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T‐495   Click here for help

GtoPdb Ligand ID: 10711

Synonyms: example 24 [WO2016208775] | T495
Compound class: Synthetic organic
Comment: T-495 is a positive allosteric modulator (PAM) of the M1 muscarinic acetylcholine receptor [1]. It was designed as a low-cooperativity PAM which was predicted to reduce the gastrointestinal (GI) side-effects (principally diarrhea) that are caused by M1R activation in the ileum, whilst retaining efficacy to improve cognitive deficits in animal models. The measure of allosteric cooperativity (α-value) of T-495 is 199. In contrast the α-value for MK-7622 is 511, indicating that this PAM more effectively increases agonist activity at the receptor than T-495. In vivo, T‐495 exhibits a wider margin between memory improvement and induction of diarrhea than MK‐7622 in rats, suggesting that the hypothesis re low PAM cooperativity and reduced GI adverse reaction was valid. T-495 effectively reverses memory deficits in a mouse model of dementia with Lewy bodies and Parkinson's disease in which acetylcholine levels are reduced.
2D Structure
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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.

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Physico-chemical Properties
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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.

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Hydrogen bond acceptors 4
Hydrogen bond donors 1
Rotatable bonds 3
Topological polar surface area 62.66
Molecular weight 406.09
XLogP 3.7
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
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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/)

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Canonical SMILES O[C@H]1CCC[C@@H]1N1COc2c(C1=O)cc(c(c2Cl)C)Cc1ccc(nc1)Cl
Isomeric SMILES O[C@H]1CCC[C@@H]1N1COc2c(C1=O)cc(c(c2Cl)C)Cc1ccc(nc1)Cl
InChI InChI=1S/C20H20Cl2N2O3/c1-11-13(7-12-5-6-17(21)23-9-12)8-14-19(18(11)22)27-10-24(20(14)26)15-3-2-4-16(15)25/h5-6,8-9,15-16,25H,2-4,7,10H2,1H3/t15-,16-/m0/s1
InChI Key BWJHJLINOYAPEG-HOTGVXAUSA-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/)
Classification Click here for help
Compound class Synthetic organic
IUPAC Name Click here for help
8-chloro-6-[(6-chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclopentyl]-7-methyl-2H-1,3-benzoxazin-4-one
Synonyms Click here for help
example 24 [WO2016208775] | T495
Database Links Click here for help
Specialist databases
GPCRdb Ligand T‐495
Other databases
GtoPdb PubChem SID 404859158
PubChem CID 124155515
Search Google for chemical match using the InChIKey BWJHJLINOYAPEG-HOTGVXAUSA-N
Search Google for chemicals with the same backbone BWJHJLINOYAPEG
UniChem Compound Search for chemical match using the InChIKey BWJHJLINOYAPEG-HOTGVXAUSA-N
UniChem Connectivity Search for chemical match using the InChIKey BWJHJLINOYAPEG-HOTGVXAUSA-N