Details of the Drug

General Information of Drug (ID: DMWZCIF)

• Drug Name: TTA-A8
• Synonyms: TTA-A2; TTA-P2; T-type calcium channel antagonists, Merck & Co

Indication

Disease Entry	ICD 11	Status	REF
Insomnia	7A00-7A0Z	Preclinical	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 430.4
  Topological Polar Surface Area (xlogp); 3
  Rotatable Bond Count (rotbonds); 7
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 8
• Chemical Identifiers:
  Formula: C22H21F3N4O2
  IUPAC Name: 2-[4-(3-methylpyrazin-2-yl)phenyl]-N-[(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl]acetamide
  Canonical SMILES: CC1=NC=CN=C1C2=CC=C(C=C2)CC(=O)N[C@H](C)C3=NC=C(C=C3)OCC(F)(F)F
  InChI: InChI=1S/C22H21F3N4O2/c1-14(19-8-7-18(12-28-19)31-13-22(23,24)25)29-20(30)11-16-3-5-17(6-4-16)21-15(2)26-9-10-27-21/h3-10,12,14H,11,13H2,1-2H3,(H,29,30)/t14-/m1/s1
  InChIKey: OURCOVUGQRXRTE-CQSZACIVSA-N
• Cross-matching ID:
  PubChem CID: 42609962
  TTD ID: D0X5OV

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Voltage-gated calcium channel alpha Cav3.2 (CACNA1H)	TTZPWGN	CAC1H_HUMAN	Antagonist	[3]

Molecular Expression Atlas of This Drug

• The Studied Disease: Insomnia
• ICD Disease Classification: 7A00-7A0Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Voltage-gated calcium channel alpha Cav3.2 (CACNA1H)	DTT	CACNA1H	1.31E-04	-0.76	-2.12

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: 7724).
• [2] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010094)
• [3] Short-acting T-type calcium channel antagonists significantly modify sleep architecture in rodents. ACS Med Chem Lett. 2010 Aug 24;1(9):504-9.
• [4] Acute renal failure. Clin Evid (Online). 2008 Sep 3;2008. pii: 2001.
• [5] Positive allosteric interaction of structurally diverse T-type calcium channel antagonists. Cell Biochem Biophys. 2009;55(2):81-93.
• [6] 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.
• [7] Mibefradil block of cloned T-type calcium channels. J Pharmacol Exp Ther. 2000 Oct;295(1):302-8.
• [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] 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.
• [10] 3,4-Dihydroquinazoline derivatives as novel selective T-type Ca2+ channel blockers. Bioorg Med Chem Lett. 2004 Jul 5;14(13):3379-84.
• [11] Synthesis and biological evaluation of novel T-type calcium channel blockers. Bioorg Med Chem Lett. 2007 Jan 15;17(2):471-5.
• [12] Morpholin-2-one derivatives as novel selective T-type Ca2+ channel blockers. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5244-8.