169605-18-9Relevant academic research and scientific papers
Design, synthesis, and in vitro activities of benzamide-core glycoprotein IIb/IIIa antagonists: 2,3-Diaminopropionic acid derivatives as surrogates of aspartic acid
Xue, Chu-Biao,Roderick, John,Jackson, Sharon,Rafalski, Maria,Rockwell, Arlene,Mousa, Shaker,Olson, Richard E.,DeGrado, William F.
, p. 693 - 705 (1997)
In an effort to discover novel nonpeptide glycoprotein IIb/IIIa (GPIIb/IIa, α(IIb)/β3) inhibitors, we investigated RGD mimetics featuring a 3-substituted benzoic acid as the core, benzamidine as the basic moiety, and a series of β- and α-substituted β-alanine derivatives as aspartic acid surrogates. It was found that the use of β-methyl β-alanine slightly improved the anti-aggregant potency in human platelet-rich plasma over the unsubstituted β-alanine compound, while β-substitution with a trifluoromethyl group resulted in considerable loss in activity. Significant enhancement (up to 100-fold) in potency was obtained when the β-alanine was replaced with N2-substituted L-2,3-diaminopropionic acid derivatives. Among the three types of α-substituents (carbamate, amide, and sulfonamide) investigated, no apparent preference was observed with respect to in vitro potency. However, alkyl groups were more favorable than arylalkyl groups (Cbz) in the carbamate analogues. We also investigated piperidine, piperazine, and N-formamidinopiperidine as replacements for the benzamidine moiety. The former two replacements led to a drop in potency while the latter replacement resulted in maintenance of activity as compared with the corresponding benzamidine analogue.
Discovery of Potent, Selective, and Direct Acid Sphingomyelinase Inhibitors with Antidepressant Activity
Yang, Kan,Yu, Jinying,Nong, Keyi,Wang, Youzhi,Niu, Ao,Chen, Wenlu,Dong, Jibin,Wang, Jinxin
, p. 961 - 974 (2020/03/10)
Recent studies on sphingolipids suggest that acid sphingomyelinase (ASM), which plays a central role in the pathogenesis of major depression, is emerging to be a novel target for developing antidepressants. Herein we first described the design, synthesis,
Discovery of N-hydroxy-3-alkoxybenzamides as direct acid sphingomyelinase inhibitors using a ligand-based pharmacophore model
Yang, Kan,Nong, Keyi,Gu, Qinlan,Dong, Jibin,Wang, Jinxin
, p. 389 - 400 (2018/04/12)
Acid sphingomyelinase (ASM) has been shown to be involved in many physiological processes, emerging to be a promising drug target. In this study, we constructed a ligand-based pharmacophore model of ASM inhibitors and applied this model to optimize the lead compound α-mangostin, a known inhibitor of ASM. 23 compounds were designed and evaluated in vitro for ASM inhibition, of these, 10 compounds were found to be more potent than α-mangostin. This high hit ratio confirmed that the presented model is very effective and practical. The most potent hit, 1c, was found to selectively and competitively inhibit the enzyme and inhibit the generation of ceramide in a dose-dependent manner. Furthermore, 1c showed favorable anti-apoptosis and anti-inflammatory activity. Interactions with key residues and the Zn2+ cofactor of 1c were found by docking simulation. These results provide promising leads and important guidance for further development of efficient ASM inhibitors and drug candidates.
Aromatic compounds containing basic and acidic termini useful as fibrinogen receptor antagonists
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, (2008/06/13)
This invention relates to novel compounds containing basic and acidic termini, pharmaceutical compositions containing such compounds, processes for preparing such compounds, and to methods of using these compounds, alone or in combination with other therapeutic agents, for the inhibition of platelet aggregation, as thrombolytics, and/or for the treatment of thromboembolic disorders.
