- The Synthesis of the High-Potency Sweetener, NC-00637. Part 2: Preparation of the Pyridine Moiety
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The pyridine moiety within the high-potency sweetener, NC-00637 (1), 5-amino-2-cyanopyridine (4), was prepared from 2-hydroxy-5-nitropyridine (10). The sequence involved the conversion of the hydroxy group to bromide followed by substitution with cyanide to give 2-cyano-5-nitropyridine (8). Reduction of the nitro group proved to be troublesome when catalytic hydrogenation was used. Iron with an acid gave a reproducible reaction that could be used at scale.
- Ager, David J.,Erickson, Robert A.,Froen, Diane E.,Prakash, Indra,Zhi, Ben
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- Preparation of novel heteroisoindoles from nitropyridines and nitropyridones
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The reaction of nitropyridine derivatives with ethyl isocyanoacetate in the presence of 1,8-diazabicyclo[5.4.0]undecene proceeded tandem cyclization to give polycyclic pyrrolopyridines or imidazopyridines. On the other hand, N-protected 3-nitro- and 5-nitropyridones and N,N-diprotected 5-nitrouracil gave corresponding bicyclic pyrroles in good yields under the similar conditions.
- Murashima, Takashi,Nishi, Keiji,Nakamoto, Ken-ichi,Kato, Atsushi,Tamai, Ryuji,Uno, Hidemitsu,Ono, Noboru
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Read Online
- Preparation method of 2-nitrile-5-hydroxypyridine
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The invention relates to a preparation method of 2-nitrile-5-hydroxypyridine. The method comprises the steps: taking 2-bromine-5-nitropyridine, NaCN, CuCN, dimethylformamide, KH2PO4 and the like as starting raw materials to generate 2-nitrile-5-nitropyridine, adding ethyl acetate, an appropriate amount of reduced Fe powder and an enough amount of acetic acid, adding an appropriate amount of H2SO4 solution and NaNO2, and performing filtering and drying to obtain orange-yellow solid 2-nitrile-5-hydroxypyridine. The method is mild in reaction condition and low in cost; the raw materials are easy to obtain; and the method is suitable for mass production of a plant.
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Paragraph 0021; 0022; 0023
(2017/08/29)
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- QUINOLINE COMPOUNDS AS MODULATORS OF RAGE ACTIVITY AND USES THEREOF
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Quinoline compounds are disclosed that have a formula represented by the following: and wherein Cy, R1, R4a, R4b, and n are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, diabetes complications, inflammation, and neurodegeneration, obesity, cancer, ischemia/reperfusion injury, cardiovascular disease and other diseases related to RAGE activity.
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Page/Page column 00383
(2017/11/15)
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- NOVEL AZA-OXO-INDOLES FOR THE TREATMENT AND PROPHYLAXIS OF RESPIRATORY SYNCYTIAL VIRUS INFECTION
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The invention provides novel compounds having the general formula: wherein R1, R2, R3, R4, R5, W and X are as described herein, compositions including the compounds and methods of using the compounds.
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Page/Page column 27; 28
(2015/02/25)
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- COMPOUND HAVING BENZAMIDE SKELETON AND CYCLOOXYGENASE (COX-1)-SELECTIVE INHIBITORY ACTIVITY
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This invention provides a novel COX-1-selective inhibitor. This invention relates to a novel compound represented by the formula below or a salt thereof. This invention also relates to an analgesic agent, an antiinflammatory agent, an antitumor agent, an antiplatelet aggregation agent, and a cyclooxygenase-1-selective inhibitor comprising, as an active ingredient, such compound or salt thereof.
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Page/Page column 11-12
(2009/07/10)
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- Discovery of inhibitors of aberrant gene transcription from libraries ofdna binding molecules: Inhibition of LEF-1-mediated gene transcription and oncogenic transformation
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The screening of a >9000 compound library of synthetic DNA binding molecules for selective binding to the consensus sequence of the transcription factor LEF-1 followed by assessment of the candidate compounds in a series of assays that characterized functional activity (disruption of DNA-LEF-1 binding) at the intended target and site (inhibition of intracellular LEF-1-mediated gene transcription) resulting in a desired phenotypic cellular change (inhibit LEF-1-driven cell transformation) provided two lead compounds: lefmycin-1 and lefmycin-2. The sequence of screens defining the approach assures that activity in the final functional assay may be directly related to the inhibition of gene transcription and DNA binding properties of the identified molecules. Central to the implementation of this generalized approach to the discovery of DNA binding small molecule inhibitors of gene transcription was (1) the use of a technically nondemanding fluorescent intercalator displacement (FID) assay for initial assessment of the DNA binding affinity and selectivity of a library of compounds for any sequence of interest, and (2) the technology usedto prepare a sufficiently large library of DNA binding compounds.
- Stover, James S.,Shi, Jin,Jin, Wei,Vogt, Peter K.,Boger, Dale L.
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supporting information; experimental part
p. 3342 - 3348
(2009/07/30)
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- Cyclooxygenase-1-selective inhibitors are attractive candidates for analgesics that do not cause gastric damage. Design and in vitro/in vivo evaluation of a benzamide-type cyclooxygenase-1 selective inhibitor
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Although cyclooxygenase-1 (COX-1) inhibition is thought to be a major mechanism of gastric damage by nonsteroidal anti-inflammatory drugs (NSAIDs), some COX-1-selective inhibitors exhibit strong analgesic effects without causing gastric damage. However, it is not clear whether their analgesic effects are attributable to COX-1-inhibitory activity or other bioactivities. Here, we report that N-(5-amino-2-pyridinyl)-4-(trifluoromethyl)benzamide (18f, TFAP), which has a structure clearly different from those of currently available COX-1-selective inhibitors, is a potent COX-1-selective inhibitor (COX-1 IC 50 = 0.80 ± 0.05 μM, COX-2 IC50 = 210 ± 10 μM). This compound causes little gastric damage in rats even at an oral dose of 300 mg/kg, though it has an analgesic effect at as low a dose as 10 mg/kg. Our results show that COX-1-selective inhibitors can be analgesic agents without causing gastric damage.
- Kakuta, Hiroki,Zheng, Xiaoxia,Oda, Hiroyuki,Harada, Shun,Sugimoto, Yukio,Sasaki, Kenji,Tai, Akihiro
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p. 2400 - 2411
(2008/12/22)
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- Compounds and compositions as anticoagulants
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The present invention relates to novel biheterocyclic derivatives which are factor Xa inhibitors; the pharmaceutically acceptable salts and N-oxides thereof; their uses as therapeutic agents and the methods of their making.
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- Novel potassium channel openers: Synthesis and pharmacological evaluation of new N-(substituted-3-pyridyl)-N'-alkylthioureas and related compounds
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This report describes the synthesis and pharmacological evaluation of a series of novel potassium channel openers related to the pinacidil-type compounds. Thioureas, cyanoguanidines, and pyridine N-oxides were systematically evaluated for their effects on both the inhibition of spontaneous mechanical activity in rat portal vein (in vitro) and their antihypertensive activity (in vivo), and the structure-activity relationship for this series of compounds was discussed. Good correlation between in vitro and iv antihypertensive activity was observed for these compounds. Among them, cyanoguanidines bearing a conformationally rigid unit such as a norbornyl group generally possessed potent activity in both in vitro and in vivo studies. Especially, N-(6-amino-3-pyridyl)-N'-cyano-N''-(1-methyl-2- norbornyl)guanidine (23d) was identified as a more potent potassium channel opener in vitro (EC100 = 3 x 10-8 M) than pinacidil (EC100 = 10-7 M).
- Takemoto,Eda,Okada,Sakashita,Matzno,Gohda,Ebisu,Nakamura,Fukaya,Hihara,Eiraku,Yamanouchi,Yokoyama
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- Aminopyridine compounds
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An aminopyridine compound represented by the formula: STR1 wherein n represents 0 or 1; Z represents =S, =O, =NCN or =CHNO2 ; R1 represents --CN, --NR3 R4, --CONR3 R4, --NHNR3 R4, --NHCONHR3, --NHSO2 R3 or --SR3 ; R2 represents H, or substituted or unsubstituted alkyl; R3 and R4, which may be the same or different, represent H, substituted or unsubstituted alkyl, aryl, substituted or unsubstituted acyl or alkoxycarbonyl group; and R3 and R4 may form a heterocyclic ring together with a nitrogen atom to which R3 and R4 are bound, through another heteroatom or without it; or an acid salt thereof, which is excellent in pharmacological effect and repressed in side effects as a drug for circulatory diseases.
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- The preparation of Some 4- and 5-Substituted Pyridine-2-carboxylic Acids as Fusaric Acid Analogues.
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In view of future studies on the structure-activity relationships involved in the inhibition of dopamine β-hydroxylase, the authors synthetized 5-substituted picolinic acids and 4-substituted fusaric acids selected by means of a random sampling procedure suited for small series.On this occasion, they succeeded in improving markedly the well-known synthesis of 5-nitropicolinic acid via a Rosenmund-v.Braun reaction with 2-bromo-5-nitropyridine. 5-Hydroxypicolinic acid which is easily accessible in the same way could be converted into 5-alkyloxypicolinic acids by reaction with alkyl halides in DMSO in the presence of silver oxide. 4-Substituted fusaric acids became accessible via 5-n-butyl-2-methyl-4-nitropyridine-N-oxide.
- Oehlke, J.,Schroetter, E.,Dove, S.,Schick, H.,Niedrich, H.
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p. 591 - 596
(2007/10/02)
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