- Aryl alkylamine compound, preparation method thereof and application of aryl alkylamine compound in medicines
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The invention relates to an aryl alkylamine compound, a preparation method thereof and application of the aryl alkylamine compound in medicines. Particularly, the compound disclosed by the invention is suitable for being used as a calcium-sensitive recept
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Paragraph 0362-0368
(2021/07/17)
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- Synthesis of All-Carbon Quaternary Centers by Palladium-Catalyzed Olefin Dicarbofunctionalization
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The redox-neutral dicarbofunctionalization of tri- and tetrasubstituted olefins to form a variety of (hetero)cyclic compounds under photoinduced palladium catalysis is described. This cascade reaction process was used to couple styrenes or acryl amides with a broad range of highly decorated olefins tethered to aryl or alkyl bromides (>50 examples). This procedure enables one or two contiguous all-carbon quaternary centers to be formed in a single step. The products could be readily diversified and applied in the synthesis of a bioactive oxindole analogue.
- Koy, Maximilian,Bellotti, Peter,Katzenburg, Felix,Daniliuc, Constantin G.,Glorius, Frank
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supporting information
p. 2375 - 2379
(2020/01/24)
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- Preparation method and application of 3-(substituted phenyl) oxetane-3-carboxylic acid and intermediate thereof
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The preparation method comprises the following steps: taking 3-oxetanone (compound II) as an initial raw material, and carrying out Wittig reaction on the initial raw material and triethyl phosphonotriacetate under an alkaline condition to obtain a compound III; carrying out coupling reaction on the compound III and a boric acid compound IV to obtain a compound V; reducing the ester group of the compound V to generate a compound VI; carrying out nucleophilic substitution reaction on hydroxyl of the compound VI and sulfonyl chloride/sulfonic anhydride to generate a compound VII; reacting hydroxyl of the compound VI with a halogenating reagent to generate a compound VIII; carrying out elimination reaction on the compound VII or the compound VIII to generate a compound IX; and finally, oxidizing the double bonds of the compound IX to generate 3-(substituted phenyl) oxetane-3-carboxylic acid (compound I). The method is easy and convenient to operate and high in yield, the total yield can reach 35%, and large-scale production can be achieved.
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Paragraph 0051-0054; 0065-0068; 0079-0082; 0092-0095; 0106
(2020/11/12)
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- Design and Identification of a GPR40 Full Agonist (SCO-267) Possessing a 2-Carbamoylphenyl Piperidine Moiety
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GPR40/FFAR1 is a G-protein-coupled receptor expressed in pancreatic β-cells and enteroendocrine cells. GPR40 activation stimulates secretions of insulin and incretin, both of which are the pivotal regulators of glycemic control. Therefore, a GPR40 agonist
- Furukawa, Hideki,Miyamoto, Yasufumi,Hirata, Yasuhiro,Watanabe, Koji,Hitomi, Yuko,Yoshitomi, Yayoi,Aida, Jumpei,Noguchi, Naoyoshi,Takakura, Nobuyuki,Takami, Kazuaki,Miwatashi, Seiji,Hirozane, Yoshihiko,Hamada, Teruki,Ito, Ryo,Ookawara, Mitsugi,Moritoh, Yusuke,Watanabe, Masanori,Maekawa, Tsuyoshi
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p. 10352 - 10379
(2020/10/02)
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- GPR40 receptor stimulant, and preparation method, pharmaceutical composition and application thereof
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The invention discloses a GPR40 receptor stimulant, and a preparation method, a pharmaceutical composition and application thereof. The invention particularly discloses a GPR40 receptor stimulant shown in general formula (I) and pharmacologically acceptable salt thereof, a preparation process of the compound, a pharmaceutical composition containing the compound of general formula (I), and application of the compound and the pharmaceutical composition in anti-diabetes.
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Paragraph 0163; 0199; 0227-0229
(2019/10/15)
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- Macrocyclic MCL-1 inhibitors and methods of use
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The present disclosure provides for compounds of Formula (I) wherein A2, A3, A4, A6, A7, A8, A15, RA, R5, R9, R10A, R10B, R11, R12, R13, R14, R16, W, X, and Y have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents for the treatment of diseases and conditions, including cancer. Also provided are pharmaceutical compositions comprising compounds of Formula (I).
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Paragraph 0895
(2019/02/28)
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- COMPOUNDS, COMPOSITIONS AND METHODS OF USE
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Herein, compounds, compositions and methods for modulating inclusion formation and stress granules in cells related to the onset of neurodegenerative diseases, musculoskeletal diseases, cancer, ophthalmological diseases, and viral infections are described.
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Page/Page column 55; 74
(2018/11/22)
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- Synthesis of 6-Azaspiro[4.3]alkanes: Innovative Scaffolds for Drug Discovery
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New scaffolds for drug discovery, 6-azaspiro[4.3]alkanes, have been synthesized in two steps from four-membered-ring ketones: cyclobutanone, thienone, N-Boc-azetidinone (Boc = tert-butoxycarbonyl), etc. The key transformation was the reaction between electron-deficient exocyclic alkenes and an in-situ generated N-benzylazomethine ylide.
- Chalyk, Bohdan A.,Isakov, Andrei A.,Butko, Maryna V.,Hrebeniuk, Kateryna V.,Savych, Olena V.,Kucher, Olexandr V.,Gavrilenko, Konstantin S.,Druzhenko, Tetiana V.,Yarmolchuk, Vladimir S.,Zozulya, Sergey,Mykhailiuk, Pavel K.
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p. 4530 - 4542
(2017/08/30)
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- Synthesis method of 4-hydroxymethyl-dihydro-furan-2(3H)-ketone
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The invention belongs to the field of organic synthesis and drug synthesis, and particularly relates to a synthesis method of 4-hydroxymethyl-dihydro-furan-2(3H)-ketone. The synthesis method is carried out by a first step of mixing and stirring 3-oxetanone and ethoxyformyl methylidene triphenyl phosphorane solvent and obtaining an intermediate product 2-(oxetane-3-radical) ethyl acetate; a second step of hydrolyzing the intermediate product 2-(oxetane-3-radical) ethyl acetate through palladium carbon hydrogenation reduction under the alkali condition; meanwhile, completing rearrangement of reduction and oxygen heterocycles; obtaining 4-hydroxymethyl-dihydro-furan-2(3H)-ketone. The reaction condition of the synthesis method involved in the invention is easy to control, raw materials are low-price and easy to obtain; the operation and post treatment processes are simple; besides, the method is possessed of the industrial production value.
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Paragraph 0021; 0022; 0023; 0024; 0025; 0026; 0027
(2017/08/28)
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- Discovery and optimisation of potent and highly subtype selective Nav1.8 inhibitors with reduced cardiovascular liabilities
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Voltage-gated sodium channels, in particular Nav1.8, can be targeted for the treatment of neuropathic and inflammatory pain. Herein, we describe the discovery and optimisation of a Nav1.8 inhibiting phenyl imidazole series that delivers chemical equity that possesses high potency and selectivity and is capable of demonstrating good oral pharmacokinetics.
- Bagal, Sharan K.,Kemp, Mark I.,Bungay, Peter J.,Hay, Tanya L.,Murata, Yoshihisa,Payne, C. Elizabeth,Stevens, Edward B.,Brown, Alan,Blakemore, David C.,Corbett, Matthew S.,Miller, Duncan C.,Omoto, Kiyoyuki,Warmus, Joseph S.
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supporting information
p. 1925 - 1931
(2016/10/22)
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- SUBSTITUTED HETEROCYCLIC DERIVATIVES AS GPR AGONISTS AND USES THEREOF
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The present invention generally relates to substituted heterocyclic derivatives (the compounds of Formula (I)), processes for their preparation, pharmaceutical compositions containing said compounds, their use as G-protein coupled receptor (GPR) agonists, particularly as GPR40 agonists and methods of using these compounds in the treatment of GPR40 mediated diseases or conditions such as Type 2 diabetes, obesity, dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.
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Page/Page column 83; 84
(2015/03/16)
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- Concise synthesis and characterization of novel seco-steroids bearing a spiro-oxetane instead of a metabolically labile C3-hydroxy group
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Two novel stereoisomeric analogues of 1,25-dihydroxyvitamin D3 bearing a spiro-oxetane at the C3 position of the A-ring have been designed and synthesized in a convergent manner. The absolute configuration at the C1 position of the synthesized
- Fujishima, Toshie,Suenaga, Tsutomu,Nozaki, Takato
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supporting information
p. 3805 - 3808
(2014/07/07)
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- IMIDAZO[4,5-C]QUINOLINE DERIVATIVES AND USES THEREOF
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The present invention relates to substituted imidazo[4,5-c]quinoline derivatives represented by the compounds formula (I), processes for their preparation, pharmaceutical compositions comprising said compounds and their use in the treatment of diseases or disorders mediated by one or more kinases (such as PI3 kinase, mTOR and ALK-1), particularly proliferative diseases or disorders such as cancer. The compounds of formula (I) can also be used in the treatment of inflammation, angiogenesis related disorders and bacterial infections.
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Page/Page column 42
(2014/09/29)
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- IDO INHIBITORS
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There are disclosed compounds that modulate or inhibit the enzymatic activity of indoleamine 2,3-dioxygenase (IDO), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders, such as cancer, viral infections and/or autoimmune diseases utilizing the compounds of the invention. Formula (I).
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Page/Page column 54
(2014/10/04)
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- CHEMICAL COMPOUNDS
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The invention relates to imidazole derivatives, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. More particularly the invention relates to a new imidazole Nav
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Page/Page column 67
(2013/05/21)
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- PHENYL ALKANOIC ACID DERIVATIVES AS GPR AGONISTS
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The present invention relates to phenyl alkanoic acid derivatives (the compounds of Formula (I)); and their isotopic forms, stereoisomeric and tautomeric forms and mixtures thereof in all ratios, or pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugs, polymorphs, N-oxides, S-oxides or carboxylic acid isosteres thereof. The invention also relates to processes for the preparation of compounds of Formula (I) and pharmaceutical compositions comprising one or more of the compounds of Formula (I). The said compounds and the pharmaceutical composition function as GPR (G-protein coupled receptor) agonists, particularly as GPR40 agonists, and are useful in the treatment of diseases or conditions mediated by GPR40. The present invention further relates to a method of treatment of diseases or conditions mediated by GPR40comprising administering to a subject in need thereof a therapeutically effective amount of the compounds of Formula (I).
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Page/Page column 84
(2013/09/12)
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- AMIDO SPIROCYCLIC AMIDE AND SULFONAMIDE DERIVATIVES
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Provided are amido spirocyclic amide and sulfonamide compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.
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Page/Page column 170
(2013/09/12)
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- NOVEL P2X7R ANTAGONISTS AND THEIR USE
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The present application is directed to novel P2X7R antagonists that are N-indol-3-yl-acetamide and N-azaindol-3-yl-acetamide compounds, pharmaceutical compositions comprising the same and their use for the prophylactic or therapeutic treatment of diseases mediated by P2X7R activity.
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Page/Page column 33; 34; 39; 40
(2012/09/10)
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- OXADIAZOLE SUBSTITUTED INDAZOLE DERIVATIVES FOR USE AS SPHINGOSINE 1-PHOSPHATE 1 (S1P1) RECEPTOR AGONISTS
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Oxadiazole substituted indazole derivatives of formula (I) or pharmaceutical salts thereof having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their uses in the treatment of various disorders mediated by S1P1 receptors are disclosed.
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Page/Page column 29
(2012/11/13)
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- An improved synthesis of 2-oxa-7-azaspiro[3,5]nonane and analogs as novel reagents in medicinal chemistry
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A detailed synthesis of novel spirocyclic oxetane analogs is described for the first time.
- Xu, Ruo,Czarniecki, Michael,Man, Jos De,Pan, Jianping,Qiang, Li,Root, Yuriko,Ying, Shihong,Su, Jing,Sun, Xijun,Zhang, Yuping,Yu, Tao,Zhang, Yang,Hu, Tao,Chen, Shu-Hui
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scheme or table
p. 3266 - 3270
(2011/07/08)
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- NITROGEN HETEROCYCLIC COMPOUNDS USEFUL AS PDE10 INHIBITORS
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Unsaturated nitrogen heterocyclic compounds of formula (I): (I), as defined in the specification, compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, Huntington's Disease, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.
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Page/Page column 189
(2011/12/02)
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- OXADIAZOLE SUBSTITUTED INDAZOLE DERIVATIVES FOR USE AS SPHINGOSINE 1-PHOSPHATE 1 (S1P1) RECEPTOR AGONISTS
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Oxadiazole substituted indazole derivatives of formula (I) or pharmaceutical salts thereof having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their uses in the treatment of various disorders mediated by S1P1 receptor are disclosed.
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Page/Page column 18-19; 54-55
(2011/07/07)
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- Oxetanes in drug discovery: Structural and synthetic insights
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An oxetane can trigger profound changes in aqueous solubility, lipophilicity, metabolic stability, and conformational preference when replacing commonly employed functionalities such as gem-dimethyl or carbonyl groups. The magnitude of these changes depends on the structural context. Thus, by substitution of a gem-dimethyl group with an oxetane, aqueous solubility may increase by a factor of 4 to more than 4000 while reducing the rate of metabolic degradation in most cases. The incorporation of an oxetane into an aliphatic chain can cause conformational changes favoring synclinal rather than antiplanar arrangements of the chain. Additionally spirocyclic oxetanes (e.g., 2-oxa-6-aza-spiro[3.3]heptane) bear remarkable analogies to commonly used fragments in drug discovery, such as morpholine, and are even able to supplant the latter in its solubilizing ability. A rich chemistry of oxetan-3-one and derived Michael acceptors provide venues for the preparation of a broad variety of novel oxetanes not previously documented, thus providing the foundation for their broad use in chemistry and drug discovery.
- Wuitschik, Georg,Carreira, Erick M.,Wagner, Bj?rn,Fischer, Holger,Parrilla, Isabelle,Schuler, Franz,Rogers-Evans, Mark,Müller, Klaus
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supporting information; scheme or table
p. 3227 - 3246
(2010/08/19)
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- Gold-catalyzed one-step practical synthesis of oxetan-3-ones from readily available propargylic alcohols
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A general solution for the synthesis of various oxetan-3-ones is developed. This reaction uses readily available propargylic alcohols as substrates and proceeds without the exclusion of moisture or air ("open flask"). Notably, oxetan-3-one, a highly valuable substrate for drug discovery, can be prepared in one step from propargyl alcohol in a fairly good yield. The facile formation of the strained oxetane ring provides strong support for the intermediacy of α-oxo gold carbenes. This safe and efficient generation of gold carbenes via intermolecular alkyne oxidation offers a potentially general entry into α-oxo metal carbene chemistry without using hazardous diazo ketones.
- Ye, Longwu,He, Weimin,Zhang, Liming
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supporting information; experimental part
p. 8550 - 8551
(2010/08/06)
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- [1H- PYRAZOLO [3, 4-B] PYRIDINE-4-YL] -PHENYLE OR -PYRIDIN-2-YLE DERIVATIVES AS PROTEIN KINASE C-THETA
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The present invention relates to compounds of formula (I) and (IA) useful as inhibitors of protein kinase (1a). The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders. The invention also provides processes for preparing compounds of the inventions. (a) : in particular protein kinase C theta, wherein A and A' are independently -N- or -C(R+) -. Ring B is five- or six-membered saturated carbocyclic or heterocyclic R1, R2, R3, R4, R5, R6, R7, x and y are as described herein.
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Page/Page column 164
(2009/07/17)
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- COMPOUNDS FOR TREATING VIRAL INFECTIONS
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The invention relates to compounds, pharmaceutical compositions and methods useful for treating viral infection.
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Page/Page column 87-88
(2008/12/08)
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- Oxetanes as promising modules in drug discovery
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(Chemical Equation Presented) Ring the changes: Introduction of an oxetane ring results in remarkably improved physico- and biochemical properties of the underlying scaffold. The oxetane ring confers enhanced solubility, reduces the metabolic degredation, lipophilicity, and amphiphilicity, and modulates the basicity of a nearby amine group.
- Wuitschik, Georg,Rogers-Evans, Mark,Mueller, Klaus,Fischer, Holger,Wagner, Bjoern,Schuler, Franz,Polonchuk, Liudmila,Carreira, Erick M.
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p. 7736 - 7739
(2007/10/03)
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