclic moiety to which is bound an imodazolylalkyl group; R represents a carbamate, urea, amide or sulfonamide group; and the remaining substituents are as defined herein. Also disclosed is a method of treating cancer and a method of inhibiting farnesyl protein transferase using the disclosed compounds.
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Page/Page column 30-31
(2010/02/11)
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- HUMAN ADAM-10 INHIBITORS
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The present invention provides compounds useful for inhibiting the ADAM-10 protein, with selectivity versus MMP-1. Such compounds are useful in the in vitro study of the role of ADAM-10 (and its inhibition) in biological processes. The present invention also comprises pharmaceutical compositions comprising one or more ADAM-10 inhibitors according to the invention in combination with a pharmaceutically acceptable carrier. Such compositions are useful for the treatment of cancer, arthritis, and diseases related to angiogenesis. Correspondingly, the invention also comprises methods of treating forms of cancer, arthritis, and diseases related to angiogenesis in which ADAM-10 plays a critical role.
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- Inhibitors of farnesyl-protein transferase
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Novel compounds and pharmaceutical compositions are disclosed which are inhibitors of the enzyme, farnesyl protein transferase. Also disclosed is a method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells. The method comprises administering the novel aminooxyamide compound to a biological system. In particular, the method inhibits the abnormal growth of cells in a mammals such as a human.
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