26211-90-5Relevant academic research and scientific papers
Palladium-catalyzed cyclization reaction of N-(2-Haloaryl)alkynylimines: Synthesis of 3-acylindoles using water as the sole solvent and oxygen source
Zhang, An-An,Meng, Tuanjie,Wang, Wenli,Liu, Xueli,Zhu, Yupei,Liu, Lantao
, (2020/02/04)
A simple and efficient strategy for the preparation of 3-acylindoles via palladium-catalyzed cyclization reaction of N-(2-haloaryl)alkynylimines in water has been developed. The reaction tolerates a wide range of functional groups, and the corresponding 3-acylindoles were obtained in high yields using water as the sole solvent and oxygen sources. Additionally, this method could provide a short synthesis route for Pravadoline, a phase II analgesic drug.
Cyclooctatetraene: A Bioactive Cubane Paradigm Complement
Xing, Hui,Houston, Sevan D.,Chen, Xuejie,Ghassabian, Sussan,Fahrenhorst-Jones, Tyler,Kuo, Andy,Murray, Cody-Ellen P.,Conn, Kyna-Anne,Jaeschke, Kara N.,Jin, Da-Yun,Pasay, Cielo,Bernhardt, Paul V.,Burns, Jed M.,Tsanaktsidis, John,Savage, G. Paul,Boyle, Glen M.,De Voss, James J.,McCarthy, James,Walter, Gimme H.,Burne, Thomas H. J.,Smith, Maree T.,Tie, Jian-Ke,Williams, Craig M.
supporting information, p. 2729 - 2734 (2019/02/03)
Cubane was recently validated as a phenyl ring (bio)isostere, but highly strained caged carbocyclic systems lack π character, which is often critical for mediating key biological interactions. This electronic property restriction associated with cubane has been addressed herein with cyclooctatetraene (COT), using known pharmaceutical and agrochemical compounds as templates. COT either outperformed or matched cubane in multiple cases suggesting that versatile complementarity exists between the two systems for enhanced bioactive molecule discovery.
Synthesis of indoles and quinazolines via additive-controlled selective C-H activation/annulation of N -arylamidines and sulfoxonium ylides
Lai, Ruizhi,Wu, Xiaohua,Lv, Songyang,Zhang, Chen,He, Maoyao,Chen, Yuncan,Wang, Qiantao,Hai, Li,Wu, Yong
, p. 4039 - 4042 (2019/04/10)
Selective synthesis of indole and quinazoline products was achieved through a precise control of the C-H activation/annulation by changing the additives from NaOAc to CuF2/CsOAc. This strategy constructs indole and quinazoline scaffolds efficie
Application of hypervalent iodine reagent-mediated in preparation of indole derivatives
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Paragraph 0061, (2018/11/22)
The invention relates to application of hypervalent iodine reagent-mediated in preparation of indole derivatives, in particular to the application of organic trivalent iodine reagent iodoyl benzene aminosulfonate in preparing N-protected 2-substituted indole compounds and indomethacin, zidometacin, pravadoline. The invention relates to the application of organic trivalent iodine reagent iodoyl benzene aminosulfonate in preparing N-protected 2-substituted indole compounds, and the reaction undergoes functional group exchange of a substrate. In addition, iodoyl benzene aminosulfonate plays two important roles in this application, as an oxidant and as Bronsted acid. The application has the advantages of good regioselectivity, wide substrate range, mild conditions, simple operation and amplification of experimental steps. The application of the organic trivalent iodine reagent iodoyl benzene aminosulfonate in the preparation of indomethacin, zidomeprin and pravadoline provided by the invention has the advantages of high synthesis efficiency, simple operation and the like.
Collective Synthesis of 3-Acylindoles, Indole-3-carboxylic Esters, Indole-3-sulfinic Acids, and 3-(Methylsulfonyl)indoles from Free (N-H) Indoles via Common N-Indolyl Triethylborate
Zhang, Zhi-Wei,Xue, Hong,Li, Hailing,Kang, Huaiping,Feng, Juan,Lin, Aijun,Liu, Shouxin
supporting information, p. 3918 - 3921 (2016/08/16)
A general and direct C3 functionalization of free (N-H) indoles with readily available electrophiles such as acid chlorides, chloroformates, thionyl chloride, and methylsulfonyl chloride via a common N-indolyl triethylborate intermediate is reported. The reaction proceeds smoothly under mild conditions in up to 93% yield. Indoles with substituents at the C2, C4, C5, C6, and C7 positions are well tolerated. The easy accessibility of a variety of important 3-acylindoles, indole-3-carboxylic esters, indole-3-sulfinic acids, and 3-(methylsulfonyl)indoles demonstrates the high degree of compatibility and practicability of this method.
Synthesis of indoles through Rh(III)-catalyzed C-H cross-coupling with allyl carbonates
Gong, Tian-Jun,Cheng, Wan-Min,Su, Wei,Xiao, Bin,Fu, Yao
supporting information, p. 1859 - 1862 (2014/03/21)
A practical Rh-catalyzed reaction was developed to achieve 2-alkyl-substituted indole synthesis. The reaction can tolerate a variety of synthetically important functional groups. The indole products can also be transformed into other important skeletons. Two bioactive compounds, that is indomethacin and pravadoline were prepared using the new method.
C-attached aminoalkylindoles: Potent cannabinoid mimetics
D'Ambra, Thomas E.,Eissenstat, Michael A.,Abt, Jeffrey,Ackerman, James H.,Bacon, Edward R.,Bell, Malcolm R.,Carabateas, Philip M.,Josef, Kurt A.,Kumar, Virendra,Weaver III, John D.,Arnold, Renee,Casiano, Frances M.,Chippari, Susan M.,Haycock, Dean A.,Kuster, Joan E.,Luttinger, Daniel A.,Stevenson, Joan I.,Ward, Susan J.,Hill, W. Adam,Khanolkar, Atmaram,Makriyannis, Alexandros
, p. 17 - 22 (2007/10/03)
Aminoalkylindoles (AAIs) with potent cannabinoid agonist activity have been synthesized where the aminoalkyl chain is attached to the indole ring via a carbon atom of the cyclic amine.
Transfer of Activation from Indoles to Alcohols: A New Method for the Synthesis of Aminoethylindoles.
Eissenstat, Michael A.,Weaver, John D.
, p. 2029 - 2032 (2007/10/02)
Transfer of a sulfonyl group from an indole nitrogen to a β-amino alkoxide generates an indole anion and an aminoethylsulfonate which react to give aminoethylindoles.
2-Substituted-3-acylindoles through the palladium-catalysed carbonylative cyclization of 2-alkynyltrifluoroacetanilides with aryl halides and vinyl triflates
Arcadi,Cacchi,Carnicelli,Marinelli
, p. 437 - 452 (2007/10/02)
The palladium-catalysed reaction of readily accessible 2- alkynyltrifluoroacetanilides with aryl halides and vinyl triflates under a carbon monoxide atmosphere (1 or 7 atm) and in the presence of potassium carbonate produces 2-substituted-3-acyl indoles in fair to good yield. The acidity of the nitrogen-hydrogen bond proved to be of primary importance for the success of the reaction. The methodology has been applied to the synthesis of pravadoline, a drug that shows analgesic activity against postoperative pain in man.
Antinociceptive (Aminoalkyl)indoles
Bell, Malcolm R.,D'Ambra, Thomas E.,Kumar, Virendra,Eissenstat, Michael A.,Herrmann, John L.,et al.
, p. 1099 - 1110 (2007/10/02)
The (aminoalkyl)indole (AAI) derivative pravadoline (1a) inhibited prostaglandin (PG) synthesis in mouse brain microsomes in vitro and ex vivo and exhibited antinociceptive activity in several rodent assays.In vitro structure-activity relationship studies of this new class of PG synthesis inhibitors revealed a correspondence in three respects to those reported for the arylacetic acids: (1) "α-methylation" caused an increase in PG inhibitory potency, (2) the (R)-α-methyl isomer was more active than the S isomer, (3) the hypothesized aroyl group conformation of the 2-methyl derivatives corresponded to the proposed and reported "active" conformations of the aroyl and related aromatic acetic acid derivatives.The 1H NMR chemical shift of the C-4 hydrogen of pravadoline in comparison to the deshielding seen with 50, which lacks a substituent at C-2, suggested that the carbonyl group of pravadoline is located near C-2 but is located near C-4 in 50.Associated with this conformational change of the carbonyl group of 1a is a diminution of PG synthetase inhibitory activity.The results of UV and difference nuclear Overhauser studies of the two compounds were consistent with these conformational assignments.The low eudismic ratios of the α-methyl derivatives and the observation that the side chain may be extended by three methylene groups without significant loss of PG inhibitory potency suggests that this class of inhibitors bound less strongly and less selectively to the active site of PG synthetase than do the arylacetic acids.Two AAIs, 1a and 30, were found to be metabolized to the corresponding acetic acid derivatives, both of which inhibited PG synthesis.An exception to the observation that the antinociceptive activity of the AAIs was associated with PG synthetase inhibitory activity was the 1-naphthoyl derivative 67 since neither it nor its acetic acid metabolite 74 inhibited PG synthesis.Yet 67 was antinociceptive in four different rodent assays.This naphthoyl derivative, like opioids, also inhibited electrically stimulated contractions in the mouse vas deferens (MVD) preparation.Unlike opioids, however, the inhibition was not antagonized by naloxone.A subseries of AAIs was identified, of which 67 was prototypic.These compounds lacked PG synthetase inhibitory activity, but their inhibitory potency in MVD preparations correlated roughly with their antinociceptive potency in vivo.Pravadoline was also inhibitory in MVD.Is antinociceptive activity, therefore, may be a consequence of both its PG synthease inhibitory potency and another antinociceptive mechanism, the latter associated with its inhibitory potency in the MVD.The evidence is summarized which suggests that this second antinociceptive mechanism is associated with binding to the recently characterized cannabinoid receptor.
