- Biomimetic carbene cascades enabled imine derivative migration from carbene -bearing thiocarbamates
-
Inspired by the body circulation of Omeprazole (irreversible proton pump inhibitor), we disclose the carbene-triggered cascades for the synthesis of 2-aminobenzofuran derivatives from N-sulfonyl-1,2,3-triazoles or benzothioazole-bearing thiocarbamates, which represents an unprecedented imine derivative migration process. Furthermore, the desulfurizing reagent-free Barton-Kellogg-type reactions starting from N-sulfonyl-1,2,3-triazoles have also been achieved for the first time, and elemental sulfur is confirmed as a byproduct during this transformation. Both experimental data and DFT calculations further thoroughly explained the unique reactivity.
- Li, Xue,Chen, Haohua,Xuan, Qingqing,Mai, Shaoyu,Lan, Yu,Song, Qiuling
-
supporting information
p. 3518 - 3523
(2021/05/29)
-
- Pd-Catalyzed ipso, meta-Dimethylation of ortho-Substituted Iodoarenes via a Base-Controlled C-H Activation Cascade with Dimethyl Carbonate as the Methyl Source
-
A methyl group can have a profound impact on the pharmacological properties of organic molecules. Hence, developing methylation methods and methylating reagents is essential in medicinal chemistry. We report a palladium-catalyzed dimethylation reaction of ortho-substituted iodoarenes using dimethyl carbonate as a methyl source. In the presence of K2CO3 as a base, iodoarenes are dimethylated at the ipso- and meta-positions of the iodo group, which represents a novel strategy for meta-C-H methylation. With KOAc as the base, subsequent oxidative C(sp3)-H/C(sp3)-H coupling occurs; in this case, the overall transformation achieves triple C-H activation to form three new C-C bonds. These reactions allow expedient access to 2,6-dimethylated phenols, 2,3-dihydrobenzofurans, and indanes, which are ubiquitous structural motifs and essential synthetic intermediates of biologically and pharmacologically active compounds.
- Wu, Zhuo,Wei, Feng,Wan, Bin,Zhang, Yanghui
-
supporting information
p. 4524 - 4530
(2021/05/04)
-
- Catalyst-Controlled Regioselective Chlorination of Phenols and Anilines through a Lewis Basic Selenoether Catalyst
-
We report a highly efficient ortho-selective electrophilic chlorination of phenols utilizing a Lewis basic selenoether catalyst. The selenoether catalyst resulted in comparable selectivities to our previously reported bis-thiourea ortho-selective catalyst, with a catalyst loading as low as 1%. The new catalytic system also allowed us to extend this chemistry to obtain excellent ortho-selectivities for unprotected anilines. The selectivities of this reaction are up to >20:1 ortho/para, while the innate selectivities for phenols and anilines are approximately 1:4 ortho/para. A series of preliminary studies revealed that the substrates require a hydrogen-bonding moiety for selectivity.
- Dinh, Andrew N.,Maddox, Sean M.,Vaidya, Sagar D.,Saputra, Mirza A.,Nalbandian, Christopher J.,Gustafson, Jeffrey L.
-
p. 13895 - 13905
(2020/11/03)
-
- Iodine(III)-Mediated, Controlled Di- or Monoiodination of Phenols
-
An oxidative procedure for the electrophilic iodination of phenols was developed by using iodosylbenzene as a nontoxic iodine(III)-based oxidant and ammonium iodide as a cheap iodine atom source. A totally controlled monoiodination was achieved by buffering the reaction medium with K3PO4. This protocol proceeds with short reaction times, at mild temperatures, in an open flask, and generally with high yields. Gram-scale reactions, as well as the scope of this protocol, were explored with electron-rich and electron-poor phenols as well as heterocycles. Quantum chemistry calculations revealed PhII(OH)·NH3 to be the most plausible iodinating active species as a reactive "I+" synthon. In light of the relevance of the iodoarene moiety, we present herein a practical, efficient, and simple procedure with a broad functional group scope that allows access to the iodoarene core unit.
- Satkar, Yuvraj,Yera-Ledesma, Luisa F.,Mali, Narendra,Patil, Dipak,Segura-Quezada, Luis A.,Ramírez-Morales, Perla I.,Solorio-Alvarado, César R.,Navarro-Santos, Pedro
-
p. 4149 - 4164
(2019/04/30)
-
- Oxyacylation of Iodoalkynes: Gold(I)-Catalyzed Expeditious Access to Benzofurans
-
(Acetonitrile)[1,3-bis(2,6-diisopropylphenyl)-imidazole-2-ylidene] gold(I) catalyzes the cycloisomerization of 2-(iodoethynyl)aryl esters to give 3-iodo-2-acyl benzofurans. This catalytic transformation is the result of an unprecedented selective syntheti
- Fernández-Canelas, Paula,Rubio, Eduardo,González, José M.
-
supporting information
p. 6566 - 6569
(2019/08/20)
-
- Oxahelicene NHC ligands in the asymmetric synthesis of nonracemic helicenes
-
A straightforward approach to enantiopure 2H-pyran-modified amino[5]helicenes and amino[6]helicenes was developed. They were converted to 1,3-disubstituted imidazolium salts and used as NHC ligand precursors in the Ni0-catalysed enantioselective [2+2+2] cycloisomerisation of aromatic triynes to obtain the model helicene derivatives in up to 86% ee.
- Sánchez, Isabel Gay,?ámal, Michal,Nejedly, Jind?ich,Karras, Manfred,Klívar, Ji?í,Rybá?ek, Ji?í,Budě?ínsky, Milo?,Bednárová, Lucie,Seidlerová, Beata,Stará, Irena G.,Stary, Ivo
-
supporting information
p. 4370 - 4373
(2017/04/21)
-
- Isoquinolinium Dichromate and Chlorochromate as Efficient Catalysts for Oxidative Halogenation of Aromatic Compounds under Acid-Free Conditions
-
Isoquinolinium dichromate and isoquinolinium chlorochromate were found as efficient catalysts to trigger oxidative bromination and iodination of aromatic hydrocarbons with KBr/KI and KHSO4 under acid-free conditions. Reaction times reduced highly significantly under sonication, followed by corresponding mono bromo derivatives in very good yield with high regioselectivity.
- Rao, A. Sambashiva,Rajanna,Reddy, K. Rajendar,Kulkarni, Subhash
-
p. 832 - 837
(2016/02/12)
-
- The Catalyst-Controlled Regiodivergent Chlorination of Phenols
-
Different catalysts are demonstrated to overcome or augment a substrate's innate regioselectivity. Nagasawa's bis-thiourea catalyst was found to overcome the innate para-selectivity of electrophilic phenol chlorination, yielding ortho-chlorinated phenols that are not readily obtainable via canonical electrophilic chlorinations. Conversely, a phosphine sulfide derived from 2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) was found to enhance the innate para-preference of phenol chlorination.
- Maddox, Sean M.,Dinh, Andrew N.,Armenta, Felipe,Um, Joann,Gustafson, Jeffrey L.
-
supporting information
p. 5476 - 5479
(2016/11/17)
-
- Greener iodination of arenes using sulphated ceria-zirconia catalysts in polyethylene glycol
-
An environmentally benign method for the selective monoiodination of diverse aromatic compounds has been developed using reusable sulphated ceria-zirconia under mild conditions. The protocol provides moderate to good yields and selectively introduces iodine at the para/ortho position in monosubstituted arenes. SO42-/Ce0.07Zr 0.93O2 was found to be the best choice for the synthesis of aryl iodides in high yield, presumably due to the maximum number of acid sites (4.23 mmol g-1) among the various compositions of the catalyst system.
- Kahandal, Sandeep S.,Kale, Sandip R.,Gawande, Manoj B.,Zboril, Radek,Varma, Rajender S.,Jayaram, Radha V.
-
p. 6267 - 6274
(2014/01/23)
-
- One-pot synthesis of 2,2′-bisbenzofurans using cuprous chloride as a catalyst
-
A variety of novel 5,5′-disubstituted-2,2′-bisbenzofuran derivatives were synthesized by treatment of 4-substituted-2-(2- trimethylsilylethynyl)phenyl tert-butyldimethylsilyl ether analogues with CuCl as a catalyst in 62-82% isolated yields. This novel st
- Pan, Wen-Bin,Chen, Chin-Chau,Wei, Li-Lan,Wei, Li-Mei,Wu, Ming-Jung
-
p. 2655 - 2657
(2013/06/05)
-
- A quantitative structure-reactivity assessment of phenols by investigation of rapid iodination kinetics using hydrodynamic voltammetry: Applicability of the Hammett equation in aqueous medium
-
Halogenations of aromatic substrates in aqueous medium are essentially electrophilic substitutions proceeding at rates concomitant with the nature of the substrates and substituent motifs. Kinetics as an investigatory tool for the quantitative assessment of the structure-reactivity correlation in these reactions for a diverse range of substrates has rarely been reported, presumably due to the rapidity of these reactions in aqueous medium. We have used hydrodynamic voltammetry to investigate the rapid kinetics of uncatalyzed iodination of phenol and eight substituted phenols by iodine monochloride at constant pH in aqueous medium. The Arrhenius plots for these reactions yield comprehensive kinetic and thermodynamic data. The quantitative structure-reactivity correlation stemming from the regio- and stereospecificity of the substituent motifs on the substrates has been examined through the Hammett plot, which shows a negative slope of 1.87. The magnitudes of the rate constants, energies of activation, frequency factors, and entropy change obtained for the nine fast reactions reported, reflect the relative ease of the reaction dynamics in quantitative terms thereby ascertaining the relative reactivities of the phenols studied herein.
- Borkar, Vitthal T.,Bonde, Shantaram L.,Dangat, Vijay T.
-
p. 693 - 702
(2013/10/21)
-
- Synthesis of 1,4-benzoxazepine derivatives via a novel domino aziridine ring-opening and isocyanide-insertion reaction
-
A novel and efficient domino process has been developed for the synthesis of 1,4-benzoxazepine derivatives from a range of readily accessible N-tosylaziridines, 2-iodophenols and isocyanides. This process involves the aziridine ring-opening reaction with 2-iodophenol, followed by a palladium-catalyzed isocyanide-insertion reaction. This regioselective and high-yielding transformation could be extended to its application for the synthesis of natural products and biologically interesting heterocycles. Copyright
- Ji, Fei,Lv, Mei-Fang,Yi, Wen-Bin,Cai, Chun
-
p. 3401 - 3406
(2013/12/04)
-
- 2,2′-biphenols via protecting group-free thermal or microwave-accelerated suzuki-miyaura coupling in water
-
User-friendly protocols for the protecting group-free synthesis of 2,2′-biphenols via Suzuki-Miyaura coupling of o-halophenols and o-boronophenol are presented. The reactions proceed in water in the presence of simple additives such as K2CO3, KOH, KF, or TBAF and with commercially available Pd/C as precatalyst. Expensive or laboriously synthesized ligands or other additives are not required. In the case of bromophenols, efficient rate acceleration and short reaction times were accomplished by microwave irradiation.
- Schmidt, Bernd,Riemer, Martin,Karras, Manfred
-
p. 8680 - 8688
(2013/09/24)
-
- Iodination of activated aromatic compounds using nanostructure solid acid catalyst
-
Nanoporous silica anchored with sulfonic acid groups effectively catalyzes the iodination of aromatic compounds. The reaction was performed in water using hydrogen peroxide as oxidant. The recyclability of catalyst in green media significantly contributes to the environmental friendliness of the procedure.
- Hosseini, Abolfazl,Khalilzadeh, Mohammad A.,Keipour, Hoda,Tajbakhsh, Mahmood
-
experimental part
p. 2407 - 2414
(2012/07/02)
-
- Green and efficient method for the iodination of phenols in water
-
In this article, green conversion of phenols to the corresponding iodide derivatives is reported. The reactions were conducted in water, using potassium iodide as the source of iodine and potassium ferrate as the oxidizing agent. The selected phenols were successfully iodinated in good to excellent yields in mild and non-toxic reaction conditions. Copyright Taylor & Francis Group, LLC.
- Tajik, Hassan,Dadras, Akbar,Hosseini, Abolfazl
-
experimental part
p. 258 - 261
(2011/06/26)
-
- METHOD OF PRODUCING IODIZING AGENT, AND METHOD OF PRODUCING AROMATIC IODINE COMPOUND
-
A method of the present invention, for producing an iodizing agent, includes the step of electrolyzing iodine molecules in a solution by using an acid as a supporting electrolyte. This realizes (i) a method of producing an iodine cation suitable for use as an iodizing agent that does not require a sophisticated separation operation after iodizing reaction is completed, and (ii) an electrolyte used in the method. Further, a method of the present invention, for producing an aromatic iodine compound, includes the step of causing an iodizing agent, and an aromatic compound whose nucleus has one or more substituent groups and two or more hydrogen atoms, to react with each other under the presence of a certain ether compound. This realizes such a method of producing an aromatic iodine compound that position selectivity in iodizing reaction of an aromatic compound is improved.
- -
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Page/Page column 12
(2010/05/13)
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- A mild and simple iodination of phenols with trichloroisocyanuric acid/I2/wet SiO2 system
-
Molecular iodine in the presence of trichloroisocyanuric acid and wet sio2 has been utilized efficiently for iodination of phenols under mild reaction conditions.
- Akhlaghinia, Batool,Rahmani, Marzieh
-
experimental part
p. 3 - 6
(2010/08/19)
-
- Domino synthesis of 2-arylbenzo[b]furans by copper(II)-catalyzed coupling of o-iodophenols and aryl acetylenes
-
A wide range of 2-arylbenzo[b]furans are synthesized through domino intermolecular C(aryl)-C(alkynyl) bond formation followed by intramolecular C(alkynyl)-O bond forming cyclization via copper(II)-catalyzed coupling of o-iodophenols and aryl terminal acetylenes. This method requires neither expensive palladium catalyst nor oxophilic phosphine ligands, can tolerate different functional groups. The methodology is successfully utilized in formal synthesis of β-amyloid aggregation inhibitor 5-chloro-3-[4-(3-diethylaminopropoxy)benzoyl]-2-(4-methoxyphenyl) benzofuran.
- Jaseer,Prasad,Sekar, Govindasamy
-
scheme or table
p. 2077 - 2082
(2010/04/29)
-
- Mild and efficient oxy-iodination of alkynes and phenols with potassium iodide and tert-butyl hydroperoxide
-
An efficient synthesis of 1-iodoalkynes and iodophenols was easily achieved by employing simple KI and TBHP. The reaction does not involve the use of a metal and base combination. A variety of substituted alkynes and phenols were prepared with good to excellent yield.
- Rajender Reddy,Venkateshwar,Uma Maheswari,Santhosh Kumar
-
supporting information; experimental part
p. 2170 - 2173
(2010/06/14)
-
- Domino ring-opening/carboxamidation reactions of N-tosyl aziridines and 2-halophenols/pyridinol: Efficient synthesis of 1,4-benzo- And pyrido-oxazepinones
-
"Chemical Equation Presented" A domino process is described for the synthesis of 1,4-benzo- and pyrido-oxazepinones by one-pot sequential ring-opening/carboxamidation reactions of various N-tosylaziridines with a range of 2-halophenols/pyridinol under phase-transfer catalysis.
- Chouhan, Gagan,Alper, Howard
-
supporting information; experimental part
p. 192 - 195
(2010/04/02)
-
- Regiospecific oxyhalogenation of aromatics over SBA-15-supported nanoparticle group IV-VI metal oxides
-
TiOx, VOx, MoOx and WOx supported on SBA-15 exhibit efficient catalytic activity for oxyhalogenation of aromatics with the H2O2-halide ion system. Unlike the hitherto known solid catalysts, these reusable catalysts yield the para-halogenated product with 100% selectivity at 298 K and moderate acidic pH (3-5). The catalytic activity was enhanced by five orders of magnitude when supported on SBA-15. Springer Science+Business Media, LLC 2010.
- Saikia,Rajesh,Srinivas,Ratnasamy
-
scheme or table
p. 190 - 201
(2010/11/05)
-
- Selection and development of the manufacturing route for EP1 antagonist GSK269984B
-
A potential manufacturing route for the EP1 antagonist GSK269984B was developed. Four synthetic approaches were examined, and a successful realisation of each is presented. The rationale supporting selection of the preferred route is discussed.
- Whiting, Matthew,Harwood, Kathy,Hossner, Frank,Turner, Peter G.,Wilkinson, Mark C.
-
scheme or table
p. 820 - 831
(2011/03/19)
-
- Regioselective iodination of phenol and analogues using N-iodosuccinimide and p-toluenesulfonic acid
-
Mild and highly regioselective monoiodination of phenol and analogues is achieved in high to excellent yields at room temperature with a combination of stoichiometric p-toluenesulfonic acid and N-iodosuccinimide.
- Bovonsombat, Pakorn,Leykajarakul, Juthamard,Khan, Chiraphorn,Pla-on, Kawin,Krause, Michael M.,Khanthapura, Pratheep,Ali, Rameez,Doowa, Niran
-
scheme or table
p. 2664 - 2667
(2009/08/09)
-
- Syntheses and bioactivity of o- or p-trifluoromethylphenyl phosphates
-
o- and p-Trifluoromethylphenyl phosphates designed as mechanism-based phosphotyrosine phosphatase inactivators have been prepared. Some of them show herbicidal activities.
- Zhou, Xinming,He, Yantao,Wang, Miao,Ding, Yixiang
-
experimental part
p. 651 - 659
(2009/11/30)
-
- Discovery of sodium 6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-2-pyridinecarboxylate (GSK269984A) an EP1 receptor antagonist for the treatment of inflammatory pain
-
We describe the medicinal chemistry programme that led to the identification of the EP1 receptor antagonist GSK269984A (8h). GSK269984A was designed to overcome development issues encountered with previous EP1 antagonists such as GW8
- Hall, Adrian,Billinton, Andy,Brown, Susan H.,Chowdhury, Anita,Clayton, Nicholas M.,Giblin, Gerard M.P.,Gibson, Mairi,Goldsmith, Paul A.,Hurst, David N.,Naylor, Alan,Peet, Caroline F.,Scoccitti, Tiziana,Wilson, Alexander W.,Winchester, Wendy
-
scheme or table
p. 2599 - 2603
(2010/05/19)
-
- Iodination of aromatic compounds using potassium iodide and hydrogen peroxide
-
A simple, efficient, regioselective, and ecofriendly method for oxyiodination of aromatic compounds is presented. In this method, the electrophilic substitutions of iodine generated in situ from KI as an iodine source and hydrogen peroxide as an oxygen source have been employed without any catalyst/mineral acid for the first time. Copyright Taylor & Francis Group, LLC.
- Reddy, K. Suresh Kumar,Narender,Rohitha,Kulkarni
-
experimental part
p. 3894 - 3902
(2009/04/04)
-
- Regioselective iodination of arenes using iodine/NaBO3· 4H2O system in ionic liquid
-
A mild, efficient, and simple protocol was developed for iodination of arenes and heterocyclic compounds with molecular iodine catalyzed by sodium perborate in ionic liquid. The methodology offered iodoarenes in good to excellent yields at room temperature. The protocol proved to be highly selective, as a single isomer was formed exclusively in most of the substrates. Copyright Taylor & Francis Group, LLC.
- Bhilare, Sachin V.,Deorukhkar, Amol R.,Darvatkar, Nitin B.,Salunkhe, Manikrao M.
-
p. 2881 - 2888
(2008/12/22)
-
- Modulators of muscarinic receptors
-
The present invention relates to modulators of muscarinic receptors. The present invention also provides compositions comprising such modulators, and methods therewith for treating muscarinic receptor mediated diseases.
- -
-
Page/Page column 123
(2010/11/29)
-
- A mild and simple regioselective iodination of activated aromatics with iodine and catalytic ceric ammonium nitrate
-
Molecular iodine in the presence of a catalytic amount of CAN has been utilized efficiently for regioselective iodination of activated aromatic compounds under mild reaction conditions.
- Das, Biswanath,Krishnaiah, Maddeboina,Venkateswarlu, Katta,Reddy, V. Saidi
-
-
- Eco-friendly oxyiodination of aromatic compounds using ammonium iodide and hydrogen peroxide
-
A new eco-friendly procedure for the oxyiodination of aromatic compounds with NH4I as an iodine source and H2O2 as an oxidant without any catalyst is presented.
- Narender,Reddy, K. Suresh Kumar,Mohan, K.V.V. Krishna,Kulkarni
-
p. 6124 - 6128
(2008/03/12)
-
- Facile preparation of 2-iodophenyl trifluoromethanesulfonates: Superior aryne precursors
-
A comparative study of 3-methoxyaryne precursors revealed 2-iodo-3-methoxyphenyl triflate as the most effective in nonpolar solvent. Use of Hoppe's N-isopropyl carbamate allows for the systematic preparation of a variety of 2-iodophenyl triflates via a directed ortho-lithiation-iodination- decarbamation sequence. These steps are possible without isolation of the intermediate iodophenyl carbamates. Georg Thieme Verlag Stuttgart.
- Ganta, Ashok,Snowden, Timothy S.
-
p. 2227 - 2231
(2008/02/10)
-
- PYRIDYL COMPOUNDS
-
Compounds of formula (I) or a pharmaceutically acceptable derivative thereof: wherein R1, R2, and R3 are as defined in the specification, a process for the preparation of such compounds, pharmaceutical compositions compris
- -
-
Page/Page column 20-21
(2008/06/13)
-
- Novel, water-based procedure for the mono iodination of aromatic amines and phenols
-
A mixture of potassium chlorate and potassium iodide was found to be a good iodinating agent for various aromatic amines and phenols with excellent yields in the presence of mineral acid in aqueous medium. Copyright Taylor & Francis Group, LLC.
- Sathiyapriya,Joel Karunakaran
-
p. 1915 - 1917
(2007/10/03)
-
- A convenient procedure for the iodination of arenes
-
Two different procedures for the iodination of various arenes using potassium bromate and potassium iodide in the presence of hydrochloric acid are presented. Iodination of benzene, naphthalene and deactivated arenes were carried out in aqueous acetic acid medium and good yields of iodoarenes were obtained. Activated arenes, such as anisole, substituted phenols and anilines underwent excellent conversion to their iodinated products in an aqueous methanol medium.
- Sathiyapriya,Karunakaran, R. Joel
-
p. 575 - 576
(2007/10/03)
-
- Diatomite-supported Pd nanoparticles: An efficient catalyst for Heck and Suzuki reactions
-
The Pd nanoparticles immobilized on natural diatomite were achieved by a simple procedure. The catalysts are highly active for Heck and Suzuki reactions and can be recovered and reused many times. The catalytic process was also investigated.
- Zhang, Zuhui,Wang, Zhiyong
-
p. 7485 - 7487
(2007/10/03)
-
- Discovery of novel biaryl heterocyclic EP1 receptor antagonists
-
We describe the generation of novel EP1 receptor antagonists by investigation of thiophene isosteres. In addition, we disclose preliminary in vitro and in vivo DMPK for selected compounds.
- Hall, Adrian,Bit, Rino A.,Brown, Susan H.,Chaignot, Helene M.,Chessell, Iain P.,Coleman, Tanya,Giblin, Gerard M.P.,Hurst, David N.,Kilford, Ian R.,Lewell, Xiao Q.,Michel, Anton D.,Mohamed, Shiyam,Naylor, Alan,Novelli, Riccardo,Skinner, Lee,Spalding, David J.,Tang, Sac P.,Wilson, Richard J.
-
p. 2666 - 2671
(2007/10/03)
-
- PYRIDINE COMPOUNDS FOR THE TREATMENT OF PROSTAGLANDIN MEDIATED DISEASES
-
Compounds of formula (I) or a pharmaceutiically acceptable derivative thereof: wherein X, Y, Z, R2a, R2b, R3a, R3b, R8, R9, and Rx are as defined in the specification, a process
- -
-
Page/Page column 38; 41
(2008/06/13)
-
- MODULATORS OF MUSCARINIC RECEPTORS
-
The present invention relates to modulators of muscarinic receptors. The present invention also provides compositions comprising such modulators, and methods therewith for treating muscarinic receptor mediated diseases.
- -
-
Page/Page column 88-90
(2010/10/20)
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- A novel series of non-carboxylic acid, non-hydantoin inhibitors of aldose reductase with potent oral activity in diabetic rat models: 6-(5-Chloro-3- methylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one and congeners
-
Discovery of a highly selective, potent, and safe non-carboxylic acid, non-hydantoin inhibitor of aldose reductase (AR) capable of potently blocking the excess glucose flux through the polyol pathway that prevails under diabetic conditions has been a long-standing challenge. In response, we did high-throughput screening of our internal libraries of compounds and identified 6-phenylsulfonylpyridazin-2H-3-one, 8, which showed modest inhibition of AR, both in vitro and in vivo. Initial structure-activity relationships concentrated on phenyl substituents and led to 6-(2,4-dichlorophenylsulfonyl)-2/f-pyridazin- 3-one, 81, which was more potent than 8, both in vitro and in vivo. Incorporation of extant literature findings with other aldose reductase inhibitors, including zopolrestat, resulted in the title inhibitor, 19m, which is one of the most potent and highly selective non-carboxylic acid, non-hydantoin inhibitors of AR yet described (IC50, 1 nM; ED 90 vs sciatic nerve sorbitol and fructose, respectively, 0.8 and 4.0 mg/kg). In rats, its oral bioavailability is 98% and it has a favorable plasma t1/2 (26 ± 3 h).
- Mylari, Banavara L.,Armento, Sandra J.,Beebe, David A.,Conn, Edward L.,Coutcher, James B.,Dina, Michael S.,O'Gorman, Melissa T.,Linhares, Michael C.,Martin, William H.,Oates, Peter J.,Tess, David A.,Withbroe, Gregory J.,Zembrowski, William J.
-
p. 6326 - 6339
(2007/10/03)
-
- Pd-catalyzed copper-free carbonylative Sonogashira reaction of aryl iodides with alkynes for the synthesis of alkynyl ketones and flavones by using water as a solvent
-
The Pd-catalyzed copper-free carbonylative Sonogashira coupling reaction to synthesize alkynyl ketones from terminal alkynes and aryl iodides was achieved by using water as a solvent. The reaction was carried out at room temperature under balloon pressure of CO with Et3N as a base. The developed method was successfully applied to the synthesis of flavones.
- Liang, Bo,Huang, Mengwei,You, Zejin,Xiong, Zhengchang,Lu, Kui,Fathi, Reza,Chen, Jiahua,Yang, Zhen
-
p. 6097 - 6100
(2007/10/03)
-
- NOVEL COMPOUNDS
-
Compounds of the formula (I) are disclosed which are large conductance calcium activated potassium channel openers (BK channels openers) and are useful in the treatment of urinary tract disorders: (I), or a pharmaceutically acceptable salt thereof.
- -
-
Page/Page column 21-22
(2010/02/10)
-
- Fused tricyclic compounds as inhibitors of 17beta-hydroxysteroid dehydrogenase 3
-
Fused tricyclic compounds, methods of using such compounds in the treatment of hormone sensitive diseases such as prostate cancer, and pharmaceutical compositions containing such compounds.
- -
-
Page/Page column 100
(2010/02/14)
-
- (2-((2-ALKOXY) -PHENYL) -CYCLOPENT-1-ENYL) AROMATIC CARBO AND HETEROCYCLIC ACID AND DERIVATIVES
-
Compounds of formula (I) or a pharmaceutically acceptable derivative thereof: (I) wherein A, R1 , R2 , Rx , R8 , R9 and n are as defined in the specification, a process for the preparation of such compounds, pharmaceutical compositions comprising such compounds and the use of such compounds in medicine.
- -
-
Page/Page column 24-25
(2010/02/07)
-
- Pyridazinone aldose reductase inhibitors
-
The present invention relates to novel pyridazinone compounds, pharmaceutical compositions comprising those compounds and to methods of using such compounds and compositions to inhibit aldose reductase, lower sorbitol levels and, thus, lower fructose levels, and/or treat or prevent diabetic complications such as diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic microangiopathy and diabetic macroangiopathy in mammals. This invention also relates to methods of affording cardioprotection to subjects not suffering from diabetes. This invention also relates to pharmaceutical compositions and kits comprising a combination of an aldose reductase inhibitor (ARI) of this invention and a sorbitol dehydrogenase inhibitor and to methods of using such compositions or kits to treat or prevent the above diabetic complications in mammals. This invention also relates to other combinations with the ARIs of this invention, including combinations with adendsine agonists; NHE-1 inhibitors; glycogen phosphorylase inhibitors; selective serotonin reuptake inhibitors; GABA agonists; antihypertensive agents; 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors; phosphodiesterase-5 inhibitors; and to glucose lowering agents.
- -
-
-
- Chemistry of aminophenols. Part 3: First synthesis of nitrobenzo[b]furans via a coupling-cyclization approach
-
The first synthesis of 4-, 5-, and 6-nitrobenzo[b]furans has been achieved via the Sonogashira cross-coupling reaction of 2-iodonitrophenol acetates prepared from commercially available and inexpensive 2-aminonitrophenols. The obtained 2-alkynylnitropheno
- Dai, Wei-Min,Lai, Kwong Wah
-
p. 9377 - 9380
(2007/10/03)
-
- Chalcone derivatives and drugs containing the same
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PCT No. PCT/JP97/01652 Sec. 371 Date Nov. 17, 1998 Sec. 102(e) Date Nov. 17, 1998 PCT Filed May 16, 1997 PCT Pub. No. WO97/44306 PCT Pub. Date Nov. 27, 1997This invention relates to chalcone derivatives represented by the following formula (1): wherein A represents a phenyl group, a quinolyl group or the like, W represents a vinylene group or the like, and R1 to R5 each independently represent a carboxyl, cyano, alkyloxycarbonyl or like group, or salts of the chalcone derivatives, and also to drugs containing them as effective ingredients. These compounds have excellent cys-LT receptor antagonism, and are useful as antiallergic agents or the like.
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- Flavone derivative and medicine comprising the same
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This invention relates to a flavone derivative represented by the formula (1) or a salt thereof, and also to a medicine containing the same. wherein A represents H, halogen, phenyl, naphthyl, a group of the formula (2) in which X is H or halogen, B is -CH
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- Synthesis and structure-activity relationships of carboxylated chalcones: A novel series of CysLT1 (LTD4) receptor antagonists
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The synthesis and CysLT1 antagonistic activities of a new series of 2- , 3-, and 4-(2-quinolinylmethoxy)- and 3- and 4-[2-(2-quinolinyl)ethenyl]- substituted, 2'-, 3'-, 4'-, or 5'-carboxylated chalcones are described. Structure-activity relationship studies indicate a preference for the presence of a negatively charged (acidic) moiety, although in some cases nitrile or ester analogues also exhibit moderate activity. The quinoline moiety may be substituted at either the 3- or the 4-position. Replacement of this heterocycle by other aromatic groups results in compounds with comparable affinities [2-(7-chloroquinoline), 1-(1-methyl-2-benzimidazole), or 1-(2-benzothiazole)] or substantially lower activities [1-(1- ethoxyethyl)-2-benzimidazole, 2-naphthyl, or phenyl]. The quinoline and chalcone moieties may be connected by either an ethenyl or a methoxy spacer. The acidic moiety at the chalcone B ring may be attached to the 2'-, 3'-, 4'- , or 5'-position, for both the 3- and 4-substituted chalcones. There are no general patterns to specify which substitution positions gave the most potent compounds. The series contains several potent CysLT1 receptor antagonists, with K(D) values approaching the nanomolar range, as measured by the displacement of [3H]LTD4 from guinea pig lung membranes. Antagonism of LTD4-induced contraction of guinea pig ileum, the inhibition of antigen- induced contraction of guinea pig trachea in vitro, and the inhibition of LTD4-induced increase of vascular permeability in vivo are determined for chalcones with high CysLT1 receptor affinities (K(D) values below 0.1μM). 2'-Hydroxy-4-(2-quinolinylmethoxy)-5'-(5-tetrazolyl)chalcone (14, VUF 4819) showed good activity in both in vitro and in vivo assays and has been selected for further evaluation.
- Zwaagstra, Mari?l E.,Timmerman, Hendrik,Tamura, Masahiro,Tohma, Tsutomu,Wada, Yasushi,Onogi, Kazuhiro,Zhang, Ming-Qiang
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p. 1075 - 1089
(2007/10/03)
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- A Facile Route to 3a,8a-Dihydrofurobenzofurans.
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Consecutive employment of palladium-catalysis and samarium(II)iodide-induced radical chemistry allows access to analogues of the ABC enol ether tricycle of aflatoxin B1 (1).The Pd-assisted coupling of tributylstannyl ethers of various 2-iodophenols with 2
- Holzapfel, Cedric W.,Williams, D. Bradley G.
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p. 8555 - 8564
(2007/10/02)
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- An Efficient and Selective Method for the Preparation of Iodophenols
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Direct iodination of a wide range of phenols may be achieved with unprecedented selectivity in aqueous alcohol solvents by the action of a reagent preparated in situ from sodium hypochlorite and sodium iodide.Para-substituted phenols (or ortho-substituted, when the para-position is already occupied) are obtained in fair to excellent yields by simple isolation techniques.The extent of iodination is easily controlled by stoichiometry.The technique is also useful with some anilines.
- Edgar, Kevin J.,Falling, Stephen N.
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p. 5287 - 5291
(2007/10/02)
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