- Synthesis of the γ-Secretase Modulator MK-8428
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The synthesis of the γ-secretase modulator MK-8428 (1) is described. The synthesis is highlighted by an enzyme-catalyzed reaction to access 3,4,5-trifluoro-(S)-phenylglycine, a 1-pot activation/displacement/deprotection sequence to introduce the aminooxy functionality and a dehydrative intramolecular cyclization under mild conditions to form the oxadiazine heterocycle of 1. In situ reaction monitoring was employed to understand the deleterious role of water during the formation of a methanesulfonate ester in the 1-pot activation/displacement/deprotection sequence.
- Miller, Steven P.,Morris, William J.,Orr, Robert K.,Eckert, Jeffrey,Milan, Jay,Maust, Mathew,Cowden, Cameron,Cui, Jian
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p. 2957 - 2964
(2017/03/23)
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- HETEROCYCLIC COMPOUND AND USE THEREOF
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The present invention provides a heterocycle derivative having a superior amyloid β production inhibitory activity and/or a superior γ-secretase modulation activity, and use thereof. A compound represented by the formula (I): wherein each symbol is as defined in the present specification, or a salt thereof.
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- Completely N1-selective palladium-catalyzed arylation of unsymmetric imidazoles: Application to the synthesis of nilotinib
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The completely N1-selective Pd-catalyzed arylation of unsymmetric imidazoles with aryl halides and triflates is described. This study showed that imidazoles have a strong inhibitory effect on the in situ formation of the catalytically active Pd(0)-ligand complex. The efficacy of the N-arylation reaction was improved drastically by the use of a preactivated solution of Pd2(dba)3 and L1. From these findings, it is clear that while imidazoles can prevent binding of L1 to Pd, once the ligand is bound to the metal, these heterocycles do not displace it. The utility of the present catalytic system was demonstrated by the regioselective synthesis of the clinically important tyrosine kinase inhibitor nilotinib.
- Ueda, Satoshi,Su, Mingjuan,Buchwald, Stephen L.
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supporting information; experimental part
p. 700 - 706
(2012/03/07)
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- NOVEL BENZONITRILE COMPOUNDS AND METHOD FOR PREPARING THE SAME
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By subjecting a compound represented by the following formula (II):wherein R represents a fluorine atom or a methoxy group and a compound represented by the following formula (III):to a coupling reaction, there can be prepared a compound represented by th
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- UREA TYPE CINNAMIDE DERIVATIVE
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Disclosed is a compound represented by the formula (I) below or a pharmacologically acceptable salt thereof. Also disclosed is a use of the compound or salt as a pharmaceutical product. (In the formula, Ar1 represents an imidazolyl group which may be substituted with a C1-6 alkyl group; Ar2 represents a phenyl group which may be substituted with a C1-6 alkoxy group; X1 represents a single bond; R1 and R2 respectively represent a C1-6 alkyl group or the like which may be substituted with a substituent such as a 5- to 14-membered aromatic heterocyclic group; and R3 represents a hydrogen atom or the like.)
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Page/Page column 49
(2009/02/10)
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- PROCESS FOR PRODUCTION OF CINNAMAMIDE DERIVATIVE
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A compound (8) represented by the formula: (8) wherein R1 represents a 6- to 14-membered aromatic hydrocarbon ring group which may have a substituent; and n represents 0 to 2, can be produced with good efficiency by reacting a compound (3) represented by the formula: (3) wherein R1 and n are as defined above; and Q represents a single bond or -CH(Y)- where Y represents a hydrogen atom or a C1-6 alkyl group] with 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehyde in the presence of a base.
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Page/Page column 50-51
(2008/12/07)
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- SALTS OF CYNNAMIDE COMPOUND OR SOLVATES THEREOF
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The invention provides crystals of dihydrochloride monohydrate of the compound of the following formula having an Aβ production inhibiting effect which crystals are characterized by exhibiting a diffraction peak at an angle of diffraction (2θ ± 0.2°) of 10.9° in powder X-ray diffractometry. Further, the invention also provides the compound in the form of various salts, crystal forms and amorphous forms which are suitable for the development of drugs.
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Page/Page column 15
(2008/12/07)
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- Morpholine type cinnamide compound
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The present invention relates to a compound represented by the formula (I): or a pharmacologically acceptable salt thereof, wherein R1, R2, R3, and R4 are the same or different and each represent a hydrogen atom or a C1-6 alkyl group; X1 represents a C1-6 alkylene group that may be substituted; Xa represents a methoxy group or a fluorine atom; Xb represents an oxygen atom or a methylene group, provided that Xb is only an oxygen atom when Xa is a methoxy group; and Ar1 represents an aryl group, pyridinyl group, aryloxy group, or pyridinyloxy group that may have a substituent such as a halogen atom; and to use of the compound or salt as a pharmaceutical agent.
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Page/Page column 32
(2008/06/13)
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- Multi-cyclic cinnamide derivatives
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The present invention provides a compound represented by the formula (I): or a pharmacologically acceptable salt thereof, wherein Ar1 represents an imidazolyl group that may be substituted with a C1-6 alkyl group, or the like, Ar2 represents a phenyl group that may be substituted with a C1-6 alkoxy group, or the like, X1 represents a double bond or the like, and Het represents an imidazolyl group that may be substituted with a C1-6 alkyl group, or the like, which is effective as a therapeutic or prophylactic agent for a disease caused by Aβ.
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Page/Page column 62-63
(2010/11/28)
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- Cinnamide compound
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The present invention relates to a compound represented by Formula (I): (wherein Ar1 represents an imidazolyl group which may be substituted with 1 to 3 substituents; Ar2 represents a pyridinyl group, a pyrimidinyl group, or a phenyl group which may be substituted with 1 to 3 substituents; X1 represents (1) —C≡C— or (2) a double bond etc. which may be substituted; R1 and R2 represent, for example, a C1-6 alkyl group or C3-8 cycloalkyl group which may be substituted) or a pharmacologically acceptable salt thereof and to the use thereof as pharmaceutical agents. The object of the present invention is to find a therapeutic or preventive agent for diseases caused by Aβ. According to the present invention, a therapeutic or preventive agents for diseases caused by Aβ can be provided.
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