- Synthesis of novel EP4 antagonists and their use in cancer and inflammation
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The present invention relates to a compound capable of effectively antagonizing EP4, which is a compound represented by formula I, or a tautomer, a stereoisomer, a hydrate, a solvate, a pharmaceutically-acceptable salt or a prodrug of the compound represented by formula I. R1 is selected from -CH3, -CHF2, and -CF3; R2 is selected from C2-C6 alkyl, C3-C6 cycloalkyl, halogenated C2-C6 alkyl, and halogenated C3-C6 cycloalkyl; R3 is selected from hydrogen, halogen, C1-C2 alkyl, and fluorinated C1-C2 alkyl; R4 is selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkyl, and halogenated C1-C6 alkoxy.
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Paragraph 0834; 0839-0843
(2021/09/08)
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- Nickel-Catalyzed Inter- and Intramolecular Aryl Thioether Metathesis by Reversible Arylation
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A nickel-catalyzed aryl thioether metathesis has been developed to access high-value thioethers. 1,2-Bis(dicyclohexylphosphino)ethane (dcype) is essential to promote this highly functional-group-tolerant reaction. Furthermore, synthetically challenging macrocycles could be obtained in good yield in an unusual example of ring-closing metathesis that does not involve alkene bonds. In-depth organometallic studies support a reversible Ni0/NiII pathway to product formation. Overall, this work not only provides a more sustainable alternative to previous catalytic systems based on Pd, but also presents new applications and mechanistic information that are highly relevant to the further development and application of unusual single-bond metathesis reactions.
- Delcaillau, Tristan,Bismuto, Alessandro,Lian, Zhong,Morandi, Bill
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supporting information
p. 2110 - 2114
(2019/12/24)
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- ADDITIVE FOR IMPARTING ULTRAVIOLET ABSORBENCY AND/OR HIGH REFRACTIVE INDEX TO MATRIX, AND RESIN MEMBER USING SAME
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Provided is an additive for imparting ultraviolet absorbency, or an additive for imparting a high refractive index, which has satisfactory compatibility with a resin serving as a matrix and can maintain high transparency even if added in high concentrations. Also provided is an additive with which the function of imparting both ultraviolet absorbency and a high refractive index can be realized by means of one kind of additive. This additive is represented by the following Formula (I): wherein at least one of R1a to R9a is a monovalent sulfur-containing group represented by the following Formula (i-1) or Formula (i-2): wherein R10a to R12a each represent a divalent hydrocarbon group or the like; and R13a represents a monovalent hydrocarbon group or the like.
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Paragraph 0362; 0363
(2017/08/26)
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- Metal-Free Approach to Biaryls from Phenols and Aryl Sulfoxides by Temporarily Sulfur-Tethered Regioselective C-H/C-H Coupling
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We have developed metal-free regiocontrolled dehydrogenative C-H/C-H cross-coupling of aryl sulfoxides with phenols by means of trifluoroacetic anhydride. Because the reaction would proceed through an interrupted Pummerer reaction followed by sulfonium-tethered [3,3]-sigmatropic rearrangement, the C-H/C-H coupling takes place exclusively between the ortho positions of both substrates. Various functional groups including carbonyl, halo, siloxy, and even boryl moieties are compatible. The biaryl products naturally possess hydroxy and sulfanyl groups, which allows the products to be useful synthetic intermediates, as evidenced by the syntheses of π-expanded heteroarenes such as unprecedented 7,12-dioxa[8]helicene.
- Yanagi, Tomoyuki,Otsuka, Shinya,Kasuga, Yuko,Fujimoto, Keisuke,Murakami, Kei,Nogi, Keisuke,Yorimitsu, Hideki,Osuka, Atsuhiro
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supporting information
p. 14582 - 14585
(2016/11/18)
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- Synthetic strategies to 2′-hydroxy-4′- methylsulfonylacetophenone, a key compound for the preparation of flavonoid derivatives
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Different strategies for the synthesis of 2′-hydroxy-4′- methylsulfonylacetophenone are reported in the present paper. This compound is considered as a key synthon for the synthesis of new flavonoid derivatives designed as potential cyclooxygenase-2 inhibitors. The retrosynthetic approach via 3′-methylsulfonylacetophenone, which included three synthetic pathways, did not allow us to obtain the expected compound. However, a synthesis from 3-mercaptophenol led to the desired acetophenone in three steps: thiophenol methylation, Friedel-Crafts acetylation and oxidation of the sulphide to the corresponding sulfone. The desired compound, 2′-hydroxy-4′- methylsulfonylacetophenone, will be used as a synthon for the preparation of novel flavonoid derivatives, such as 2′-hydroxychalcones, flavanones, flavones, and flavonols.
- Gueye, Rokhaya,Pouget, Christelle,Champavier, Yves,Buxeraud, Jacques,Duroux, Jean-Luc,Fagnère, Catherine
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p. 443 - 449
(2014/05/06)
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- Continuous-flow synthesis of functionalized phenols by aerobic oxidation of grignard reagents
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Phenols are important compounds in chemical industry. An economical and green approach to phenol preparation by the direct oxidation of aryl Grignard reagents using compressed air in continuous gas-liquid segmented flow systems is described. The process tolerates a broad range of functional groups, including oxidation-sensitive functionalities such as alkenes, amines, and thioethers. By integrating a benzyne-mediated in-line generation of arylmagnesium intermediates with the aerobic oxidation, a facile three-step, one-flow process, capable of preparing 2-functionalized phenols in a modular fashion, is established. Putting on airs: Aerobic oxidation of (hetero)aryl Grignard reagents using compressed air proceeds with a gas-liquid continuous-flow system, thus enabling preparation of fucntionalized phenols. By integrating an in-line generation of ArMgBr intermediates with the aerobic oxidation, ortho-functionalized phenols can be assembled. The method demonstrates good functional-group (FG) compatibility, mild reaction conditions, and short reaction times.
- He, Zhi,Jamison, Timothy F.
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supporting information
p. 3353 - 3357
(2014/04/03)
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- Practical imidazole-based phosphine ligands for selective palladium-catalyzed hydroxylation of aryl halides
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(Chemical Equation Presented) The phenol countdown: Novel imidazole-based phosphine ligands are synthesized on scales up to 100 g by a convenient lithiation-phosphorylation method. The phosphines are stable towards air and moisture and are successfully applied as ligands in the palladium-catalyzed selective hydroxylation of aryl halides (see scheme, dba=dibenzylideneacetone).
- Schulz, Thomas,Torborg, Christian,Schaeffner, Benjamin,Huang, Jun,Zapf, Alexander,Kadyrov, Renat,Boerner, Armin,Beller, Matthias
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supporting information; experimental part
p. 918 - 921
(2009/05/15)
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- Nicotinamide derivatives useful as PDE4 inhibitors
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This invention relates to nicotinamide derivatives of general formula (I): in which R1, R2 and R3 have the meanings defined herein, and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of such derivatives.
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- Nicotinamide derivatives useful as PDE4 inhibitors
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This invention relates to nicotinamide derivatives of general formula (I): in which X, Y, n, Z, L and R have the meanings defined herein, and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of such derivatives.
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- NICOTINAMIDE DERIVATIVES USEFUL AS PDE4 INHIBITORS
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This invention relates to nicotinamide derivatives of formula (I) and to pharmaceutical compositions containing, and the uses of such derivatives as PDE4 inhibitors wherein R7 is attached to the 3-or 4-position of the phenyl ring and is S(O)pR8, R8 is (C1-C4)alkyl optionally substituted by (C3-C6)cycloalkyl; m is 0 or 1; L is a (C3-C8)carbocyclic non-aromatic ring; and the remaining variables are as defined in the claims.
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Page/Page column 61-62
(2010/02/10)
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- 6-(Nonsubstituted or substituted) phenoxy picolinic acids, process of preparing the same, and agricultural/horticultural germicides containing the same
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An agricultural or horticultural fungicide containing 6-(unsubstituted or substituted) phenoxy picolinic acid represented by the general formula (I), as an effective ingredient. wherein R is a halogen atom, a C1to C4alkyl group, a C1to C4haloalkyl group, a C1to C4alkoxy group, a C1to C4haloalkoxy group, a C1to C4alkylthio group, a C1to C4alkylamino group, a di(C1to C4alkyl)amino group or a C7to C8aralkyl(C1to C4alkyl)amino group; n2is an integer of 0 to 3; Y is a C1to C4alkyl group, a C1to C4haloalkyl group, a C1to C4alkoxy group, a C1to C4haloalkoxy group, a C1to C4alkylthio group, a C1to C4haloalkylthio group or a halogen atom; and m is an integer of 0 to 5, and when m and n2are not less than 2, Rs and Ys may be the same or different, respectively. The compound is useful as an effective ingredient of agricultural or horticultural fungicides.
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- Competing reactions leading to propene loss from the molecular ions of aryl n-propyl ethers
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The mechanisms of the elimination of a propene molecule from the molecular ions of a series of 3- and 4-substituted aryl n-propyl ethers (YC6H4OC3H7, Y = H, CH3 CF3, NO2, CH3S and CH3O) were examined with the use of deuterium labelling and tandem mass spectrometry. Propene loss dominates in the ion-source reactions and is the exclusive process observed for the metastable molecular ions of most of the aryl n-propyl ethers. This process is concluded to proceed by two distinct pathways on the basis of the relative importances of the losses of C3H4D2 and C3H5D from the ionized ethers labelled with two deuterium atoms at the β-position of the n-propyl group in combination with the results of an analysis of the product ion structures. One pathway involves intermediate formation of an ion-neutral complex composed of a YC6H4O. radical and a +CH(CH3)2 carbenium ion. This complex reacts further by proton transfer prior to dissociation with the formation of product ions, which have the same structure as the corresponding ionized and substituted phenols, YC6H4OH+.. The second pathway involves a reversible 1,5-H shift from the β-position of the propyl group to the 2- or 6-position of the aromatic ring with the formation of a distonic ion, which expels propene to afford the molecular ion of a substituted cyclohexa-2,4-dienone species. The first pathway prevails for most of the ionized ethers with the exception of the molecular ions of the 3-methoxy- and 3-methylthio-substituted ethers, which expel propene largely by we second pathway. In addition, the 1,5-H shift-initiated propene loss is particularly pronounced:For the metastable molecular ions of these latter two ethers, suggesting that this reaction is associated with a lower critical energy than the reaction involving formation of an ion-neutral complex.
- Matimba, Henri E. K.,Ingemann, Steen,Nibbering, Nico M. M.
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p. 609 - 622
(2007/10/03)
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- SELECTIVE CLEAVAGE OF THE CARBON-SULPHUR AND CARBON-OXYGEN BONDS IN METHOXYTHIOANISOLES
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Selective cleavage of thioether or ether functions in methoxythioanisoles in hexamehtylphosphoramide (HMPA) with sodium gives methoxythiophenols by cleavage of the carbon-sulphur bond.Reactions with sodium isopropanethiolate give instead the thiomethoxyphenols by dealkylation of the methoxy function.When the methoxythioanisoles were treated first with sodium isopropanethiolate and then with sodium complete dealkylation was achieved with formation of mercaptophenols.The present methods have considerable advantages over existing procedures for the synthesis of methoxythiophenols, thiomethoxyphenols and mercaptophenols.The mechanistic implications of the reactions investigated are also discussed.
- Testaferri, L.,Tiecco, M.,Tingoli, M.,Chianelli, D.,Maiolo, F.
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p. 2721 - 2724
(2007/10/02)
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- Cyclic meta-sulfonium-phenoxide zwitterions
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New, highly reactive, polymerizable compounds are described, corresponding to the formula STR1 wherein R is H or lower alkyl, Z is a linking entity which is a chemical bond, lower alkylene, lower alkylenedioxy, O or the like, m is an integer 2-3 and n is
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