- Discovery of Benzopyridone-Based Transient Receptor Potential Vanilloid 1 Agonists and Antagonists and the Structural Elucidation of Their Activity Shift
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Among a series of benzopyridone-based scaffolds investigated as human transient receptor potential vanilloid 1 (TRPV1) ligands, two isomeric benzopyridone scaffolds demonstrated a consistent and distinctive functional profile in which 2-oxo-1,2-dihydroquinolin-5-yl analogues (e.g., 2) displayed high affinity and potent antagonism, whereas 1-oxo-1,2-dihydroisoquinolin-5-yl analogues (e.g., 3) showed full agonism with high potency. Our computational models provide insight into the agonist-antagonist boundary of the analogues suggesting that the Arg557 residue in the S4-S5 linker might be important for sensing the agonist binding and transmitting signals. These results provide structural insights into the TRPV1 and the protein-ligand interactions at a molecular level.
- Thorat, Shivaji A.,Lee, Yoonji,Jung, Aeran,Ann, Jihyae,Ahn, Songyeon,Baek, Jisoo,Zuo, Dongxu,Do, Nayeon,Jeong, Jin Ju,Blumberg, Peter M.,Esch, Timothy E.,Turcios, Noe A.,Pearce, Larry V.,Ha, Hee-Jin,Yoo, Young Dong,Hong, Sunhye,Choi, Sun,Lee, Jeewoo
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p. 370 - 384
(2021/02/05)
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- REARRANGED PENTANOLS, A METHOD FOR THE PRODUCTION THEREOF, AND THEIR USE AS ANTIPHLOGISTICS
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The invention relates to compounds of formula (I), to a method for the production thereof, and to their use as antiphlogistics.
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Page/Page column 24
(2008/06/13)
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- 1-AMINO-2-OXY-SUBSTITUTED TETRAHYDRONAPHTALENE DERIVATIVES, METHODS FOR THE PRODUCTION THEREOF, AND THEIR USE AS ANTIPHLOGISTICS
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The invention relates to polysubstituted tetrahydronaphtalene derivatives of formula (I), to methods for the production thereof, and to their use as antiphlogistics. The substituents are defined in Claim 1.
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Page/Page column 56
(2010/02/11)
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- Rearranged pentanols, a process for their production and their use as anti-inflammatory agents
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The invention relates to the compounds of formula I, a process for their production and their use as anti-inflammatory agents.
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Page/Page column 8-9
(2010/02/12)
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- Multiply-substituted tetrahydronaphthalene derivatives, process for their production and their use as anti-inflammatory agents
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The invention relates to multiply-substituted tetrahydronaphthalene derivatives of formula (I) process for their production and their use as anti-inflammatory agents.
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Page/Page column 16
(2010/02/14)
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- Substituted dihydroisoquinolinones and related compounds as potentiators of the lethal effects of radiation and certain chemotherapeutic agents; selected compounds, analogs and process
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The invention is selected, novel, and known analogs of isoquinolinones of the formula and pharmaceutically acceptable salts thereof; novel pharmaceutical compositions; and a method for enhancing the lethal effects for tumor cells to treatment having DNA damaging activity such as ionizing radiation or with chemotherapeutic agents.
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