- SELECTIVE FOXO INHIBITORS FOR TREATMENT OF DIABETES AND OTHER DISORDERS RELATED TO IMPAIRED PANCREATIC FUNCTION
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Various embodiments relate to a compound (represented by Formula I) or a pharmaceutically acceptable salt or tautomer thereof. The compound may selectively inhibit a Forkhead Box O1 (FOXO1) transcription factor. Various embodiments relate to methods compr
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Paragraph 0135-0136; 0148-0149
(2020/10/18)
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- A Tandem Ring Opening/Closure Reaction in A BF3-Mediated Rearrangement of Spirooxindoles
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Treatment of the readily accessible spiro-cyclohexadienones from the PhI(OCOCF3)2-mediated spiro-cyclization of N-substituted benzanilides, with BF3?Et2O initiates a tandem ring opening/closure reaction leading to the formation of the biologically interesting 8-hydroxy-phenanthridin-6(5H)-one compounds. This unique rearrangement pattern involves the ‘migration’ of the electron-deficient N-methyl carbamoyl moiety rather than the electron-rich aryl group as observed and reported previously in all other similar transformations. (Figure presented.).
- Guo, Xuliang,Xing, Qingyu,Lei, Kunhua,Zhang-Negrerie, Daisy,Du, Yunfei,Zhao, Kang
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supporting information
p. 4393 - 4398
(2017/10/23)
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- Polymerizable compound, the photopolymerizable composition and the optical anisotropic
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PURPOSE: A polymerizable naphthoic acid phenyl compound is provided to have high reflection anisotropy and high storage stability and high orientation. CONSTITUTION: A polymerizable naphthoic acid phenyl compound is represented by chemical formula 1. In chemical formula 1, one of M^1-M4 is a fluorine atom, a chlorine atom, a cyno group, a nitro group, a C1-7 alkyl group, a C1-7 alkoxy group, or a C1-7 alkanoyl group. L^1-L^6 is hydrogen, fluorine or chloride. A polymerizable liquid composition comprises the polymerizable compound. The polymer is obtained by polymerizing the polymerizable liquid compositions. An optical anisotropic object uses the polymer.
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Paragraph 0148; 0149
(2017/07/26)
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- Polymerizable liquid crystal compound
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PROBLEM TO BE SOLVED: To provide: a polymerizable compound which exhibits high storage stability, high cholesteric alignment and short pitch when a polymerizable liquid crystal compound is configured using the polymerizable compound; a polymerizable liquid crystal composition containing the polymerizable compound; a polymer obtained by polymerizing the polymerizable liquid crystal composition; and an optical anisotropic substance obtained by using the polymer.SOLUTION: The polymerizable compound represented by general formula (I) is provided. Further, there are provided the polymerizable liquid crystal composition containing the polymerizable compound, the polymer obtained by polymerizing the polymerizable liquid crystal composition, and the optical anisotropic substance obtained by using the polymer.
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Paragraph 0142; 0143
(2016/10/10)
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- Chalcone derivatives and drugs containing the same
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PCT No. PCT/JP97/01652 Sec. 371 Date Nov. 17, 1998 Sec. 102(e) Date Nov. 17, 1998 PCT Filed May 16, 1997 PCT Pub. No. WO97/44306 PCT Pub. Date Nov. 27, 1997This invention relates to chalcone derivatives represented by the following formula (1): wherein A represents a phenyl group, a quinolyl group or the like, W represents a vinylene group or the like, and R1 to R5 each independently represent a carboxyl, cyano, alkyloxycarbonyl or like group, or salts of the chalcone derivatives, and also to drugs containing them as effective ingredients. These compounds have excellent cys-LT receptor antagonism, and are useful as antiallergic agents or the like.
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- Synthesis and structure-activity relationships of carboxylated chalcones: A novel series of CysLT1 (LTD4) receptor antagonists
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The synthesis and CysLT1 antagonistic activities of a new series of 2- , 3-, and 4-(2-quinolinylmethoxy)- and 3- and 4-[2-(2-quinolinyl)ethenyl]- substituted, 2'-, 3'-, 4'-, or 5'-carboxylated chalcones are described. Structure-activity relationship studies indicate a preference for the presence of a negatively charged (acidic) moiety, although in some cases nitrile or ester analogues also exhibit moderate activity. The quinoline moiety may be substituted at either the 3- or the 4-position. Replacement of this heterocycle by other aromatic groups results in compounds with comparable affinities [2-(7-chloroquinoline), 1-(1-methyl-2-benzimidazole), or 1-(2-benzothiazole)] or substantially lower activities [1-(1- ethoxyethyl)-2-benzimidazole, 2-naphthyl, or phenyl]. The quinoline and chalcone moieties may be connected by either an ethenyl or a methoxy spacer. The acidic moiety at the chalcone B ring may be attached to the 2'-, 3'-, 4'- , or 5'-position, for both the 3- and 4-substituted chalcones. There are no general patterns to specify which substitution positions gave the most potent compounds. The series contains several potent CysLT1 receptor antagonists, with K(D) values approaching the nanomolar range, as measured by the displacement of [3H]LTD4 from guinea pig lung membranes. Antagonism of LTD4-induced contraction of guinea pig ileum, the inhibition of antigen- induced contraction of guinea pig trachea in vitro, and the inhibition of LTD4-induced increase of vascular permeability in vivo are determined for chalcones with high CysLT1 receptor affinities (K(D) values below 0.1μM). 2'-Hydroxy-4-(2-quinolinylmethoxy)-5'-(5-tetrazolyl)chalcone (14, VUF 4819) showed good activity in both in vitro and in vivo assays and has been selected for further evaluation.
- Zwaagstra, Mari?l E.,Timmerman, Hendrik,Tamura, Masahiro,Tohma, Tsutomu,Wada, Yasushi,Onogi, Kazuhiro,Zhang, Ming-Qiang
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p. 1075 - 1089
(2007/10/03)
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- Polyelectrolyte-Catalyzed Acetyl Transfer Reactions. Structure-Reactivity Relationships in the Aminolysis of Phenyl Acetates by Poly(ethyleneimine) and Glycylglycine.
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The aminolysis of a wide series of substituted phenyl acetates by poly(ethyleneimine) (PEI) is studied.Saturation kinetics are observed and the ester-polyamine association equilibrium constants, as well as the rates of decomposition of the resulting intracomplexes, are determined.Unlike the association constants, the rate constants for the reaction of the intracomplex are found to depend on the acidity of the leaving groups.Two Broensted-type relationships are found for anionic and neutral esters having different intercepts but proximate slopes -0.73 and -0.77 respectively, which decrease to lower values with very reactive phenyl acetates.Only one broken Broensted relationship is found for the bimolecular aminolysis by glycylglycine.The results are consistent with the formation of a tetrahedral intermediate by the amino groups of PEI, with a change in the rate-determining step for very reactive esters from the breakdown to the formation of the tetrahedral intermediate.The higher reactivity of PEI, which is more relevant with substrates containing anionic groups, is principally ascribed to the electrostatic polyelectrolyte-substrate binding.A minor role is played by the increase in the acidity of the conjugate acid of the leaving group, i.e. of its leaving ability, caused by the association of the ester with PEI: values of effective molarity in the range of 10 to 15 mol cm-3 are found.
- Arcelli, Antonio,Concilio, Carlo
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p. 201 - 226
(2007/10/02)
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- Bicyclo [3.1.0] hexyl-substituted ethylamino carbonyl phenoxy cardiovascular agents
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1-Alkylamino-3-(3- or 4-[2-(endobicyclo[3.1.0]-hex-6-yl)ethylaminocarbonyl]-1-phenoxy)-2-propanol and substituted derivatives thereof and methods for preparing such compounds are disclosed. 5-(3- Or 4-[2-(endobicyclo[3.1.0]hex-6-yl)ethylaminocarbonyl]-phenoxy)methyl 3-alkyl-2-optionally substituted oxazolidine and derivatives thereof, and methods for preparing such compounds are also disclosed. These compounds exhibit cardiovascular acitivity and are useful in the treatment of abnormal heart condition as well as hypertension in mammals. The former compounds are prepared by treatment of the corresponding 1,2-epoxy-3-(3- or 4-[2-(endobicyclo[3.1.0]hex-6-yl)-ethylaminocarbonyl]phenoxy)propane with the desired alkylamine or by base or acid hydrolysis of the corresponding 5-(3- or 4-[2-(endobicyclo[3.1.0]hex-6-yl)-ethylaminocarbonyl)-3-alkyl oxazolidine. The latter compounds are prepared from the corresponding 1-alkylamino-3-(3- or 4-[2-(endobicyclo[3.1.0]hex-6-yl)ethylaminocarbonyl]-1-phenoxy)-2-propanol by treatment with an aldehyde having the desired optional substituent or by treating a 3- or 4-(2-(endobicyclo[3.1.0]hex-6-yl)ethylaminocarbonyl)-optionally substituted phenol with a 5-tosyloxy or mesyloxymethyl 3-alkyl)-methyloxazolidine-2-optionally substituted oxazolidine.
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