1294496-58-4Relevant academic research and scientific papers
Discovery and Characterization of 2-Acylaminoimidazole Microsomal Prostaglandin e Synthase-1 Inhibitors
Schiffler, Matthew A.,Antonysamy, Stephen,Bhattachar, Shobha N.,Campanale, Kristina M.,Chandrasekhar, Srinivasan,Condon, Bradley,Desai, Prashant V.,Fisher, Matthew J.,Groshong, Christopher,Harvey, Anita,Hickey, Michael J.,Hughes, Norman E.,Jones, Scott A.,Kim, Euibong J.,Kuklish, Steven L.,Luz, John G.,Norman, Bryan H.,Rathmell, Richard E.,Rizzo, John R.,Seng, Thomas W.,Thibodeaux, Stefan J.,Woods, Timothy A.,York, Jeremy S.,Yu, Xiao-Peng
, p. 194 - 205 (2016/01/28)
As part of a program aimed at the discovery of antinociceptive therapy for inflammatory conditions, a screening hit was found to inhibit microsomal prostaglandin E synthase-1 (mPGES-1) with an IC50 of 17.4 μM. Structural information was used to improve enzyme potency by over 1000-fold. Addition of an appropriate substituent alleviated time-dependent cytochrome P450 3A4 (CYP3A4) inhibition. Further structure-activity relationship (SAR) studies led to 8, which had desirable potency (IC50 = 12 nM in an ex vivo human whole blood (HWB) assay) and absorption, distribution, metabolism, and excretion (ADME) properties. Studies on the formulation of 8 identified 8·H3PO4 as suitable for clinical development. Omission of a lipophilic portion of the compound led to 26, a readily orally bioavailable inhibitor with potency in HWB comparable to celecoxib. Furthermore, 26 was selective for mPGES-1 inhibition versus other mechanisms in the prostanoid pathway. These factors led to the selection of 26 as a second clinical candidate.
SUBSTITUTED BICYCLIC COMPOUNDS AS mPGES-1 INHIBITORS
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, (2014/10/29)
The present disclosure is directed to compounds of formula (I), and pharmaceutically acceptable salts thereof, as mPGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (mPGES-1) enzyme and are therefore useful in the treatment of pain and/or inflammation from a variety of diseases or conditions, such as asthma, osteoarthritis, rheumatoid arthritis, acute or chronic pain and neurodegenerative diseases.
BICYCLIC COMPOUNDS AS mPGES-1 INHIBITORS
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Paragraph 0275; 0290; 0302, (2013/08/28)
The present disclosure is directed to compounds of formula (I), and pharmaceutically acceptable salts thereof, as mPGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (mPGES-1) enzyme and are therefore useful in the treatment of pain and/or inflammation from a variety of diseases or conditions, such as asthma, osteoarthritis, rheumatoid arthritis, acute or chronic pain and neurodegenerative diseases.
PHTALAZINONE DERIVATIVES AS MPEGS -1 INHIBITORS
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, (2013/06/05)
The present patent application is directed to bicyclic compounds of formula (I) or pharmaceutically acceptable salt thereof as mPGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (m PGES-1) enzyme and are theref
SUBSTITUTED BICYCLIC HETEROARYL COMPOUNDS AS mPGES-1 INHIBITORS
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Page/Page column 78, (2013/03/28)
The present invention relates to bicyclic compounds of formula (I) or pharmaceutically acceptable salt thereof as mPGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (m PGES-1) enzyme and are therefore useful in the treatment of pain and/or inflammation from a variety of diseases or conditions, such as asthama, osteoarthritis, rheumatoid arthritis, acute or chronic pain and neurodegenerative diseases. (I)
Novel Imidazole-2-Benzamide Compounds Useful for the Treatment of Osteoarthritis
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Page/Page column 7, (2012/06/30)
The present invention provides compounds of the formula below or pharmaceutical salts thereof, wherein R1, R2 and R3 are as described herein; methods of treating osteoarthritis using the compounds; and a process for preparing the compounds.
INHIBITORS OF THE MICROSOMAL PROSTAGLANDIN E2 SYNTHASE-1
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Page/Page column 74-75, (2011/05/06)
This invention relates to compounds of formula I, their use as inhibitors of the microsomal prostaglandin E2 synthase-1 (mPGES-1), pharmaceutical compositions containing them, and their use as medicaments for the treatment and/or prevention of
New Compounds
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Page/Page column 32, (2011/11/06)
This invention relates to compounds of formula I, their use as inhibitors of the microsomal prostaglandin E2 synthase-1 (mPGES-1), pharmaceutical compositions containing them, and their use as medicaments for the treatment and/or prevention of
