885115-40-2Relevant academic research and scientific papers
TRIAZA-SPIRODECANONES AS DDR1 INHIBITORS
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Page/Page column 52; 53, (2017/01/26)
The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein L and R1 to R5 are as described herein, as well as processes for their manufacture, pharmaceutical compositions comprising them, and their use as medicaments.
Design, synthesis, and biological evaluation of halogenated N-(2-(4-Oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl)benzamides: Discovery of an isoform-selective small molecule phospholipase D2 inhibitor
Lavieri, Robert R.,Scott, Sarah A.,Selvy, Paige E.,Kim, Kwangho,Jadhav, Satyawan,Morrison, Ryan D.,Daniels, J. Scott,Brown, H. Alex,Lindsley, Craig W.
experimental part, p. 6706 - 6719 (2010/12/18)
Phospholipase D (PLD) catalyzes the conversion of phosphatidylcholine to the lipid second messenger phosphatidic acid. Two mammalian isoforms of PLD have been identified, PLD1 and PLD2, which share 53% sequence identity and are subject to different regulatory mechanisms. Inhibition of PLD enzymatic activity leads to increased cancer cell apoptosis, decreased cancer cell invasion, and decreased metastasis of cancer cells; therefore, the development of isoform-specific, PLD inhibitors is a novel approach for the treatment of cancer. Previously, we developed potent dual PLD1/PLD2, PLD1-specific (>1700-fold selective), and moderately PLD2-preferring (>10-fold preferring) inhibitors. Here, we describe a matrix library strategy that afforded the most potent (PLD2 IC50 = 20 nM) and selective (75-fold selective versus PLD1) PLD2 inhibitor to date, N-(2-(1-(3-fluorophenyl)-4-oxo-1, 3,8-triazaspiro[4.5]decan-8-yl)ethyl)-2-naphthamide (22a), with an acceptable DMPK profile. Thus, these new isoform-selective PLD inhibitors will enable researchers to dissect the signaling roles and therapeutic potential of individual PLD isoforms to an unprecedented degree.
BICYCLIC SPIROPIPERIDINE BETA-SECRETASE INHIBITORS FOR THE TREATMENT OF ALZHEIMER'S DISEASE
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Page/Page column 22-23, (2008/12/07)
The present invention is directed to bicyclic spiropiperidine compounds of formula (I) which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's d
SPIROPIPERIDINE COMPOUNDS USEFUL AS BETA-SECRETASE INHIBITORS FOR THE TREATMENT OF ALZHERMER’S DISEASE
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Page/Page column 41, (2010/11/08)
The present invention is directed to spiropiperidine compounds of formula (I) which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. T
