| Title |
Discovery of VU0467485/AZ13713945: An M4 PAM Evaluated as a Preclinical Candidate for the Treatment of Schizophrenia
|
|---|---|
| Published in |
ACS Medicinal Chemistry Letters, December 2016
|
| DOI | 10.1021/acsmedchemlett.6b00461 |
| Pubmed ID | |
| Authors |
Michael R. Wood, Meredith J. Noetzel, Bruce J. Melancon, Michael S. Poslusney, Kellie D. Nance, Miguel A. Hurtado, Vincent B. Luscombe, Rebecca L. Weiner, Alice L. Rodriguez, Atin Lamsal, Sichen Chang, Michael Bubser, Anna L. Blobaum, Darren W. Engers, Colleen M. Niswender, Carrie K. Jones, Nicholas J. Brandon, Michael W. Wood, Mark E. Duggan, P. Jeffrey Conn, Thomas M. Bridges, Craig W. Lindsley |
| Abstract |
Herein, we report the structure-activity relationships within a series of potent, selective, and orally bioavailable muscarinic acetylcholine receptor 4 (M4) positive allosteric modulators (PAMs). Compound 6c (VU0467485) possesses robust in vitro M4 PAM potency across species and in vivo efficacy in preclinical models of schizophrenia. Coupled with an attractive DMPK profile and suitable predicted human PK, 6c (VU0467485) was evaluated as a preclinical development candidate. |
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X Demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 67% |
| Unknown | 1 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 67% |
| Scientists | 1 | 33% |
Mendeley demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 34 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 18% |
| Other | 5 | 15% |
| Student > Ph. D. Student | 4 | 12% |
| Student > Master | 3 | 9% |
| Student > Doctoral Student | 2 | 6% |
| Other | 3 | 9% |
| Unknown | 11 | 32% |
| Readers by discipline | Count | As % |
|---|---|---|
| Chemistry | 8 | 24% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 12% |
| Agricultural and Biological Sciences | 4 | 12% |
| Neuroscience | 3 | 9% |
| Biochemistry, Genetics and Molecular Biology | 2 | 6% |
| Other | 2 | 6% |
| Unknown | 11 | 32% |