- Functionalization of Piperidine Derivatives for the Site-Selective and Stereoselective Synthesis of Positional Analogues of Methylphenidate
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Rhodium-catalyzed C?H insertions and cyclopropanations of donor/acceptor carbenes have been used for the synthesis of positional analogues of methylphenidate. The site selectivity is controlled by the catalyst and the amine protecting group. C?H functionalization of N-Boc-piperidine using Rh2(R-TCPTAD)4, or N-brosyl-piperidine using Rh2(R-TPPTTL)4 generated 2-substitited analogues. In contrast, when N-α-oxoarylacetyl-piperidines were used in combination with Rh2(S-2-Cl-5-BrTPCP)4, the C?H functionalization produced 4-susbstiuted analogues. Finally, the 3-substituted analogues were prepared indirectly by cyclopropanation of N-Boc-tetrahydropyridine followed by reductive regio- and stereoselective ring-opening of the cyclopropanes.
- Babl, Tobias,Davies, Huw M. L.,Liu, Wenbin,R?ther, Alexander,Reiser, Oliver
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supporting information
(2020/03/23)
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- Iron-catalyzed synthesis of arylsulfinates through radical coupling reaction
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A novel strategy for installation of a sulfonyl fragment into arenes has been accomplished via an iron-catalyzed radical coupling reaction. Arene radicals derived from diaryliodoniums via single electron transfer reaction combine with sulfoxylate anion radicals readily generated from commercially available rongalite (HOCH2SO2Na·2H2O) to afford arylsulfinates efficiently at room temperature. In this protocol, a broad range of functional groups are tolerated to give products in good yields.
- Zhang, Weixi,Luo, Meiming
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p. 2980 - 2983
(2016/02/19)
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- Metal-free synthesis of sulfonamides via iodine-catalyzed oxidative coupling of sulfonyl hydrazides and amines
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A novel, rapid, and environmentally-friendly protocol for the synthesis of sulfonamides using iodine as catalyst under solvent-free conditions is described. This method involves the oxidative coupling of sulfonyl hydrazides and amines in the presence of catalytic amount of iodine using TBHP as oxidant. This protocol does not require purification techniques such as column chromatography and recrystalization.
- Parumala, Santosh Kumar Reddy,Peddinti, Rama Krishna
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supporting information
p. 1232 - 1235
(2016/03/01)
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- SUBSTITUTED 2-AZA-BICYCLO[2.2.1]HEPTANE-3-CARBOXYLIC ACID (BENZYL-CYANO-METHYL)-AMIDES INHIBITORS OF CATHEPSIN C
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This invention relates to 2-Aza-bicyclo[2.2.1]heptane-3-carboxylic acid (benzyl-cyano-methyl)- amides of formula (1) and their use as inhibitors of Cathepsin C, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of diseases connected with dipeptidyl peptidase I activity, e.g. respiratory diseases.
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Page/Page column 206
(2014/09/29)
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- ACYCLIC CYANOETHYLPYRAZOLO PYRIDONES AS JANUS KINASE INHIBITORS
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The instant invention provides compounds of formula I which are JAK inhibitors, and as such are useful for the treatment of JAK-mediated diseases such as rheumatoid arthritis, asthma, COPD and cancer.
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Page/Page column 54
(2014/10/03)
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- SUBSTITUTED 2-AZA-BICYCLO[2.2.1]HEPTANE-3-CARBOXYLIC ACID (BENZYL-CYANO-METHYL)-AMIDES INHIBITORS OF CATHEPSIN C
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This invention relates to 2-Aza-bicyclo[2.2.1]heptane-3-carboxylic acid(benzyl-cyano-methyl)-amides of formula 1 and their use as inhibitors of Cathepsin C, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of diseases connected with dipeptidyl peptidase I activity, e.g. respiratory diseases.
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Paragraph 0523; 0524; 0525
(2014/09/29)
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- Synthesis and structure-activity relationships for 1-(4-(piperidin-1- ylsulfonyl)phenyl)pyrrolidin-2-ones as novel non-carboxylate inhibitors of the aldo-keto reductase enzyme AKR1C3
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High expression of the aldo-keto reductase enzyme AKR1C3 in the human prostate and breast has implicated it in the development and progression of leukemias and of prostate and breast cancers. Inhibitors are thus of interest as potential drugs. Most inhibitors of AKR1C3 are carboxylic acids, whose transport into cells is likely dominated by carrier-mediated processes. We describe here a series of (piperidinosulfonamidophenyl)pyrrolidin-2-ones as potent (100 nM) and isoform-selective non-carboxylate inhibitors of AKR1C3. Structure-activity relationships identified the sulfonamide was critical, and a crystal structure showed the 2-pyrrolidinone does not interact directly with residues in the oxyanion hole. Variations in the position, co-planarity or electronic nature of the pyrrolidinone ring severely diminished activity, as did altering the size or polarity of the piperidino ring. There was a broad correlation between the enzyme potencies of the compounds and their effectiveness at inhibiting AKR1C3 activity in cells.
- Heinrich, Daniel M.,Flanagan, Jack U.,Jamieson, Stephen M.F.,Silva, Shevan,Rigoreau, Laurent J.M.,Trivier, Elisabeth,Raynham, Tony,Turnbull, Andrew P.,Denny, William A.
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supporting information
p. 738 - 744
(2013/05/09)
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- Discovery of novel potent and highly selective glycogen synthase kinase-3β (GSK3β) inhibitors for Alzheimers Disease: Design, synthesis, and characterization of pyrazines
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Glycogen synthase kinase-3β, also called tau phosphorylating kinase, is a proline-directed serine/threonine kinase which was originally identified due to its role in glycogen metabolism. Active forms of GSK3β localize to pretangle pathology including dystrophic neuritis and neurofibrillary tangles in Alzheimers disease (AD) brain. By using a high throughput screening (HTS) approach to search for new chemical series and cocrystallization of key analogues to guide the optimization and synthesis of our pyrazine series, we have developed highly potent and selective inhibitors showing cellular efficacy and bloo-brain barrier penetrance. The inhibitors are suitable for in vivo efficacy testing and may serve as a new treatment strategy for Alzheimers disease.
- Berg, Stefan,Bergh, Margareta,Hellberg, Sven,Hoegdin, Katharina,Lo-Alfredsson, Yvonne,Soederman, Peter,Von Berg, Stefan,Weigelt, Tatjana,Ormoe, Mats,Xue, Yafeng,Tucker, Julie,Neelissen, Jan,Jerning, Eva,Nilsson, Yvonne,Bhat, Ratan
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p. 9107 - 9119,13
(2020/10/15)
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- NAPHTHYLACETIC ACIDS
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The invention is concerned with the compounds of formula (I) and pharmaceutically acceptable salts and esters thereof, wherein X, Q, and R1-R6 are defined in the detailed description and claims. In addition, the present invention relates to methods of manufacturing and using the compounds of formula (I) as well as pharmaceutical compositions containing such compounds. The compounds of formula (I) are antagonists or partial agonists at the CRTH2 receptor and may be useful in treating diseases and disorders associated with that receptor such as asthma.
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Page/Page column 82-83
(2010/06/15)
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- Synthesis and PKCθ inhibitory activity of a series of 5-vinyl phenyl sulfonamide-3-pyridinecarbonitriles
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A series of 5-vinyl phenyl sulfonamide-3-pyridinecarbonitriles were prepared and evaluated as PKCθ inhibitors. Optimization resulted in the identification of compound 15 with an IC50 value 0.44 nM for the inhibition of PKCθ with 150-fold select
- Shim, Jaechul,Eid, Clark,Lee, Julie,Liu, Erica,Chaudhary, Divya,Boschelli, Diane H.
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scheme or table
p. 6575 - 6577
(2010/06/12)
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- ARYL SULFONAMIDES USEFUL FOR MODULATION OF THE PROGESTERONE RECEPTOR
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In one embodiment, compounds of the following structure are described, wherein R1 to R7 are described herein. Also provided are methods for preparing these compounds and methods of contraception; treating or preventing fibroids; trea
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Page/Page column 11
(2008/12/08)
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- Trichlorophenol (TCP) sulfonate esters: A selective alternative to pentafluorophenol (PFP) esters and sulfonyl chlorides for the preparation of sulfonamides
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2,4,6-Trichlorophenol (TCP) sulfonate esters undergo effective aminolysis under conventional heating and microwave irradiation; the reactivity of these species is such that chemoselective transformations of PFP sulfonate esters can be achieved. The Royal Society of Chemistry.
- Wilden, Jonathan D.,Geldeard, Lynsey,Lee, Chieh C.,Judd, Duncan B.,Caddick, Stephen
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p. 1074 - 1076
(2007/12/29)
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- Cytoprotective compounds, pharmaceutical and cosmetic formulations, and methods
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Cytoprotective compounds, many of which are phenolic derivatives characterized by a substituted phenol having certain conjugated bonds, are useful in the treatment of certain ischemic or inflammatory conditions, including but not limited to stroke, myocardial infarction, congestive heart failure, and skin disorders characterized by inflammation or oxidative damage. They are also useful in the manufacture of pharmaceutical and cosmetic formulations for the treatment of such conditions.
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- Reactions of benzenesulfonohydrazides and benzenesulfonamides with hydrogen chloride or hydrogen bromide in acetic acid
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Benzenesulfonohydrazides capable of yielding a sulfinic acid intermediate by virtue of a basic nitrogen atom in the second position of the hydrazide moiety produced thiosulfonates when treated with 1 N hydrogen chloride in acetic acid and produced disulfides when treated with 1 N hydrogen bromide in the same solvent. In two cases, a crystalline mixture of p-nitrophenyl p-nitrobenzenethiosulfonate and bis(p-nitrophenyl) disulfide was isolated from the hydrogen chloride reactions. No reaction product was obtained from either the hydrogen chloride or hydrogen bromide reaction with benzenesulfonohydrazides that were unable to form a sulfinic acid intermediate. Reduction of benzenesulfonamides to disulfides appeared to be possible only with hydrogen bromide in acetic acid. No thiosulfonate was isolated from the treatments of benzenesulfonamides with 1 N hydrogen chloride in acetic acid. p-Nitrophenyl p-nitrobenzenethiosulfonate and p-bromophenyl p-bromobenzenethiosulfonate exhibited some antimicrobial activities against Gram-positive bacteria. The latter compound also showed analgesic properties in the phenylquinone test.
- Yung,Forrest,Manzer,Gilroy
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p. 1009 - 1012
(2007/10/06)
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