- Isoquinolinone derivatives as potent CNS multi-receptor D2/5-HT1A/5-HT2A/5-HT6/5-HT7 agents: Synthesis and pharmacological evaluation
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In this study, a series of novel Isoquinolinone derivatives were synthesized as potential multi-target antipsychotics. Among these, compound 13 showed high affinity for dopamine D2 and serotonin 5-HT1A, 5-HT2A, 5-HT6, and 5-HT7 receptors, showed low affinity for off-target receptors (5-HT2C, H1, and α1), and negligible effects on ether-a-gogo-related gene (hERG; i.e., reduced QT interval prolongation). An animal behavioral study revealed that compound 13 reversed APO-induced hyperlocomotion, MK-801-induced hyperactivity, and DOI-induced head twitch. Moreover, compound 13 exhibited a high threshold for acute toxicity, a lack of tendency to induce catalepsy, and did not cause prolactin secretion or weight gain when compared to risperidone. Furthermore, in the forced swim test, tail suspension test, and novel object recognition test, treatment with compound 13 resulted in improvements in depression and cognitive impairment. In addition, compound 13 had a favorable pharmacokinetic profile in rats. Thus, the antipsychotic drug-like effects of compound 13 indicate that it may be useful for developing a novel class of drugs for the treatment of schizophrenia.
- Cao, Xudong,Chen, Yin,Dou, Fei,Gao, Lanchang,Hao, Chao,Jin, Jian,Liu, Bi-Feng,Liu, Xin,Xiong, Jiaying,Zhang, Guisen,Zhang, Kunxiao,Zhang, Yifang
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Read Online
- Synthesis and evaluation of histamine H3 receptor ligand based on lactam scaffold as agents for treating neuropathic pain
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The synthesis and H3 receptor ligand of a new series of lactam derivatives are reported. The new compounds were evaluated in vitro in H3 and H1 receptor-binding assays. The structure-activity relationship led us to the pro
- Dou, Fei,Cao, Xudong,Jing, Peng,Wu, Chunyan,Zhang, Yuxin,Chen, Yin,Zhang, Guisen
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Read Online
- Preparation method of amide-like derivative and intermediate thereof
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The invention discloses a preparation method of an amide-like derivative and an intermediate thereof. The invention provides a preparation method of a compound as shown in a formula VI and an intermediate thereof, the compound as shown in the formula VI c
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Paragraph 0086-0089; 0113-0116
(2020/07/12)
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- Amide-like derivative impurity and application thereof
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The invention relates to an amide-like derivative impurity and application thereof. The invention belongs to the field of medical chemistry, and particularly relates to an impurity A, an impurity B, an impurity G, a preparation method thereof, and applica
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Paragraph 0141-0142; 0143
(2020/07/12)
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- Intramolecular Reductive Cyclization of o-Nitroarenes via Biradical Recombination
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A visible-light-induced/thiourea-mediated intramolecular cyclization of o-nitroarenes under mild conditions is realized for the first time, which provides an efficient and environmentally friendly way to access pharmaceutical relevant quinazolinone derivatives. The reaction can be easily extended to gram level by using a continuous-flow setup with high efficiency. Mechanistic investigation including control experiments, transient fluorescence, UV-vis spectra, and DFT calculations suggests that the formation of active biradical intermediates via intramolecular single electron transfer (SET) is key stage in the catalytic cycle.
- Lu, Cong,Su, Zhishan,Jing, Dong,Jin, Songyang,Xie, Lijuan,Li, Liangrui,Zheng, Ke
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supporting information
p. 1438 - 1443
(2019/03/07)
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- Light-Driven Intramolecular C?N Cross-Coupling via a Long-Lived Photoactive Photoisomer Complex
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Reported herein is a visible-light-driven intramolecular C?N cross-coupling reaction under mild reaction conditions (metal- and photocatalyst-free, at room temperature) via a long-lived photoactive photoisomer complex. This strategy was used to rapidly prepare the N-substituted polycyclic quinazolinone derivatives with a broad substrate scope (>50 examples) and further exploited to synthesize the natural products tryptanthrin, rutaecarpine, and their analogues. The success of gram-scale synthesis and solar-driven transformation, as well as promising tumor-suppressing biological activity, proves the potential of this strategy for practical applications. Mechanistic investigations, including control experiments, DFT calculations, UV-vis spectroscopy, EPR, and X-ray single-crystal structure of the key intermediate, provides insight into the mechanism.
- Jing, Dong,Lu, Cong,Chen, Zhuo,Jin, Songyang,Xie, Lijuan,Meng, Ziyi,Su, Zhishan,Zheng, Ke
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supporting information
p. 14666 - 14672
(2019/09/06)
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- Discovery of Cytochrome P450 4F11 Activated Inhibitors of Stearoyl Coenzyme A Desaturase
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Stearoyl-CoA desaturase (SCD) catalyzes the first step in the conversion of saturated fatty acids to unsaturated fatty acids. Unsaturated fatty acids are required for membrane integrity and for cell proliferation. For these reasons, inhibitors of SCD represent potential treatments for cancer. However, systemically active SCD inhibitors result in skin toxicity, which presents an obstacle to their development. We recently described a series of oxalic acid diamides that are converted into active SCD inhibitors within a subset of cancers by CYP4F11-mediated metabolism. Herein, we describe the optimization of the oxalic acid diamides and related N-acyl ureas and an analysis of the structure-activity relationships related to metabolic activation and SCD inhibition.
- Winterton, Sarah E.,Capota, Emanuela,Wang, Xiaoyu,Chen, Hong,Mallipeddi, Prema L.,Williams, Noelle S.,Posner, Bruce A.,Nijhawan, Deepak,Ready, Joseph M.
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p. 5199 - 5221
(2018/06/13)
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- LACTAM COMPOUND DERIVATIVE AND APPLICATION THEREOF
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The present invention relates to a lactam compound derivative, a medicine composition comprising the lactam compound derivative, and uses of the composition and the lactam compound derivative in preparation of a medicine for preventing or treating schizop
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Paragraph 0050
(2018/10/15)
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- Lactam derivative and application thereof
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The invention relates to a lactam derivative and application thereof. Particularly, a related lactam compound can act on an H3 receptor for treating diseases such as epilepsy, schizophrenia, senile dementia, sleep disorders, obesity, neuralgia and attenti
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Paragraph 0088; 0089
(2017/09/01)
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- 17a-HYDROXYLASE/C17,20-LYASE INHIBITORS
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The present invention provides compounds of Formula (I), or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, R5, R6, A and n are as defined herein. A deuteriated derivative of the compound of Formula (I) is also provided.
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Paragraph 0521
(2014/03/21)
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- 17α-HYDROXYLASE/C17,20-LYASE INHIBITORS
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The present invention provides compounds of Formula (I), or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, R5, R6, A and n are as defined herein. A deuteriated derivative of the compound of Formula (I) is also provided.
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Page/Page column 98
(2012/04/04)
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- INHIBITION OF BACTERIAL BIOFILMS WITH ARYL CARBAMATES
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Disclosure is provided for carbamate compounds that prevent, remove and/or inhibit the formation of biofilms, compositions including these compounds, devices including these compounds, and methods of using the same.
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Page/Page column 33
(2012/02/01)
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- HYDANTOIN DERIVATIVES FOR THE TREATMENT OF INFLAMMATORY DISORDERS
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This invention relates to compounds of the Formula: (I); or a pharmaceutically acceptable salt, solvate or isomer thereof, which can be useful for the treatment of diseases or conditions mediated by MMPs, ADAMs, TACE, aggrecanase, TNF-α or combinations thereof.
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Page/Page column 181
(2008/06/13)
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- Single electron transfer promoted photocyclization reactions of (aminoalkyl)cyclohexenones. Mechanistic and synthetic features of processes involving the generation and reactions of amine cation and α-amino radicals
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Mechanistic and synthetic aspects of the SET-induced photocyclization reactions of a series of α-, β-, and γ-(aminoethyl)cyclohexenones have been explored. These investigations have provided results that demonstrate that both direct (in MeOH) and SET-sensitized photocyclization reactions of members of this series containing N-(trimethylsilyl)methyl substituents serve as highly efficient methods for preparation of both fused and spiro N-heterobicyclic systems. In addition, as observed earlier, the solvent has been shown to play an important role in governing the chemoselectivity (i.e., amine cation radical desilylation vs deprotonation) of these photocyclizations. Specifically, desilylation is preferred in the polar protic solvent MeOH while deprotonation is favored in the aprotic MeCN. The results also show that the kinetic acidities of amine cation radicals, as judged by photoproduct distributions from reactions conducted in MeCN, are governed in a predictable way by substituents that control the stabilities of the resulting α-amino radical intermediates. Finally, the SET-sensitized reactions of these (aminoethyl)cyclohexenones that proceed via the radical cyclization mechanism are shown to display modest-to-low degrees of stereoselectivity.
- Xu, Wei,Zhang, Xiao-Ming,Mariano, Patrick S.
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p. 8863 - 8878
(2007/10/02)
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