- Important Hydrogen Bond Networks in Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Design Revealed by Crystal Structures of Imidazoleisoindole Derivatives with IDO1
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Indoleamine 2,3-dioxygenase 1 (IDO1), promoting immune escape of tumors, is a therapeutic target for the cancer immunotherapy. A number of IDO1 inhibitors have been identified, but only limited structural biology studies of IDO1 inhibitors are available t
- Peng, Yi-Hui,Ueng, Shau-Hua,Tseng, Chen-Tso,Hung, Ming-Shiu,Song, Jen-Shin,Wu, Jian-Sung,Liao, Fang-Yu,Fan, Yu-Shiou,Wu, Mine-Hsine,Hsiao, Wen-Chi,Hsueh, Ching-Cheng,Lin, Shu-Yu,Cheng, Chia-Yi,Tu, Chih-Hsiang,Lee, Lung-Chun,Cheng, Ming-Fu,Shia, Kak-Shan,Shih, Chuan,Wu, Su-Ying
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p. 282 - 293
(2016/01/29)
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- Pyrrolopyrazine Kinase Inhibitors
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The present invention relates to the use of novel pyrrolopyrazine derivatives of Formula I, wherein the variables n, p, q, Q, X, X′ and Y are defined as described herein, which inhibit JAK and SYK and are useful for the treatment of auto-immune and inflammatory diseases.
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Page/Page column 109
(2011/10/10)
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- Discovery of MK-5046, a potent, selective bombesin receptor subtype-3 agonist for the treatment of obesity
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We report the development and characterization of compound 22 (MK-5046), a potent, selective small molecule agonist of BRS-3 (bombesin receptor subtype-3). In pharmacological testing using diet-induced obese mice, compound 22 caused mechanism-based, dose-
- Sebhat, Iyassu K.,Franklin, Christopher,Lo, Michael M.-C.,Chen, David,Jewell, James P.,Miller, Randy,Pang, Jianmei,Palyha, Oksana,Kan, Yanqing,Kelly, Theresa M.,Guan, Xiao-Ming,Marsh, Donald J.,Kosinski, Jennifer A.,Metzger, Joseph M.,Lyons, Kathryn,Dragovic, Jasminka,Guzzo, Peter R.,Henderson, Alan J.,Reitman, Marc L.,Nargund, Ravi P.,Wyvratt, Matthew J.,Lin, Linus S.
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supporting information; experimental part
p. 43 - 47
(2011/04/17)
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- Direct synthesis of pyrroles via a silver-promoted three-component reaction involving unusual imidazole ring opening
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A novel silver-promoted three-component reaction toward the synthesis of multifunctionalized pyrroles has been developed. This reaction involves an unusual imidazole ring decomposition, presumably via 1,5-isomerization and subsequent hydrolysis.
- Zeng, Jing,Bai, Yaguang,Cai, Shuting,Ma, Jimei,Liu, Xue-Wei
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supporting information; experimental part
p. 12855 - 12857
(2012/02/03)
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- Substituted inmidazoles as bombesin receptor subtype-3 modulators
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Certain novel substituted imidazoles are ligands of the human bombesin receptor and, in particular, are selective ligands of the human bombesin receptor subtype-3 (BRS-3). They are therefore useful for the treatment, control, or prevention of diseases and disorders responsive to the modulation of BRS-3, such as obesity, and diabetes.
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Page/Page column 27-28
(2010/02/17)
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- Synthesis of 4,4'-biimidazoles
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The palladium(0) catalysed coupling reaction of 4-iodo-1-triphenylmethylimidazole (7) or its 2-methyl analogue 8 afforded the 4,4'-biimidazoles 9 and 10, respectively. Treatment of these compounds with 60% aqueous trifluoroacetic acid gave 4,4'-biimidazole and 2,2'-dimethyl-4,4'-biimidazole as their bistrifluoroacetate salts 11 and 12, respectively.
- Cliff,Pyne
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p. 681 - 682
(2007/10/02)
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- Electron Spin Resonance Studies of Electron Capture Processes. Part 7. ?* (3-Electron Covalent Bond) Radical Anions of Halogenoimidazoles
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Exposure of dilute solutions of 4-bromo- and 4-iodo-2-methylimidazole, 5-bromo- and 5-iodo-1,2-dimethylimidazole, and 4,5-dibromo- and 4,5-diiodo-1,2-dimethylimidazole in methanol (CD3OD) or methyltetrahydrofuran (MeTHF) to 60Co γ-rays at 77 K resulted in electron addition to yield not the expected ?* radical anions but ?* radical anions.In these radical anions the SOMO is primarly the C-Hal ?* molecular orbital with little delocalisation into the imidazole ring, i.e. a 3-electron ? bond.On slowly increasing the temperature of the MeTHF solutions of the bromoimidazoles the hyperfine features for the ?* radical anions were lost but with no clear concomitant growth of features assignable to 4- or 5-imidazolyl radicals.However, for the iodoimidazoles (2), (4), and (6) in CD3OD a new species was observed on annealing.The same species was observed for all three iodo compounds and is assigned to iodine atoms weakly bonded to CD3OD molecules O(D)CD3>.The results are discussed in the light of the ?* and/or ?* species obtained from electron capture by other aromatic halides and other substituted imidazoles.
- Symons, Martyn C. R.,Bowman, W. Russell
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p. 975 - 979
(2007/10/02)
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- 2(1H)-Quinolinones with Cardiac Stimulant Activity. 3. Synthesis and Biological Properties of 6-Imidazol-1-yl Derivatives
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A series of 6-imidazol-1-yl-8-methyl-2(1H)-quinolinones was synthesized and evaluated for cardiac stimulant activity in dogs.The majority of compounds were prepared from an appropriate 6-imidazol-1-yl-2(1H)-quinolinone precursor or by sulfuric acid cataly
- Bell, Andrew S.,Campbell, Simon F.,Morris, David S.,Roberts, David A.,Stefaniak, Mark H.
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p. 1552 - 1558
(2007/10/02)
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- 6-heteroaryl quinolone inotropic agents
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A series of novel heterocyclic-substituted 2-(1H)-quinolone compounds have been prepared, including the 3,4-dihydro derivatives thereof, wherein the heterocyclic ring moiety is a pyrrolyl, imidazolyl, pyrazolyl, triazolyl or tetrazolyl group attached by a nitrogen atom of said group to the 5-, 6-, 7- or 8-positions of the quinolone ring. These particular compounds are useful in therapy as highly potent inotropic agents and therefore, are of value in the treatment of various cardiac conditions. Preferred member compounds include 6-(2,4-dimethylimidazol-1-yl)-8-methyl-2-(1H)-quinolone, 6-(2,4-dimethyl-5-nitroimadazol-1-yl)-8-methyl-2-(1H)-quinolone, 8-methyl-6-(tetrazol-1-yl)-2-(1H)-quinolone, 8-methyl-6-(1,2,4-triazol-4-yl)-2-(1H)-quinolone, and 6-(4-cyano-2-methylimidazol-1-yl)-8-methyl-2-(1H)-quinolone, respectively. Methods for preparing these compounds from known starting materials are provided.
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- Methyl substituted imidazol-1-yl quinolones
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A series of novel heterocyclic-substituted 2-(1H)-quinolone compounds have been prepared wherein the heterocyclic ring moiety is a substituted pyrrolyl, imidazolyl, pyrazolyl, triazolyl or tetrazolyl group attached by a nitrogen atom of said group to the
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- Quinolone cardiac stimulants
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A quinolone cardiac stimulant of the formula:- or a pharmaceutically acceptable salt thereof,wherein R, which is attached to the 5-, 7- or 8-position of the quinolone, is H or C1-C4 alkyl;, R1 is a group of the formula -S(O)n/s
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- Kinetics of Iodination of 4-Methylimidazole and 2-Methylimidazole
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Since the rate law for the diiodination of imidazole provides information on the iodination of C4(5) but not C2 in the imidazole ring, we have investigated the kinetics of iodination of the two positions separately in 2-methylimidazole and 4-methylimidazole, respectively.The observed rate laws for the methylimidazoles exhibited hydrogen ion dependencies that differed from that of imidazole; the iodinations of all three substrates were base catalyzed, but like imidazole, 2-methylimidazole undergoes uncatalyzed iodination, while 4-methylimidazole does not.The overall rate of iodination of 4-methylimidazole was faster than that of 2-methylimidazole which was faster than that of imidazole.
- Vaughan, John D.,Vaughan, Virginia L.,Daly, Steven S.,Smith, William A.
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p. 3108 - 3111
(2007/10/02)
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