- Palladium-catalyzed cross-coupling reactions on a bromo-naphthalene scaffold in the search for novel human CC chemokine receptor 8 (CCR8) antagonists
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The naphthalene sulfonamide scaffold is known to possess CCR8 antagonistic properties. In order to expand the structure–activity relationship study of this compound class, a variety of palladium-catalyzed cross-coupling reactions was performed on a bromo-
- Verhaegen, Yenthel,Liu, Libao,Nguyen, Tien T.,Van Loy, Tom,Voet, Arnout R.D.,Schols, Dominique,Dehaen, Wim,De Jonghe, Steven
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- Development of FABP4/5 inhibitors with potential therapeutic effect on type 2 Diabetes Mellitus
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Fatty acid-binding protein 4 (FABP4) and fatty acid-binding protein 5 (FABP5) are promising therapeutic targets for the treatment of various metabolic diseases. However, the weak potency, low selectivity over FABP3, or poor pharmacokinetic profiles of currently reported dual FABP4/5 inhibitors impeded further research. Here, we described the characterization of a series of dual FABP4/5 inhibitors with improved metabolic stabilities and physicochemical properties based on our previous studies. Among the compounds, D9 and E1 exhibited good inhibitory activities against FABP4/5 and favorable selectivity over FABP3 in vitro. In cell-based assays, D9 and E1 exerted a decrease of FABP4 secretion, a strong anti-lipolytic effect in mature adipocytes, and suppression of MCP-1 expression in THP-1 macrophages. Moreover, D9 and E1 possessed good metabolic stabilities in mouse hepatic microsomes and acceptable pharmacokinetics profiles in ICR mice. Further in vivo experiments showed that D9 and E1 could potently decrease serum FABP4 levels and ameliorate glucose metabolism disorders in obese diabetic db/db mice. These results demonstrated that D9 and E1 could serve as lead compounds for the development of novel anti-diabetic drugs.
- He, Yu-Long,Chen, Meng-Ting,Wang, Ting,Zhang, Ming-Ming,Li, Ying-Xia,Wang, He-Yao,Ding, Ning
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- From hit to lead: Structure-based discovery of naphthalene-1-sulfonamide derivatives as potent and selective inhibitors of fatty acid binding protein 4
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Fatty acid binding protein 4 (FABP4) plays a critical role in metabolism and inflammatory processes and therefore is a potential therapeutic target for immunometabolic diseases such as diabetes and atherosclerosis. Herein, we reported the identification of naphthalene-1-sulfonamide derivatives as novel, potent and selective FABP4 inhibitors by applying a structure-based design strategy. The binding affinities of compounds 16dk, 16do and 16du to FABP4, at the molecular level, are equivalent to or even better than that of BMS309403. The X-ray crystallography complemented by the isothermal titration calorimetry studies revealed the binding mode of this series of inhibitors and the pivotal network of ordered water molecules in the binding pocket of FABP4. Moreover, compounds 16dk and 16do showed good metabolic stabilities in liver microsomes. Further extensive in vivo study demonstrated that 16dk and 16do exhibited a dramatic improvement in glucose and lipid metabolism, by decreasing fasting blood glucose and serum lipid levels, enhancing insulin sensitivity, and ameliorating hepatic steatosis in obese diabetic (db/db) mice.
- Gao, Ding-Ding,Dou, Hui-Xia,Su, Hai-Xia,Zhang, Ming-Ming,Wang, Ting,Liu, Qiu-Feng,Cai, Hai-Yan,Ding, Hai-Peng,Yang, Zhuo,Zhu, Wei-Liang,Xu, Ye-Chun,Wang, He-Yao,Li, Ying-Xia
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- COMPOUNDS FOR BINDING PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9)
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The present disclosure relates to novel compounds, methods, and compositions capable of binding to PCSK9, thereby modulating PCSK9 proprotein convertase enzyme activity. The compounds of the disclosure include compounds Formula (I).
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Paragraph 0318
(2017/09/15)
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- Naphthalenesulfonamide type compound, preparation method of naphthalenesulfonamide type compound and application of naphthalenesulfonamide type compound to adjustment of plant growth activity
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The invention discloses a naphthalenesulfonamide type compound, a preparation method of the naphthalenesulfonamide type compound and the application of the naphthalenesulfonamide type compound to adjustment of plant growth activity. The structure general formula of the naphthalenesulfonamide type compound is shown as the formula I. Please see the formula I in the specifications. The naphthalenesulfonamide type compound is simple in structure and has the excellent function of adjusting the plant growth activity, the preparation method of the naphthalenesulfonamide type compound is simple and practicable, and mass production is facilitated.
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Paragraph 0057; 0058; 0059
(2017/08/28)
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- COMPOSITIONS AND METHODS FOR INHIBITING BMP
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The present invention provides small-molecule inhibitors of BMP signaling and compositions and methods for inhibiting BMP signaling. These compounds and compositions may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation. These compounds and compositions may also be used to reduce circulating levels of ApoB-100 or LDL and treat or prevent acquired or congenital hypercholesterolemia or hyperlipoproteinemia; diseases, disorders, or syndromes associated with defects in lipid absorption or metabolism; or diseases, disorders, or syndromes caused by hyperlipidemia.
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Page/Page column 189
(2016/02/10)
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- Synthesis, pharmacological activity and comparative QSAR modeling of 1,5-N,N′-substituted-2-(substituted naphthalenesulphonyl) glutamamides as possible anticancer agents
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Based on our earlier QSAR study, a series of 1, 5-N,N′-substituted-2-(substituted naphthalenesulphonyl) glutamamides were synthesized as possible anticancer agents. Anticancer activities of these synthesized compounds were evaluated in vivo on Swiss Albino mice against Ehrlich Ascites Carcinoma (EAC) cells where inhibitions of tumor cell and tumor weight were considered as biological activity parameters. A comparative QSAR study was done with a set of descriptors and logarithm of tumor cell inhibition. The result shows the importance of topological parameters like ETSA and RTSA indices as well as electronic parameter like Wang-Ford charges of different atoms. Electrophilic attack at atom number 5 and increased number of chlorine atom may be favorable whereas presence of methoxy group at the atom number 8 in naphthalene ring may be detrimental to the activity.
- Halder, Amit Kumar,Adhikary, Nilanjan,Maity, Milan Kumar,Jha, Tarun
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scheme or table
p. 1760 - 1771
(2010/06/21)
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- GLYT1 TRANSPORTER INHIBITORS
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The invention provides a compound of formula (I): or a salt, solvate or a physiologically functional derivative thereof, wherein R1 to R10 are as defined in the specification and uses of such compounds. The compounds inhibit GlyT1 transporters and are useful in the treatment of certain neurological and neuropsychiatric disorders, including schizophrenia.
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Page/Page column 62
(2010/02/12)
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