128071-75-0Relevant academic research and scientific papers
'Cascade' radical reactions in synthesis: Condensed thiophenes from ketenethioacetals
Harrowven, David C.
, p. 5653 - 5656 (1993)
A novel radical centred tandem cyclisation - tandem fragmentation sequence is described for the direct convertion of ketenethioacetals e.g. 1, 6, 9, 12 and 16 into condensed thiophenes e.g. 2, 7, 10, 13 and 17.
Synthetic strategies based on aromatic metalation - Cross coupling links. A concise formal synthesis of the azaphenanthrene alkaloid eupolauramine
Wang,Snieckus
, p. 4883 - 4884 (1991)
An efficient synthesis of azaphenanthraquinone 9, previously converted into eupolauramine (10), has been achieved using combinational metalation (ortho and remote) - cross coupling tactics.
Synthesis, Structure and Basicity of 1,16-Diazahelicene
Staab, Heinz A.,Diehm, Michael,Krieger, Claus
, p. 8357 - 8360 (1994)
The extension of 'proton sponges' 1 and 2 by further anellation to 1,16-diazahelicene (3) was of interest to define scope and limitation of 'proton sponge' properties. 3 was prepared by photocyclisation of 2,7-bis(3-pyridylvinyl)naphthalene 4 and by Pd-catalyzed aryl-aryl coupling of the corresponding tetrabromo derivative 7.As consequence of the helical structure, 3 does not show 'proton sponge' basicity.X-ray structure analyses of 3 and 3*2HBr are in accordance with these findings.
Improved synthesis of 2-bromonicotin-aldehyde and acid
Melnyk,Gasche,Thal
, p. 2727 - 2730 (1993)
Synthetically useful 2-bromonicotinaldehyde and 2-bromonicotinic acid can be conveniently prepared in high yield from the directed ortho metalation of 2-bromopyridine.
Synthesis method of 3, 4-dihydro-2H-pyrano [2, 3-b] pyridine
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Paragraph 0007; 0010; 0013, (2021/05/26)
The invention relates to a synthesis method of 3, 4-dihydro-2H-pyrano [2, 3-b] pyridine. The problems of difficult availability of raw materials, expensive reagents, complicated operation, high risk, high energy consumption and the like in the existing route are mainly solved. The method is realized through the following technical scheme: (1) reacting 2-bromopyridine with a formylation reagent under the action of alkali to generate 2-bromo-3-formylpyridine; (2) reacting an aldehyde group of the 2-bromine-3-formylpyridine with triethyl phosphonoacetate to generate 2-bromine-3-pyridine ethyl acrylate; (3) simultaneously reducing double bonds and ester groups of 2-bromo-3-pyridine ethyl acrylate by lithium borohydride in one step while enabling bromine not to be influenced, so as to obtain 2-bromo-3-pyridine propanol; and (4) carrying out ring closing on the 2-bromo-3-pyridyl propanol under the action of alkali to obtain a target compound.
S29434, a quinone reductase 2 inhibitor: Main biochemical and cellular characterization
Boutin, Jean A.,Bouillaud, Frederic,Janda, Elzbieta,Gacsalyi, István,Guillaumet, Gérald,Hirsch, Etienne C.,Kane, Daniel A.,Nepveu, Fran?oise,Reybier, Karine,Dupuis, Philippe,Bertrand, Marc,Chhour, Monivan,Le Diguarher, Thierry,Antoine, Mathias,Brebner, Karen,Da Costa, Hervé,Ducrot, Pierre,Giganti, Adeline,Goswami, Vishalgiri,Guedouari, Hala,Michel, Patrick P.,Patel, Aakash,Paysant, Jér?me,Stojko, Johann,Viaud-Massuard, Marie-Claude,Ferry, Gilles
supporting information, p. 269 - 285 (2019/05/14)
Quinone reductase 2 (QR2, E.C. 1.10.5.1) is an enzyme with a feature that has attracted attention for several decades: in standard conditions, instead of recognizing NAD(P)H as an electron donor, it recognizes putative metabolites of NADH, such as N-methyl- and N-ribosyl-dihydronicotinamide. QR2 has been particularly associated with reactive oxygen species and memory, strongly suggesting a link among QR2 (as a possible key element in pro-oxidation), autophagy, and neurodegeneration. In molecular and cellular pharmacology, understanding physiopathological associations can be difficult because of a lack of specific and powerful tools. Here, we present a thorough description of the potent, nanomolar inhibitor [2-(2-methoxy-5H-1,4b,9-triaza(indeno[2,1-a]inden-10-yl)ethyl]-2-furamide (S29434 or NMDPEF; IC505 5–16 nM) of QR2 at different organizational levels. We provide full detailed syntheses, describe its cocrystallization with and behavior at QR2 on a millisecond timeline, show that it penetrates cell membranes and inhibits QR2-mediated reactive oxygen species (ROS) production within the 100 nM range, and describe its actions in several in vivo models and lack of actions in various ROS-producing systems. The inhibitor is fairly stable in vivo, penetrates cells, specifically inhibits QR2, and shows activities that suggest a key role for this enzyme in different pathologic conditions, including neurodegenerative diseases.
Strategies to develop selective CB2 receptor agonists from indole carboxamide synthetic cannabinoids
Moir, Michael,Lane, Samuel,Lai, Felcia,Connor, Mark,Hibbs, David E.,Kassiou, Michael
, p. 291 - 309 (2019/07/17)
Activation of the CB2 receptor is an attractive therapeutic strategy for the treatment of a wide range of inflammatory diseases. However, receptor subtype selectivity is necessary in order to circumvent the psychoactive effects associated with activation of the CB1 receptor. We aimed to use potent, non-selective synthetic cannabinoids designer drugs to develop selective CB2 receptor agonists. Simple structural modifications such as moving the amide substituent of 3-amidoalkylindole synthetic cannabinoids to the 2-position and bioisosteric replacement of the indole core to the 7-azaindole scaffold are shown to be effective and general strategies to impart receptor subtype selectivity. 2-Amidoalkylindole 16 (EC50 CB1 > 10 μM, EC50 CB2 = 189 nM) and 3-amidoalkyl-7-azaindole 21 (EC50 CB1 > 10 μM, EC50 = 49 nM) were found to be potent and selective agonists with favourable physicochemical properties. Docking studies were used to elucidate the molecular basis for the observed receptor subtype selectivity for these compounds.
Zincation and Magnesiation of Functionalized Silylated Cyanohydrins Using TMP-Bases
Castelló-Micó, Alicia,Knochel, Paul
, p. 155 - 169 (2017/10/07)
Polyfunctional silylated cyanohydrins are readily magnesiated or zincated with TMPMgCl·LiCl or TMP 2 Zn·2MgCl 2 ·2LiCl leading to the corresponding metallated derivatives. These Mg- or Zn-derivatives react with various electrophiles such as benzylic bromides, allylic bromides, acid chlorides, aldehydes, NCCO 2 Et, or MeSO 2 SMe. Subsequently, TBAF-deprotection provides the corresponding keto or 1,2-diketo derivatives.
Approach to 5-substituted 6,7,8,9-tetrahydro-5H-pyrido[3,2-c]azepines
Subota, Andrii I.,Artamonov, Oleksiy S.,Gorlova, Alina,Volochnyuk, Dmitriy M.,Grygorenko, Oleksandr O.
supporting information, p. 1989 - 1991 (2017/04/27)
An approach to 5-substituted 6,7,8,9-tetrahydro-5H-pyrido[3,2-c]azepines via the cyclization of 1-(2-(3-azidopropyl)pyridin-3-yl)alkanones under Staudinger–aza-Wittig reaction conditions is described. The overall reaction sequence includes eight steps and allows for the preparation of gram quantities of the title products. In some cases, the formation of 5,7,8,9-tetrahydrooxepino[4,3-b]pyridine derivatives was observed.
1,3,8-TRIAZASPIRO[4,5]DECAN-4-ONE DERIVATIVES USEFUL FOR THE TREATMENT OF ORL-1 RECEPTOR MEDIATED DISORDERS
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Paragraph 0201-0203, (2017/02/28)
The present invention is directed to novel 1,3,8-triazaspiro[4.5]decan-4-one derivatives of the general formulawherein all variables are as defined herein, useful in the treatment of disorders and conditions mediated by the ORL-1 G-protein coupled receptor. More particularly, the compounds of the present invention are useful in the treatment of disorders and conditions such as anxiety, depression, substance abuse, neuropathic pain, acute pain, migraine, asthma, cough and for improved cognition.
