General Information of Drug (ID: DMHA5ME)

Drug Name
AZD-9684
Synonyms
Laudanosine; DL-Laudanosine; 1699-51-0; (+-)-Laudanosine; Laudanosine (R,S); (R,S)-Laudanosine; EINECS 216-923-9; NSC 94267; AI3-61890; 20412-65-1; NSC35045; 1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline; (+-)-1,2,3,4-Tetrahydro-6,7-dimethoxy-2-methyl-1-veratrylisoquinoline; 1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline; ISOQUINOLINE, 1,2,3,4-TETRAHYDRO-6,7-DIMETHOXY-2-METHYL-1-VERATRYL-, (+-)-
Indication
Disease Entry ICD 11 Status REF
Thrombosis DB61-GB90 Discontinued in Phase 2 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 226.3
Topological Polar Surface Area (xlogp) 1
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 5
Chemical Identifiers
Formula
C10H14N2O2S
IUPAC Name
(2S,3R)-2-[(6-aminopyridin-3-yl)methyl]-3-sulfanylbutanoic acid
Canonical SMILES
C[C@H]([C@@H](CC1=CN=C(C=C1)N)C(=O)O)S
InChI
InChI=1S/C10H14N2O2S/c1-6(15)8(10(13)14)4-7-2-3-9(11)12-5-7/h2-3,5-6,8,15H,4H2,1H3,(H2,11,12)(H,13,14)/t6-,8-/m1/s1
InChIKey
GYIYAOUGKJSCCG-HTRCEHHLSA-N
Cross-matching ID
PubChem CID
87609775
DrugBank ID
DB05712
TTD ID
D0F7FX

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Carboxypeptidase B2 (CPB2) TTP18AY CBPB2_HUMAN Inhibitor [2]
Neuronal acetylcholine receptor alpha-2/alpha-3 (CHRNA2/A3) TTMT0HG ACHA2_HUMAN; ACHA3_HUMAN Antagonist [3]
Neuronal acetylcholine receptor alpha-7 (CHRNA7) TTLA931 ACHA7_HUMAN Antagonist [3]
Neuronal acetylcholine receptor beta-2 (CHRNB2) TT5KPZR ACHB2_HUMAN Antagonist [3]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Thrombosis
ICD Disease Classification DB61-GB90
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Neuronal acetylcholine receptor beta-2 (CHRNB2) DTT CHRNB2 7.10E-08 -0.15 -0.85
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018349)
2 Clinical pipeline report, company report or official report of AstraZeneca.
3 Blockade and activation of the human neuronal nicotinic acetylcholine receptors by atracurium and laudanosine. Anesthesiology. 2001 Apr;94(4):643-51.
4 The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
5 Pharmacological characteristics and binding modes of caracurine V analogues and related compounds at the neuronal alpha7 nicotinic acetylcholine re... J Med Chem. 2007 Sep 20;50(19):4616-29.
6 Clinical pipeline report, company report or official report of Roche (2009).
7 3,5-Bicyclic aryl piperidines: a novel class of alpha4beta2 neuronal nicotinic receptor partial agonists for smoking cessation. Bioorg Med Chem Lett. 2005 Nov 15;15(22):4889-97.
8 Normalizing effects of EVP-6124, an alpha-7 nicotinic partial agonist, on event-related potentials and cognition: a proof of concept, randomized trial in patients with schizophrenia. J Psychiatr Pract. 2014 Jan;20(1):12-24.
9 The brain alpha7 nicotinic receptor may be an important therapeutic target for the treatment of Alzheimer's disease: studies with DMXBA (GTS-21). Behav Brain Res. 2000 Aug;113(1-2):169-81.
10 Allosteric alpha-7 nicotinic receptor modulation and P50 sensory gating in schizophrenia: a proof-of-mechanism study. Neuropharmacology. 2013 Jan;64:197-204.
11 A phase 2 randomized, controlled trial of the alpha7 agonist ABT-126 in mild-to-moderate Alzheimer's dementia. Alzheimer's & Dementia: Translational Research & Clinical Interventions Volume 1, Issue 1, June 2015, Pages 81-90.
12 ClinicalTrials.gov (NCT01293669) Glycemic Control, Safety and Tolerability of TC-6987 Monotherapy in Type 2 Diabetes Mellitus. U.S. National Institutes of Health.
13 AQW051, a novel and selective nicotinic acetylcholine receptor alpha7 partial agonist, reduces l-Dopa-induced dyskinesias and extends the duration of l-Dopa effects in parkinsonian monkeys. Parkinsonism Relat Disord. 2014 Nov;20(11):1119-23.
14 Nicotine, brain nicotinic receptors, and neuropsychiatric disorders. Arch Med Res. 2000 Mar-Apr;31(2):131-44.
15 Antagonism of alpha 3 beta 4 nicotinic receptors as a strategy to reduce opioid and stimulant self-administration. Eur J Pharmacol. 2002 Mar 1;438(1-2):99-105.
16 Epibatidine isomers and analogues: structure-activity relationships. Bioorg Med Chem Lett. 2006 Nov 1;16(21):5493-7.
17 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
18 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
19 The nicotinic acetylcholine receptor agonist ABT-594 increases FGF-2 expression in various rat brain regions. Neuroreport. 1999 Dec 16;10(18):3909-13.
20 Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 rec... J Med Chem. 2010 Sep 9;53(17):6386-97.
21 Synthesis and characterization of in vitro and in vivo profiles of hydroxybupropion analogues: aids to smoking cessation. J Med Chem. 2010 Jun 24;53(12):4731-48.
22 Aporphine metho salts as neuronal nicotinic acetylcholine receptor blockers. Bioorg Med Chem. 2007 May 15;15(10):3368-72.
23 TAFIa inhibitors in the treatment of thrombosis. Curr Opin Drug Discov Devel. 2008 Jul;11(4):480-6.
24 Oxygenated analogues of UK-396082 as inhibitors of activated thrombin activatable fibrinolysis inhibitor. Bioorg Med Chem Lett. 2010 Jan 1;20(1):92-6.
25 Clinical pipeline report, company report or official report of Daiichi Sankyo.
26 Carboxypeptidase U (TAFIa): a new drug target for fibrinolytic therapy . Journal of Thrombosis and Haemostasis Volume 7, Issue 12, pages 1962-1971, December 2009.
27 Synthesis and evaluation of imidazole acetic acid inhibitors of activated thrombin-activatable fibrinolysis inhibitor as novel antithrombotics. J Med Chem. 2003 Dec 4;46(25):5294-7.
28 A new type of five-membered heterocyclic inhibitors of basic metallocarboxypeptidases. Eur J Med Chem. 2009 Aug;44(8):3266-71.
29 3-Mercaptopropionic acids as efficacious inhibitors of activated thrombin activatable fibrinolysis inhibitor (TAFIa). Bioorg Med Chem Lett. 2007 Mar 1;17(5):1349-54.
30 Imidazole acetic acid TAFIa inhibitors: SAR studies centered around the basic P(1)(') group. Bioorg Med Chem Lett. 2004 May 3;14(9):2141-5.