- Tautomerism of 4-hydroxy-4(1H) quinolon
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The tautomerism of 4-Hydroxy-4(1H) quinolon I was studied using infrared spectroscopy, 1H,13C NMR spectroscopy and X-ray crystallography. The keto-form of I is favored in the crystal form and at room temperature in polar solutions like water and dimethylsulfoxide.
- Nasiri, Hamid Reza,Bolte, Michael,Schwalbe, Harald
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- Deuterated Aryl Alkyl Ethers Synthesis via Nucleophilic Etherification of Aryl Alkyl Ethers and Thioethers with Deuterated Alcohols
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A transition-metal-free etherification protocol that is capable of synthesizing deuterated ethers is described. A wide range of aryl alkyl ethers and thioethers were suitable for this transformation owing to the mild reaction conditions. Besides, a series of sterically bulky deuterated alcohols were successfully incorporated into cyano-substituted arenes. The results of mechanistic studies suggested this reaction might take place via nucleophilic aromatic substitution pathway.
- Li, Shuai,Wang, Xia,Wang, Xue-Qiang,Yang, Xin-Ge,Yu, Gui-Quan
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supporting information
p. 1805 - 1809
(2019/09/09)
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- Discovery of MK-8318, a Potent and Selective CRTh2 Receptor Antagonist for the Treatment of Asthma
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A novel series of tricyclic tetrahydroquinolines were identified as potent and selective CRTh2 receptor antagonists. The agonism and antagonism switch was achieved through structure-based drug design (SBDD) using a CRTh2 receptor homologue model. The challenge of very low exposures in pharmacokinetic studies was overcome by exhaustive medicinal chemistry lead optimization through focused SAR studies on the tricyclic core. Further optimization resulted in the identification of the preclinical candidate 4-(cyclopropyl((3aS,9R,9aR)-7-fluoro-4-(4-(trifluoromethoxy)benzoyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl)amino)-4-oxobutanoic acid (15c, MK-8318) with potent and selective CRTh2 antagonist activity and a favorable PK profile suitable for once daily oral dosing for potential treatment of asthma.
- Huang, Xianhai,Brubaker, Jason,Zhou, Wei,Biju, Purakkattle J.,Xiao, Li,Shao, Ning,Huang, Ying,Dong, Li,Liu, Zhidan,Bitar, Rema,Buevich, Alexei,Jung, Joon,Peterson, Scott L.,Butcher, John W.,Close, Joshua,Martinez, Michelle,Maccoss, Rachel N.,Zhang, Hongjun,Crawford, Scott,McCormick, Kevin D.,Aslanian, Robert,Nargund, Ravi,Correll, Craig,Gervais, Francois,Qiu, Hongchen,Yang, Xiaoxin,Garlisi, Charles,Rindgen, Diane,Maloney, Kevin M.,Siliphaivanh, Phieng,Palani, Anandan
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supporting information
p. 679 - 684
(2018/07/05)
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- PYRAZOLE DERIVATIVES AS MALT1 INHIBITORS
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Disclosed are compounds, compositions and methods for treating of diseases, syndromes, conditions, and disorders that are affected by the modulation of MALT1. Such compounds are represented by Formula (I) as follows: wherein R1, R2, R3, R4, R5, R6, R5, G1, and G2 are defined herein.
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- General and Practical Potassium Methoxide/Disilane-Mediated Dehalogenative Deuteration of (Hetero)Arylhalides
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Herein we describe a general, mild and scalable method for deuterium incorporation by potassium methoxide/hexamethyldisilane-mediated dehalogenation of arylhalides. With CD3CN as a deuterium source, a wide array of heteroarenes prevalent in pharmaceuticals and bearing diverse functional groups are labeled with excellent deuterium incorporation (>60 examples). The ipso-selectivity of this method provides precise access to libraries of deuterated indoles and quinolines. The synthetic utility of our method has been demonstrated by the incorporation of deuterium into complex natural and drug-like compounds.
- Wang, Xin,Zhu, Ming-Hui,Schuman, David P.,Zhong, Dayou,Wang, Wen-Yan,Wu, Lin-Yang,Liu, Wei,Stoltz, Brian M.,Liu, Wen-Bo
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supporting information
p. 10970 - 10974
(2018/09/06)
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- QUINOLINE DERIVATIVES AS SMO INHIBITORS
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Disclosed are quinoline derivatives as hedgehog pathway inhibitors, especially as SMO inhibitors. Compounds of the present invention can be used in treating diseases relating to hedgehog pathway including cancer.
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Paragraph 0349; 0350
(2017/02/28)
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- N-Methylimidazole-mediated synthesis of aryl alkyl ethers under microwave irradiation and solvent free conditions
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A microwave-assisted three-component reaction was established for the synthesis of aryl alkyl ethers. The reaction was performed under solvent-free conditions in the presence of N-methylimidazole and dialkyl acetylene-dicarboxylate to furnish a novel approach to O-alkylation of phenol derivatives in high yield.
- Djahaniani, Hoorieh,Aghadadashi-Abhari, Laila,Mohtat, Bita
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p. 459 - 464
(2015/06/16)
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- Chiral helical oligotriazoles: New class of anion-binding catalysts for the asymmetric dearomatization of electron-deficient N -heteroarenes
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Helical chirality and selective anion-binding processes are key strategies used in nature to promote highly enantioselective chemical reactions. Although enormous efforts have been made to develop simple helical chiral systems and thus open new possibilities in asymmetric catalysis and synthesis, the efficient use of synthetic oligo- and polymeric helical chiral catalysts is still very challenging and rather unusual. In this work, structural unique chiral oligotriazoles have been developed as C-H bond-based anion-binding catalysts for the asymmetric dearomatization of N-heteroarenes. These rotational flexible catalysts adopt a reinforced chiral helical conformation upon binding to a chloride anion, allowing high levels of chirality transfer via a close chiral anion-pair complex with a preformed ionic substrate. This methodology offers a straightforward and potent entry to the synthesis of chiral (bioactive)heterocycles with added synthetic value from simple and abundant heteroarenes.
- Zurro, Mercedes,Asmus, S?ren,Beckendorf, Stephan,Mück-Lichtenfeld, Christian,Mancheo, Olga Garca
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supporting information
p. 13999 - 14002
(2015/01/08)
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- Direct, catalytic, and regioselective synthesis of 2-alkyl-, aryl-, and alkenyl-substituted N -Heterocycles from n -oxides
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A one-step transformation of heterocyclic N-oxides to 2-alkyl-, aryl-, and alkenyl-substituted N-heterocycles is described. The success of this broad-scope methodology hinges on the combination of copper catalysis and activation by lithium fluoride or magnesium chloride. The utility of this method for the late-stage modification of complex N-heterocycles is exemplified by facile syntheses of new structural analogues of several antimalarial, antimicrobial, and fungicidal agents.
- Larionov, Oleg V.,Stephens, David,Mfuh, Adelphe,Chavez, Gabriel
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p. 864 - 867
(2014/03/21)
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- Gold(I)-catalyzed protodecarboxylation of (Hetero)aromatic carboxylic acids
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Readily available, inexpensive and easy to handle, carboxylic acids have been shown to be very effective, greener coupling partners compared to costly organometallic reagents for the formation of C-C bonds. The use of well-defined gold complexes furnished 3 in slightly better yield with butyric acid, and in quantitative yield with adamantane-1-carboxylic acid. All reactions reached completion within 16 h. As with silver systems, this reactivity trend highlights, as previously observed, the benefits of potential coordinating groups in the ortho position to the gold binding site, which possibly facilitate the decarboxylation step. Additional reaction time and increased temperatures were necessary to afford the gold aryl products in satisfactory yields. Yet, some substrates such as 2-nitrobenzoic acids reacted poorly and could only be transformed in 50% yield.
- Dupuy, Stéphanie,Nolan, Steven P.
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supporting information
p. 14034 - 14038
(2013/11/19)
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- Continuous flow coupling and decarboxylation reactions promoted by copper tubing
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A convenient and efficient flow method for Ullmann condensations, Sonogashira couplings, and decarboxylation reactions using a commercially available copper tube flow reactor (CTFR) is described. The heated CTFR effects these transformations without added metals (e.g., Pd), ligands, or reagents, and in greater than 90% yield in most cases examined.
- Zhang, Yun,Jamison, Timothy F.,Patel, Sejal,Mainolfi, Nello
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supporting information; experimental part
p. 280 - 283
(2011/04/15)
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- Asymmetric synthesis of C2-symmetric vicinal diamines via reductive dimerization of N-acylpyridinium and related salts
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(Chemical Equation Presented) A new route to C2-symmetric diamines via an asymmetric reductive dimerization of 1-acylpyridinium salts and their benzo derivatives is described. This method is practical as the starting heterocycles and chiral aux
- Bharathi, Pandi,Comins, Daniel L.
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p. 221 - 223
(2008/09/18)
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- NOVEL NITROGENATED HETEROCYCLIC COMPOUND AND SALT THEREOF
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A nitrogen-containing heterocyclic compound represented by the general formula: wherein the dashed line represents a single bond or a double bond; R1, R2, R3, R4 and R5 independently represent a hydrogen atom, halogen atom, a lower alkyl, aryl, lower alkoxy or monocyclic heterocyclic group which may be substituted or the like; R6 represents a lower alkyl, aryl, monocyclic heterocyclic, bicyclic heterocyclic or tricyclic heterocyclic group which may be substituted; X1 represents a lower alkylene group or the like; X2 represents a lower alkylene, lower alkenylene or lower alkynylene group which may be substituted; X3 represents an oxygen atom, sulfur atom, a sulfinyl group, sulfonyl group or the like; Y1 represents a bivalent cyclic group, containing a nitrogen, which may be substituted or the like; and Z1 represents a nitrogen atom, a carbon atom which may be substituted or the like, or a salt thereof. The compound or salt has a potent antibacterial activity and a high safety, and is therefore useful as an excellent antibacterial agent.
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Page/Page column 118
(2010/11/30)
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- Tetrahydroquinoline derivatives as CRTH2 antagonists
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The invention relates to compounds of formula (I) wherein R1, R2, R3, R4, R5, R6, R7 and R8 are as defined in the description, their use as medicament, pharmaceutical compositions containing them and processes for their preparation.
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- Quinoline derivatives as CRTH2 antagonists
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The invention relates to compounds of formula (I) wherein R1, R2, R3, R4, R5, R6, R7 and R8 are as defined in the description, their use as medicament, pharmaceutical compositions containing them and processes for their preparation.
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- Efficient nucleophilic substitution reactions of quinolyl and isoquinolyl halides with nucleophiles under focused microwave irradiation
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Nucleophilic substitution reactions of 2-chloroquinoline, 3-bromoquinoline and 4-bromoisoquinoline with thiolate, alkoxy ions and aniline were completed within several minutes under microwave irradiation. This method gives the desired products with yields up to 99% in a short reaction time, and is superior to the classical heating process.
- Cherng, Yie-Jia
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p. 1125 - 1129
(2007/10/03)
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- Photoelectron spectroscopy of quinoline derivatives. Correlation of experimental ionization potentials with calculated molecular energies
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Experimental ionization potentials of quinoline 1 and substituted quinolines: 6-methylquinoline 2, 2,6-dimethylquinoline 3, 6-methoxyquinoline 4, 3-bromoquinoline 5, 2-chloro-4-methylquinoline 6, 4-hydroxyquinoline 7, 4-hydroxy-2-methylquinoline 8, 2-hydroxy-4-methylquinoline 9, 4-methoxyquinoline 10, 4- methoxy-2-methylquinoline 11, 2-methoxy-4-methylquinoline 12, were measured by photoelectron spectroscopy. Molecular orbital energies of the same derivatives were calculated by the Austin Method 1. The assignments of the bands of the photoelectron spectra were done with the aid of the theoretical calculations and on the basis of the substituent effects. For quinolines 1-6 a good agreement was found between the experimental ionization potentials and the calculated orbital energies.
- Ahmed,Julliard,Chanon,Chanon,Gracian,Pfister-Guillouzo
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p. 335 - 343
(2007/10/03)
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- SYNTHESIS OF 4-ALKOXYQUINOLINES FROM QUINOLINE REISSERT COMPOUNDS
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The quinoline Reissert compound (5a) was converted to 1-benzoyl-3-bromo-2-cyano-1,2,3,4-tetrahydro-4-methoxyquinoline (6a) by successive treatment in methanol with bromine and aq. sodium carbonate.Hydrolysis of 6a with hydrochloric acid gave 3-bromoquinoline (4; R=H), but that with aq. sodium hydroxide afforded 4-methoxyquinoline (7a).Reissert compounds derived from some quinoline derivatives (5) gave the corresponding 4-methoxyquinolines (7) through tetrahydroquinolines (6) in a similar way.
- Sugiura, Michiharu,Sakurai, Yoshie,Hamada, Yoshiki
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p. 561 - 568
(2007/10/02)
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- NEW METHODS AND REAGENTS IN ORGANIC SYNTHESIS. 46.1) TRIMETHYLSILYLDIAZOMETHANE: A CONVENIENT REAGENT FOR THE O-METHYLATION OF PHENOLS AND ENOLS
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Trimethylsilyldiazomethane reacts smoothly with phenols and enols in methanolic acetonitrile solution in the presence of N,N-diisopropylethylamine to give methyl ethers. KEYWORDS --- trimethylsilyldiazomethane; phenol; enol; O-methylation; methyl ether
- Aoyama, Toyohiko,Terasawa, Satomi,Sudo, Kimio,Shioiri, Takayuki
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p. 3759 - 3760
(2007/10/02)
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- Electrolytic Adamantylation by Reductive Coupling of Quinolinylhalides in the Presence of 1-Bromoadamantane
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Electrochemically generated anion radicals of a number of halogen-substituted quinolines 1a-g dehalogenate in N,N-dimethylformamide to halogen anions and radicals, which may stabilize by hydrogen abstraction from the solvent.In the presence of 1-bromoadamantane the fragments of reductive dehalogenation may be used synthetically for indirect generation of 1-bromoadamantane-radicals, which react predominantly to cross-coupled 2- and 7-monoadamantylated dihydroquinoline- and quinoline-structures, independent of the original halogen position.If C-2 is blocked, adamantylation takes place in the carbocyclic ring.Product distribution and cyclic-voltammetric results are discussed in terms of mechanism.
- Hess, U.,Huhn, D.
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p. 381 - 392
(2007/10/02)
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