7035-09-8Relevant academic research and scientific papers
Discovery of carbon-11 labeled sulfonamide derivative: A PET tracer for imaging brain NLRP3 inflammasome
Xu, Yulong,Xu, Yiming,Blevins, Hallie,Lan, Yu,Liu, Yan,Yuan, Gengyang,Striar, Robin,Zagaroli, Julia S.,Tocci, Darcy R.,Langan, Amelia G.,Zhang, Can,Zhang, Shijun,Wang, Changning
supporting information, (2021/01/18)
We report herein the discovery of a positron emission tomography (PET) tracer for the (NOD)-like receptor protein 3 (NLRP3). Our recent medicinal chemistry campaign on developing sulfonamide-based NLRP3 inhibitors led to an analog, 1, with a methoxy subst
COMPOUNDS AS NLRP3 INFLAMMASOME INHIBITORS AND COMPOSITIONS AND USES THEREOF
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Page/Page column 29, (2021/02/12)
Scaffold compounds are used to design small molecule compounds and structure- activity relationship studies identify inhibitors of inflammation· Methods include pharmaceutical compositions of the small molecule compounds to inhibit, prevent and treat dise
Asymmetric total synthesis of (+)-asenapine
Szcze?niak, Piotr,Staszewska-Krajewska, Olga,Mlynarski, Jacek
, p. 3225 - 3231 (2019/03/26)
Asymmetric total synthesis of (+)-asenapine, an atypical antipsychotic drug, used for treating schizophrenia and acute mania associated with bipolar disorder, is reported. The key steps are the organocatalytic Michael addition of aldehydes to trans-nitroa
Discovery of Second-Generation NLRP3 Inflammasome Inhibitors: Design, Synthesis, and Biological Characterization
Jiang, Yuqi,He, Liu,Green, Jakob,Blevins, Hallie,Guo, Chunqing,Patel, Sulay Harsiddhbhai,Halquist, Matthew S.,McRae, MaryPeace,Venitz, Jürgen,Wang, Xiang-Yang,Zhang, Shijun
, p. 9718 - 9731 (2019/11/13)
NLRP3 inflammasomes have recently emerged as an attractive drug target for neurodegenerative disorders. In our continuing studies, a new chemical scaffold was designed as selective inhibitors of NLRP3 inflammasomes. Initial characterization of the lead HL
Metal-Free Thermal Activation of Molecular Oxygen Enabled Direct α-CH2-Oxygenation of Free Amines
Ghosh, Santanu,Jana, Chandan K.
, p. 260 - 266 (2018/02/19)
Direct oxidation of α-CH2 group of free amines is hard to achieve due to the higher reactivity of amine moiety. Therefore, oxidation of amines involves the use of sophisticated metallic reagents/catalyst in the presence or absence of hazardous oxidants under sensitive reaction conditions. A novel method for direct C-H oxygenation of aliphatic amines through a metal-free activation of molecular oxygen has been developed. Both activated and unactivated free amines were oxygenated efficiently to provide a wide variety of amides (primary, secondary) and lactams under operationally simple conditions without the aid of metallic reagents and toxic oxidants. The method has been applied to the synthesis of highly functionalized amide-containing medicinal drugs, such as O-Me-alibendol and -buclosamide.
Iron(III)-Catalyzed Chlorination of Activated Arenes
Mostafa, Mohamed A. B.,Bowley, Rosalind M.,Racys, Daugirdas T.,Henry, Martyn C.,Sutherland, Andrew
, p. 7529 - 7537 (2017/07/26)
A general and regioselective method for the chlorination of activated arenes has been developed. The transformation uses iron(III) triflimide as a powerful Lewis acid for the activation of N-chlorosuccinimide and the subsequent chlorination of a wide range of anisole, aniline, acetanilide, and phenol derivatives. The reaction was utilized for the late-stage mono- and dichlorination of a range of target compounds such as the natural product nitrofungin, the antibacterial agent chloroxylenol, and the herbicide chloroxynil. The facile nature of this transformation was demonstrated with the development of one-pot, tandem, iron-catalyzed dihalogenation processes allowing highly regioselective formation of different carbon-halogen bonds. The synthetic utility of the resulting dihalogenated aryl compounds as building blocks was established with the synthesis of natural products and pharmaceutically relevant targets.
Synthesis and bioevaluation of substituted chalcones, coumaranones and other flavonoids as anti-HIV agents
Cole, Amy L.,Hossain, Sandra,Cole, Alex M.,Phanstiel, Otto
, p. 2768 - 2776 (2016/06/08)
A series of chalcone, flavone, coumaranone and other flavonoid compounds were screened for their anti HIV-1 activity in two cell culture models using TZM-bl and PM1 cells. Within the systems evaluated, the most promising compounds contained either an α- or β-hydroxy-carbonyl motif within their structure (e.g., 8 and 9). Efficacious substituents were identified and used to design new HIV inhibitors with increased potency and lower cytotoxicity. Of the scaffolds evaluated, specific chalcones were found to provide the best balance between anti-HIV potency and low host cell toxicity. Chalcone 8l was shown to inhibit different clinical isolates of HIV in a dose-dependent manner (e.g., IC50 typically ≤ 5 μM). Inhibition of HIV infection experiments using TZM-bl cells demonstrated that chalcone 8l and flavonol 9c had IC50 values of 4.7 μM and 10.4 μM, respectively. These insights were used to design new chalcones 8o and 8p. Rewardingly, chalcones 8o and 8p (at 10 μM) each gave >92% inhibition of viral propagation without impacting PM1 host cell viability. Inhibition of viral propagation significantly increased (60-90%) when PM1 cells were pre-incubated with chalcone 8o, but not with the related flavonol 9c. These results suggested that chalcone 8o may be of value as both a HIV prophylactic and therapy. In summary, O-benzyl-substituted chalcones were identified as promising anti-HIV agents for future investigation.
SELECTIVE NAV1.7 INHIBITORS FOR THE TREATMENT OF DIABETES
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Paragraph 00435; 00436, (2016/06/01)
Provided herein are methods for treating or preventing prediabetes or diabetes, or maintaining or lowering blood or plasma glucose or maintaining or lowering blood or plasma glycated hemoglobin comprising administering to a subject in need thereof a therapeutically effective amount of a compound selectively inhibiting NaVl.7. In particular, provided herein are processes for the preparation of and intermediates used in the preparation of compounds selectively inhibiting NaV1.7, such as the compounds of Formula (I) or compounds of Formula (I').
SODIUM CHANNEL MODULATORS FOR THE TREATMENT OF PAIN AND DIABETES
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Paragraph 0735; 0736, (2016/06/06)
Provided herein are sodium channel modulating Compounds, in particular NaV1.7 modulating compounds of Formula I or compounds of Formula I′: In particular, provided herein are processes for the preparation of, intermediates used in the preparation of, pharmaceutical compositions comprising, and therapeutic methods comprising administering such compounds. In particular, provided herein are compounds for the treatment of pain and diabetes.
Highly Regioselective Iodination of Arenes via Iron(III)-Catalyzed Activation of N-Iodosuccinimide
Racys, Daugirdas T.,Warrilow, Catherine E.,Pimlott, Sally L.,Sutherland, Andrew
supporting information, p. 4782 - 4785 (2015/10/12)
An iron(III)-catalyzed method for the rapid and highly regioselective iodination of arenes has been developed. Use of the powerful Lewis acid, iron(III) triflimide, generated in situ from iron(III) chloride and a readily available triflimide-based ionic liquid allowed activation of N-iodosuccinimide (NIS) and efficient iodination under mild conditions of a wide range of substrates including biologically active compounds and molecular imaging agents.
