- Discovery and optimization of thienopyridine derivatives as novel urea transporter inhibitors
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Urea transporters (UTs) play an important role in the urine concentrating mechanism and are recognized as novel targets for developing small molecule inhibitors with salt-sparing diuretic activity. Thienoquinoline derivatives, a class of novel UT-B inhibitors identified by our group, play a significant diuresis in animal model. However, the poor solubility and low bioavailability limited its further development. To overcome these shortcomings, the structure modification of thienoquinoline was carried out in this study, which led to the discovery of novel thienopyridine derivatives as specific urea transporter inhibitors. Further optimization obtained the promising preclinical candidate 8n with not only excellent inhibition effect on urea transporters and diuretic activity on rat model, but also suitable water solubility and Log P value.
- Zhao, Yan,Li, Min,Li, Bowen,Zhang, Shun,Su, Aoze,Xing, Yongning,Ge, Zemei,Li, Runtao,Yang, Baoxue
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p. 131 - 142
(2019/04/08)
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- Pyrazolo [3,4 - the b] pyridine and [...] composition preparation method and use of (by machine translation)
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The present invention provides a pyrazolo [3,4 - the b] pyridine and [...] compound of preparation and use, in particular, the present invention provides a following formula (I) compounds are shown, wherein the definition of each group as described in the specification. The compounds of the invention has excellent tyrosine kinase inhibiting activity, so can be used for preparing a series of treating diseases associated with the tyrosine kinase activity of the drug. (by machine translation)
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- PYRIDO [3',2' :4,5] THIENO [3, 2-D] PYRIMIDIN- 4 - YLAMINE DERIVATIVES AND THEIR THERAPEUTICAL USE
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The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain fused triaryl amine compounds of the following formula (for convenience, collectively referred to herein as "FTA compounds"), which, inter alia, inhibit LIM kinase (LIMK) activity. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit LIMK activity, and in the treatment of diseases and conditions that are mediated by LIMK, that are ameliorated by the inhibition of LIMK activity, etc., including proliferative conditions such as cancer (e.g., breast cancer, prostate cancer, melanoma, glioma, etc.), as well as vasodilation (including, e.g., hypertension, angina, cerebral vasospasm, and ischemia following subarachnoid hemorrhage), neurodegenerative disorders, atherosclerosis, fibrosis, and inflammatory diseases (including, e.g., Crohn's disease and chronic obstructive pulmonary disease (COPD)), and glaucoma (also known as ocular hypertension).
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Page/Page column 115
(2012/10/18)
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- A facile method for the synthesis of nicotinonitriles from ketones via a one-pot chloromethyleneiminium salt mediated three-component reaction
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Simple enolizable ketones such as acetophenones and benzalacetones were treated with malononitrile under Vilsmeier-Haack reaction conditions to afford 2-chloronicotinonitriles. The reaction proceeds via a one-pot chloromethyleneiminium salt mediated three
- Asokan,Anabha,Thomas, Ajith Dain,Jose, Ann Maria,Lethesh,Prasanth,Krishanraj
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p. 5641 - 5643
(2008/02/10)
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- 2-Chloro-3-cyano-6-phenylpyridine
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The molecular structure of the title compound (2-chloro-6-phenylpyridine-3-carbonitrile, C12H7ClN2) is presented. The molecule is nearly planar. Despite strong substituent interactions, the aromaticity of the pyridine frag
- Cyranski, Michal K.,Mieczkowski, Jozef
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p. 1521 - 1523
(2007/10/03)
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