- Crystalline inhibitor of 4-hydroxyphenylpyruvate dioxygenase, and a process of synthesis and crystallization thereof
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The present invention relates to an improved synthesis and crystallization process of the 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione, also known as nitisinone or NTBC.
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Page/Page column 7-8
(2017/10/28)
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- SUBSTITUTED BENZANILIDE COMPOUND OR SALTS THEREOF, AGRICULTURAL ANTIBACTERIAL AGENT CONTAINING THE COMPOUND AND USE METHOD THEREOF
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PROBLEM TO BE SOLVED: To provide a novel compound which is an antibacterial agent having low environmental toxicity and exhibiting not only effect on an agent-treated part, but also high effect on a part where unevenness of spraying occurs or a peripheral part which is not treated with an agent, such a leaf opening after agent treatments, from the point of view of labor saving. SOLUTION: There is provided a benzanilide compound represented by the formula (I) or salts thereof. (I), where R1 is a (C1 to C3)alkyl group, R2 is a halo(C1 to C3)alkyl group, R3 is a (C1 to C3)alkylcarbonyl group, R4 is Cl, Br or I, R5 is a halo(C1 to C3)alkyl group or a halo C1 alkoxy group. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT
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Paragraph 0102
(2018/03/30)
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- PHARMACEUTICAL COMPOSITION
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The present invention relates to oral pharmaceutical compositions comprising nitisinone, or a pharmaceutically acceptable salt thereof, their use in the treatment of tyrosinemia, such as Hereditary Tyrosinemia type-1 (HT-1), or alkaptonuria. The compositi
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Page/Page column 8; 9
(2015/07/16)
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- Identification of orally-bioavailable antagonists of the TRPV4 ion-channel
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Abstract Antagonists of the TRPV4 receptor were identified using a focused screen, followed by a limited optimization program. The leading compounds obtained from this exercise, RN-1665 23 and RN-9893 26, showed moderate oral bioavailability when dosed to
- Wei, Zhi-Liang,Nguyen, Margaret T.,O'Mahony, Donogh J.R.,Acevedo, Alejandra,Zipfel, Sheila,Zhang, Qingling,Liu, Luna,Dourado, Michelle,Chi, Candace,Yip, Victor,Defalco, Jeff,Gustafson, Amy,Emerling, Daniel E.,Kelly, Michael G.,Kincaid, John,Vincent, Fabien,Duncton, Matthew A.J.
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supporting information
p. 4011 - 4015
(2015/08/24)
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- Pyrazolone-quinazolone hybrids: A novel class of human 4-hydroxyphenylpyruvate dioxygenase inhibitors
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4-Hydroxyphenylpyruvate dioxygenase (HPPD), converting 4-hydroxyphenylpyruvate acid to homogentisate, is an important target for treating type I tyrosinemia and alkaptonuria due to its significant role in tyrosine catabolism. However, only one commercial drug, NTBC, also known as nitisinone, has been available for clinical use so far. Herein, we have elucidated the structure-based design of a series of pyrazolone-quinazolone hybrids that are novel potent human HPPD inhibitors through the successful integration of various techniques including computational simulations, organic synthesis, and biochemical characterization. Most of the new compounds displayed potent inhibitory activity against the recombinant human HPPD in nanomolar range. Compounds 3h and 3u were identified as the most potent candidates with Kivalues of around 10 nM against human HPPD, about three-fold more potent than NTBC. Molecular modeling indicated that the interaction between the pyrazolone ring and ferrous ion, and the hydrophobic interaction of quinazolone with its surrounding residues, such as Phe347 and Phe364, contributed greatly to the high potency of these inhibitors. Therefore, compounds 3h and 3u could be potentially useful for the treatment of type I tyrosinemia and other diseases with defects in tyrosine degradation.
- Xu, Yu-Ling,Lin, Hong-Yan,Cao, Run-Jie,Ming, Ze-Zhong,Yang, Wen-Chao,Yang, Guang-Fu
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p. 5194 - 5211
(2014/12/11)
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- CTGF EXPRESSION INHIBITOR
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A CTGF expression inhibitor comprising a compound of the formula I: a pharmaceutically acceptable salt or solvate thereof as an active ingredient, (wherein Y is hydroxy or a group of the formula: -NH-SO2-Y' (wherein Y' is optionally substituted
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Page/Page column 66
(2008/06/13)
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- 1H NMR, 13C NMR, and computational DFT studies of the structure of 2-acylcyclohexane-1,3-diones and their alkali metal salts in solution
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1H and 13C NMR spectra of 2-acyl-substituted cyclohexane-1,3-diones (acyl = formyl, 1; 2-nitrobenzoyl, 2; 2-nitro-4-trifluoromethylbenzoyl, 3) and lithium sodium and potassium salts of 1 have been measured. The compound 3, known as NTBC, is a life-saving medicine applied in tyrosinemia type I. The optimum molecular structures of the investigated objects in solutions have been found using the DFT method with B3LYP functional and 6-31G** and/or 6-311G(2d,p) basis set. The theoretical values of the NMR parameters of the investigated compounds have been calculated using GIAO DFT B3LYP/6-311G(2d,p) method. The theoretical data obtained for compounds 1-3 have been exploited to interpret their experimental NMR spectra in terms of the equilibrium between different tautomers. It has been found that for these triketones an endo-tautomer prevails. The differences in NMR spectra of the salts of 1 can be rationalized taking into account the size of the cation and the degree of salt dissociation. It seems that in DMSO solution the lithium salt exists mainly as an ion pair stabilized by the chelation of a lithium cation with two oxygen atoms. The activation free energy the of formyl group rotation for this salt has been estimated to be 51.5 kJ/mol. The obtained results suggest that in all the investigated objects, including the free enolate ions, all atoms directly bonded to the carbonyl carbons lie near the same plane. Some observations concerning the chemical shift changes could indicate strong solvation of the anion of 1 by water molecules. Implications of the results obtained in this work for the inhibition mechanism of (4-hydroxyphenyl) pyruvate dioxygenase by NTBC are commented upon.
- Szczecinski, Przemyslaw,Gryff-Keller, Adam,Molchanov, Sergey
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p. 4636 - 4641
(2007/10/03)
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- AMIDE TYPE CARBOXAMIDE DERIVATIVE
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The present invention provides an amide-type carboxamide derivative of the formula [1]: wherein X is a group of the formula: -N= or the formula: - CH=; R1 is a halogen atom, a lower alkyl group, and the like; R2 is a group of the formula: and the like; Y1 and Y2 are the same or different and each is a group selected from a halogen atom, a lower alkyl group, a lower alkoxy group, and the like; Ring A is phenyl group, and the like, or a pharmaceutically acceptable salt thereof, which is useful as an inhibitor of FXa.
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Page/Page column 17
(2010/11/08)
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- An unexpected and green synthetic protocol for ethyl 1-aroyl/aroylmethyl-5- methyl-3-methylthiopyrazole-4-carboxylates: High regioselectivity in alkylation and acylation reactions between n-1 and n-2 of a pyrazole ring
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Two series, totaling twelve, of new compounds, ethyl 1-aroyl/(aroylmethyl)- 5-methyl-3-methylthiopyrazole-4-carboxylates (5/6), have been synthesized via highly regioselectively acylation and alkylation reactions of ethyl 3-methyl-5-methylthio-1H-pyrazole
- Wen, Li-Rong,Wang, Shu-Wen,Li, Ming,Qi, Wen-Ying,Zhang, Xiu-Li,Yang, Hua-Zheng
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p. 1021 - 1028
(2007/10/03)
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- Structure-activity relationships of substituted benzothiophene-anthranilamide factor Xa inhibitors
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Compound 1 was identified by high throughput screening as a novel, potent, non-amidine factor Xa inhibitor with good selectivity against thrombin and trypsin. A series of modifications of the three aromatic groups of 1 was investigated. Substitution of chlorine or bromine for fluorine on the aniline ring led to the discovery of subnanomolar factor Xa inhibitors. Positions on the anthranilic acid ring that can accommodate further substitution were also identified.
- Chou, Yuo-Ling,Davey, David D.,Eagen, Keith A.,Griedel, Brian D.,Karanjawala, Rushad,Phillips, Gary B.,Sacchi, Karna L.,Shaw, Kenneth J.,Wu, Shung C.,Lentz, Dao,Liang, Amy M.,Trinh, Lan,Morrissey, Michael M.,Kochanny, Monica J.
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p. 507 - 511
(2007/10/03)
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- Benzyl-piperidine derivatives
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Benzly-piperidine derivatives of formula I and their pharmaceutically acceptable salts are used in the control of psychotic disorders which are caused by damage to the dopamine system, especially schizophrenia. STR1 A is STR2 B is STR3 R 1, R 2 and R 3 are independently hydrogen, amino, nitro, halogen, lower-alkly or lower-alkoxy. R 4, R 5 and R 6 are independently hydrogen, nitro, halogen, lower-alkyl, lower-alkoxy, cyano, trifluoromethyl, amino, lower-alkylamino or di-lower-alkylamino. R 7, R 2 and R 9 are independently hydrogen, amino or nitro.
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