- Design and Synthesis of Novel Spiro Derivatives as Potent and Reversible Monoacylglycerol Lipase (MAGL) Inhibitors: Bioisosteric Transformation from 3-Oxo-3,4-dihydro-2 H-benzo[ b][1,4]oxazin-6-yl Moiety
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The therapeutic potential of monoacylglycerol lipase (MAGL) inhibitors in central nervous system-related diseases has attracted attention worldwide. However, the availability of reversible-type inhibitor is still limited to clarify the pharmacological eff
- Ikeda, Shuhei,Sugiyama, Hideyuki,Tokuhara, Hidekazu,Murakami, Masataka,Nakamura, Minoru,Oguro, Yuya,Aida, Jumpei,Morishita, Nao,Sogabe, Satoshi,Dougan, Douglas R.,Gay, Sean C.,Qin, Ling,Arimura, Naoto,Takahashi, Yasuko,Sasaki, Masako,Kamada, Yusuke,Aoyama, Kazunobu,Kimoto, Kouya,Kamata, Makoto
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p. 11014 - 11044
(2021/08/24)
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- OXEPINOPYRAZOLE DERIVATIVES AS INHIBITORS OF PI3-KINASE ACTIVITY
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The invention is directed to compounds of formula (I), and salts thereof. The compounds are inhibitors of kinase activity, in particular PI3-kinase activity.
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- MUSCARINIC AGONISTS
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This invention relates to compounds that are agonists of the muscarinic receptor and/or M4 receptor and which are useful in the treatment of muscarinic M1/M4 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds include those according to formula (1a) or a salt thereof, wherein p, q, r, s, Q, R3 and R4 are as defined herein.
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Page/Page column 66
(2017/02/28)
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- A group of protein methylase EZH2 method for the synthesis of inhibitor intermediates (by machine translation)
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The invention relates to a group of protein methylase EZH2 inhibitors of synthesis method of intermediate I, this method, in order to compound 1 as raw materials, after reduction, sulfonylation, substituted and hydrolysis to obtain compound I, the reaction of simple operation, after treatment is convenient, is not required to be purified, high total yield, environment-friendly, is simple and easy to obtain reaction materials, suitable for industrial production. (by machine translation)
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- Improved Cav2.2 channel inhibitors through a gem -dimethylsulfone bioisostere replacement of a labile sulfonamide
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We report the investigation of sulfonamide-derived Cav2.2 inhibitors to address drug-metabolism liabilities with this lead class of analgesics. Modification of the benzamide substituent provided improvements in both potency and selectivity. However, we discovered that formation of the persistent 3-(trifluoromethyl)benzenesulfonamide metabolite was an endemic problem in the sulfonamide series and that the replacement of the center aminopiperidine scaffold failed to prevent this metabolic pathway. This issue was eventually addressed by application of a bioisostere strategy. The new gem-dimethyl sulfone series retained Cav2.2 potency without the liability of the circulating sulfonamide metabolite.
- Shao, Pengcheng P.,Ye, Feng,Chakravarty, Prasun K.,Herrington, James B.,Dai, Ge,Bugianesi, Randal M.,Haedo, Rodolfo J.,Swensen, Andrew M.,Warren, Vivien A.,Smith, McHardy M.,Garcia, Maria L.,McManus, Owen B.,Lyons, Kathryn A.,Li, Xiaohua,Green, Mitchell,Jochnowitz, Nina,McGowan, Erin,Mistry, Shruti,Sun, Shu-Yu,Abbadie, Catherine,Kaczorowski, Gregory J.,Duffy, Joseph L.
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supporting information
p. 1064 - 1068
(2013/12/04)
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- GPR119 Agonists
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GPR119 agonist compounds of the formula: and pharmaceutical compositions for the treatment of diabetes and obesity.
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Page/Page column 6
(2011/02/18)
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- BICYCLIC COMPOUNDS AND USE AS ANTIDIABETICS
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The present invention relates to novel compounds that are useful in the treatment of metabolic disorders, particularly type II diabetes mellitus and related disorders, and also to the methods for the making and use of such compounds.
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Page/Page column 77
(2010/03/02)
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- SUBSTITUTED ARYL SULFONE DERIVATIVES AS CALCIUM CHANNEL BLOCKERS
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A series of substituted aryl sulfone derivatives represented by Formula I, or pharmaceutically acceptable salts thereof. Pharmaceutical compositions comprise an effective amount of the instant compounds, either alone, or in combination with one or more other therapeutically active compounds, and a pharmaceutically acceptable carrier. Methods of treating conditions associated with, or caused by, calcium channel activity, including, for example, acute pain, chronic pain, visceral pain, inflammatory pain, neuropathic pain, urinary incontinence, itchiness, allergic dermatitis, epilepsy, diabetic neuropathy, irritable bowel syndrome, depression, anxiety, multiple sclerosis, sleep disorder, bipolar disorder and stroke, comprise administering an effective amount of the present compounds, either alone, or in combination with one or more other therapeutically active compounds.
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Page/Page column 34
(2009/05/29)
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- N-acyl cyclic amine derivatives
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The invention relates to compounds represented by the general formula [I][wherein Ar means an aryl group or a heteroaryl group which may have a substitutive group selected from a group consisting of a halogen atom, a lower alkyl group and a lower alkoxy group; R1 means a C3-C6 cycloalkyl group which is substitutable with a fluorine atom; R2 and R4 mean hydrogen atoms, groups represented by -(A1)m-NH-B or the like; R3 and R5 mean hydrogen atoms, C1-C6 aliphatic hydrocarbon groups or the like which are substitutable with a lower alkyl group(s); n means 0 or 1; and X means an oxygen atom or a sulfur atom]. Compounds according to the invention, since they not only have potent selective antagonistic activity against muscarinic M3 receptors but also exhibit excellent oral activity, durability of action and pharmacokinetics, are very useful as safe and effective remedies against respiratory, urinary and digestive diseases with little adverse side effects.
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- ETHER DERIVATIVES OF ALKYL PIPERIDINES AND PYRROLIDINES AS ANTIPSYCHOTIC AGAENTS
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Novel unsaturated ether derivatives of alkyl piperidine and pyrrolidine compounds, pharmaceutical compositions containing them, methods of preparation and methods of using these compounds as antipsychotic agents are disclosed.
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