159635-49-1

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• Sequential Photocatalytic Reactions for the Diastereoselective Synthesis of Cyclobutane Scaffolds
• The synthesis of densely functionalized cyclobutanes containing all-carbon quaternary stereocenters in high regio- and diastereoselectivity remains synthetically challenging. Herein, we show that this can be achieved by using a sequential photocatalysis strategy, wherein 3-chloromaleimides undergo triplet sensitized [2 + 2] photocycloadditions with alkynes or alkenes followed by photoredox-catalyzed dechlorinative C-C bond forming reactions to install quaternary stereocenters. This allows the rapid assembly of structurally complex and sterically congested 3-azabicyclo[3.2.0]heptane scaffolds from readily available starting materials.
• Deeprose, Mark J.,Lowe, Martin,Noble, Adam,Booker-Milburn, Kevin I.,Aggarwal, Varinder K.
• supporting information

  p. 137 - 141

  (2021/12/17)
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• Merging Halogen-Atom Transfer (XAT) and Cobalt Catalysis to Override E2-Selectivity in the Elimination of Alkyl Halides: A Mild Route towardcontra-Thermodynamic Olefins
• We report here a mechanistically distinct tactic to carry E2-type eliminations on alkyl halides. This strategy exploits the interplay of α-aminoalkyl radical-mediated halogen-atom transfer (XAT) with desaturative cobalt catalysis. The methodology is high-yielding, tolerates many functionalities, and was used to access industrially relevant materials. In contrast to thermal E2 eliminations where unsymmetrical substrates give regioisomeric mixtures, this approach enables, by fine-tuning of the electronic and steric properties of the cobalt catalyst, to obtain high olefin positional selectivity. This unprecedented mechanistic feature has allowed access tocontra-thermodynamic olefins, elusive by E2 eliminations.
• Zhao, Huaibo,McMillan, Alastair J.,Constantin, Timothée,Mykura, Rory C.,Juliá, Fabio,Leonori, Daniele
• supporting information

  p. 14806 - 14813

  (2021/09/18)
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• Site-Specific Alkene Hydromethylation via Protonolysis of Titanacyclobutanes
• Methyl groups are ubiquitous in biologically active molecules. Thus, new tactics to introduce this alkyl fragment into polyfunctional structures are of significant interest. With this goal in mind, a direct method for the Markovnikov hydromethylation of alkenes is reported. This method exploits the degenerate metathesis reaction between the titanium methylidene unveiled from Cp2Ti(μ-Cl)(μ-CH2)AlMe2 (Tebbe's reagent) and unactivated alkenes. Protonolysis of the resulting titanacyclobutanes in situ effects hydromethylation in a chemo-, regio-, and site-selective manner. The broad utility of this method is demonstrated across a series of mono- and di-substituted alkenes containing pendant alcohols, ethers, amides, carbamates, and basic amines.
• Bartfield, Noah M.,Frederich, James H.,Law, James A.
• supporting information

  p. 14360 - 14364

  (2021/05/27)
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• Synthesis of sp 3-Enriched β-Fluoro Sulfonyl Chlorides
• A three-step approach to the synthesis of sp 3-enriched β-fluoro sulfonyl chlorides starting from alkenes is reported. The method was successfully applied to a wide range of acyclic and cyclic substrates, bearing either an exocyclic or an endocyclic double bond. The procedure worked with a wide range of substrates and tolerated a number of functional and protecting groups. Moreover, the target cyclic compounds were obtained as single cis diastereomers on a multigram scale. The title compounds are promising building blocks for drug discovery that can be used to obtain sp 3-enriched β-fluoro and α,β-unsaturated sulfonamides.
• Gurbanov, Rustam,Sokolov, Andriy,Golovach, Sergey,Melnykov, Kostiantyn,Dobrydnev, Alexey V.,Grygorenko, Oleksandr O.

• p. 1771 - 1784

  (2020/12/28)
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• Methylenation for Aldehydes and Ketones Using 1-Methylbenzimidazol-2-yl Methyl Sulfone
• The methylenation reagent 1-methylbenzimidazol-2-yl methyl sulfone 2 reacts with various aldehydes and ketones in the presence of t-BuOK (room temperature, 1 h) in dimethylformamide to give the corresponding terminal alkenes generally in high yields. For sensitive substrates, the reaction is better carried out at low temperature using sodium hexamethyldisilazide in 1,2-dimethoxyethane. The byproduct is easily removed from the products, and the reaction conditions are mild and practical. Reagent 2 can be easily prepared from commercially available 2-mercaptobenzimidazole 5 in 95% yield without any expensive reagents.
• Ando, Kaori,Oguchi, Mai,Kobayashi, Takahisa,Asano, Haruka,Uchida, Nariaki

• p. 9936 - 9943

  (2020/09/04)
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• Br?nsted Acid Catalyzed Peterson Olefinations
• A mild and facile Peterson olefination has been developed employing low catalyst loading of the Br?nsted acid HNTf2. The reactions are typically performed at room temperature, with the reaction tolerant to a range of useful functionalities. Furthermore, we have extended this methodology to the synthesis of enynes.
• Britten, Thomas K.,McLaughlin, Mark G.

• p. 301 - 305

  (2019/12/25)
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• Bromomethyl Silicate: A Robust Methylene Transfer Reagent for Radical-Polar Crossover Cyclopropanation of Alkenes
• A general protocol for visible-light-induced cyclopropanation of alkenes was developed with bromomethyl silicate as a methylene transfer reagent, offering a robust tool for accessing highly valuable cyclopropanes. In addition to α-aryl or methyl-substituted Michael acceptors and styrene derivatives, the unactivated 1,1-dialkyl ethylenes were also shown to be viable substrates. Apart from realizing the cyclopropanation of terminal alkenes, the methyl transfer reaction has been further demonstrated to be amenable to the internal olefins. The photocatalytic cyclopropanation of 1,3-bis(1-arylethenyl)benzenes was also achieved, giving polycyclopropane derivatives in excellent yields. With late-stage cyclopropanation as the key strategy, the synthetic utility of this transformation was also demonstrated by the total synthesis of LG100268.
• Luo, Wenping,Fang, Yewen,Zhang, Li,Xu, Tianhang,Liu, Yongjun,Li, Yan,Jin, Xiaoping,Bao, Jiakan,Wu, Xiaodong,Zhang, Zongyong
• supporting information

  p. 1778 - 1781

  (2020/03/11)
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• Aminoxyl-Catalyzed Electrochemical Diazidation of Alkenes Mediated by a Metastable Charge-Transfer Complex
• We report the development of a new aminoxyl radical catalyst, CHAMPO, for the electrochemical diazidation of alkenes. Mediated by an anodically generated charge-transfer complex in the form of CHAMPO-N3, radical diazidation was achieved across a broad scope of alkenes without the need for a transition metal catalyst or a chemical oxidant. Mechanistic data support a dual catalytic role for the aminoxyl serving as both a single-electron oxidant and a radical group transfer agent.
• Siu, Juno C.,Parry, Joseph B.,Lin, Song
• supporting information

  p. 2825 - 2831

  (2019/02/14)
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• Hydroalkylation of Olefins to Form Quaternary Carbons
• Metal-hydride hydrogen atom transfer (MHAT) functionalizes alkenes with predictable branched (Markovnikov) selectivity. The breadth of these transformations has been confined to π-radical traps; no sp3 electrophiles have been reported. Here we describe a Mn/Ni dual catalytic system that hydroalkylates unactivated olefins with unactivated alkyl halides, yielding aliphatic quaternary carbons.
• Green, Samantha A.,Huffman, Tucker R.,McCourt, Ruairí O.,Van Der Puyl, Vincent,Shenvi, Ryan A.
• supporting information

  (2019/05/22)
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• Hydroalkylation of Olefins to Form Quaternary Carbons
• Metal-hydride hydrogen atom transfer (MHAT) functionalizes alkenes with predictable branched (Markovnikov) selectivity. The breadth of these transformations has been confined to π-radical traps; no sp3 electrophiles have been reported. Here we describe a Mn/Ni dual catalytic system that hydroalkylates unactivated olefins with unactivated alkyl halides, yielding aliphatic quaternary carbons.
• Green, Samantha A.,Huffman, Tucker R.,McCourt, Ruairí O.,Van Der Puyl, Vincent,Shenvi, Ryan A.
• supporting information

  p. 7709 - 7714

  (2019/05/22)
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• Rhodium(III)-Catalyzed Cyclopropanation of Unactivated Olefins Initiated by C-H Activation
• We have developed a rhodium(III)-catalyzed cyclopropanation of unactivated olefins initiated by an alkenyl C-H activation. A variety of 1,1-disubstituted olefins undergo efficient cyclopropanation with a slight excess of alkene stoichiometry. A series of mechanistic interrogations implicate a metal carbene as an intermediate.
• Phipps, Erik J. T.,Piou, Tiffany,Rovis, Tomislav
• supporting information

  p. 1787 - 1790

  (2019/09/09)
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• A process for the preparation and synthetic ChondriamideA and ChondriamideC method (by machine translation)
• The invention provides a process for the preparation of synthetic Chondriamide A and Chondriamide C and method, wherein the invention provides a process for the preparation, including: formula (I) compounds of structure, palladium catalyst, phosphorus ligand, alkali and organic solvent at room temperature the illumination reaction, formula (II) structure obtained olefin; wherein through the selection of a particular phosphorus ligand; make the method of the invention can be under the photocatalysis, room temperature to realize high-efficient catalytic conversion, and the mild reaction conditions, simple operation, in line with the development of green environment-friendly chemical requirements, and the range of choice of substrate and functional group compatibility has more universal, and has outstanding chemical selectivity; and the method can be successfully applied to complex molecular introducing carbon-carbon double bond to the programme, to optimize a part of the drug molecular synthesis strategy, improve the synthesis efficiency, reduce the cost, with industrial synthetic value and prospects. (by machine translation)
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• Paragraph 0078-0082; 0122-0125

  (2018/09/13)
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• FXR receptor modulator, and preparation method and application thereof
• The invention discloses a FXR receptor modulator, and a preparation method and application thereof, belonging to the field of pharmaceutical chemistry. The FXR receptor modulator with structural characteristics as shown in a formula I which is described i
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• Paragraph 0297; 0300-0301

  (2018/09/08)
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• 1-azaspirocycle compound, and preparation method and applications thereof
• The invention discloses a 1-azaspirocycle compound, and preparation method and applications thereof, and belongs to the field of pharmaceutical chemistry. The 1-azaspirocycle compound with a structurerepresented by formula I, or a pharmaceutically acceptable salt or a stereisomer or a solvate or a prodrug thereof is capable of realzing combination with Autotaxin, can be taken as an Autotaxin inhibitor, and can be used for prevention and treatment of diseases with Autotaxin expression increasing pathological characteristics such as cancer and fibrosis diseases especially pulmonary fibrosis andhepatic fibrosis, metabolic diseases, myelodysplastic syndrome, cardiovascular diseases, autoimmune diseases, inflammation, neurological diseasses, or pain. Compared with single component inhibitors,the 1-azaspirocycle compound and the derivatives possesses following advantages: blocking and interfacing at the upsteam of a plurality of key signal channels are realized, tumor cell growth and transfer are relieved or dalyed, early caused drug resistance is avoided, and novel means are provided for treatment of tumor cells.
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• Paragraph 0333; 0335; 0338; 0339

  (2018/09/14)
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• FXR RECEPTOR MODULATOR, PREPARATION METHOD THEREFOR, AND USES THEREOF
• The present disclosure disclosed a modulator of FXR receptor and preparation and use thereof, which relates to the technical filed of medicinal chemistry. The present disclosure provides a modulator of FXR receptor having a structural formula I or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof, which can combine with FXR receptor (that is NR1H4) and be acted as a FXR agonist or a partial agonist for preventing and treating the disease mediated by FXR, such as chronic intrahepatic or extrahepatic cholestasis, hepatic fibrosis caused by chronic cholestasis or acute intrahepatic cholestasis, chronic hepatitis B, gallstone, hepatic carcinoma, colon cancer or intestinal inflammatory disease, etc. Specifically, for some chemical compounds, their EC50 for FXR agonist activity reach below 100nM, which show an excellent FXR agonist activity and an excellent prospect to provide a new pharmaceutical selection in clinical treatment for the disease mediated by FXR.
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• Paragraph 0047; 0048; 0054

  (2018/11/27)
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• Iron-Nickel Dual-Catalysis: A New Engine for Olefin Functionalization and the Formation of Quaternary Centers
• Alkene hydroarylation forms carbon-carbon bonds between two foundational building blocks of organic chemistry: olefins and aromatic rings. In the absence of electronic bias or directing groups, only the Friedel-Crafts reaction allows arenes to engage alkenes with Markovnikov selectivity to generate quaternary carbons. However, the intermediacy of carbocations precludes the use of electron-deficient arenes, including Lewis basic heterocycles. Here we report a highly Markovnikov-selective, dual-catalytic olefin hydroarylation that tolerates arenes and heteroarenes of any electronic character. Hydrogen atom transfer controls the formation of branched products and arene halogenation specifies attachment points on the aromatic ring. Mono-, di-, tri-, and tetra-substituted alkenes yield Markovnikov products including quaternary carbons within nonstrained rings.
• Green, Samantha A.,Vásquez-Céspedes, Suhelen,Shenvi, Ryan A.
• supporting information

  p. 11317 - 11324

  (2018/09/18)
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• Generation and Alkylation of α-Carbamyl Radicals via Organic Photoredox Catalysis
• Strategies for the direct C-H functionalization of amines are valuable as these compounds comprise a number of pharmaceuticals, agrochemicals and natural products. This work describes a novel method for the C-H functionalization of carbamate-protected secondary amines via α-carbamyl radicals generated using photoredox catalysis. The use of the highly oxidizing, organic acridinium photoredox catalyst allows for direct oxidation of carbamate-protected amines with high redox potentials to give the corresponding carbamyl cation radical. Following deprotonation, the resultant open-shell species can be intercepted by a variety of Michael acceptors to give elaborate α-functionalized secondary amines. The reaction proceeds under mild conditions without the requirement of exogenous redox mediators or substrate prefunctionalization. Additionally, we were able to showcase the utility of this methodology through the enantioselective synthesis of the indolizidine alkaloid, (+)-monomorine I.
• McManus, Joshua B.,Onuska, Nicholas P. R.,Nicewicz, David A.
• supporting information

  p. 9056 - 9060

  (2018/07/21)
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• Synthetic methods of 7-azaspiro[3,5]-nonane-2-ol and hydrochloride compound thereof
• The invention discloses 7-azaspiro-[3,5]-nonane-2-ol and a hydrochloride compound thereof. Concretely, N-Boc-4-piperidone is used as a raw material, a wittig reaction is carried out in order to prepare N-Boc-4-methylenepiperidine, zinc/copper is used for catalysis of trichloroacetyl chloride in order to carry out [2+2] cyclisation for preparing N-Boc-7-azaspiro ketone; the azaspiro ketone intermediate is reduced into N-Boc-7-azaspiro-ol by sodium borohydride at a room temperature, and finally 2mol/L hydrochloric acid-ethyl acetate is used for removing Boc in order to prepare a target product hydrochloride whose purity reaches 98%. The product has the advantages of economical and easily available reagents and raw materials which are needed, simple operation, and high product purity; and the product is suitable for batch production.
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• Paragraph 0035-0036

  (2017/07/11)
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• Novel Compounds as Autotaxin Inhibitors and Pharmaceutical Compositions Comprising the Same
• The present invention relates to a novel autotaxin inhibitor compound for preventing and treating disease or symptoms due to an increase in concentration of lysophosphatidic acid or activation of autotaxin. The present invention further relates to a pharmaceutical composition containing the same. The novel compound of the present invention is an autotaxin inhibitor which inhibits production of lysophosphatidic acid, and thus is useful for treating or preventing cardiovascular disease, cancer, metabolic disease, kidney disease, liver disease, inflammatory diseases, nervous disease, respiratory disease, desmoid disease, eye disease, cholestatic symptoms, other types of chronic pruritus or acute, or chronic rejection of transplanted organs.COPYRIGHT KIPO 2017
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• Paragraph 0483-0486

  (2018/05/17)
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• Free-Radical Carbo-Alkenylation of Olefins: Scope, Limitations and Mechanistic Insights
• The three-component free-radical carbo-alkenylation of electron-rich olefins has been studied, varying the substitution pattern in the alkene, in the radical precursor and in the final acceptor. New vinylsulfones were also prepared and their reactivity investigated. The scope and limitations of the process was established, and the reaction mechanism clarified using selected dienes as radical clocks. It was thus recognised that the reversible addition onto the olefin of the released sulfonyl group is an important event, which should not be overlooked when using such multicomponent carbo-alkenylation reactions.
• Beniazza, Redouane,Liautard, Virginie,Poittevin, Clément,Ovadia, Benjamin,Mohammed, Shireen,Robert, Frédéric,Landais, Yannick
• supporting information

  p. 2439 - 2447

  (2017/02/23)
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• SUBSTITUTED PYRIDINES AS INHIBITORS OF DNMT1
• The invention is directed to substituted pyridine derivatives. Specifically, the invention is directed to compounds according to Formula (Iar): (Iar) wherein Yar, X1ar, X2ar, R1ar, R2ar, R3ar, R4ar and R5ar are as defined herein; or a pharmaceutically acceptable salt or prodrug thereof. The compounds of the invention are selective inhibitors of DNMT1 and can be useful in the treatment of cancer, pre-cancerous syndromes, beta hemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and beta thalassemia, and diseases associated with DNMT1 inhibition. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting DNMT1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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• Page/Page column 586-587

  (2018/01/20)
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• Search for potent and selective Aurora A inhibitors based on general Ser/Thr kinase pharmacophore model
• Based on the data for compounds known from the literature to be active against various types of Ser/Thr kinases, a general pharmachophore model for these types of kinases was developed. The search for the molecules fitting to this pharmacophore among the ASINEX proprietary library revealed a number of compounds, which were tested and appeared to possess some activity against Ser/Thr kinases such as Aurora A, Aurora B and Haspin. Our work on the optimization of these molecules against Aurora A kinase allowed us to achieve several hits in a 3-5 nM range of activity with rather good selectivity and Absorption, Distribution, Metabolism, and Excretion (ADME) properties, and cytotoxicity against 16 cancer cell lines. Thus, we showed the possibility to fine-tune the general Ser/Thr pharmacophore to design active and selective compounds against desired types of kinases.
• Vasilevich, Natalya I.,Tatarskiy, Victor V.,Aksenova, Elena A.,Kazyulkin, Denis N.,Afanasyev, Ilya I.

• (2016/05/02)
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• General Ser/Thr Kinases Pharmacophore Approach for Selective Kinase Inhibitors Search as Exemplified by Design of Potent and Selective Aurora A Inhibitors
• A general pharmachophore model for various types of Ser/Thr kinases was developed. Search for the molecules fitting to this pharmacophore among ASINEX proprietary library revealed a number of compounds, which were tested and appeared to possess some activity against several Ser/Thr kinases such as Aurora A, Aurora B and Haspin. The possibility of performing the fine-tuning of the general Ser/Thr pharmacophore to desired types of kinase to get active and selective inhibitors was exemplified by Aurora A kinase. As a result, several hits in 3–5?nm range of activity against Aurora A kinase with rather good selectivity and ADME properties were obtained.
• Vasilevich, Natalya I.,Aksenova, Elena A.,Kazyulkin, Denis N.,Afanasyev, Ilya I.

• p. 54 - 65

  (2016/07/09)
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• Tigecycline derivatives (by machine translation)
• The invention belongs to the medicinal technical field, and in particular relates to a tigecycline derivative of general formula (I), a pharmaceutically acceptable salt, precursor drug, solvate or isomer thereof, wherein R2a, R2b, R3, R4a, R4b, R5, R6a, R
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• Paragraph 0270-0272; 0381-0383

  (2016/10/10)
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• Design, Synthesis, and Biological Evaluation of First-in-Class Dual Acting Histone Deacetylases (HDACs) and Phosphodiesterase 5 (PDE5) Inhibitors for the Treatment of Alzheimer's Disease
• Simultaneous inhibition of phosphodiesterase 5 (PDE5) and histone deacetylases (HDAC) has recently been validated as a potentially novel therapeutic approach for Alzheimer's disease (AD). To further extend this concept, we designed and synthesized the first chemical series of dual acting PDE5 and HDAC inhibitors, and we validated this systems therapeutics approach. Following the implementation of structure- and knowledge-based approaches, initial hits were designed and were shown to validate our hypothesis of dual in vitro inhibition. Then, an optimization strategy was pursued to obtain a proper tool compound for in vivo testing in AD models. Initial hits were translated into molecules with adequate cellular functional responses (histone acetylation and cAMP/cGMP response element-binding (CREB) phosphorylation in the nanomolar range), an acceptable therapeutic window (>1 log unit), and the ability to cross the blood-brain barrier, leading to the identification of 7 as a candidate for in vivo proof-of-concept testing (Cuadrado-Tejedor, M.; Garcia-Barroso, C.; Sánchez-Arias, J. A.; Rabal, O.; Mederos, S.; Ugarte, A.; Franco, R.; Segura, V.; Perea, G.; Oyarzabal, J.; Garcia-Osta, A. Neuropsychopharmacology 2016, in press, doi: 10.1038/npp.2016.163).
• Rabal, Obdulia,Sánchez-Arias, Juan A.,Cuadrado-Tejedor, Mar,De Miguel, Irene,Pérez-González, Marta,García-Barroso, Carolina,Ugarte, Ana,Estella-Hermoso De Mendoza, Ander,Sáez, Elena,Espelosin, Maria,Ursua, Susana,Haizhong, Tan,Wei, Wu,Musheng, Xu,Garcia-Osta, Ana,Oyarzabal, Julen

• p. 8967 - 9004

  (2016/10/22)
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• Practical Methylenation Reaction for Aldehydes and Ketones Using New Julia-Type Reagents
• A new Julia-type methylenation reagent, 1-methyl-2-(methylsulfonyl)benzimidazole (1e), reacts with a variety of aldehydes and ketones in the presence of either NaHMDS (-55 °C to rt) or t-BuOK (rt, 1 h) in DMF to give the corresponding terminal alkenes in high yields. The byproducts are easily removed, and the reaction conditions are mild and practical.
• Ando, Kaori,Kobayashi, Takahisa,Uchida, Nariaki
• supporting information

  p. 2554 - 2557

  (2015/05/27)
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• Spiroisoxazoline Compounds Having an Activity Potentiating the Activity of an Antibiotic
• The present invention concerns a spiroisoxazoline compound of general formula (I): in which m and n are 0 or 1, R1 represents, inter alia, an optionally substituted alkyl chain, in particular substituted with fluorine or with a cyclic group, and R2 is chosen from phenyl and optionally substituted benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the heterocycles having 5 or 6 vertices comprising at least one atom chosen from S, N and O. The present invention also concerns the use of this compound as a drug, in particular in the treatment of bacterial and mycobacterial infections such as tuberculosis in combination with an antibiotic that is active against bacteria and/or mycobacteria, said compound potentiating the activity of said antibiotic.
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• Paragraph 0053; 0054

  (2015/12/23)
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• NOVEL KINASE INHIBITORS
• The present invention provides derivatives of thiazolylamino-substituted heterocycles. These compounds are inhibitors of kinases, including compounds that show antiproliferative activity against cells, including against tumor cells, and are useful in the treatment of diseases including cancer.
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• Paragraph 0211

  (2014/05/07)
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• GLYCOSIDASE INHIBITORS
• Compounds of formula (I) wherein X1, X2, W, R1 to R5, L and m have the meaning according to the claims, are glucosidase inhibitors, and can be employed, inter alia, for the treatment of Alzheimer's disease.
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• Page/Page column 102; 103

  (2014/10/15)
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• NOVEL COMPOUNDS AS DUAL INHIBITORS OF PHOSPHODIESTERASES AND HISTONE DEACETYLASES
• It relates to certain compounds having a polycyclic structure and a hydroxamic acid moiety, wherein the polycyclic structure comprises at least three ring systems, wherein one ring system is a polycyclic ring system comprising from 2 to 4 rings; at least one ring is an aromatic ring; and wherein the structure comprises at least 3 nitrogen atoms and 1 oxygen atom. It also relates to a process for their preparation, as well as to pharmaceutical compositions containing them, and to their use in medicine, in particular in the treatment and/or prevention of neurological disorders coursing with a cognition deficit or impairment, or neurodegenerative diseases. wherein B1 is a radical selected from the group consisting of formula (A"), formula (B"), formula (C"), and formula (D"):
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• Page/Page column 76

  (2014/09/16)
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• SPIROCYCLIC MOLECULES AS PROTEIN KINASE INHIBITORS
• The present invention relates to spirocyclic compounds of formula I, namely spirocyclic (1H-pyrazol-4-yl)-3-(1-(2,6-dichloro-3-fiuorophenyl) ethoxy)pyridin-2-amines having protein kinase inhibitory activity, and methods of synthesizing and using such compounds. Preferred compounds are c-Met and/or ALK inhibitors useful for the treatment of abnormal cell growth, such as cancers
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• Paragraph 00196-00198

  (2013/03/26)
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• (HETERO)ARYL CYCLOPROPYLAMINE COMPOUNDS AS LSD1 INHIBITORS
• The invention relates to (hetero)aryl cyclopropylamine compounds, including particularly the compounds of formula I as described and defined herein, and their use in therapy, including, e.g., in the treatment or prevention of cancer, a neurological disease or condition, or a viral infection.
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• Page/Page column 155

  (2013/05/09)
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• ANTICANCER AGENT
• An anticancer agent comprising a compound represented by the formula (I) [R1 represents hydrogen atom, hydroxyl group, a C1-6alkoxy group and the like; R2 and R3 represents hydrogen atom, a halogen atom, a C1-6alkyl group and the like; R4 represents hydrogen atom, a C1-6alkyl group, a C1-6alkylsulfonyl group and the like; R5 represents hydrogen atom or a substituent; .... represents a single bond or a double bond; R6 and R7 represents hydrogen atom, a C1-6alkyl group and the like; R8 represents hydrogen atom, a C1-6alkyl group and the like; A represents -O-, -S-, or - CH2-; D represents -C= or -N=; X represents methylene group, -O-, or -CO-; Q represents -N= or -C(R8)=; and Y represents a heterocyclic group or amino group], which shows a superior inhibitory activity against pim-1 kinase.
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• Paragraph 0532

  (2013/03/26)
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• NOVEL SUBSTITUTED TRIAZOLYL PIPERAZINE AND TRIAZOLYL PIPERIDINE DERIVATIVES AS GAMMA SECRETASE MODULATORS
• The present invention is concerned with novel substituted triazolyl piperazine and triazolyl piperidine derivatives of Formula (I) wherein R1, R2, R3, R4a, R4b, R5, X, Y1, Y
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• Page/Page column 37

  (2012/10/08)
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• Discovery of fused bicyclic agonists of the orphan G-protein coupled receptor GPR119 with in vivo activity in rodent models of glucose control
• We herein outline the design of a new series of agonists of the pancreatic and GI-expressed orphan G-protein coupled receptor GPR119, a target that has been of significant recent interest in the field of metabolism, starting from our prototypical agonist
• Semple, Graeme,Ren, Albert,Fioravanti, Beatriz,Pereira, Guillherme,Calderon, Imelda,Choi, Karoline,Xiong, Yifeng,Shin, Young-Jun,Gharbaoui, Tawfik,Sage, Carleton R.,Morgan, Michael,Xing, Charles,Chu, Zhi-Liang,Leonard, James N.,Grottick, Andrew J.,Al-Shamma, Hussein,Liang, Yin,Demarest, Keith T.,Jones, Robert M.
• scheme or table

  p. 3134 - 3141

  (2011/06/26)
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• PHOSPHODIESTARASE INHIBITORS
• The present invention relates to phosphodiesterase (PDE) type 4, phosphodiesterase (PDE) type 7 and dual PDE type 4 /PDE type 7 inhibitors. Compounds disclosed herein can be useful in the treatment, prevention, inhibition or suppression of CNS diseases, f
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• Page/Page column 40

  (2010/05/13)
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• Substituted Indole Compounds
• Substituted indole compounds corresponding to the formula I: In which R8, R9a, R9b, R10, R11, R200, R210, A, D, T, q, s and t have defined meanings, processes for the preparation thereof, pharmaceutical compositions containing such compounds and the use of substituted indole compounds for the treatment or inhibition of pain and other conditions which are at least partly mediated by Bradykinin 1 receptors (B1R).
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• Page/Page column 55

  (2010/09/07)
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• Substituted Spiroamide Compounds
• Substituted spiroamide compounds corresponding to formula (I): wherein A, B, Q1, Q2, Q3, Q4, R1, R8, R9a, R9b, R12, R13, R200 and R210 have defined meanings, processes for their preparation, pharmaceutical compositions containing such compounds, and the use of such compounds for treating or inhibiting pain or other conditions mediated at least in part by the bradykinin 1 receptor (B1R).
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• Page/Page column 42

  (2010/09/18)
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• SUBSTITUTED BENZIMIDAZOLES, BENZOTHIAZOLES AND BENZOXAZOLES
• The present invention relates to substituted benzimidazoles, benzothiazoles and benzoxazoles, processes for their preparation, medicaments containing these compounds and the use of these compounds for the preparation of medicaments.
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• Page/Page column 145

  (2010/12/29)
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• HETEROARYL-SUBSTITUTED UREA MODULATORS OF FATTY ACID AMIDE HYDROLASE
• Certain heteroaryl-substituted piperidinyl and piperazinyl urea compounds are described, which are useful as FAAH inhibitors. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by fatty acid amide hydrolase (FAAH) activity, such as anxiety, pain, inflammation, sleep disorders, eating disorders, insulin resistance, diabetes, osteoporosis, and movement disorders (e.g., multiple sclerosis).
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• Page/Page column 68

  (2010/07/02)
• 

• 7-AZASPIRO[3.5]NONANE-7-CARBOXAMIDE COMPOUNDS
• Provided herein are 7-azaspiro[3.5]nonane-7-carboxamide compounds and the pharmaceutically acceptable salts of such compounds useful in treating diseases or conditions associated with fatty acid amide hydrolase (FAAH) activity, conditions including including acute pain, chronic pain, neuropathic pain, nociceptive pain, inflammatory pain, cancer and cancer pain, fibromyalgia, rheumatoid arthritis, inflammatory bowel disease, lupus, diabetes, allergic asthma, vascular inflammation, urinary incontinence, overactive bladder, emesis, cognitive disorders, anxiety, depression, sleeping disorders, eating disorders, movement disorders, glaucoma, psoriasis, multiple sclerosis, cerebrovascular disorders, brain injury, gastrointestinal disorders, hypertension, or cardiovascular disease
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• Page/Page column 15

  (2010/05/13)
• 

• COMPOUNDS
• The present invention features compounds of Formula (I) and (Ia), pharmaceutical compositions and use in the treatment of viral disease:
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• Page/Page column 39

  (2010/08/08)
• 

• COMPOUNDS FOR THE TREATMENT OF INFLAMMATORY DISORDERS
• This invention relates to compounds of the Formula (I): (Chemical formula should be inserted here as it appears on abstract in paper form) (I) or a pharmaceutically acceptable salt, solvate or isomer thereof, which can be useful for the treatment of diseases or conditions mediated by MMPs, ADAMs, TACE, aggrecanase, TNF- or combinations thereof.
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• Page/Page column 124

  (2010/06/11)
• 

• Bicyclic Benzimidazole Compounds and Their Use as Metabotropic Glutamate Receptor Potentiators
• Compounds of Formula I: wherein A, B, D, L, R1, R2, R3, R4, m, and n are as defined for Formula I in the description. The invention also relates to processes for the preparation of the compounds and to new intermediates employed in the preparation, pharmaceutical compositions containing the compounds, and to the use of the compounds in therapy.
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• Page/Page column 65-66

  (2009/08/14)
• 

• Preparation of a spiroisoxazolinopiperidinylbenzamide-based scaffold
• A route to spiroisoxazolinopiperidinylbenzamides has been developed. N-Boc-4-piperidone underwent a Wittig olefination and Boc-deprotection followed by a nucleophilic substitution reaction with 4-fluoro-3-nitrobenzoic acid to yield the starting scaffold 3
• Milinkevich, Kristin A.,Kurth, Mark J.
• experimental part

  p. 3019 - 3023

  (2010/03/05)
• 

• Substituted Spiro Compounds and Their Use for Producing Pain-Relief Medicaments
• The present invention relates to substituted spiro compounds, to processes for preparing them, to medicaments comprising these compounds and to the use of these compounds for producing medicaments.
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• (2008/12/04)
• 

• HETEROCYCLIC DERIVATIVES AND THEIR USE AS MEDIATORS OF STEAROYL-COA DESATURASE
• Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (I): Formula (I) where x, y, G, J, L, M, V, W, R2, R3, R4, R5, R5a, R6, R6a, R7, R7a, R8 and R8a are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.
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• Page/Page column 50

  (2010/10/20)
• 

• ISOINDOLONE COMPOUNDS AND THEIR USE AS METABOTROPIC GLUTAMATE RECEPTOR POTENTIATORS
• The present invention is directed to compounds of formula (I), wherein R1 is a ring and n is a number from 1 to 8. The invention also relates to use of the compounds in therapy as metabotropic glutamate receptor modulators, particularly in neurological and psychiatric disorders.
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• Page/Page column 101-102

  (2008/06/13)
• 

• Cytokine inhibitors
• Disclosed are compounds of formula (I) which inhibit production of cytokines involved in inflammatory processes and are thus useful for treating diseases and pathological conditions involving inflammation such as chronic inflammatory disease. Also disclos
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• Page/Page column 33-34

  (2008/06/13)
• 

• Improved Julia-Kocienski conditions for the methylenation of aldehydes and ketones
• The scope of the methylenation of aldehydes and ketones under optimized Julia-Kocienski conditions is broadened by using 1-tert-butyl-1H-tetrazol-5- ylmethyl sulfone. Two different Barbier-type procedures are applied with NaHMDS at -78 °C or Cs2CO3 at 70 °C. The latter conditions are also adapted for the preparation of 1,2-disubstituted olefins and intramolecular olefination reactions.
• Aissa, Christophe

• p. 360 - 363

  (2007/10/03)
•