- The Synthesis and Transition Temperatures of Ester Derivatives of 2-Fluoro-4-hydroxy- and 3-Fluoro-4-hydroxybenzonitriles also Incorporating Aliphatic Ring Systems
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The synthesis and liquid-crystal transition temperatures of forty ester derivatives of 2-fluoro-4-hydroxybenzonitrile and 3-fluoro-4-hydroxybenzonitrile are reported.The esters contain the trans-1,4-disubstituted cyclohexane or the 1,4-disubstituted bicyclooctane rings (some contain an additional phenyl ring).Many of the novel F-substituted esters exhibit substantially higher nematic-isotropic transition temperatures than the corresponding unsubstituted esters.The order of clearing points of these laterally substituted esters differing only in the presence of a benzene ring and the above-mentioned rings is established.
- Kelly, Stephen M.,Schad, Hanspeter
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- Design, synthesis and biological evaluation of 2-(4-alkoxy-3-cyano)phenyl-6-oxo-1,6-dihydropyrimidine-5-carboxylic acid derivatives as novel xanthine oxidase inhibitors
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In our previous study, we reported a series of 1-hydroxy-2-phenyl-1H-imidazole-5-carboxylic acid derivatives that presented excellent in vitro xanthine oxidase (XO) inhibitory potency. To further investigate the structure-activity relationships of these compounds, the imidazole ring was transformed to a pyrimidine ring to design 2-(4-alkoxy-3-cyano)phenyl-6-oxo-1,6-dihydropyrimidine-5-carboxylic acids (8a-8j), 2-(4-alkoxy-3-cyano)phenyl-4-methyl-6-oxo-1,6-dihydropyrimidine-5-carboxylic acids (9c, 9e, 9j, 9l) and 2-(4-alkoxy-3-cyano)phenyl-6-imino-1,6-dihydropyrimidine-5-carboxylic acids (10c, 10e, 10j, 10l). These compounds exhibited remarkable in vitro XO inhibitory potency with IC50 values ranging from 0.0181 μM to 0.5677 μM. Specifically, compounds 10c and 10e, with IC50 values of 0.0240 μM and 0.0181 μM, respectively, emerged as the most potent XO inhibitors, and their potencies were comparable to that of febuxostat. Structure-activity relationship analysis revealed that the methyl group at 4-position of pyrimidine ring could damage the potency, and the XO inhibitory potency was maintained when carbonyl group was changed to an imino group. Lineweaver-Burk plot analysis revealed that the representative compound 10c acted as a mixed-type inhibitor. A potassium oxonate induced hyperuricemia model in rats was chosen to further confirm the hypouricemic effect of compound 10c, and the results showed that compound 10c (5 mg/kg) was able to significantly lower the serum uric acid level. Furthermore, in acute oral toxicity study, no sign of toxicity was observed when the mice were administered with a single 2000 mg/kg oral dose of compound 10c. These results suggested that compound 10c was a potent and promising uric acid-lowing agent for the treatment of hyperuricemia.
- Mao, Qing,Dai,Xu, Gaoyang,Su, Yu,Zhang, Bing,Liu, Dan,Wang, Shaojie
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- Preparation method and use of 2-phenyl-1,6-dihydropyrimidine-5-carboxylic acid derivative
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The invention belongs to the technical field of medicines, and relates to a preparation method and a use of a 2-phenyl-1,6-dihydropyrimidine-5-carboxylic acid derivative. The invention provides the 2-phenyl-1,6-dihydropyrimidine-5-carboxylic acid derivative represented by general formula I, or a pharmaceutically acceptable salt, an isomer, a polymorph and a medicinal solvate thereof, and further provides an intermediate for preparing the 2-phenyl-1,6-dihydropyrimidine-5-carboxylic acid derivative or the pharmaceutically acceptable salt thereof. The structure of the intermediate is representedby general formula II, III or IV; and in the formulas, R, R and R are as defined in claims and the description.
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Paragraph 0059; 0074-0075
(2019/09/14)
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- PROCESS FOR THE PREPARATION OF 2-[3-CYANO-4-(2-METHYLPROPOXY)PHENYL]-4-METHYLTHIAZOLE-5-CARBOXYLIC ACID AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
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The present invention relates to novel and improved processes for the preparation of 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid compound of formula-1 and its pharmaceutically acceptable salts thereof. the present invention also provides the novel process for the preparation of crystalline forms of 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid compound of formula-1 and its intermediates.
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Page/Page column 43-44
(2011/12/02)
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- COMPOUNDS CONTAINING FUSED RINGS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF
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The invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating Alzheimer's disease.
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Page/Page column 95
(2011/11/01)
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- New oxabispidine compounds for the treatment of cardiac arrhythmias
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There is provided compounds of formula I, wherein R1, R2, R3, R41 to R46, X, Y and Z have meanings given in the description, which compounds are useful in the prophylaxis and in the treatment of arrhythmias, in particular atrial and ventricular arrhythmias.
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Page/Page column 62
(2008/06/13)
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- Nonspecific medium effects versus specific group positioning in the antibody and albumin catalysis of the base-promoted ring-opening reactions of benzisoxazoles
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The mechanisms by which solvents, antibodies, and albumins influence the rates of base-catalyzed reactions of benzisoxazoles have been explored theoretically. New experimental data on substituent effects and rates of reactions in several solvents, in an antibody, and in an albumin are reported. Quantum mechanical calculations were carried out for the reactions in water and acetonitrile, and docking of the transition state into a homology model of antibody 34E4 and an X-ray structure of human serum albumin was accomplished. A microenvironment made up of catalytic polar groups (glutamate in antibody 34E4 and lysine in human serum albumin) surrounded by relatively nonpolar groups is present in both catalytic proteins.
- Hu, Yunfeng,Houk,Kikuchi, Kazuya,Hotta, Kinya,Hilvert, Donald
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p. 8197 - 8205
(2007/10/03)
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- Aromatic Nitro-group Displacement Reactions. Part 3. Minor Products of the o-Cyanophenol Synthesis
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In dipolar aprotic solvents, the action of cyanide ions on a moderately activated aromatic or heteroaromatic nitro-compound yields, in addition to the o-cyanophenol, a range of products generated through nitro-group reduction.
- Gorvin, John H.
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p. 738 - 762
(2007/10/02)
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- Aromatic Nitro group Displacement Reactions. Part 2. The Synthesis of Diarylamines and some Heteroaromatic Analogues.
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In dipolar aprotic solvents, activated aromatic nitro-groups can usually be displaced by anilines of enhanced N-acidity in the presence of the heavier alkali-metal carbonates.When catalysed by potassium t-butoxide, however, attack occurs preferentially at other reactive centers in the molecule, except where the nitro-group is highly activated.Some of the resulting diarylamines (the term is here expanded to include arylaminoxanthen-9-ones) are intermediates in the synthesis of heterocycles.
- Gorvin, John H.
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p. 1662 - 1681
(2007/10/02)
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- NEMATOGENS FOR MATRIX-ADDRESSED TWISTED NEMATIC DISPLAYS - 1.
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Nematogens with small DELTA epsilon / epsilon // PERPEND for matrix-addressed TN-displays were synthesized. The effect of introducing lateral cyano groups on the dielectric constants and the thermodynamic stability of the mesophase of 4-cyanophenyl esters is described. Fluoro-PCH's suitable for matrix addressing were prepared and the effect of the fluoro substituent on the clearing point was studied.
- Osman,Huynh-Ba
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p. 331 - 338
(2007/10/02)
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- Preparation of cyanophenols
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A process for the preparation of a cyanophenol of formula (I) SPC1 wherein Z is a substituent in the 4- or 6-position with respect to the hydroxy group, characterized in that cyanide ions are reacted in a dipolar aprotic solvent with a nitrobenzene of formula (II) SPC2 wherein Z has the same value as in formula (I) and is a group, other than a nitro group, known to withdraw electrons in substitution reactions and which does not contain a proton capable of ionizing under the defined reaction conditions if such ionization would inhibit the electron-withdrawing effect of the group Z. In formula (I) and (II) the benzene ring is optionally substituted by one or more non electron-withdrawing groups, or by one or more electron-withdrawing groups provided that such electron-withdrawing groups are in positions other than the 4- and 6-positions with respect to the hydroxy group. The compounds of formula (I) are of value in being readily hydrolysed to the corresponding salicylic acids of formula (III) SPC3 certain of which have been described in the literature as possessing a variety of pharmacological properties.
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