- N-Heterocyclic Carbene Copper(I) Complex Catalyzed Coupling of (Hetero)aryl Chlorides and Nitrogen Heterocycles: Highly Efficient Catalytic System
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A highly efficient catalytic system for the N-arylation reactions of (hetero)aryl chlorides and nitrogen heterocycles with a copper(I) complex containing a 1,10-phenanthroline analogue N-heterocyclic carbene (NHC) has been reported. The complex was characterized by 1H NMR and 13C NMR spectroscopy and elemental analysis, and its structure was determined by single-crystal X-ray diffraction. The NHC-copper(I) complex was employed as pre-catalyst for Ullmann type N-arylation reactions of (hetero)aryl chlorides with various azoles. A variety of hindered and functionalized azoles and (hetero)aryl chlorides were transformed in good to excellent yields.
- Zhang, Mengyao,Zhang, Yingying,Zhang, Huixin,Zeng, Yongfei,Liu, Guiyan
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p. 1252 - 1256
(2020/08/05)
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- Methyl-α-d-glucopyranoside as Green Ligand for Selective Copper-Catalyzed N-Arylation
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In the selective N-arylation of amines or azoles with aryl halidesa-, methyl-α-d-glucopyranoside (MG) was found to function as a green ligand of copper powder. In addition, nitrogen heterocyclic amine compounds can also undergo the N-arylation coupling with heterocyclic aryl chlorides. This process allows access to a variety of aromatic amines and aryl azoles under mild reaction conditions, has good tolerance, and proceeds in moderate to high yield.
- Chen, Fengyang,Chen, Guoliang,Chen, Yuanguang,Du, Fangyu,Zhou, Qifan
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p. 4590 - 4600
(2019/12/11)
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- α-d-Galacturonic Acid as Natural Ligand for Selective Copper-Catalyzed N-Arylation of N-Containing Heterocycles
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The first application of α-d-galacturonic acid hydrate (GalA) is reported here, as a potential O-donor ligand. The C-N couplings of N-heterocycles with aryl halides or arylboronic acids could be readily conducted and exhibited good functional group tolerance with characters of selectivity. These N-Arylazoles allow rapid access to several pharmaceutical intermediates and can be easily transformed into a variety of other interesting scaffolds as well.
- Yuan, Chunling,Zhao, Yingdai,Zheng, Li
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p. 2173 - 2180
(2019/11/25)
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- L -(-) -Quebrachitol as a Ligand for Selective Copper(0)-Catalyzed N-Arylation of Nitrogen-Containing Heterocycles
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l-(-)-Quebrachitol (QCT) has been found as a ligand of copper powder for selective N-arylation of nitrogen-containing heterocycles with aryl halides. Furthermore, another potential catalytic system (copper powder/QCT/t-BuOK) was successfully adapted to unactivated aryl chlorides.
- Zhou, Qifan,Du, Fangyu,Chen, Yuanguang,Fu, Yang,Sun, Wenjiao,Wu, Ying,Chen, Guoliang
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p. 8160 - 8167
(2019/06/28)
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- Functional 1,8-naphthyridine copper(I) complex as efficient catalyst for n-arylation of imidazoles coupling reactions
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The functional 1,8-naphthyridine copper(I) complex, synthesized through a non-catalyst C(sp3)-H methylenation, catalyzes the cross-coupling reaction of aryl halides with imidazoles, by C?N bond formation. The Cu(I) complex catalyzes the reaction with a low catalyst loading (1%, molar fraction) and cheap base even under aerobic conditions. The procedure tolerates aryl halides with various functional groups (such as methyl, methoxy, acetyl, fluoro, nitrile and nitro groups) and gives the corresponding coupling products in moderate to high yields.
- Gou, Gao-Zhang,Wu, Na,Zhang, Ju-Cheng,Shi, Ling,Liu, Gui-Yang,Liu, Wei,Mang, Chao-Yong,Chi, Shao-Ming
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p. 181 - 185
(2018/02/28)
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- N-ARYLATED ANALOGUES AND USES THEREOF
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The present invention provides novel compounds of Formula (I′) and (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Als
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Paragraph 00280; 00281
(2018/06/30)
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- Antimicrobial peptide-inspired NH125 analogues: Bacterial and fungal biofilm-eradicating agents and rapid killers of MRSA persisters
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During microbial infection, antimicrobial peptides are utilized by the immune response to rapidly eradicate microbial pathogens through the destruction of cellular membranes. Inspired by antimicrobial peptides, quaternary ammonium cationic (QAC) compounds have emerged as agents capable of destroying bacterial membranes leading to rapid bacterial death, including the eradication of persistent, surface-attached bacterial biofilms. NH125, an imidazolium cation with a sixteen membered fatty tail, was recently reported to eradicate persister cells and was our starting point for the development of novel antimicrobial agents. Here, we describe the design, chemical synthesis and biological investigations of a collection of 30 diverse NH125 analogues which provided critical insights into structural features that are important for antimicrobial activities in this class. From these studies, multiple NH125 analogues were identified to possess potent antibacterial and antifungal activities, eradicate both bacterial and fungal biofilms and rapidly eradicate MRSA persister cells in stationary phase. NH125 analogues also demonstrated more rapid persister cell killing activities against MRSA when tested alongside a panel of diverse membrane-active agents, including BAC-16 and daptomycin. NH125 analogues could have a significant impact on persister- and biofilm-related problems in numerous biomedical applications.
- Basak, Akash,Abouelhassan, Yasmeen,Zuo, Ran,Yousaf, Hussain,Ding, Yousong,Huigens, Robert W.
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supporting information
p. 5503 - 5512
(2017/07/12)
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- Mechanistic Studies on the Palladium-Catalyzed Direct C-5 Arylation of Imidazoles: The Fundamental Role of the Azole as a Ligand for Palladium
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An in-depth mechanistic study on the palladium-catalyzed direct arylation of imidazoles at the C-5 position is presented. The interactions of triphenylphosphine (PPh3)-ligated aryl-Pd species with 1,2-dimethyl-1H-imidazole (dmim) have been studied in detail. In contrast with previous suggestions, phosphine-ligated organo-Pd species are not active and the reaction proceeds through imidazole-ligated organo-Pd intermediates. The kinetics of the oxidative addition of aryl halides with dmim-ligated Pd(0) species have been characterized in a Pd(dba)2/dmim model system. A thorough study of the equilibria involving novel [ArPd(dmim)2X] complexes (X=I, OAc) and the unexpected cationic [ArPd(dmim)3]+ is also reported. The ability of these species to effect the C-H arylation of dmim at room temperature in the presence of acetate is also demonstrated.
- Perego, Luca Alessandro,Grimaud, Laurence,Bellina, Fabio
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supporting information
p. 597 - 609
(2016/02/27)
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- A cyano-bridged copper(II)-copper(I) mixed-valence coordination polymer as a source of copper oxide nanoparticles with catalytic activity in C-N, C-O and C-S cross-coupling reactions
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A cyano-bridged copper(ii)-copper(i) mixed valence polymer, namely {[Cu4(CN)5(C5H5N)4]} n (1), was synthesized and characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis, differential scanning calorimetric analysis, and single crystal X-ray crystallography. Single crystal X-ray studies show that the coordination polymer 1 is linked by the cyanide anions with μ-1κN:2κC bridging modes to the copper centers, generating a two-dimensional (2D) layered network. The coordination polymer 1, upon pyrolyzing, yielded copper oxide nanoparticles, which have been characterized by TEM and powder X-ray diffraction. The catalytic properties of the resulting copper oxide nanoparticles have also been studied in C-N, C-O, and C-S cross-coupling reactions with aryl halides. The C-N, C-O and C-S coupling products were obtained in moderate to good yields (66-90%, 72-98%, and 50-86%), respectively. the Partner Organisations 2014.
- Trivedi, Manoj,Ujjain, Sanjeev Kumar,Sharma, Raj Kishore,Singh, Gurmeet,Kumar, Abhinav,Rath, Nigam P.
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p. 4267 - 4274
(2014/11/08)
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- Efficient and reusable catalytic system of Cul-PEG for n-arylation of imidazoles
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A simple, efficient, and recyclable catalytic system of CuI-poly(ethylene glycol) (PEG) was developed for the N-arylation of imidazoles with aryl halides to afford corresponding N-arylimidazoles in good to excellent yields under mild conditions and free of any additional ligands and solvents. The isolation of the products was readily performed by simple extraction with ether, and the catalytic system could be reused without remarkable loss of activity even after six runs.
- Zhang, Qiang,Luo, Jun,Wei, Yunyang
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experimental part
p. 114 - 121
(2011/11/01)
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- NOVEL THIOPHENE INHIBITORS OF S-NITROSOGLUTATHIONE REDUCTASE
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The present invention is directed to novel thiophene inhibitors of S-nitrosoglutathione reductase (GSNOR), pharmaceutical compositions comprising such GSNOR inhibitors, and methods of making and using the same.
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Page/Page column 53
(2011/07/07)
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- Cross coupling of arylboronic acids with imidazoles by sulfonatocopper(II) (salen) complex in water
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A mild and clean protocol for the cross coupling reactions between imidazoles and arylboronic acids has been developed in good to excellent yields up to 98% in the presence of sulfonatocopper(II)(salen) catalyst in water without addition of other additives and bases.
- Wang, Lixia,Jiang, Zhaoqiong,Yu, Lintao,Li, Lili,Li, Zhengkai,Zhou, Xiangge
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supporting information; experimental part
p. 764 - 765
(2011/01/11)
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- CuO nanoparticles catalyzed C-N, C-O, and C-S cross-coupling reactions: Scope and mechanism
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CuO nanoparticles have been studied for C-N, C-O, and C-S bond formations via cross-coupling reactions of nitrogen, oxygen, and sulfur nucleophiles with aryl halides. Amides, amines, imidazoles, phenols, alcohols and thiols undergo reactions with aryl iodides in the presence of a base such as KOH, Cs 2CO3, and K2CO3 at moderate temperature. The procedure is simple, general, ligand-free, and efficient to afford the cross-coupled products in high yield.
- Jammi, Suribabu,Sakthivel, Sekarpandi,Rout, Laxmidhar,Mukherjee, Tathagata,Mandai, Santu,Mitra, Raja,Saha, Prasenjit,Punniyamurthy, Tharmalingam
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supporting information; experimental part
p. 1971 - 1976
(2009/07/01)
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- Pyridine N-oxides as ligands in Cu-catalyzed Af-arylation of imidazoles in water
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N-Arylation of imidazoles with aryl halides catalyzed by a combination of copper(II) sulfate and 1,2-bis(2-pyridyl)-ethane-N,N′-dioxide in water afforded up to 95% yield.
- Liang, Lei,Li, Zhengkai,Zhou, Xiangge
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supporting information; experimental part
p. 3294 - 3297
(2009/11/30)
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- A simple and efficient catalytic system for N-arylation of imidazoles in water
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A study was conducted to develop a simple and efficient catalytic system for N-arylation of immidazoles in water. Demonstrations revealed that the catalytic system contained a number of significant advantages. Some of these advantages included the use of water as a green solvent in place of volatile organic solvents and the catalysis was performed without an inert gas atmosphere and with low catalyst loading. Investigations revealed that the presence of catalyst and PTC were essential for the catalysis reaction. The scope of aryl halide substrates was investigated by using the catalytic system under the optimized reaction conditions. It was also demonstrated that the catalytic system tolerated a variety of functionalized aryl halides in the reaction, including nitrile, nitro, acetyl, and ether groups. The new catalytic system was applied to a variety of imidazole derivatives to expand the scope of the methodology.
- Wang, Yi,Wu, Zhiqing,Wang, Lixia,Li, Zhengkai,Zhou, Xiangge
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supporting information; experimental part
p. 8971 - 8974
(2010/04/05)
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- NITROGEN CONTAINING HETEROAROMATICS AS FACTOR Xa INHIBITORS
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The present application describes nitrogen containing heteroaromatics and derivatives thereof of formula (I) or pharmaceutically acceptable salt or prodrug forms thereof, wherein J is N or NH and D may be C(=NH)NH2, which are useful as inhibitors of factor Xa.
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Page/Page column 64-65
(2009/10/01)
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- PYRROLOTHIAZOLES AS PI3-KINASE INHIBITORS
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A series of 4,5-dihydro-6H-pyrrolo[3,4-d][1,3]thiazol-6-one derivatives, and analogues thereof, which are substituted in the 2-position by an optionally substituted morpholin-4-yl moiety, being selective inhibitors of PI3 kinase enzymes, are accordingly o
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Page/Page column 83
(2009/07/17)
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- N,N′-(Phenylmethylene)diacetamide analogues as economical and efficient ligands in copper-catalyzed arylation of aromatic nitrogen-containing heterocycles
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N,N′-(Phenylmethylene)diacetamide analogues which were simply prepared from the condensation reaction of an aldehyde with an amide or urea were found to be efficient ligands in copper-catalyzed coupling reaction of aryl halides with various azole nucleophiles. The newly developed ligand showed broad application scope in this conversion. Compounds including imidazoles, benzoimidazoles, pyrrole, indole, and benzotriazole were successfully arylated with diversified aromatic halides to give corresponding products in moderate to excellent yields. Georg Thieme Verlag Stuttgart.
- Wan, Jie-Ping,Chai, Yun-Feng,Wu, Jian-Mei,Pan, Yuan-Jiang
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experimental part
p. 3068 - 3072
(2009/06/28)
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- Discovery of 1-(3′-aminobenzisoxazol-5′-yl)-3-trifluoromethyl- N-[2-fluoro-4-[(2′-dimethylaminomethyl)imidazol-1-yl]phenyl] -1H-pyrazole-5-carboxyamide hydrochloride (razaxaban), a highly potent, selective, and orally bioavailable factor Xa inhibitor
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Modification of a series of pyrazole factor Xa inhibitors to incorporate an aminobenzisoxazole as the P1 ligand resulted in compounds with improved selectivity for factor Xa relative to trypsin and plasma kallikrein. Further optimization of the P4 moiety led to compounds with enhanced permeability and reduced protein binding. The SAR and pharmacokinetic profile of this series of compounds is described herein. These efforts culminated in 1-(3′-aminobenzisoxazol-5′-yl)-3-trifluoromethyl-N-[2-fluoro-4- [(2′-dimethylaminomethyl)imidazol-1-yl]phenyl]-1H-pyrazole-5-carboxyamide (11d), a potent, selective, and orally bioavailable inhibitor of factor Xa. On the basis of its excellent in vitro potency and selectivity profile, high free fraction in human plasma, good oral bioavailability, and in vivo efficacy in antithrombotic models, the HCl salt of this compound was selected for clinical development as razaxaban (DPC 906, BMS-561389).
- Quan, Mimi L.,Lam, Patrick Y. S.,Han, Qi,Pinto, Donald J. P.,He, Ming Y.,Li, Renhua,Ellis, Christopher D.,Clark, Charles G.,Teleha, Christopher A.,Sun, Jung-Hui,Alexander, Richard S.,Bai, Steve,Luettgen, Joseph M.,Knabb, Robert M.,Wong, Pancras C.,Wexler, Ruth R.
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p. 1729 - 1744
(2007/10/03)
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- NOVEL GUANIDINE MIMICS AS FACTOR Xa INHIBITORS
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The present application describes nitrogen containing heteroaromatics and derivatives thereof of formula (I) or pharmaceutically acceptable salt forms thereof, wherein rings D-E represent guanidine mimics, which are useful as inhibitors of factor Xa.
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Page/Page column 52
(2010/02/13)
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- 1-(2-Naphthyl)-1H-pyrazole-5-carboxylamides as potent factor Xa inhibitors. Part 2: A survey of P4 motifs
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A variety of P4 motifs have been examined to increase the binding affinity and in vitro anticoagulant potency of our biphenyl 1-(2-naphthyl)-1H-pyrazole-5- carboxylamide-based fXa inhibitors. Highly potent 2-naphthyl-P1 fXa inhibitors (Ki≤2 nM) with improved in vitro anticoagulant activity (2×TG≤1 μM) and respectable pharmacokinetic properties have been discovered.
- Jia, Zhaozhong J.,Wu, Yanhong,Huang, Wenrong,Zhang, Penglie,Clizbe, Lane A.,Goldman, Erick A.,Sinha, Uma,Arfsten, Ann E.,Edwards, Susan T.,Alphonso, Merlyn,Hutchaleelaha, Athiwat,Scarborough, Robert M.,Zhu, Bing-Yan
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p. 1221 - 1227
(2007/10/03)
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- Nitrogen containing heteroaromatics as factor Xa inhibitors
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The present application describes nitrogen containing heteroaromatics and derivatives thereof of formula I: or pharmaceutically acceptable salt or prodrug forms thereof, wherein J is N or NH and D may be C(=NH)NH2, which are useful as inhibitors of factor Xa.
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- Synthesis and serotonergic activity of N,N-dimethyl-2-[5-(1,2,4-triazol- 1-ylmethyl)-1H-indol-3-yl]ethylamine and analogues: Potent agonists for 5- HT(1D) receptors
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The synthesis and the 5-HT receptor activity of a novel series of N,N- dimethyltryptamines substituted in the 5-position with an imidazole, triazole, or tetrazole ring are described. The objective of this work was to identify potent and selective 5-HT(1D) receptor agonists with high oral bioavailability and low central nervous system penetration. Compounds have been prepared in which the azole ring is attached through either nitrogen or carbon to the indole. Conjugated and methylene-bridged derivatives have been studied (n = 0 or 1). Substitution of the azole ring has been explored either α or β to the point of attachment to indole. In a series of N-linked azoles (X = N), simple unsubstituted compounds have high affinity and selectivity for 5-HT(1D) receptors. It is proposed that for good affinity and selectivity a hydrogen bond acceptor interaction with the 5-HT(1D) receptor, through a β-nitrogen in the azole ring, is required. In a series of C-linked triazoles and tetrazoles (X = C), optimal affinity and selectivity for the 5-HT(1D) receptor was observed when the azole ring is substituted at the 1-position with a methyl or ethyl group. This study has led to the discovery of the 1,2,4-triazole 10a (MK-462) as a potent and selective 5-HT(1D) receptor agonist which has high oral bioavailability and rapid oral absorption. The in vitro activity and the preliminary pharmacokinetics of compounds in this series are presented.
- Street,Baker,Davey,Guiblin,Jelley,Reeve,Routledge,Sternfeld,Watt,Beer,Middlemiss,Noble,Stanton,Scholey,Hargreaves,Sohal,Graham,Matassa
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p. 1799 - 1810
(2007/10/02)
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- Triazole containing indole derivatives
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A class of substituted imidazole, triazole and tetrazole derivatives are selective agonists of 5-HT 1 -like receptors and are therefore useful in the treatment of clinical conditions, in particular migraine and associated disorders, for which a selective agonist of these receptors is indicated.
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- Bis-aryl amide and urea antagonists of platelet activating factor
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Bis-aryl amide and urea compounds of the general formula: STR1 wherein X is a divalent amide or urea substituent and Y is a nitrogen containing heterocycle, which compounds are inhibitors of platelet activating factor. Pharmaceutical compositions containing the compounds and methods of treating platelet activating factor associated conditions are also included.
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- Method of preparing bis-aryl amide and urea antagonists of platelet activating factor
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Methods of preparing bis-aryl amide and urea compounds of the general formula: STR1 wherein x is a divalent amide or urea substituent and Y is a nitrogen containing heterocycle, which compounds are inhibitors of platelet activating factor.
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