1255206-69-9Relevant academic research and scientific papers
Discovery of a potent and selective ROMK inhibitor with pharmacokinetic properties suitable for preclinical evaluation
Walsh, Shawn P.,Shahripour, Aurash,Tang, Haifeng,Teumelsan, Nardos,Frie, Jessica,Zhu, Yuping,Priest, Birgit T.,Swensen, Andrew M.,Liu, Jessica,Margulis, Michael,Visconti, Richard,Weinglass, Adam,Felix, John P.,Brochu, Richard M.,Bailey, Timothy,Thomas-Fowlkes, Brande,Alonso-Galicia, Magdalena,Zhou, Xiaoyan,Pai, Lee-Yuh,Corona, Aaron,Hampton, Caryn,Hernandez, Melba,Bentley, Ross,Chen, Jing,Shah, Kashmira,Metzger, Joseph,Forrest, Michael,Owens, Karen,Tong, Vincent,Ha, Sookhee,Roy, Sophie,Kaczorowski, Gregory J.,Yang, Lihu,Parmee, Emma,Garcia, Maria L.,Sullivan, Kathleen,Pasternak, Alexander
, p. 747 - 752 (2015)
A new subseries of ROMK inhibitors exemplified by 28 has been developed from the initial screening hit 1. The excellent selectivity for ROMK inhibition over related ion channels and pharmacokinetic properties across preclinical species support further pre
FACTOR XI ACTIVATION INHIBITORS
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Paragraph 34-35, (2020/12/11)
The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XI activation inhibitors.
INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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, (2017/07/31)
The present invention provides compounds of Formula (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylax
INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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, (2016/05/19)
The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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, (2016/08/23)
The present invention provides compounds of Formula I (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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, (2016/10/06)
The present invention provides compounds of Formula Ia and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention.
INHIBITORS OF RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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, (2016/09/22)
Disclosed are compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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, (2016/09/26)
no abstract published
Inhibitors of the renal outer medullary potassium channel
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, (2016/12/07)
This invention relates to compounds of Formula I having the following general structure: [in-line-formulae]Z1—Y1—(CH2)n1—R—(CH2)n2—Y2—Z2 [/in-line-formulae] wherein R
Discovery of MK-7145, an Oral Small Molecule ROMK Inhibitor for the Treatment of Hypertension and Heart Failure
Tang, Haifeng,Zhu, Yuping,Teumelsan, Nardos,Walsh, Shawn P.,Shahripour, Aurash,Priest, Birgit T.,Swensen, Andrew M.,Felix, John P.,Brochu, Richard M.,Bailey, Timothy,Thomas-Fowlkes, Brande,Pai, Lee-Yuh,Hampton, Caryn,Corona, Aaron,Hernandez, Melba,Metzger, Joseph,Forrest, Michael,Zhou, Xiaoyan,Owens, Karen,Tong, Vincent,Parmee, Emma,Roy, Sophie,Kaczorowski, Gregory J.,Yang, Lihu,Alonso-Galicia, Magdalena,Garcia, Maria L.,Pasternak, Alexander
supporting information, p. 697 - 701 (2016/07/26)
ROMK, the renal outer medullary potassium channel, is involved in potassium recycling at the thick ascending loop of Henle and potassium secretion at the cortical collecting duct in the kidney nephron. Because of this dual site of action, selective inhibitors of ROMK are expected to represent a new class of diuretics/natriuretics with superior efficacy and reduced urinary loss of potassium compared to standard-of-care loop and thiazide diuretics. Following our earlier work, this communication will detail subsequent medicinal chemistry endeavors to further improve lead selectivity against the hERG channel and preclinical pharmacokinetic properties. Pharmacological assessment of highlighted inhibitors will be described, including pharmacodynamic studies in both an acute rat diuresis/natriuresis model and a subchronic blood pressure model in spontaneous hypertensive rats. These proof-of-biology studies established for the first time that the human and rodent genetics accurately predict the in vivo pharmacology of ROMK inhibitors and supported identification of the first small molecule ROMK inhibitor clinical candidate, MK-7145.
