- Design, synthesis, and biological evaluation of novel dual PPARα/δ agonists for the treatment of T2DM
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Dual PPARα/δ agonists have been considered as potential therapeutics for the treatment of type 2 diabetes mellitus. After comprehensive structure–activity relationship study based on GFT505, a novel dual PPARα/δ agonist compound 6 was identified with highly activities on PPARα/δ and higher selectivity against PPARγ than that of GFT505. The modeling study revealed that compound 6 binds well to the binding pockets of PPARα and PPARδ, which formed multiple hydrogen bonds with key residues related to the activation of PPARα and PPARδ. Moreover, oral glucose tolerance test exhibited that compound 6 exerts dose-dependent anti-diabetic effects in ob/ob mice and reveals similar potency to that of GFT505, the most advanced candidate in this field. These findings suggested that compound 6 is a promising candidate for further researches, and the extended chemical space might help us to explore better PPARα/δ agonist.
- Deng, Liming,Hu, Lijun,Li, Zheng,Ren, Qiang,Wang, Xuekun,Xie, Rongrong,Zhou, Zongtao
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- Preparation method of Deracoxib
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The invention discloses a preparation method of Deracoxib, and belongs to the field of Deracoxib preparation. The preparation method of Deracoxib disclosed by the invention comprises the following steps: (1) taking methane chloride as a reaction solvent, and reacting 2-fluoroanisole with acetylchloride under the effect of acid so as to obtain 3-fluoro-4-methoxyacetophenone; (2) taking methane chloride as a reaction solvent, and reacting 3-fluoro-4-methoxyacetophenone with ethyl difluoroacetate under the effect of alkaline so as to obtain 4,4-difluoro-1-(3-fluoro-4-methoxyphenyl)-1,3-butanedione; and (3) under the existence of an ethyl alcohol solvent, reacting 4,4-difluoro-1-(3-fluoro-4-methoxyphenyl)-1,3-butanedione with para-sulfamine phenylhydrazine or salt thereof so as to obtain Deracoxib. According to the preparation method of Deracoxib disclosed by the invention, dichloromethane is used as a solvent, the toxicity of the solvent is low, the cost of the solvent is lower than thatof methyl tertiary butyl ether, and the production cost is obviously reduced on the premise of guaranteeing the yield.
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Paragraph 0041; 0053; 0054
(2018/03/26)
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- Fries rearrangement: Scalable synthesis of key fluoro building blocks 3-fluoro-4-methoxybenzoyl chloride and 1,2-diethoxy-3-fluorobenzene
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Lewis acid catalyzed Fries rearrangement of 2-fluorophenyl acetate (3) was performed on kg scale. The ortho 5 and para 4 isomers obtained were separated in an industrially feasible way. Compound 4 was then converted into fluorinated building block 3-fluoro-4-methoxybenzoyl chloride (1) while compound 5 was converted into 1,2-diethoxy-3-fluorobenzene (2) in high yields.
- Yerande, Swapnil G.,Shendage, Deepak M.,Wakchaure, Prasad B.,Phadtare, Ganesh R.,Bhoite, Madhavrao Y.,Gangopadhyay, Ashok Kumar,Nagarajan, Kuppuswamy,Rupp, Richard Helmut
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p. 2426 - 2429
(2014/05/06)
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- Transformations of organic molecules with F-TEDA-BF4 in ionic liquid media
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The transformations of organic molecules with F-TEDA-BF4 (1) were investigated in the hydrophilic ionic liquid (IL) 1-butyl-3-methyl- imidazolium tetrafluoroborate ([bmim][BF4], 2) and the hydrophobic IL 1-butyl-3-methyl-imidazolium hexafluorophosphate ([bmim][PF6], 3). The range of substrates included alkyl substituted phenols 4a-c, 9, 13, 1,1-diphenylethene (15), alkyl aryl ketones 19-22, aldehydes 23-25 and methoxy-substituted benzene derivatives 26-30. The evaluation of the outcome of reactions performed in IL media in comparison to those of the corresponding reactions in conventional organic solvents revealed that the transformations in IL are less efficient and selective. The effect of the presence of a nucleophile (MeOH, H2O, MeCN) on the course of reaction was also studied.
- Pavlinac, Jasminka,Zupan, Marko,Stavber, Stojan
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experimental part
p. 2394 - 2409
(2009/12/03)
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- PHARMACEUTICAL COMPOUNDS
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The invention provides a compound of the formula (I) or a salt, solvate, tautomer or N-oxide thereof; wherein A is a saturated hydrocarbon linker group; E is a monocyclic or bicyclic carbocyclic or heterocyclic group; L1 is a bond or a linker selected from C1-C4 alkenylene, C1-C4 alkynylene, -CONR’, -NR’CO, -S, -C(O)-, -C(NR11)-, -C(S)-, -N(R11)2, C(=CHR11), -SO- and -SO2-; or L1 together with t R16 forms and 8-12 membered fused bicyclic heteroaryl ring system; L3 is a bond or a linker selected from CONH and HNCO; provided that L1 and L3 cannot both be linkers simultaneously; and provided also that L1 and L3 cannot both be a bond simultaneously; R16 is an optionally substituted 5- to 12-membered monocyclic or bicyclic carbocyclic or heterocyclic ring; L2 is absent or is a linker selected from C]-C4 alkylene, Ci-C4 alkenylene, Ci-C4 alkynylene, -CONR’-, -NR’CO-, -O-, -S-, -C(O)-, C(=CHR11), C(S)-, -N(R11)2, C3-4 cycloalkanediyl, -SO- and -SO2-; R17 is absent or is C1-6 alkyl or an optionally substituted 5 to 12 membered carbocyclic or heterocyclic ring; provided that when R17 is absent, then L2 is also absent; and R2, R3, R4, R5, R11 and R’ are as defined in the claims.
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Page/Page column 123
(2010/11/25)
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- Treatment of inflammation and inflammation-related disorders with a combination of a cyclooxygenase-2 inhibitors and a leukotriene B4 receptor antagonist
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Combinations of a cyclooxygenase-2 inhibitor and a leukotriene B4receptor antagonist are described for treatment of inflammation and inflammation-related disorders.
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Page column 28
(2010/01/30)
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- Immunosuppressive effects of administration of a cyclooxygenase-2 inhibitor and a 5-lipoxygenase inhibitor
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A method to suppress immune, acute or delayed-type hypersensitivity by treatment with a combination of a therapeutically-effective amount of a 5-lipoxygenase inhibitor and a cyclooxygenase-2 inhibitor is reported. The method may be used, for example, to suppress the immune response associated with organ transplantation, graft versus host disease, and conditions with underlying autoimmune or inflammatory reactivities or responses.
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- Immunosuppressive effects of administration of a cyclooxygenase-2 inhibitor and a leukotriene A4 hydrolase inhibitor
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Treatment with a cyclooxygenase-2 inhibitor and a leukotriene A4hydrolase inhibitor is described as being useful in reducing recipient rejection of transplanted organs and for treatment of autoimmnune diseases.
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- IMMUNOSUPPRESSIVE EFFECTS OF ADMINISTRATION OF A CYCLOOXYGENASE-2 INHIBITOR AND A LEUKOTRIENE B4 RECEPTOR ANTAGONIST
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Treatment with a cyclooxygenase-2 inhibitor and a leukotriene B 4 receptor antagonist is described as being useful in reducing recipient rejection of transplanted organs and for treatment of autoimmune diseases.
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- Solvent directing immediate fluorination of aromatic ketones using 1- fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate)
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Reactions of aryl alkyl ketones with 1-fluoro-4-hydroxy1,4- diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Accufluor(TM) NFTh) in methanol result in selective and almost quantitative formation of the corresponding α-fluoroketones, while in acetonitrile exclusive fluorofunctionalisation of the activated aromatic ring take place.
- Stavber, Stojan,Jereb, Marjan,Zupan, Marko
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p. 1323 - 1324
(2007/10/03)
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- Treatment of inflammation and inflammation-related disorders with a combination of a cyclooxygenase-2 inhibitor and a 5-lipoxygenase inhibitor
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Combinations of a cyclooxygenase-2 inhibitor and a 5-lipoxygenase inhibitor are described for treatment of inflammation and inflammation-related disorders.
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- Treatment of inflammation and inflammation-related disorders with a combination of a cyclooxygenase-2 inhibitor and a leukotriene A4 hydrolase inhibitor
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Combinations of a cyclooxygenase-2 inhibitor and a leukotriene A4 hydrolase inhibitor are described for treatment of inflammation and inflammation-related disorders.
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- Substituted pyrazolyl benzenesulfonamides for use in veterinary therapies
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A method of using pyrazolyl benzenesulfonamide compounds in treating inflammation and inflammation-related disorders in companion animals is disclosed.
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- Substituted pyrazolyl benzenesulfonamides for the treatment of inflammation
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A class of pyrazolyl benzenesulfonamide compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula II: STR1 or a pharmaceutically-acceptable salt thereof.
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- TREATMENT OF INFLAMMATION AND INFLAMMATION-RELATED DISORDERS WITH A COMBINATION OF A CYCLOOXYGENASE-2 INHIBITOR AND A LEUKOTRIENE A4 HYDROLASE INHIBITOR
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Combinations of a cyclooxygenase-2 inhibitor and a leukotriene A4 hydrolase inhibitor are described for treatment of inflammation and inflammation-related disorders
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- High yield direct fluorofunctionalisation of ketones using accufluor - NFTh fluorinating reagent
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Direct regioselective conversion of a variety of cyclic and acyclic ketones to α-fluoroketones was achieved in high to excellent yield using 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2,2,2]octane bis(tetrafluoroborate) [Accufluor - NFTh] in acetonitrile solution. Copyright
- Stavber, Stojan,Zupan, Marko
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p. 3591 - 3594
(2007/10/03)
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- Substituted pyrazolyl benzenesulfonamide for the treatment of inflammation
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A class of pyrazolyl benzenesulfonamide compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula I: STR1
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- Ferroelectric liquid crystal compounds containing halogenated cores and chiral haloalkoxy tail units
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The subject application discloses chiral nonracemic compositions of the general formula: STR1 wherein R1 is an achiral tail of two to sixteen carbons; Ar is an achiral FLC core of at least two rings; * denotes a chiral or potentially chiral carbon; Q and D are H or a methyl group, provided that q and D are not both methyl; X and Z are halides and Y is H or a halide; and R2 is one to ten carbon atoms. The --O--C*HQ--C*DX--C*HY-- segment comprises the chiral proximal segment of the chiral tail. Z can be an ortho halide alone, or ortho and meta halides on adjacent carbons on the aromatic ring of the core adjacent to the proximal segment. R2 is the distal segment of the chiral tail. The proximal segment is selected from the diastereomers and enantiomers: STR2
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- Ferroelectric liquid crystal compositions containing halogenated cores and chiral halogenated cores and chiral haloalkoxy tail units
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The subject application discloses chiral nonracemic compositions of the general formula: STR1 wherein R1 is an achiral tail of two to sixteen carbons; Ar is an achiral FLC core of at least two rings; * denotes a chiral or potentially chiral carbon; Q is H or a methyl group; X and Z are halides and Y is H or a halide; and R2 is one to ten carbon atoms. The --O--C*HQ--C*HX--C*HY-- segment comprises the chiral proximal segment of the chiral tail. Z can be an ortho halide alone, or ortho and meta halides on adjacent carbons on the aromatic ring of the core adjacent to the proximal segment. R2 is the distal segment of the chiral tail. The proximal segment is selected from the diastereomers and enantiomers: ______________________________________2S-halo 2R-halo1S-methyl-2S-halo 1R-methyl-2R-halo1S-methyl-2R-halo 1R-methyl-2S-halo2S,3S-dihalo 2R,3R-dihalo2R,3S-dihalo 2S,3R-dihalo1R-methyl-2R,3R-dihalo 1S-methyl-2S,3S-dihalo1R-methyl-2R,3S-dihalo 1S-methyl-2S,3R-dihalo1R-methyl-2R,3S-dihalo 1S-methyl-2S,3R-dihalo1R-methyl-2R,3S-dihalo 1S-methyl-2S,3R-dihalo______________________________________
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- Novel halogen-containing ester compounds, and their intermediates, and method of producing the same as well as liquid crystal compositions containing the same and light switching elements
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This invention provides a novel halogen-containing ester compound represented by the following general formula (I): STR1 (wherein R is an alkyl group, A is selected from a single bond, --O--, --COO-- and --CO--, both of X and Y are halogen atoms or either one of X and Y is a halogen atom and the other is a hydrogen atom, each of m and n is 0 or 1, m+n=0 or 1, each of k and l is an integer of 1 or more, provide kl), a liquid crystal composition and a light switching element each containing the above compound as well as a novel fluorophenol compound represented by the following general formula (II): STR2 (wherein each of k and l is an integer of 1 or more, provided kl) as an intermediate for the synthesis of the above ester compound and a method of producing the same.
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- Triazine derivatives, a process for preparing the derivatives, and herbicides containing the derivatives as the effective component
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A triazine derivative represented by the general formula: STR1 wherein R1 and R2 are each an alkyl group having 1 to 4 carbon atoms, and X1 and X2 are each a halogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxyl group having 1 to 4 carbon atoms, or an alkylthio group having 1 to 4 carbon atoms. This invention also provides a process for efficiently preparing said triazine derivative and a herbicide containing said triazine derivative as effective component.
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