- Design and Identification of a Novel, Functionally Subtype Selective GABAA Positive Allosteric Modulator (PF-06372865)
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The design, optimization, and evaluation of a series of novel imidazopyridazine-based subtype-selective positive allosteric modulators (PAMs) for the GABAA ligand-gated ion channel are described. From a set of initial hits multiple subseries were designed and evaluated based on binding affinity and functional activity. As designing in the desired level of functional selectivity proved difficult, a probability-based assessment was performed to focus the project's efforts on a single subseries that had the greatest odds of delivering the target profile. These efforts ultimately led to the identification of two precandidates from this subseries, which were advanced to preclinical safety studies and subsequently to the identification of the clinical candidate PF-06372865.
- Owen, Robert M.,Blakemore, David,Cao, Lishuang,Flanagan, Neil,Fish, Rebecca,Gibson, Karl R.,Gurrell, Rachel,Huh, Chan Woo,Kammonen, Juha,Mortimer-Cassen, Elisabeth,Nickolls, Sarah A.,Omoto, Kiyoyuki,Owen, Dafydd,Pike, Andy,Pryde, David C.,Reynolds, David S.,Roeloffs, Rosemarie,Rose, Colin,Stead, Clara,Takeuchi, Mifune,Warmus, Joseph S.,Watson, Christine
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p. 5773 - 5796
(2019/05/15)
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- Chemical Compounds
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The present invention relates to imidazopyridazine derivatives. More particularly, it relates to 4-(biphenyl-3-yl)-7H-imidazo[4,5-c]pyridazine derivatives of formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4 and R5 are as defined in the description. The imidazopyridazine derivatives of the present invention modulate the activity of the GABAA receptor. They are useful in the treatment of a number of conditions, including pain.
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Paragraph 0480; 0481; 0482; 0483
(2014/06/25)
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- NEW BICYCLIC COMPOUND FOR MODULATING G PROTEIN-COUPLED RECEPTORS
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The present invention relates to a bicyclic compound for modulating G protein-coupled receptors. The inventive compound provides preventing or treating a disease associated with the modulation of G protein-coupled receptors, particularly GPR119 G protein-coupled receptors.
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Paragraph 0189-0191
(2013/10/22)
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- NEW BICYCLIC COMPOUND FOR MODULATING G PROTEIN-COUPLED RECEPTORS
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The present invention relates to a bicyclic compound for modulating G protein-coupled receptors. The inventive compound provides preventing or treating a disease associated with the modulation of G protein-coupled receptors, particularly GPR119 G protein-coupled receptors.
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Page/Page column 26
(2012/07/27)
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- BICYCLIC COMPOUNDS AND USE AS ANTIDIABETICS
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The present invention relates to novel compounds that are useful in the treatment of metabolic disorders, particularly type II diabetes mellitus and related disorders, and also to the methods for the making and use of such compounds.
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Page/Page column 36
(2010/03/02)
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- NAPHTHYLACETIC ACIDS
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The invention is concerned with the compounds of formula (I) and pharmaceutically acceptable salts and esters thereof, wherein X, Q, and R1-R6 are defined in the detailed description and claims. In addition, the present invention relates to methods of manufacturing and using the compounds of formula (I) as well as pharmaceutical compositions containing such compounds. The compounds of formula (I) are antagonists or partial agonists at the CRTH2 receptor and may be useful in treating diseases and disorders associated with that receptor such as asthma.
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Page/Page column 77
(2010/06/15)
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