- 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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- Novel 6-fused heteroaryldihydropyrimidines for the treatment and prophylaxis of hepatitis B virus infection
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The invention provides novel compounds having the general formula: wherein R1, R2, R3, R4, R5, R6, X, Y, W and n are as described herein, compositions including the compounds and methods of using the compounds.
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Paragraph 0469; 0470; 0471
(2015/11/02)
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- PYRAZOLOPYRIDINE KINASE INHIBITORS
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The present invention relates to compounds useful as inhibitors of protein kinase. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, co
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Page/Page column 42-43
(2011/08/21)
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- TRI-CYCLIC PYRAZOLOPYRIDINE KINASE INHIBITORS
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The present invention relates to compounds useful as inhibitors of protein kinase. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, co
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Page/Page column 110
(2010/04/03)
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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 26
(2009/07/17)
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- A practical synthesis of differentially protected 2-(Hydroxymethyl) piperazines
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(Chemical Equation Presented) An efficient and scalable synthesis of three differentially protected 2-(hydroxymefhyl)piperazines is presented, starting from optically active and commercially available (2S)-piperazine-2-carboxylic acid dihydrochloride. These synthetic building blocks are useful in the preparation of biologically active compounds and as chemical scaffolds for the construction of combinatorial libraries.
- Gao, Hongwu,Renslo, Adam R.
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p. 8591 - 8592
(2008/02/13)
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- FARNESYL PROTEIN TRANSFERASE INHIBITORS AND METHODS FOR TREATING PROLIFERATIVE DISEASES
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Disclosed are compounds of the Formula: (1.0) wherein the substituents are as defined herein. Also disclosed are uses of the compounds of formula 1.0 for the manufacture of a medicament for treating cancer and for inhibiting farnesyl protein transferase.
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Page/Page column 192
(2010/11/08)
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