- QUINAZOLINE COMPOUND FOR EGFR INHIBITION
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Disclosed is a novel quinazoline compound. Specifically, disclosed are a compound represented by the formula (I) and a pharmacologically acceptable salt.
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Paragraph 0173; 0176
(2019/11/21)
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- Design, synthesis and biological evaluation of novel spiro-pentacylamides as acetyl-CoA carboxylase inhibitors
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Acetyl-CoA carboxylase (ACC) catalyzes the rate-determining step in de novo lipogenesis and plays an important role in the regulation of fatty acid oxidation. Therefore, ACC inhibition offers a promising option for intervention in nonalcoholic fatty liver disease (NAFLD), type 2 diabetes (T2DM) and cancer. In this paper, a series of spiropentacylamide derivatives were synthesized and evaluated for their ACC1/2 inhibitory activities and anti-proliferation effects on A549, H1975, HCT116, SW620 and Caco-2 cell lines in vitro. Compound 6o displayed potent ACC1/2 inhibitory activity (ACC1 IC50 = 0.527 μM, ACC2 IC50 = 0.397 μM) and the most potent anti-proliferation activities against A549, H1975, HCT116, SW620 and Caco-2 cell lines, with IC50 values of 1.92 μM, 0.38 μM, 1.22 μM, 2.05 μM and 5.42 μM respectively. Further molecular docking studies revealed that compound 6o maintained hydrogen bonds between the two carbonyls and protein backbone NHs (Glu-B2026 and Gly-B1958). These results indicate that compound 6o is a promising ACC1/2 inhibitor for the potent treatment of cancer.
- Wei, Qiangqiang,Mei, Liankuo,Yang, Yifei,Ma, Hui,Chen, Hongyi,Zhang, Huibin,Zhou, Jinpei
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p. 3866 - 3874
(2018/07/30)
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- INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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- INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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The present invention provides compounds of Formula I (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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- Spiro aryl phosphorus oxide or sulfide
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The invention discloses a spiro aryl phosphorus oxide or sulfide as ALK inhibitor, and in particular discloses a compound shown in a formula (I) as an ALK inhibitor or a pharmaceutically acceptable salt thereof.
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Paragraph 0228; 0229; 0230; 0231
(2016/10/08)
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- INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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The present invention provides compounds of Formula (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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Page/Page column 50; 51
(2016/11/07)
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- MUSCARINIC RECEPTOR AGONISTS
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This invention relates to compounds that are agonists of the muscarinic M1 receptor and which are useful in the treatment of muscarinic M1 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula where m, p, q, W, Z, Y, X1, X2, R1, R2 R3 and R4 are as defined herein.
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Page/Page column 44
(2015/12/09)
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- INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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Page/Page column 62
(2015/02/25)
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- INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention.
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Page/Page column 37; 38
(2014/02/16)
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- SPIRO - FUSED PIPERIDINE DERIVATIVES FOR USE AS INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention.
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Page/Page column 40; 41
(2014/02/16)
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- Design, syntheses, and SAR of 2,8-diazaspiro[4.5]decanones as T-type calcium channel antagonists
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It was hypothesized that an appropriately substituted 2,8-diazaspiro[4.5] decan-1-one could effectively approximate a 5-feature T-type pharmacophore model published in the literature. Compounds were designed and synthesized to test our hypothesis and were found to be potent T-type calcium channel inhibitors with modest selectivity over L-type calcium channels. The synthesis and SAR of the series is described.
- Fritch, Paul C.,Krajewski, Jeffrey
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scheme or table
p. 6375 - 6378
(2010/11/18)
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- Rifamycin derivatives
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Novel rifamycin derivatives of formula I (both hydroquinone and corresponding quinone (C1-C4) forms): or their salts, hydrates or prodrugs thereof, wherein: a preferred R comprises hydrogen, acetyl; L is a linker, a preferred linker group elements selected from any combination of 1 to 5 groups shown FIG. 1, provided L is not wherein R1 is H, methyl or alkyl. The inventive compounds exhibit valuable antibiotic properties. Formulations having these compounds can be used in the control or prevention of infectious diseases in mammals, both humans and non-humans. In particular, the compounds exhibit a pronounced antibacterial activity, even against multiresistant strains of microbes.
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Page/Page column 55
(2008/06/13)
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- New Spiropiperidines as Potent and Selective Non-Peptide Tachykinin NK2 Receptor Antagonists
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The synthesis of a series of 2-(5-fluoro-1H-indol-3-yl)ethyl spiropiperidines is described together with their tachykinin NK2 receptor affinities measured in a rat colon binding assay.Equivalent NK2 receptor binding affinity was observed for the spirooxalidinone 3-benzyl-8--1-oxa-3,8-diazaspirodecan-2-one (3a), the imidazolidinone 3-benzyl-8--1,3,8-triazaspirodecan-2-one (3s), and the pyrrolidinone 2-benzyl-8--2,8-diazaspirodecan-3-one (3t).Substitution in the phenyl ring of compound 3a produced no significant enhancement in NK2 binding affinity.Replacement of the phenyl ring in 3a with other aromatic rings resulted in a significant loss in binding affinity.Compound 3a was shown to be a potent NK2 receptor antagonist in guinea pig trachea where it also demonstrated 1000-fold selectivity for NK2 receptors over NK1.In the anesthesized guinea pig, compound 3a administered by the intravenous or oral route displayed potent and long-lasting antagonist activity against NK2 receptor agonist induced bronchoconstriction.
- Smith, Paul W.,Cooper, Anthony W. J.,Bell, Richard,Beresford, Isabel J. M.,Gore, Paul M.,et al.
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p. 3772 - 3779
(2007/10/03)
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