Deane M. Nason
Pfizer
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Featured researches published by Deane M. Nason.
Tetrahedron Letters | 1988
V. John Jasys; Paul R. Kelbaugh; Deane M. Nason; Douglas Phillips; Nicholas Alex Saccomano; Robert A. Volkmann
Practical syntheses of three polyamine spider toxins isolated from the venom of Argiope aurantia are described.
Journal of Medicinal Chemistry | 2016
Jennifer Elizabeth Davoren; Che-Wah Lee; Michelle Renee Garnsey; Michael Aaron Brodney; Jason Cordes; Keith Dlugolenski; Jeremy R. Edgerton; Anthony R. Harris; Christopher John Helal; Stephen Jenkinson; Gregory W. Kauffman; Terrence P. Kenakin; John T. Lazzaro; Susan M. Lotarski; Yuxia Mao; Deane M. Nason; Carrie Northcott; Lisa Nottebaum; Steven V. O’Neil; Betty Pettersen; Michael Popiolek; Veronica Reinhart; Romelia Salomon-Ferrer; Stefanus J. Steyn; Damien Webb; Lei Zhang; Sarah Grimwood
It is hypothesized that selective muscarinic M1 subtype activation could be a strategy to provide cognitive benefits to schizophrenia and Alzheimers disease patients while minimizing the cholinergic side effects observed with nonselective muscarinic orthosteric agonists. Selective activation of M1 with a positive allosteric modulator (PAM) has emerged as a new approach to achieve selective M1 activation. This manuscript describes the development of a series of M1-selective pyridone and pyridine amides and their key pharmacophores. Compound 38 (PF-06767832) is a high quality M1 selective PAM that has well-aligned physicochemical properties, good brain penetration and pharmacokinetic properties. Extensive safety profiling suggested that despite being devoid of mAChR M2/M3 subtype activity, compound 38 still carries gastrointestinal and cardiovascular side effects. These data provide strong evidence that M1 activation contributes to the cholinergic liabilities that were previously attributed to activation of the M2 and M3 receptors.
Tetrahedron Letters | 1989
Deane M. Nason; Vytautus John Jasys; Paul R. Kelbaugh; Douglas Phillips; Nicholas Alex Saccomano; Robert A. Volkmann
Abstract Efficient and practical synthetic routes to the polyamine spider venom principles, NSTX-3 and JSTX-3 are described.
Bioorganic & Medicinal Chemistry Letters | 2016
Jennifer Elizabeth Davoren; Steven V. O’Neil; Dennis P. Anderson; Michael Aaron Brodney; Lois K. Chenard; Keith Dlugolenski; Jeremy R. Edgerton; Michael Green; Michelle Renee Garnsey; Sarah Grimwood; Anthony R. Harris; Gregory W. Kauffman; Erik LaChapelle; John T. Lazzaro; Che-Wah Lee; Susan M. Lotarski; Deane M. Nason; R. Scott Obach; Veronica Reinhart; Romelia Salomon-Ferrer; Stefanus J. Steyn; Damien Webb; Jiangli Yan; Lei Zhang
Selective activation of the M1 receptor via a positive allosteric modulator (PAM) is a new approach for the treatment of the cognitive impairments associated with schizophrenia and Alzheimers disease. A novel series of azaindole amides and their key pharmacophore elements are described. The nitrogen of the azaindole core is a key design element as it forms an intramolecular hydrogen bond with the amide N-H thus reinforcing the bioactive conformation predicted by published SAR and our homology model. Representative compound 25 is a potent and selective M1 PAM that has well aligned physicochemical properties, adequate brain penetration and pharmacokinetic (PK) properties, and is active in vivo. These favorable properties indicate that this series possesses suitable qualities for further development and studies.
ACS Medicinal Chemistry Letters | 2012
Jennifer Elizabeth Davoren; Mark W. Bundesmann; Qi T. Yan; Elizabeth M. Collantes; Scot Mente; Deane M. Nason; David L. Gray
When stable atropisomers are encountered by drug discovery teams, they can have important implications due to potential differences in their biological activity, pharmacokinetics, and toxicity. Knowledge of an atropisomers activation parameters for interconversion is required to facilitate informed decisions on how to proceed. Herein, we communicate the development of a new method for the rapid measurement of atropisomer racemization kinetics utilizing segmented flow technology. This method leverages the speed, accuracy, low sample requirement, safety, and semiautomated nature of flow instrumentation to facilitate the acquisition of kinetics data required for experimentally probing atropisomer activation parameters. Measured kinetics data obtained for the atropo isomerization of AMPA antagonist CP-465021 using segmented flow and traditional thermal methods were compared to validate the method.
European Journal of Pharmacology | 2004
Dane Liston; Jann A. Nielsen; Anabella Villalobos; Douglas S. Chapin; Shawn B. Jones; Sean T. Hubbard; Ismail Shalaby; Andres D. Ramirez; Deane M. Nason; W. Frost White
Journal of Organic Chemistry | 1992
Robert A. Volkmann; Paul R. Kelbaugh; Deane M. Nason; V. John Jasys
Journal of Medicinal Chemistry | 1995
Anabella Villalobos; Todd William Butler; Douglas S. Chapin; Chen Yl; DeMattos Sb; Jeffrey L. Ives; Shawn B. Jones; Dane Liston; Arthur Adam Nagel; Deane M. Nason
Journal of Organic Chemistry | 1992
V. John Jasys; Paul R. Kelbaugh; Deane M. Nason; Douglas Phillips; Kenneth J. Rosnack; Nicholas Alex Saccomano; Justin G. Stroh; Robert A. Volkmann; James T. Forman
Journal of Medicinal Chemistry | 2004
John A. Lowe; Weimin Qian; Susan E. Drozda; Robert A. Volkmann; Deane M. Nason; Robert B. Nelson; Charles E. Nolan; Dane Liston; Karen M. Ward; Steve Faraci; Kim Verdries; Pat Seymour; Michael Majchrzak; and Anabella Villalobos; W. Frost White