GtoPdb is requesting financial support from commercial users. Please see our sustainability page for more information.

PF-06767832   Click here for help

GtoPdb Ligand ID: 9228

Synonyms: PF-6767832 | PF06767832
Compound class: Synthetic organic
Comment: PF-06767832 (compound 38) is an orally bioavailable, positive allosteric modulator (PAM) selective for the M1 muscarinic acetylcholine receptor (CHRM1) [2]. It is one of the compounds claimed in patent WO2016009297 [1]. M1 receptor PAMs are being designed for their potential to provide novel therapies for the treatment of M1-mediated diseases and disorders such as Alzheimer's disease.
Click here for help

Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

✖

View interactive charts of activity data across species
2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 112.58
Molecular weight 409.15
XLogP 3.05
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

✖
Canonical SMILES OC1COCCC1NC(=O)c1ncc(c(c1)Cc1ccc(cc1)c1cscn1)C
Isomeric SMILES O[C@H]1COCC[C@@H]1NC(=O)c1ncc(c(c1)Cc1ccc(cc1)c1cscn1)C
InChI InChI=1S/C22H23N3O3S/c1-14-10-23-19(22(27)25-18-6-7-28-11-21(18)26)9-17(14)8-15-2-4-16(5-3-15)20-12-29-13-24-20/h2-5,9-10,12-13,18,21,26H,6-8,11H2,1H3,(H,25,27)/t18-,21-/m0/s1
InChI Key VVZZHFMLRHJXTO-RXVVDRJESA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Brodney MA, Davoren JE, Garnsey MR, Zhang L, O'neil SV. (2016)
Pyridine derivatives as muscarinic m1 receptor positive allosteric modulators.
Patent number: WO2016009297. Assignee: Pfizer Inc.. Priority date: 18/07/2014. Publication date: 21/01/2016.
2. Davoren JE, Lee CW, Garnsey M, Brodney MA, Cordes J, Dlugolenski K, Edgerton JR, Harris AR, Helal CJ, Jenkinson S et al.. (2016)
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.
J Med Chem, 59 (13): 6313-28. [PMID:27275946]
3. Fisher A. (2000)
Therapeutic strategies in Alzheimer's disease: M1 muscarinic agonists.
Jpn J Pharmacol, 84 (2): 101-12. [PMID:11128032]
4. Khajehali E, Valant C, Jörg M, Tobin AB, Conn PJ, Lindsley CW, Sexton PM, Scammells PJ, Christopoulos A. (2018)
Probing the binding site of novel selective positive allosteric modulators at the M1 muscarinic acetylcholine receptor.
Biochem Pharmacol, 154: 243-254. [PMID:29777683]
5. Walker LC, Campbell EJ, Huckstep KL, Chen NA, Langmead CJ, Lawrence AJ. (2022)
M1 muscarinic receptor activation decreases alcohol consumption via a reduction in consummatory behavior.
Pharmacol Res Perspect, 10 (1): e00907. [PMID:34962108]