Details of the Drug

General Information of Drug (ID: DM5IPHE)

Drug Name
1192U90
Synonyms
LS-25359; 2-Amino-N-(4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl)benzamide; 2-Amino-N-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]butyl] benzamide; 2-amino-N-[4-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]butyl]benzamide
Indication
Disease Entry ICD 11 Status REF
Psychotic disorder 6A20-6A25 Phase 1 [1]
Schizophrenia 6A20 Terminated [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 409.5
Topological Polar Surface Area (xlogp) 4.1
Rotatable Bond Count (rotbonds) 7
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 6
Chemical Identifiers
Formula
C22H27N5OS
IUPAC Name
2-amino-N-[4-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]butyl]benzamide
Canonical SMILES
C1CN(CCN1CCCCNC(=O)C2=CC=CC=C2N)C3=NSC4=CC=CC=C43
InChI
InChI=1S/C22H27N5OS/c23-19-9-3-1-7-17(19)22(28)24-11-5-6-12-26-13-15-27(16-14-26)21-18-8-2-4-10-20(18)29-25-21/h1-4,7-10H,5-6,11-16,23H2,(H,24,28)
InChIKey
GMDXHLCLNHCEIC-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
127912
CAS Number
155289-31-9
TTD ID
D0C7WO

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
5-HT 1A receptor (HTR1A) TTSQIFT 5HT1A_HUMAN Agonist [2]
5-HT 2A receptor (HTR2A) TTJQOD7 5HT2A_HUMAN Antagonist [2]
Dopamine D2 receptor (D2R) TTEX248 DRD2_HUMAN Antagonist [2]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Psychotic disorder
ICD Disease Classification 6A20-6A25
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
5-HT 1A receptor (HTR1A) DTT HTR1A 5.70E-01 -0.13 -0.53
Dopamine D2 receptor (D2R) DTT DRD2 2.20E-03 -0.51 -1.35
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 1192U90 in animal tests that predict antipsychotic efficacy, anxiolysis, and extrapyramidal side effects. Neuropsychopharmacology. 1996 Sep;15(3):231-42.
2 The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
3 Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors. Naunyn Schmiedebergs Arch Pharmacol. 2004 Aug;370(2):114-23.
4 Current and novel approaches to the drug treatment of schizophrenia. J Med Chem. 2001 Feb 15;44(4):477-501.
5 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
6 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
7 Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
8 Anxiolytic effects of aniracetam in three different mouse models of anxiety and the underlying mechanism. Eur J Pharmacol. 2001 May 18;420(1):33-43.
9 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
10 Beneficial effects of sarpogrelate hydrochloride, a 5-HT2A receptor antagonist, supplemented with pioglitazone on diabetic model mice. Endocr Res. 2009;34(1-2):18-30.
11 Pimavanserin, a selective serotonin (5-HT)2A-inverse agonist, enhances the efficacy and safety of risperidone, 2mg/day, but does not enhance efficacy of haloperidol, 2mg/day: comparison with reference dose risperidone, 6mg/day.Schizophr Res.2012 Nov;141(2-3):144-52.
12 Clinical pipeline report, company report or official report of Lundbeck.
13 The Detection of Dopamine Gene Receptors (DRD1-DRD5) Expression on Human Peripheral Blood Lymphocytes by Real Time PCR. Iran J Allergy Asthma Immunol. 2004 Dec;3(4):169-74.
14 Dopaminergic synapses in the matrix of the ventrolateral striatum after chronic haloperidol treatment. Synapse. 2002 Aug;45(2):78-85.
15 CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time course of prolactin response to perphenazine. Pharmacogenet Genomics. 2007 Nov;17(11):989-93.
16 Synthesis and in vitro binding of N-phenyl piperazine analogs as potential dopamine D3 receptor ligands. Bioorg Med Chem. 2005 Jan 3;13(1):77-87.
17 Screening of domperidone in wastewater by high performance liquid chromatography and solid phase extraction methods. Talanta. 2006 Jan 15;68(3):928-31.
18 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: 3639).
19 Receptor reserve-dependent properties of antipsychotics at human dopamine D2 receptors. Eur J Pharmacol. 2009 Apr 1;607(1-3):35-40.
20 [The benzamides tiapride, sulpiride, and amisulpride in treatment for Tourette's syndrome]. Nervenarzt. 2007 Mar;78(3):264, 266-8, 270-1.
21 Modulatory role of dopamine D2 receptors and fundamental role of L-type Ca2+ channels in the induction of long-term potentiation in the basolateral... Eur J Pharmacol. 2009 Mar 15;606(1-3):90-3.
22 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
23 Interactions between corticotropin-releasing hormone and serotonin: implications for the aetiology and treatment of anxiety disorders. Handb Exp Pharmacol. 2005;(169):181-204.
24 Effects of brexpiprazole, a novel serotonin-dopamine activity modulator, on phencyclidine-induced cognitive deficits in mice: a role for serotonin 5-HT1A receptors.Pharmacol Biochem Behav.2014 Sep;124:245-9.
25 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
26 Synthesis of new derivatives of 8-OH-DPAT: Influence of substitution on the aromatic ring on the pharmacological profile, Bioorg. Med. Chem. Lett. 3(10):2035-2038 (1993).
27 Urapidil. A reappraisal of its use in the management of hypertension. Drugs. 1998 Nov;56(5):929-55.
28 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
29 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031127)
30 Clinical pipeline report, company report or official report of Jazz Pharmaceuticals.