- Synthesis and diabetic neuropathic pain-alleviating effects of 2N-(pyrazol-3-yl)methylbenzo[d]isothiazole-1,1-dioxide derivatives
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A novel series of fused-benzensulfonamide 2-N-(pyrazol-3-yl)methylbenzo[. d]isothiazole-1,1-dioxide derivatives was designed and synthesized as metabolically stable T-type calcium channel inhibitors. Several compounds, 9, 10, and 17, displayed potent T-type channel inhibitory activity. Among them, compounds 10 and 17 showed good metabolic stability in human liver microsomes, and low hERG channel and CYP450 inhibition. Compound 10 exhibited diabetic neuropathic pain-alleviating effects in a streptozotocin-induced peripheral diabetic neuropathy (PDN) model. The maximum efficacy of compound 10, which was 3-fold more potent than gabapentin, was observed at 1. h after administration, and co-administration of compound 10 with gabapentin showed a considerable synergic effect.
- Hong, Jin Ri,Choi, Young Jin,Keum, Gyochang,Nam, Ghilsoo
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- NITROSATION REAGENTS AND METHODS
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Provided are compounds that can find use as nitrosation reagents. Provided are nitrosation methods that include reacting a substrate with one of the provided nitrosation reagents and thereby generating a nitrosation product. Provided are kits including a nitrosation reagent. Provided are compositions wherein the nitrosation reagent is enriched in the 15N isotope.
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Paragraph 00152
(2022/02/06)
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- Synthesis of Sultams and Cyclic N-Sulfonyl Ketimines via Iron-Catalyzed Intramolecular Aliphatic C-H Amidation
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Cyclic sulfonamides (sultams) play a unique role in drug discovery and synthetic chemistry. A direct synthesis of sultams by an intramolecular C(sp3)-H amidation reaction using an iron complex in situ derived from Fe(ClO4)2 and aminopyridine ligand is reported. This strategy features a readily available catalyst and tolerates a broad variety of substrates as demonstrated by 22 examples (up to 89% yield). A one-pot iron-catalyzed amidation/oxidation procedure for the synthesis of cyclic N-sulfonyl ketimines is also realized with up to 92% yield (eight examples). The synthetic utility of the method is validated by a gram-scale reaction and derivatization of the products to ring-fused sultams.
- Zhong, Dayou,Wu, Di,Zhang, Yan,Lu, Zhiwu,Usman, Muhammad,Liu, Wei,Lu, Xiuqiang,Liu, Wen-Bo
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supporting information
p. 5808 - 5812
(2019/08/26)
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- Sultam compound and preparation method thereof
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The invention provides a sultam compound and a preparation method thereof. The method provided by the invention specifically comprises the following steps: putting a catalyst C, sulfamide B and an oxidant D into an organic solvent, performing a reaction,
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Paragraph 0054-0057; 0108-0111
(2019/11/12)
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- MONOCYCLIC COMPOUNDS USEFUL AS GPR120 MODULATORS
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Provided herein are compounds, compositions including them, and methods of modulating GPR120 activity and treating diseases mediated by GPR120 by administering such compounds and compositions.
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Page/Page column 25
(2018/03/28)
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- 1,1,1-TRIFLUORO-3-HYDROXYPROPAN-2-YL CARBAMATE DERIVATIVES AND 1,1,1-TRIFLUORO-4-HYDROXYBUTAN-2-YL CARBAMATE DERIVATIVES AS MAGL INHIBITORS
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The present invention provides, in part, compounds of Formula I and pharmaceutically acceptable salts thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses
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Page/Page column 174
(2017/02/28)
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- Non-Acidic Free Fatty Acid Receptor 4 Agonists with Antidiabetic Activity
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The free fatty acid receptor 4 (FFA4 or GPR120) has appeared as an interesting potential target for the treatment of metabolic disorders. At present, most FFA4 ligands are carboxylic acids that are assumed to mimic the endogenous long-chain fatty acid agonists. Here, we report preliminary structure-activity relationship studies of a previously disclosed nonacidic sulfonamide FFA4 agonist. Mutagenesis studies indicate that the compounds are orthosteric agonists despite the absence of a carboxylate function. The preferred compounds showed full agonist activity on FFA4 and complete selectivity over FFA1, although a significant fraction of these noncarboxylic acids also showed partial antagonistic activity on FFA1. Studies in normal and diet-induced obese (DIO) mice with the preferred compound 34 showed improved glucose tolerance after oral dosing in an oral glucose tolerance test. Chronic dosing of 34 in DIO mice resulted in significantly increased insulin sensitivity and a moderate but significant reduction in bodyweight, effects that were also present in mice lacking FFA1 but absent in mice lacking FFA4.
- Azevedo, Carlos M.G.,Watterson, Kenneth R.,Wargent, Ed T.,Hansen, Steffen V.F.,Hudson, Brian D.,K?pczyńska, Ma?gorzata A.,Dunlop, Julia,Shimpukade, Bharat,Christiansen, Elisabeth,Milligan, Graeme,Stocker, Claire J.,Ulven, Trond
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supporting information
p. 8868 - 8878
(2016/10/22)
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- COMPOUNDS CAPABLE OF INHIBITING VOLTAGE GATED CALCIUM ION CHANNEL, AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
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Disclosed herein are an N-(pyrazolylmethyl)arylsulfonamide derivative useful as a calcium ion channel blocker, a pharmaceutically acceptable salt thereof, and the medicinal use thereof as a therapeutic agent using its calcium ion channel blocking effect.
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Paragraph 0294; 0295
(2015/12/12)
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- Catalytic asymmetric Exo-selective [C+NC+CC] reaction
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A catalytic asymmetric version of the exo-selective [C+NC+CC] reaction is reported. This multicomponent reaction utilizes a readily prepared achiral glycyl sultam as the "NC" component and commercially available catalyst components. The method can be applied to a variety of aldehydes ("C" component) and activated alkenes ("CC" component) to provide substituted pyrrolidines in good yields and high enantioselectivities. Of particular note is the ability to employ labile enolizable aldehydes (e.g., acetaldehyde and propionaldehyde) in this reaction.
- Joseph, Ryan,Murray, Charles,Garner, Philip
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supporting information
p. 1550 - 1553
(2014/04/17)
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- Saccharin derivatives as inhibitors of interferon-mediated inflammation
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A series of novel, saccharin-based antagonists have been identified for the interferon signaling pathway. Through in vitro high-throughput screening with the Colorado Center for Drug Discovery (C2D2) Pilot Library, we identified hit compound 1, which was the basis for extensive structure-activity relationship studies. Our efforts produced a lead anti-inflammatory compound, tert-butyl N-(furan-2-ylmethyl)-N-{4-[(1,1,3-trioxo-2,3-dihydro-1λ6,2- benzothiazol-2-yl)methyl]benzoyl}carbamate CU-CPD103 (103), as a potent inhibitor using an established nitric oxide (NO) signaling assay. With further studies of its inhibitory mechanisms, we demonstrated that 103 carries out this inhibition through the JAK/STAT1 pathway, providing a drug-like small molecule inflammation suppressant for possible therapeutic uses.
- Csakai, Adam,Smith, Christina,Davis, Emily,Martinko, Alexander,Coulup, Sara,Yin, Hang
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supporting information
p. 5348 - 5355
(2014/07/08)
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- Carbazole-Containing Sulfonamides as Cryptochrome Modulators
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The subject matter herein is directed to carbazole-containing sulfonamide derivatives and pharmaceutically acceptable salts or hydrates thereof of structural formula I wherein the variable R1, R2, R3, R4, R5, R6, R7, A, B, C, D, E, F, G, H, a, and b are accordingly described. Also provided are pharmaceutical compositions comprising the compounds of formula I to treat a Cry-mediated disease or disorder, such as diabetes, obesity, metabolic syndrome, Cushing's syndrome, and glaucoma.
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Paragraph 0268-0269
(2013/11/19)
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- TiCl4-mediated direct N-alkylation of sulfonamides with inactive ethers
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A TiCl4-mediated intermolecular or intramolecular direct N-alkylation reaction of sulfonamides with inactive ethers as alkylating agents was successfully achieved. This method provides a novel approach towards N-alkyl sulfonamides from inactive ethers via an easy workup procedure. Georg Thieme Verlag Stuttgart · New York.
- Chen, Jiayan,Dang, Ling,Li, Qiang,Ye, Yong,Fu, Shaomin,Zeng, Wei
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p. 595 - 600
(2012/03/27)
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- Penultimate group effects in free radical telomerizations of acrylamides
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The telomerization of several acrylamides, most containing chiral auxiliary groups, was investigated. The first-formed stereogenic center in the n = 2 telomer (the penultimate center) has a significant effect on the configuration of the second (ultimate) center in the product. The penultimate chiral center of oxazolidine-derived acrylamides directs the configuration of the ultimate center such that the erythro n = 2 product is preferred. Sultam-substituted acrylamides preferentially lead, on the other hand, to threo products or give products with little stereoselectivity.
- Porter, Ned A.,Carter, Randall L.,Mero, Christopher L.,Roepel, Michael G.,Curran, Dennis P.
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p. 4181 - 4198
(2007/10/03)
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- Sulfonamidyls. 5. Electron Spin Resonance Spectroscopic Evidence for Four- and Five-Membered-Ring Sulfonamidyls and Sulfonyl Nitroxides
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Cyclic sulfonamidyl radicals, generated by photolysis of the N-bromo (or N-chloro) β- and γ-sultams 1-3 and of N-bromo-2,3-dihydro-1,2-benzisothiazole 1,1-dioxide (4) have been characterized by solution ESR studies.The nitrogen and β hyperfine splitting c
- Teeninga, Herman,Engberts, Jan B. F. N.
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p. 537 - 542
(2007/10/02)
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- Hypolipidemic activity of phthalimide derivatives. 3. A comparison of phthalimide and 1,2-benzisothiazolin-3-one 1,1-dioxide derivatives to phthalimidine and 1,2-benzisothiazoline 1,1-dioxide congeners
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Previously it has been observed that N-substituted phthalimide derivatives with chain lengths of four carbon or oxygen atoms showed potent hypolipidemic activity in rodents at 20 (mg/kg)/day ip. The 1,2-benzisothiazolin-3-one 1,1-dioxide (saccharin) nucleus, itself, had also been observed to be active at the same dose. An investigation was undertaken to examine a series of 1,2-benzisothiazolin-3-one 1,1-dioxide analogues for their hypolipidemic activity in mice and to compare them to their respective phthalimide congeners. In addition, a series of 1,2-benzisothiazoline 1,1-dioxide and phthalimidine analogues was prepared, and their hypolipidemic activity was compared to the phthalimide analogues. These studies show that the respective congeners of 1,2-benzisothiazolin-3-one 1,1-dioxide compared favorably to phthalimide congeners in reducing serum triglyceride and cholesterol levels in male CF1 mice at 20 (mg/kg)/day ip. Of the saccharin derivatives, 3-oxo-1,2-benzisothiazoline-2-propionic acid 1,1-dioxide was the most effective in lowering serum cholesterol levels by 53% after 16 days dosing and 3-oxo-1,2-dibenzothiazoline-2-valeric acid 1,1-dioxide lowered serum triglycerides 56% after 14 days dosing. The 1,2-benzisothiazoline 1,1-dioxide and phthalimidine compounds were less active as hypolipidemic agents than their 1,2-benzisothiazolin-3-one 1,1-dioxide and phthalimide analogues, respectively.
- Chapman Jr.,Cocolas,Hall
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p. 243 - 246
(2007/10/02)
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