- Synthetic method of 2,6-dihalopyridine-3-carboxylic acid
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The invention discloses a synthetic method of 2,6-dihalopyridine-3-carboxylic acid and belongs to the field of medicine intermediate synthesis. The synthetic method comprises the following steps: dissolving 2,6-dihalopyridine and Boc2O in an organic solvent; dropwise adding LDA or i-Pr2NMgCl-LiCl to react at a low temperature; then adding an acid-water solution to raise the temperature to react; and adding alkali to adjust pH to obtain 2,6-dihalopyridine-3-carboxylic acid. In addition, by adding LDA into 2,6-dihalopyridine at an ultralow temperature to abstract protons, and then adding DBU-CO2to react and quenching the solution, the 2,6-dihalopyridine-3-carboxylic acid is obtained. The two methods solve the problem that the yield is low by adopting a conventional CO2 introducing method for scaled production and the inter-batch operating repeatability is good.
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Paragraph 0020
(2019/04/06)
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- COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR
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Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereo
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Page/Page column 86-87
(2011/11/06)
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- COMPOSITION FOR AGRICULTURAL USE FOR CONTROLLING OR PREVENTING PLANT DISEASES CAUSED BY PLANT PATHOGENS
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Disclosed is a composition for agricultural use, which is used for controlling or preventing plant diseases caused by plant pathogens. The composition for agricultural use contains a compound represented by formula (1), a salt thereof or a hydrate of the compound or the salt. (1) [In the formula, Z represents an oxygen atom, a sulfur atom or NRz; and E represents a furyl group, a thienyl group, a pyrrolyl group, a tetrazolyl group, a thiazolyl group, a pyrazolyl group, a phenyl group or the like.]
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Page/Page column 273; 278-279
(2010/11/19)
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- Tricyclic heterocyclic compound and use thereof
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The present invention provides a tricyclic heterocyclic compound having a serotonin 5-HT2C receptor activation action and the like. A 5-HT2C receptor activator containing a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof or a prodrug thereof.
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Page/Page column 24
(2009/12/28)
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- HETEROCYCLIC 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 a triazolyl group or the l
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Page/Page column 111
(2009/02/10)
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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 44
(2008/06/13)
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- COMPOUNDS AND METHODS OF USE
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Selected compounds are effective for prophylaxis and treatment of diseases, such as angiogenesis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
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Page/Page column 118
(2010/11/27)
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- HETEROBICYLIC INHIBITORS OF HCV
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Fused bicyclic pyrimidine compounds having an amide-substituted pyridylamine group at C-4 of the pyrimidine of formula (I) ring are useftul in the treatment of conditions associated with HCV.
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Page/Page column 29
(2008/06/13)
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- The structural proliferation of 2,6-difluoropyridine through organometallic intermediates
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Contrary to a literature claim, 2,6-difluoropyridine-3-carboxaldehyde can be readily prepared by consecutive treatment of 2,6-difluoropyridine with lithium diisopropylamide and N,N-dimethylformamide. Regioselective displacements of fluorine from the aldehyde by nucleophiles were carried out. To demonstrate the versatility of the organometallic approach, some two dozens of further 2,6-difluoropyridine derivatives were prepared applying a combination of modern organometallic methods such as site selective hydrogen/metal and halogen/metal permutations and deprotonation-triggered heavy halogen migrations. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Schlosser, Manfred,Rausis, Thierry
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p. 1018 - 1024
(2007/10/03)
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- (R)-5-bromo-N-(1-ethyl-4-methylhexahydro-1H-1,4-diazepin-6-yl)-2-methoxy-6-methylamino-3-pyridinecarboxamide, process for producing the same and medicinal composition containing the same
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This invention discloses a compound which is expressed by formula (I) below: STR1 or physiologically acceptable acid addition salts thereof. The claimed compound exhibits excellent antiemetic effect based on its potent serotonin S3 and dopamine
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- Synthesis of some piperazinylpyrazolo[3,4-b]pyridines as selective serotonin re-uptake inhibitors
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A number of 3-substituted 6-piperazinylpyrazolo[3,4-b]pyridines were synthesized from 2,6-difluoropyridine by directed ortho metallation and sequential intra- and intermolecular displacement of fluorine. Three derivatives with a cyano group in the 3-position showed activity as selective serotonin re-uptake inhibitors.
- Shutske, Gregory M.,Roehr, Joachim E.
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p. 789 - 795
(2007/10/03)
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- Nicotinamide derivatives as a new class of gastric (H+/K+)-ATPase inhibitors. II. Synthesis and structure-activity relationships of 2-[(2,4- dimethoxyhenzyl)sulfinyl]-N-(4-pyridinyl)pyridine-3-carboxamides
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Members of a new series of 2-[(2,4-dimethoxybenzyl)sulfinyl]-N-(4- pyridinyl)pyridine-3-carboxamides were synthesized and evaluated for their gastric antisecretory activity and the ability to inhibit cytochrome P450- dependent O-dealkylation of 7-ethoxycoumarin (7-EC) in rat liver microsomes. Several of the compounds synthesized exhibited potent inhibitory activities against both [14C]aminopyrine accumulation stimulated by dibutyryl cyclic AMP in isolated rabbit parietal cells and histamine-induced gastric acid secretion in pylorus-ligated rats when administered intraduodenally; their inhibitory activities were equivalent to or superior to those of the parent compound [2[(2,4-dimethoxybenzyl)sulfinyl]-N-(4-pyridinyl)pyridine-3- carboxamide] and omeprazole. Among the compounds having potent antisecretory activity in vitro and in vivo, 2-[(2,4-dimethoxybenzyl)sulfinyl]-N-(2,5- dimethyl-4-pyridinyl)pyridine-3-carboxamide and 2-[(2,4- dimethoxybenzyl)sulfinyl]-N-(2,6-dimethyl-4-pyridinyl)pyridine-3-carboxamide in particular showed lower inhibitory activity against the 7-EC deethylase than omeprazole. It seems probable that, unlike omeprazole, these compounds do not interact with a metabolism of other drugs in vivo. These compounds, therefore, are considered to be more promising candidate agents for treating acid-related gastrointestinal disorders than the parent compound reported previously.
- Terauchi, Hideo,Tanitame, Akihiko,Tada, Keiko,Nakamura, Keiji,Seto, Yasuhiro,Nishikawa, Yoshinori
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p. 1027 - 1038
(2007/10/03)
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- Tyrosine kinase inhibitors. 10. Isomeric 4-[(3-bromophenyl)amino]pyrido[d]-pyrimidines are potent ATP binding site inhibitors of the tyrosine kinase function of the epidermal growth factor receptor
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Following the discovery of the very high inhibitory ability of the 4-[(3-bromophenyl)amino]-quinazolines against the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) (e.g., 3, IC50 0.029 nM), four series of related pyrido[d]pyrimidines bearing electron-donating groups at the 6- or 7-positions have been synthesized and evaluated. The compounds were prepared by nucleophilic substitution of the corresponding 6- and 7-fluoro analogues. While members of all series showed potent inhibitory activity against isolated EGFR, there were important differences between the different isomeric pyrido[d]pyrimidines and the parent quinazolines. Overall, the [3,4-d] and [4,3-d] series were the most potent, followed by the [3,2-d] compounds, with the [2,3-d] analogues being least active. Whereas in the parent quinazoline series the addition of steric bulk to a 6- or 7-NH2 substituent (i.e., NHMe and NMe2 groups) dramatically decreased potency, no such trend was discernable in the [3,2-d] series. Furthermore, in the 7-substituted pyrido[4,3-d]- and 6-substituted pyrido[3,4-d]pyrimidine series, and to a limited extent in the 7-substituted pyrido[2,3-d] series, such substitution increased potency dramatically, to the extent that the 7-(methylamino)pyrido[4,3-d]pyrimidine (5f) (IC50 0.13 nM) and 6-(methylamino)pyrido[3,4-d]pyrimidine (7f) (IC50 0.008 nM) constitute important new leads. Selected compounds were evaluated for their ability to inhibit EGFR autophosphorylation in A431 cells, and a positive quantitative correlation was found between this activity and inhibitory activity against the isolated enzyme.
- Rewcastle, Gordon W.,Palmer, Brian D.,Thompson, Andrew M.,Bridges, Alexander J.,Cody, Donna R.,Zhou, Hairong,Fry, David W.,McMichael, Amy,Denny, William A.
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p. 1823 - 1835
(2007/10/03)
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