- Preparation method of 2-bromo-3-methoxypyridine
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The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 2-bromine-3-methoxypyridine, which comprises the following reaction steps: (1) preparation of 2-bromine-3-hydroxypyridine, and (2) preparation of 2-bromine-3-methoxypyridine: cooling the sodium hydroxide aqueous solution to -10 DEG C to 0 DEG C by using an ice salt bath, and dropwise adding liquid bromine within the temperature range, dissolving 3-hydroxypyridine in a sodium hydroxide aqueous solution, dropwise adding the solution into the liquid bromine solution, and keepingthe system temperature at 10-15 DEG C, after dropwise adding, stirring the mixed solution for 2.5-3 hours at room temperature, and then adjusting the pH value to 7 by using acid; and recrystallizing the obtained crude product to obtain the 2-bromo-3-hydroxypyridine. The method has the beneficial effects of mild reaction conditions, short route and high yield.
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Paragraph 0014; 0016; 0017; 0019-0021; 0023
(2020/02/14)
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- A 2 - bromo -3 - methoxy pyridine preparation method
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The invention belongs to the field of organic synthetic technology, in particular to a 2 - bromo - 3 - methoxy pyridine of the preparation method, the reaction steps are as follows: (1) 2 - bromo - 3 - hydroxy pyridine, (2) 2 - bromo - 3 - methoxy pyridine; ice salt bath for the aqueous sodium hydroxide solution cooled to - 10 - 0 °C, in this temperature range, [...]; the 3 - hydroxy pyridine dissolved in the sodium hydroxide solution, then the solution is dropped to the above bromine solution, to maintain the system temperature is 10 - 15 °C; drops, room temperature stirring 2.5 - 3 hours, then use acid to adjust pH to 7; the resulting crude product recrystallized, to 2 - bromo - 3 - hydroxy pyridine. The beneficial effect of the invention is: mild reaction conditions, route is short, high yield.
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Paragraph 0014; 0016; 0017; 0019; 0021; 0023
(2019/05/28)
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- Iridium(iii) complex-based electrochemiluminescent probe for H2S
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Since abnormal levels of hydrogen sulphide (H2S) correlate with various diseases, simple methods for its rapid and sensitive detection are highly required. Herein, we introduce a new electrochemiluminescent probe 1 for H2S based on a cyclometalated iridium(iii) complex. o-(Azidomethyl)benzoate ester groups on the main ligands of probe 1 react selectively with H2S, resulting in cascade reactions involving H2S-mediated reduction and intramolecular cyclization/ester cleavage. With this structural change induced by H2S, the intrinsic electrochemiluminescence (ECL) of 1 decreased greatly due to the unfavourable electron transfer of a tripropylamine (TPA) radical. Probe 1 showed a high ECL turn-off ratio and good selectivity for H2S over various anions and biothiols. The sensing mechanism of H2S was elucidated using1H NMR spectroscopy and MALDI-TOF mass spectrometry analyses.
- Park, Joonho,Kim, Taemin,Kim, Hoon Jun,Hong, Jong-In
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p. 4565 - 4573
(2019/04/05)
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- 1 -(CYCLOPENT-2-EN-1 -YL)-3-(2-HYDROXY-3-(ARYLSULFONYL)PHENYL)UREA DERIVATIVES AS CXCR2 INHIBITORS
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The invention relates to 1-(3-sulfonylphenyl)-3-(cyclopent-2-en-1-yl)urea derivatives, and their use in treating or preventing diseases and conditions mediated by the CXCR2 receptor. In addition, the invention relates to compositions containing the derivatives and processes for their preparation.
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Page/Page column 131
(2015/12/18)
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- USE OF NOVEL COMPOUND HAVING AFFINITY FOR AMYLOID, AND PROCESS FOR PRODUCTION OF THE SAME
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The invention provides a reagent for detecting amyloid in a biological tissue which can detect amyloid in vitro and in vivo with high sensitivity using a compound which has affinity with amyloid and is suppressed in toxicity such as mutagenicity. The reagent for detecting amyloid deposited in a biological tissue comprises the compound represented by the following formula (1) or a salt thereof: wherein A1, A2, A3 and A4 independently represent a carbon or a nitrogen, and R3 is a group represented by the following formula: wherein R1 is a radioactive halogen substituent; m is an integer of 0 to 4; and n is an integer of 0 or 1, provided that at least one of A1, A3, A3 and A4 represents a carbon, and R5 binds to a carbon represented by A1, A2, A3 or A4.
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- NOVEL COMPOUND HAVING AFFINITY FOR AMYLOID
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A compound effective as a probe targeting amyloid for image diagnosis and a reagent comprising the compound for detecting amyloid deposited on a biological tissue are provided. Provided are a compound represented by the following formula (1): wherein R1, R2 and R3 independently represent a group selected from the group consisting of a hydrogen, hydroxyl group, alkyl substituent with 1 to 4 carbon atoms, alkoxy substituent having alkyl chain with 1 to 4 carbon atoms and halogen substituent, excluding the case where two or more of the substituents R1, R2 and R3 are hydrogen, R4 is a group selected from the group consisting of a hydrogen, hydroxy group, alkoxy substituent having alkyl chain with 1 to 4 carbon atoms and halogen substituent, and m is an integer of 1 to 4, provided that at least one of R1, R2, R3 and R4 represents a radioactive halogen substituent, and a reagent comprising the same.
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Page/Page column 8-9; 24
(2010/08/09)
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- NOVEL COMPOUND HAVING AFFINITY FOR AMYLOID
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A compound effective as a probe targeting amyloid for image diagnosis and a reagent comprising the compound for detecting amyloid deposited on a biological tissue are provided. Provided are a compound represented by the following formula (1): wherein R1 is a group selected from the group consisting of a halogen substituent, alkyl substituent with 1 to 4 carbon atoms, alkoxy substituent having alkyl chain with 1 to 4 carbon atoms and hydroxyl group, R2 is a group selected from the group consisting of a cyano substituent, alkyl substituent with 1 to 4 carbon atoms and halogen substituent, is a group selected from the group consisting of a hydroxyl group, halogen substituent and substituent represented by the following formula: (wherein R4 is a hydrogen, halogen substituent or hydroxyl group, and m is an integer of 1 to 4), provided that a t least one of R1, R2, R3 and R4 represents a radioactive halogen, and a reagent comprising the same.
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Page/Page column 15; 27
(2010/08/09)
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- NOVEL COMPOUND HAVING AFFINITY TO AMYLOID
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The invention relates to a compound which has affinity with amyloid, shows sufficiently rapid clearance from normal tissues and is suppressed in toxicity such as mutagenicity, and also relates to a low-toxic diagnostic agent for Alzheimer's disease containing the compound. The compound is represented by the following formula (1) or a salt thereof: wherein A1, A2, A3 and A4 independently represent a carbon or a nitrogen, and R3 is a group represented by the following formula: wherein R1 is a radioactive halogen substituent; m is an integer of 0 to 4; and n is an integer of 0 or 1, provided that at least one of A1, A2, A3 and A4 represents a carbon, and R3 binds to a carbon represented by A1, A2, A3 or A4.
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Page/Page column 10; 28
(2009/03/07)
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- NOVEL COMPOUND HAVING AFFINITY FOR AMYLOID
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A compound that has affinity with amyloid, exhibits sufficiently rapid clearance from normal tissues, and is suppressed in toxicity such as mutagenicity is provided, which is represented by the following formula (1): or a salt thereof, wherein R1 is a group selected from hydrogen, hydroxyl group, carboxyl group, sulfate group, amino group, nitro group, cyano group, an alkyl substituent with one to 4 carbon atoms or an alkoxy substituent with one to 4 carbon atoms; R2 is a radioactive halogen substituent; and m is an integer of 0 to 2, and a low-toxic diagnostic agent for Alzheimer's disease comprising a compound represented by the above formula or a salt thereof is also provided.
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Page/Page column 2; 7-9; 15; 24-25
(2009/04/23)
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- NOVEL COMPOUNDS WITH AFFINITY FOR AMYLOID
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It is intended to provide a compound effective as an image diagnosis probe targeting amyloid and a diagnostic agent for Alzheimer's disease comprising the compound. Provided is a compound represented by the following formula or a salt thereof: wherein A1, A2, A3 and A4 independently represents a carbon or nitrogen, R1 is a group selected from the group consisting of hydrogen, hydroxyl group, carboxyl group, sulfuric acid group, amino group, nitro group, cyano group, non-radioactive halogen substituents, alkyl substituents with 1-4 carbon atoms and alkoxy substituents with 1-4 carbon atoms, and R3 is a radioactive halogen substituent, provided that at least one of A1 A2, A3 and A4 represents a carbon, and R1 binds to a carbon represented by A1, A2, A3 or A4, as well as a diagnostic agent for Alzheimer's disease comprising the compound represented by the above formula or a salt thereof.
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Page/Page column 9-10
(2009/09/26)
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- Acridone-based inhibitors of inosine 5′-monophosphate dehydrogenase: Discovery and SAR leading to the identification of N-(2-(6-(4-ethylpiperazin-1- yl)pyridin-3-yl)propan-2-yl)-2-fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide (BMS-566419)
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Inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo synthesis of guanosine nucleotides, catalyzes the irreversible nicotinamide-adenine dinucleotide dependent oxidation of inosine-5′- monophosphate to xanthosine-5′-monophosphate. Mycophenolate Mofetil (MMF), a prodrug of mycophenolic acid, has clinical utility for the treatment of transplant rejection based on its inhibition of IMPDH. The overall clinical benefit of MMF is limited by what is generally believed to be compound-based, dose-limiting gastrointestinal (GI) toxicity that is related to its specific pharmacokinetic characteristics. Thus, development of an IMPDH inhibitor with a novel structure and a different pharmacokinetic profile may reduce the likelihood of GI toxicity and allow for increased efficacy. This article will detail the discovery and SAR leading to a novel and potent acridone-based IMPDH inhibitor 4m and its efficacy and GI tolerability when administered orally in a rat adjuvant arthritis model.
- Watterson, Scott H.,Chen, Ping,Zhao, Yufen,Gu, Henry H.,Dhar, T. G. Murali,Xiao, Zili,Ballentine, Shelley K.,Shen, Zhongqi,Fleener, Catherine A.,Rouleau, Katherine A.,Obermeier, Mary,Yang, Zheng,McIntyre, Kim W.,Shuster, David J.,Witmer, Mark,Dambach, Donna,Chao, Sam,Mathur, Arvind,Chen, Bang-Chi,Barrish, Joel C.,Robl, Jeffrey A.,Townsend, Robert,Iwanowicz, Edwin J.
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p. 3730 - 3742
(2008/02/12)
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- HETEROCYCLIC METHYL SULFONE DERIVATIVE
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Provided is a compound capable of inhibiting production or secretion of β amyloid protein. A compound represented by the following formula (1): (wherein, R1 represents a heterocyclic group which may have a substituent, R2 represents a cyclic hydrocarbon group which may have a substituent or a heterocyclic group which may have a substituent, R3 represents a cyclic hydrocarbon group which may have a substituent or a heterocyclic group which may have a substituent, R4 represents a hydrogen atom or a C1-6 alkyl group, and X represents -S-,-SO- or -SO2-) an N-oxide or S-oxide thereof; a salt thereof; or a solvate thereof; and a medicament containing any of them.
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Page/Page column 18-19
(2010/11/08)
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- BIPYRIDYL AMINES AND ETHERS AS MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR-5
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The present invention is directed to novel bipyridyl amine and ether compounds such as those of Formula (I): (I) (where R?1#191, R?2#191, R?3#191, X and Y are as defined herein) which are mGluR5 modulators useful in the treatment or prevention of diseases and conditions in which mGluR5 is involved, including but not limited to psychiatric and mood disorders such as schizophrenia, anxiety, depression, bipolar disorders, and panic, as well as in the treatment of pain, Parkinson’s disease, cognitive dysfunction, epilepsy, circadian rhythm and sleep disorders, such as shift-work induced sleep disorder and jet-lag, drug addiction, drug abuse, drug withdrawal, obesity and other diseases. The invention is also directed to pharmaceutical compositions comprising these compounds. This invention further provides a method of treatment of these disorders and conditions by the administration of an effective amount of these novel bipyridyl amine and/or ether compounds and/or compositions containing these compounds.
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Page/Page column 26-27
(2010/02/11)
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- BETA-AMYLOID PROTEIN PRODUCTION/SECRETION INHIBITORS
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Provided are novel compounds having an inhibitory activity against production or secretion of β-amyloid protein. They embrace compounds represented by the following formula (1): and capable of being replaced with a variety of substituents; and salts thereof, and solvates of any one of them.
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- Calcilytic compounds
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Novel calcilytic compounds and methods of using them are provided.
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- Anilide derivative, production and use thereof
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This invention is to provide a compound of the formula: wherein R1 is an optionally substituted 5- to 6-membered ring: C is a divalent group of the formula: wherein the ring A is an optionally substituted 5- to 6-membered aromatic ring, X is an optionally substituted C, N or O atom, and the ring B is an optionally substituted 5- to 7-membered ring; Z is a chemical bond or a divalent group; R2 is (1) an optionally substituted amino group in which a nitrogen atom may form a quaternary ammonium, etc., or a salt thereof, which is useful for antagonizing MCP-1 receptor.
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- Palladium(0)-catalyzed heteroarylation of 2- and 3-indolylzinc derivatives. An efficient general method for the preparation of (2-pyridyl)indoles and their application to indole alkaloid synthesis
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Palladium(0)-catalyzed coupling of (1-(benzenesulfonyl)-2-indolyl)zinc chloride (1) and (1-(tert-butyldimethylsilyl)-3-indolyl)zinc chloride (6) with diversely substituted (alkyl, methoxy, methoxycarbonyl, nitro, hydroxy) 2-halopyridines gives the corresponding 2- and 3-(2-pyridyl)indoles [4 and 7 (or 8), respectively] in excellent yields. A series of other 3-(heteroaryl)indoles (pyrazinyl, furyl, thienyl, indolyl) have been similarly prepared from 6. The potential of some of these (2-pyridyl)indoles in alkaloid synthesis is demonstrated. Thus, from 2-(2-pyridyl)indole 4b, a new synthetic entry to the indolo[2,3-a]quinolizidine system, involving stereoselective hydrogenation of the pyridine ring with subsequent electrophilic cyclization upon the indole 3-position from an appropriately N(b)-substituted 2-(2-piperidyl)indole, is reported. For this purpose, Pummerer cyclizations have been extensively studied. Whereas the indole-unprotected sulfoxide 17 gives the corresponding indoloquinolizidine 19 in low yield and mainly undergoes an abnormal Pummerer cyclization that ultimately leads to sulfide 18, the N(a)-protected sulfoxides 24a and 24b afford the respective indoloquinolizidines 25a,b in 70% yield. On the other hand, the conversion of 3-(2-pyridyl)indole 8k into tetracyclic ketone 35 by stereoselective hydrogenation, followed by cyclization of the resulting all-cis-3-(2-piperidyl)indole 34, represents a formal synthesis of Strychnos alkaloids with the strychnan skeletal type (tubifoline, tubifolidine, 19,20-dihydroakuammicine). A similar conversion of 8j into nordasycarpidone constitutes a formal synthesis of the alkaloids of the uleine group. Reduction of nordasycarpidone leads to tetracycle 37, an advanced intermediate in a previous synthesis of tubotaiwine, a Strychnos alkaloid with the aspidospermatan skeletal type. Finally, piperidylindole 34 was transformed into tetracycle 41, an ABDE substructure of akuammiline alkaloids, by a sequence involving the skeletal rearrangement of an intermediate spiroindolenine as the crucial step.
- Amat, Mercedes,Hadida, Sabine,Pshenichnyi, Grigorii,Bosch, Joan
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p. 3158 - 3175
(2007/10/03)
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- Bipyridyls and their use as inks
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Process employing bipyridyls as inks, of the general formula STR1 in which R, R' are, for example, alkyl and R1, R2, R3, R4, R5, R6 are, for example hydrogen or alkyl radicals, or R1 and R2 or R2 and R3, and/or R4 and R5 or R5 and R6 together with the pyridine ring form in isoquinoline or quinoline ring system.
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- A Simple Synthesis of 3-Methoxypyridine and of Analogues by Alkylation Reactions
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Solid potassium hydroxide in dimethylsulfoxide has high basicity but only low nucleophilicity and is used as a base for the methylation of 3-hydroxypyridine (1) and of analogues with methyl iodide.The reaction is not interferred by the addition of small amounts of water and gives yields of 40 percent for the reaction of 1 and up to 100 percent for analogues.The described reagent therefore may be an alternative to lithium diisopropylamide.
- Finkentey, Christel,Langhals, Elke,Langhals, Heinz
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p. 2394 - 2397
(2007/10/02)
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