- Discovery of novel Tricyclic full agonists for the G-protein-coupled niacin receptor 109A with minimized flushing in rats
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Tricyclic analogues were rationally designed as the high affinity niacin receptor G-protein-coupled receptor 109A (GPR109A) agonists by overlapping three lead structures. Various tricyclic anthranilide and cycloalkene carboxylic acid full agonists were di
- Shen, Hong C.,Ding,Deng, Qiaolin,Wilsie, Larissa C.,Krsmanovic, Mihajlo L.,Taggart, Andrew K.,Carballo-Jane, Ester,Ren, Ning,Cai,Wu,Wu, Kenneth K.,Cheng, Kang,Chen, Qing,Wolff, Michael S.,Tong, Xinchun,Holt, Tom G.,Waters, M. Gerard,Hammond, Milton L.,Tata, James R.,Colletti, Steven L.
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supporting information; experimental part
p. 2587 - 2602
(2010/01/15)
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- Tricyclic 6-alkylidene-penems as class-D beta-lactamases inhibitors
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This invention relates to certain tricyclic 6-alkylidene penems which act as a inhibitor of class-D enzymes. β-Lactamases hydrolyze β-lactam antibiotics, and as such serve as the primary cause of bacterial resistance. The compounds of the present inventio
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Page/Page column 9
(2010/11/25)
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- Structure-activity relationship of 6-methylidene penems bearing tricyclic heterocycles as broad-spectrum β-lactamase inhibitors: Crystallographic structures show unexpected binding of 1,4-thiazepine intermediates
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The design and synthesis of a series of seven tricyclic 6-methylidene penems as novel class A and C serine β-lactamase inhibitors is described. These compounds proved to be very potent inhibitors of the TEM-1 and AmpC β-lactamases and less so against the class B metallo-β-lactamase CcrA. In combination with piperacillin, their in vitro activities enhanced susceptibility of all class C resistant strains from various bacteria. Crystallographic structures of a serine-bound reaction intermediate of 17 with the class A SHV-1 and class C GC1 enzymes have been established to resolutions of 2.0 and 1.4 A?, respectively, and refined to R-factors equal 0.163 and 0.145. In both β-lactamases, a seven-membered 1,4-thiazepine ring has formed. The stereogenic C7 atom in the ring has the R configuration in the SHV-1 intermediate and has both R and S configurations in the GC1 intermediate. Hydrophobic stacking interactions between the tricyclic C7 substituent and a tyrosine side chain, rather than electrostatic or hydrogen bonding by the C3 carboxylic acid group, dominate in both complexes. The formation of the 1,4- thiazepine ring structures is proposed based on a 7-endo-trig cyclization.
- Venkatesan, Aranapakam M.,Gu, Yansong,Santos, Osvaldo Dos,Abe, Takao,Agarwal, Atul,Yang, Youjun,Petersen, Peter J.,Weiss, William J.,Mansour, Tarek S.,Nukaga, Michiyoshi,Hujer, Andrea M.,Bonomo, Robert A.,Knox, James R.
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p. 6556 - 6568
(2007/10/03)
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- Process for preparing 6-alkylidene penem derivatives
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The present invention provides a process of making compounds of formula I, which are useful for the treatment of bacterial infection or disease.
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- HETEROTRICYCLYL 6-ALKYLIDENE-PENEMS AS ΒΕΤΑ-LACTAMASE INHIBITORS
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The present invention provides a compound of formula I, pharmaceutical compositions and the use thereof for the treatment of bacterial infection or disease in a patient in need thereof.
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Page/Page column 96
(2008/06/13)
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- PROCESS FOR PREPARING 6-ALKYLIDENE PENEM DERIVATIVES
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The present invention provides a process of making compounds of Formula (I), which are useful for the treatment of bacterial infection or disease.
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Page/Page column 82
(2010/02/07)
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- (Imidazopyrimidin-2-yl)phenylmethanones and Related Compounds as Potential Nonsedative Anxiolytics
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Several series of heterocyclic carboxylic esters were found to be active in the benzodiazepine receptor binding assay, a typical example being ethyl 7-ethyl-5-methoxyimidazoquinoline-2-carboxylate (4b) with an IC50 of 150 nM.The correspo
- Clements-Jewery, Stephen,Danswan, Geoffrey,Gardner, Colin R.,Matharu, Saroop S.,Murdoch, Robert,et al.
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p. 1220 - 1226
(2007/10/02)
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