Design and Synthesis of Clinical Candidate PF-06852231 (CVL-231): A Brain Penetrant, Selective, Positive Allosteric Modulator of the M<sub>4</sub> Muscarinic Acetylcholine Receptor-Reference-Cited by-同舟云学术

Design and Synthesis of Clinical Candidate PF-06852231 (CVL-231): A Brain Penetrant, Selective, Positive Allosteric Modulator of the M₄ Muscarinic Acetylcholine Receptor

Published:2024-06-18 Issue:13 Volume:67 Page:10831-10847
ISSN:0022-2623
Container-title:Journal of Medicinal Chemistry
language:en
Short-container-title:J. Med. Chem.

Author:

Butler Christopher R.¹^ORCID,Popiolek Michael²^ORCID,McAllister Laura A.¹^ORCID,LaChapelle Erik A.³,Kramer Melissa⁴,Beck Elizabeth M.¹,Mente Scot¹,Brodney Michael A.¹^ORCID,Brown Matthew³,Gilbert Adam³^ORCID,Helal Chris³,Ogilvie Kevin³,Starr Jeremy³,Uccello Daniel³,Grimwood Sarah²,Edgerton Jeremy²,Garst-Orozco Jonathan²,Kozak Rouba²,Lotarski Susan²,Rossi Amie²,Smith Deborah²,O’Connor Rebecca⁵,Lazzaro John⁵,Steppan Claire⁵,Steyn Stefanus J.⁴

Affiliation:

1. Medicine Design, Medicinal Chemistry, Pfizer Inc., Cambridge, Massachusetts 02139, United States

2. Internal Medicine, Pfizer Inc., Cambridge, Massachusetts 02139, United States

3. Medicine Design, Medicinal Chemistry, Pfizer Inc., Groton, Connecticut 06340, United States

4. Medicine Design, Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Groton, Connecticut 06340, United States

5. Discovery Sciences, Primary Pharmacology, Pfizer Inc., Groton, Connecticut 06340, United States

Publisher

American Chemical Society (ACS)

Link

https://pubs.acs.org/doi/pdf/10.1021/acs.jmedchem.4c00293

Reference53 articles.

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2. Muscarinic receptor subtype distribution in the central nervous system and relevance to aging and Alzheimer's disease

3. Muscarinic Acetylcholine Receptor Agonists as Novel Treatments for Schizophrenia

4. Discovery of the Potent and Selective M1 PAM-Agonist N-[(3R,4S)-3-Hydroxytetrahydro-2H-pyran-4-yl]-5-methyl-4-[4-(1,3-thiazol-4-yl)benzyl]pyridine-2-carboxamide (PF-06767832): Evaluation of Efficacy and Cholinergic Side Effects

5. In Vivo Modulation of Hippocampal Excitability by M4 Muscarinic Acetylcholine Receptor Activator: Implications for Treatment of Alzheimer’s Disease and Schizophrenic Patients