Details of the Drug

General Information of Drug (ID: DM3D21X)

Drug Name
ML218
Synonyms ML-218; ML 218
Indication
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 369.3
Topological Polar Surface Area (xlogp) 4.9
Rotatable Bond Count (rotbonds) 6
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 2
Chemical Identifiers
Formula
C19H26Cl2N2O
IUPAC Name
3,5-dichloro-N-[[(1R,5S)-3-(3,3-dimethylbutyl)-3-azabicyclo[3.1.0]hexan-6-yl]methyl]benzamide
Canonical SMILES
CC(C)(C)CCN1C[C@@H]2[C@H](C1)C2CNC(=O)C3=CC(=CC(=C3)Cl)Cl
InChI
InChI=1S/C19H26Cl2N2O/c1-19(2,3)4-5-23-10-16-15(17(16)11-23)9-22-18(24)12-6-13(20)8-14(21)7-12/h6-8,15-17H,4-5,9-11H2,1-3H3,(H,22,24)/t15?,16-,17+
InChIKey
GSJIGYLGKSBYBC-ALOPSCKCSA-N
Cross-matching ID
PubChem CID
45115620
ChEBI ID
CHEBI:91745
TTD ID
D09PWJ

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Voltage-gated calcium channel alpha Cav3.1 (CACNA1G) TT729IR CAC1G_HUMAN Blocker (channel blocker) [2]
Voltage-gated calcium channel alpha Cav3.2 (CACNA1H) TTZPWGN CAC1H_HUMAN Blocker (channel blocker) [2]
Voltage-gated calcium channel alpha Cav3.3 (CACNA1I) TTQZFTH CAC1I_HUMAN Blocker (channel blocker) [2]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction 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: 7720).
2 The Discovery and Characterization of ML218: A Novel, Centrally Active T-Type Calcium Channel Inhibitor with Robust Effects in STN Neurons and in a Rodent Model of Parkinson's Disease. ACS Chem Neurosci. 2011 Dec 21;2(12):730-742.
3 Acute renal failure. Clin Evid (Online). 2008 Sep 3;2008. pii: 2001.
4 Positive allosteric interaction of structurally diverse T-type calcium channel antagonists. Cell Biochem Biophys. 2009;55(2):81-93.
5 Effects of a T-type calcium channel blocker, ABT-639, on spontaneous activity in C-nociceptors in patients with painful diabetic neuropathy: a randomized controlled trial. Pain. 2015 Nov;156(11):2175-83.
6 Mibefradil block of cloned T-type calcium channels. J Pharmacol Exp Ther. 2000 Oct;295(1):302-8.
7 Short-acting T-type calcium channel antagonists significantly modify sleep architecture in rodents. ACS Med Chem Lett. 2010 Aug 24;1(9):504-9.
8 Discovery of (2S)-1-(4-amino-2,3,5- trimethylphenoxy)-3-[4-[4-(4- fluorobenzyl)phenyl]-1-piperazinyl]-2-propanol dimethanesulfonate (SUN N8075): a ... J Med Chem. 2000 Sep 7;43(18):3372-6.
9 3,4-Dihydroquinazoline derivatives as novel selective T-type Ca2+ channel blockers. Bioorg Med Chem Lett. 2004 Jul 5;14(13):3379-84.
10 Synthesis and biological evaluation of novel T-type calcium channel blockers. Bioorg Med Chem Lett. 2007 Jan 15;17(2):471-5.
11 Morpholin-2-one derivatives as novel selective T-type Ca2+ channel blockers. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5244-8.
12 Mechanism of tissue-selective drug action in the cardiovascular system. Mol Interv. 2005 Apr;5(2):84-93.
13 Maladaptive homeostatic plasticity in a rodent model of central pain syndrome: thalamic hyperexcitability after spinothalamic tract lesions. J Neurosci. 2008 Nov 12;28(46):11959-69.
14 Prophylactic and therapeutic functions of T-type calcium blockers against noise-induced hearing loss. Hear Res. 2007 Apr;226(1-2):52-60.
15 Block of cloned human T-type calcium channels by succinimide antiepileptic drugs. Mol Pharmacol. 2001 Nov;60(5):1121-32.
16 Differential inhibition of T-type calcium channels by neuroleptics. J Neurosci. 2002 Jan 15;22(2):396-403.
17 Pfizer. Product Development Pipeline. March 31 2009.
18 Discovery of potent T-type calcium channel blocker. Bioorg Med Chem Lett. 2007 Nov 1;17(21):5740-3.