Details of the Drug

General Information of Drug (ID: DMSQ4TL)

Drug Name
NNC 11-1314
Synonyms
NNC 11-1314; CHEMBL99521; 8-[4-(3-phenylprop-2-ynoxy)-1,2,5-thiadiazol-3-yl]-1-azabicyclo[2.2.2]octane; GTPL291; SCHEMBL6198562; 3-[4-(3-Phenyl-prop-2-ynyloxy)-[1,2,5]thiadiazol-3-yl]-1-aza-bicyclo[2.2.2]octane; BDBM50072228
Indication
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [1]
Drug Type
Small molecular drug
Structure
3D MOL is unavailable 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 325.4
Topological Polar Surface Area (xlogp) 3.2
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 5
Chemical Identifiers
Formula
C18H19N3OS
IUPAC Name
3-(1-azabicyclo[2.2.2]octan-3-yl)-4-(3-phenylprop-2-ynoxy)-1,2,5-thiadiazole
Canonical SMILES
C1CN2CCC1C(C2)C3=NSN=C3OCC#CC4=CC=CC=C4
InChI
InChI=1S/C18H19N3OS/c1-2-5-14(6-3-1)7-4-12-22-18-17(19-23-20-18)16-13-21-10-8-15(16)9-11-21/h1-3,5-6,15-16H,8-13H2
InChIKey
SNSMIIQEKVYNOH-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
10426487
TTD ID
D02MJE

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Muscarinic acetylcholine receptor (CHRM) TTOXS3C NOUNIPROTAC Agonist [2]
Muscarinic acetylcholine receptor M3 (CHRM3) TTQ13Z5 ACM3_HUMAN Agonist [2]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Discovery agent
ICD Disease Classification N.A.
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Muscarinic acetylcholine receptor M3 (CHRM3) DTT CHRM3 4.61E-07 -0.59 -0.73
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 291).
2 Synthesis and pharmacological evaluation of dimeric muscarinic acetylcholine receptor agonists. J Pharmacol Exp Ther. 2001 Sep;298(3):1260-8.
3 Thiochrome enhances acetylcholine affinity at muscarinic M4 receptors: receptor subtype selectivity via cooperativity rather than affinity. Mol Pharmacol. 2004 Jan;65(1):257-66.
4 Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases. J Pharmacol Exp Ther. 2013 May;345(2):260-70.
5 Characterisation of [3H]-darifenacin as a novel radioligand for the study of muscarinic M3 receptors. J Recept Signal Transduct Res. 1997 Jan-May;17(1-3):177-84.
6 Lithocholylcholine, a bile acid/acetylcholine hybrid, is a muscarinic receptor antagonist. J Pharmacol Exp Ther. 2002 Oct;303(1):29-35.
7 Pharmacological comparison of the cloned human and rat M2 muscarinic receptor genes expressed in the murine fibroblast (B82) cell line. J Pharmacol Exp Ther. 1998 Feb;284(2):500-7.
8 Effects of propiverine hydrochloride (propiverine) on the muscarinic receptor binding affinity in guinea pig tissues and on salivation in conscious dogs. Nihon Yakurigaku Zasshi. 1999 Mar;113(3):157-66.
9 Clinical pipeline report, company report or official report of GlaxoSmithKline.
10 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
11 The amygdala modulates morphine-induced state-dependent memory retrieval via muscarinic acetylcholine receptors. Neuroscience. 2009 May 5;160(2):255-63.
12 Competitive and non-competitive antagonism exhibited by 'selective' antagonists at atrial and ileal muscarinic receptor subtypes. Br J Pharmacol. 1987 Apr;90(4):701-7.
13 Signal transduction underlying carbachol-induced contraction of human urinary bladder. J Pharmacol Exp Ther. 2004 Jun;309(3):1148-53.
14 Design, synthesis, and neurochemical evaluation of 5-(3-alkyl-1,2,4- oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines as M1 muscarinic receptor agonists. J Med Chem. 1993 Apr 2;36(7):842-7.
15 DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
16 Role of parasympathetic nerves and muscarinic receptors in allergy and asthma.Chem Immunol Allergy.2012;98:48-69.
17 M(1) and M(3) muscarinic receptors are involved in the release of urinary bladder-derived relaxant factor. Pharmacol Res. 2009 May;59(5):300-5.
18 Muscarinic M3-receptors mediate cholinergic synergism of mitogenesis in airway smooth muscle. Am J Respir Cell Mol Biol. 2003 Feb;28(2):257-62.
19 Demonstration of bladder selective muscarinic receptor binding by intravesical oxybutynin to treat overactive bladder. J Urol. 2004 Nov;172(5 Pt 1):2059-64.
20 Comparison of muscarinic receptor selectivity of solifenacin and oxybutynin in the bladder and submandibular gland of muscarinic receptor knockout ... Eur J Pharmacol. 2009 Aug 1;615(1-3):201-6.
21 Interaction of neuromuscular blocking drugs with recombinant human m1-m5 muscarinic receptors expressed in Chinese hamster ovary cells. Br J Pharmacol. 1998 Nov;125(5):1088-94.
22 Degradation of submandibular gland AQP5 by parasympathetic denervation of chorda tympani and its recovery by cevimeline, an M3 muscarinic receptor ... Am J Physiol Gastrointest Liver Physiol. 2008 Jul;295(1):G112-G123.