- Route to pyrrolo[1,2-a]quinoxalines via a furan ring opening-pyrrole ring closure sequence
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A method was developed for the synthesis of pyrrolo[1,2-a]quinoxalines based on an acid-promoted furan ring opening of readily accessible N-(furan-2-ylmethyl)-2-nitroanilines or their heterocyclic analogues followed by a key reductive Paal-Knorr cyclization of the corresponding nitro-1,4-diketones.
- Nevolina, Tatyana A.,Skvortsov, Dmitry A.,Sorotskaja, Ludmila N.,Trushkov, Igor V.,Uchuskin, Maxim G.,Zelina, Elena Y.
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- Copper-Catalyzed Direct Nitration on Aryl C-H Bonds by Concomitant Azidation-Oxidation with TMS Azide and TBHP under Aerobic Conditions
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An unprecedented copper-catalyzed in situ azidation-oxidation for the nitration of anilides and sulfonamides has been developed by direct CAr-H functionalization. This novel and efficient nitration protocol is achieved employing TMSN3 and TBHP without the exclusion of air or moisture. The synthetic applications of the 2-nitroanilides have been explored.
- Vinayak, Botla,Chandrasekharam, Malapaka
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supporting information
p. 3528 - 3531
(2017/07/17)
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- Folding Patterns in a Family of Oligoamide Foldamers
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A series of small, unsymmetrical pyridine-2,6-dicarboxylamide oligoamide foldamers with varying lengths and substituents at the end groups were synthetized to study their conformational properties and folding patterns. The @-type folding pattern resembled the oxyanion-hole motifs of enzymes, but several alternative folding patterns could also be characterized. Computational studies revealed several alternative conformers of nearly equal stability. These folding patterns differed from each other in their intramolecular hydrogen-bonding patterns and aryl-aryl interactions. In the solid state, the foldamers adopted either the globular @-type fold or the more extended S-type conformers, which were very similar to those foldamers obtained computationally. In some cases, the same foldamer molecule could even crystallize into two different folding patterns, thus confirming that the different folding patterns are very close in energy in spite of their completely different shapes. Finally, the best match for the observed NOE interactions in the liquid state was a conformation that matched the computationally characterized helix-type fold. Erase and refold: Like peptides, oligoamide foldamers fold into a number of different conformers that are very close in energy (see picture, stability energies in kcal mol-1 given in parentheses). By using a combination of computational, single-crystal X-ray diffraction, and NMR spectroscopic studies, these folding patterns have been identified and characterized for a family of seven different foldamers with varying substituents.
- Kortelainen, Minna,Suhonen, Aku,Hamza, Andrea,Pápai, Imre,Nauha, Elisa,Yliniemel?-Sipari, Sanna,Nissinen, Maija,Pihko, Petri M.
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p. 9493 - 9504
(2015/06/30)
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- Effective nitration of anilides and acrylamides by tert-butyl nitrite
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Nitro compounds are important intermediates in synthetic organic chemistry and the chemical industry. Herein, the efficient copper-catalyzed [10% Cu(NO3)2·3H2O] nitration of anilides was developed by using TBN (tert-butyl nitrite) as a nitrating reagent to give the corresponding nitro-substituted aromatic products in good to excellent yields. The use of TBN also led to the selective nitration of acrylamides at room temperature to afford only the (E) isomer of the nitration product. A series of anilides and acrylamides with a broad array of functional groups were well-tolerated by this procedure. This synthetic method has many advantages, which include inexpensive starting materials, mild reaction conditions, a fast reaction rate, and high yields. A mechanistic investigation indicates that a nitro radical, which is generated from the thermal homolysis of TBN, is involved in the two nitration processes. The efficient nitration of both anilides and acrylamides was achieved by using TBN (tert-butyl nitrite) as a metal-free nitrating reagent. This synthetic method has many advantages such as mild reaction conditions, a fast reaction rate, good to excellent yields, and a broad substrate scope. Our investigation indicates that a nitro radical is involved in the reaction mechanism.
- Ji, Yi-Fei,Yan, Hong,Jiang, Qi-Bai
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p. 2051 - 2060
(2015/03/18)
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- CuSO4-mediated decarboxylative C-N cross-coupling of aromatic carboxylic acids with amides and anilines
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CuSO4-mediated decarboxylative C-N cross-coupling of aromatic carboxylic acid with amide has been developed, leading to N-arylamides in modest to excellent yields. Anilines bearing electron-withdrawing substituents could also couple efficiently
- Sheng, Wei-Jian,Ye, Qing,Yu, Wu-Bin,Liu, Ren-Rong,Xu, Meng,Gao, Jian-Rong,Jia, Yi-Xia
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supporting information
p. 599 - 601
(2015/02/19)
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- A journey from benzanilides to dithiobenzanilides: Synthesis of selective spasmolytic compounds
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A series of dithiobenzanilide derivatives was synthesized and each compound was evaluated for its ability to reduce KCl-induced contractions of smooth muscle preparations of the guinea pig. Starting from a recent publication describing benzanilide derivatives as antispasmodic agents, structure-activity guided synthesis was performed to obtain compounds with improved spasmolytic activity. First, compounds with two amide bonds were designed and second, both amide oxygens were replaced by two sp2 sulfur atoms resulting in dithiobenzanilide derivatives. The most potent antispasmodic dithiobenzanilide 19 showed improved activity with an IC50 value of 0.4 μM. Moreover, the study also demonstrated that these active compounds were able to antagonize the effect of spasmogens like acetylcholine and phenylephrine and that the activity is not mediated by activation of ATP-dependent potassium channels (KATP-channels) or inhibition of endothelial nitric oxide synthase (eNOS).
- Brunhofer, Gerda,Granig, Walter H.,Studenik, Christian R.,Erker, Thomas
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experimental part
p. 994 - 1001
(2011/03/18)
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- Expedient access to fused quinoxalines via Dess-Martin periodinane-mediated cyclization of unsymmetrical phenylenediamide derivatives
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One-pot cyclization of various 2-N-amido-homoallylanilides mediated by 4 equiv of Dess-Martin periodinane produced pyrrolo[1,2-a]quinoxalines (11 examples, up to 93% yield).
- Dobrotǎ, Cristian,Graeupner, Jonathan,Dumitru, Ioana,Matache, Mihaela,Paraschivescu, Codruta C.
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supporting information; experimental part
p. 1262 - 1264
(2010/04/29)
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- Synthesis and biological activity of novel 1,2-disubstituted benzene derivatives as factor Xa inhibitors
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Factor Xa (fXa) is a serine protease that plays a pivotal role in the coagulation cascade. High-throughput screening of the Yamanouchi compound library yielded lead compound 1 with the ability to inhibit fXa at micromolar concentrations. To improve its fX
- Koshio, Hiroyuki,Hirayama, Fukushi,Ishihara, Tsukasa,Shiraki, Ryouta,Shigenaga, Takeshi,Taniuchi, Yuta,Sato, Kazuo,Moritani, Yumiko,Iwatsuki, Yoshiyuki,Kaku, Seiji,Katayama, Naoko,Kawasaki, Tomihisa,Matsumoto, Yuzo,Sakamoto, Shuichi,Tsukamoto, Shin-Ichi
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p. 1305 - 1323
(2007/10/03)
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- Antithrombotic agents
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This application relates to a compound of formula (I), a pharmaceutically acceptable salt of the compound, or a prodrug thereof, as defined herein, pharmaceutical compositions thereof, and its use as an inhibitor of factor Xa, as well as a process for its
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- Structure-based design of potent, amidine-derived inhibitors of factor Xa: Evaluation of selectivity, anticoagulant activity, and antithrombotic activity
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To enhance the potency of 1,2-dibenzamidobenzene-derived inhibitors of factor Xa (fXa), an amidine substituent was incorporated on one of the benzoyl side chains to interact with Asp189 in the S1 specificity pocket. Lead molecule I was docked into the act
- Wiley, Michael R.,Weir, Leonard C.,Briggs, Steven,Bryan, Nancy A.,Buben, John,Campbell, Charles,Chirgadze, Nickolay Y.,Conrad, Richard C.,Craft, Trelia J.,Ficorilli, James V.,Franciskovich, Jeffry B.,Froelich, Larry L.,Gifford-Moore, Donetta S.,Goodson Jr., Theodore,Herron, David K.,Klimkowski, Valentine J.,Kurz, Kenneth D.,Kyle, Jeffery A.,Masters, John J.,Ratz, Andrew M.,Milot, Guy,Shuman, Robert T.,Smith, Tommy,Smith, Gerald F.,Tebbe, Ann Louise,Tinsley, Jennifer M.,Towner, Richard D.,Wilson, Alexander,Yee, Ying K
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p. 883 - 899
(2007/10/03)
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- Reaction of N-Aryl- and N-Alkyl-benzimidoyl Chlorides with Silver Nitrate
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N-Arylbenzimidoyl chlorides, in which the N-aryl group is unsubstituted at the ortho- and para-positions, react with AgNO3 to yield N-(nitroaryl)benzamides, in which the NO2 group resides in the ortho- or para-position.N-Arylbenzimidoyl chlorides, in which the N-aryl ring is 2,4,6-trisubstituted, react with AgNO3 to yield the corresponding N-aryl-N-nitrobenzamides.The formation of both types of product can be explained by the intermediacy of an O-nitro imidate.Spectroscopic and chemical evidence is presented for the formation of this intermediate in the reaction of N-(2,4,6-trisubstituted phenyl)benzimidoyl chlorides with AgNO3.Rearrangement of the O-nitro imidate is unimolecular and intramolecular.The rate of rearrangement is independent of the substituent in the C-aryl ring, but increases with the electon-withdrawing ability of the substituents in the N-aryl ring.A mechanism is proposed in which the imidoyl chloride reacts with AgNO3 to produce first a nitrilium ion which goes on to form an O-nitro imidate that subsequently rearranges via a homolytic cleavage of the O-NO2 bond.The ortho:para ratios of N-(nitroaryl)benzamides obtained in the present work indicate that O-nitro imidates are not responsible for the high 1/2ortho:para ratios sometimes observed in the nitration of anilides.N-Alkylbenzimidoyl chlorides react with AgNO3 to form the corresponding N-nitro- and N-nitrosobenzamides.The mechanism of formation of the N-alkyl-N-nitrobenzamide arises from a pathway analogous to that for N-aryl-N-nitrobenzamides, involving a nitrilium ion that gives rise to an O-nitro imidate.The evidence for the formation of the N-nitrosobenzamide points to an alternative reaction of the imidoyl chloride with AgNO3.One possible mechanism for this reaction is described.
- Iley, Jim,Carvalho, Emilia,Norberto, Fatima,Rosa, Eduarda
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p. 281 - 290
(2007/10/02)
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