- DIPEPTIDE PIPERIDINE DERIVATIVES
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The disclosure relates to pharmaceutical compositions, to methods of preparing such compositions, and to methods for using such compositions for treating or preventing a disease or condition associated with arginase activity.
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- INHIBITORS OF CYCLIN DEPENDNT KINASE 7 (CDK7)
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The present invention provides novel compounds of Formula (I) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of cyclin-dependent kinase 7 (CDK7), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.
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Paragraph 341
(2018/02/28)
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- A sub-milligram-synthesis protocol for in vitro screening of HDAC11 inhibitors
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This work demonstrated the high efficiency of a sub-milligram-synthesis based medicinal chemistry method. Totally 72 compounds, consisting a tri-substituted pyrrolidine core, were prepared. Around 0.1 mg of each compound was solid-phase synthesized. Based on the additive property of UV absorptions of unconjugated chromophores of a molecule, these compounds were quantified by UV measurement. A hit, whose IC50 value was 1.2 μM in HDAC11 inhibition assays, highlights the applicability of the approach reported here in future optimization works.
- Tian, Yinping,Jin, Jin,Wang, Congying,Lv, Wenhui,Li, Xuewei,Che, Xiaona,Gong, Yanchao,Li, Yanjun,Li, Quanli,Hou, Jingli,Wang, Peng G.,Shen, Jie
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p. 2434 - 2437
(2016/07/07)
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- A short diastereoselective synthesis of cis-(2S,4S) and cis-(2R,4R)-4-hydroxyprolines
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A concise synthesis of (2R,4R)-4-hydroxyproline (1) and (2S,4S)-4-hydroxyproline (2) has been developed in enantiomerically pure form from commercially available starting materials with excellent diastereoselectivity. The tightly bound chelation controlled transition state formed during the 5-exo-tet ring closure reaction is assumed to be the origin of high diastereoselectivity.
- Gajare, Vikas S.,Khobare, Sandip R.,Malavika,Rajana, Nagaraju,Venkateswara Rao,Syam Kumar
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p. 3743 - 3746
(2015/06/08)
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- COMPOUNDS
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The present invention relates to novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, to compositions containing them and to their use in the treatment of or prevention of diseases characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS).
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Page/Page column 187
(2015/09/23)
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- BRUTON'S TYROSINE KINASE INHIBITORS
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The present invention provides compounds useful as inhibitors of Btk, compositions thereof, and methods of using the same.
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Page/Page column 153; 154
(2011/04/14)
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- Design, Synthesis, and Properties of (4S)-7-(4-Amino-2-substituted-pyrrolidin-1-yl)quinolone-3-carboxylic Acids
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The quinolinecarboxylic acids constitute a class of extremely potent and orally active broad-spectrum antibacterial agents.These compounds have been shown to inhibit DNA gyrase, a key enzyme in bacterial DNA replication.The 7-(3-aminopyrrolidinyl)quinolone A-60969 (1) is a particularly potent member of this class and is currently undergoing clinical evaluation.We have studied a series of enantiomerically homogeneous (4S)-7-(4-amino-2-substituted-pyrrolidinyl)quinolones in an effort to utilize the 2-position of the pyrrolidine moiety to improve upon the solubility and pharmacokinetic properties of this class of compounds while still maintaining potent antibacterial activity.We have found that the absolute stereochemistry at the 2-position of the pyrrolydine ring is critical to the maintenance of such activity.In this paper, we report the full details of the asymmetric synthesis and the in vitro and in vivo structure-activity relationships of this series of compounds as well as the physiochemical properties, such as water solubility and log P, associated with the structural modifications.We also discuss the pharmacokinetic properties of several of these compounds in mice and the pharmacokinetics of 59, which has the best overall properties of agents in this study, in dog.
- Rosen, Terry,Chu, Daniel T. W.,Lico, Isabella M.,Fernandes, Prabhavathi B.,Marsh, Kennan,et al.
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p. 1598 - 1611
(2007/10/02)
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