- Synthesis and in vitro antibacterial activity of novel fluoroquinolone derivatives containing substituted piperidines
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We report herein the synthesis of novel 7-(4-alkoxyimino-3-aminomethyl-3- methylpiperidin-1-yl) fluoroquinolone derivatives. The antibacterial activity of the newly synthesized compounds was evaluated and correlated with their physicochemical properties.
- Chai, Yun,Liu, Mingliang,Wang, Bo,You, Xuefu,Feng, Lianshun,Zhang, Yibin,Cao, Jue,Guo, Huiyuan
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- GNE-781, A Highly Advanced Potent and Selective Bromodomain Inhibitor of Cyclic Adenosine Monophosphate Response Element Binding Protein, Binding Protein (CBP)
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Inhibition of the bromodomain of the transcriptional regulator CBP/P300 is an especially interesting new therapeutic approach in oncology. We recently disclosed in vivo chemical tool 1 (GNE-272) for the bromodomain of CBP that was moderately potent and selective over BRD4(1). In pursuit of a more potent and selective CBP inhibitor, we used structure-based design. Constraining the aniline of 1 into a tetrahydroquinoline motif maintained potency and increased selectivity 2-fold. Structure-activity relationship studies coupled with further structure-based design targeting the LPF shelf, BC loop, and KAc regions allowed us to significantly increase potency and selectivity, resulting in the identification of non-CNS penetrant 19 (GNE-781, TR-FRET IC50 = 0.94 nM, BRET IC50 = 6.2 nM; BRD4(1) IC50 = 5100 nM) that maintained good in vivo PK properties in multiple species. Compound 19 displays antitumor activity in an AML tumor model and was also shown to decrease Foxp3 transcript levels in a dose dependent manner.
- Romero, F. Anthony,Murray, Jeremy,Lai, Kwong Wah,Tsui, Vickie,Albrecht, Brian K.,An, Le,Beresini, Maureen H.,De Leon Boenig, Gladys,Bronner, Sarah M.,Chan, Emily W.,Chen, Kevin X.,Chen, Zhongguo,Choo, Edna F.,Clagg, Kyle,Clark, Kevin,Crawford, Terry D.,Cyr, Patrick,De Almeida Nagata, Denise,Gascoigne, Karen E.,Grogan, Jane L.,Hatzivassiliou, Georgia,Huang, Wei,Hunsaker, Thomas L.,Kaufman, Susan,Koenig, Stefan G.,Li, Ruina,Li, Yingjie,Liang, Xiaorong,Liao, Jiangpeng,Liu, Wenfeng,Ly, Justin,Maher, Jonathan,Masui, Colin,Merchant, Mark,Ran, Yingqing,Taylor, Alexander M.,Wai, John,Wang, Fei,Wei, Xiaocang,Yu, Dong,Zhu, Bing-Yan,Zhu, Xiaoyu,Magnuson, Steven
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p. 9162 - 9183
(2017/12/05)
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- PYRAZOLOPYRIDINE DERIVATIVES FOR THE TREATMENT OF CANCER
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The present invention relates to a compound formula (I): and to salts thereof, wherein R1, R2X, and Y have any of the values defined herein, and compositions and uses thereof. The compounds are useful as inhibitors of CBP and/or EP300. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various CBP and/or EP300-mediated disorders such as cancer, inflammatory disorders and autoimmune diseases.
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- 4,5,6,7-TETRAHYDRO-1 H-PYRAZOLO[4,3-C]PYRIDIN-3-AMINE COMPOUNDS AS CBP AND/OR EP300 INHIBITORS
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The present invention relates to compounds of formula (I) or formula (II): and to salts thereof, wherein R1-R4 of formula (I) and R1-R3 of formula (II) have any of the values defined herein, and compositions and uses thereof. The compounds are useful as inhibitors of CBP and/or EP300. Also included are pharmaceutical compositions comprising a compound of formula (I) of formula (II) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various CBP and/or EP300-mediated disorders.
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- Protein Kinase Inhibitors and Uses Thereof
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The invention is compounds of formula (I), and salts thereof, compositions thereof, and methods of use therefor. In particular, disclosed herein are certain compounds that can be useful for inhibiting protein kinase, including Bruton's tyrosine kinase (Btk), and for treating disorders mediated thereby.
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- Synthesis and in vitro antibacterial activity of 7-(3-Amino-6,7-dihydro-2- methyl-2H-pyrazolo[4,3-c] pyridin-5(4H)-yl)fluoroquinolone derivatives
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A series of novel 7-(3-amino-6,7-dihydro-2-methyl-2H-pyrazolo[4,3-c] pyridin- 5(4H)-yl)fluoroquinolone derivatives were designed, synthesized and characterized by 1H-NMR, MS and HRMS. These fluoroquinolones were evaluated for their in vitro antibacterial
- Guo, Xin,Liu, Ming Liang,Guo, Hui Yuan,Wang, Yu Cheng,Wang, Ju Xian
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p. 2626 - 2635
(2011/05/16)
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