Details of the Drug

General Information of Drug (ID: DM537OH)

Drug Name
Clobenpropit
Synonyms
clobenpropit; 145231-45-4; Vuf-9153; Vuf 9153; UNII-RKU631JF4H; S-(3-(4(5)-Imidazolyl))propyl-N-(4-chlorobenzyl)isothiourea; CHEBI:64177; RKU631JF4H; 3-(1h-imidazol-5-yl)propyl n'-(4-chlorobenzyl)carbamimidothioate; 3-(1H-imidazol-4-yl)propyl ((4-chlorophenyl)methyl)carbamimidothioate; Carbamimidothioic acid, ((4-chlorophenyl)methyl)-, 3-(1H-imidazol-4-yl)propyl ester; 3-(1H-imidazol-4-yl)propyl N-(4-chlorobenzyl)carbamimidothioate; Carbamimidothioic acid,N-[(4-chlorophenyl)methyl]-, 3-(1H-imidazol-5-yl)propyl ester
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) 308.8
Topological Polar Surface Area (xlogp) 3
Rotatable Bond Count (rotbonds) 7
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 3
Chemical Identifiers
Formula
C14H17ClN4S
IUPAC Name
3-(1H-imidazol-5-yl)propyl N'-[(4-chlorophenyl)methyl]carbamimidothioate
Canonical SMILES
C1=CC(=CC=C1CN=C(N)SCCCC2=CN=CN2)Cl
InChI
InChI=1S/C14H17ClN4S/c15-12-5-3-11(4-6-12)8-18-14(16)20-7-1-2-13-9-17-10-19-13/h3-6,9-10H,1-2,7-8H2,(H2,16,18)(H,17,19)
InChIKey
UCAIEVHKDLMIFL-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
2790
ChEBI ID
CHEBI:64177
CAS Number
145231-45-4
TTD ID
D0T8OD

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Histamine H3 receptor (H3R) TT9JNIC HRH3_HUMAN Antagonist [2], [3]
Histamine H4 receptor (H4R) TTXJ178 HRH4_HUMAN Agonist [4], [5]
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
Histamine H3 receptor (H3R) DTT HRH3 3.62E-02 -0.09 -0.22
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: 1223).
2 The histamine H3 receptor: from gene cloning to H3 receptor drugs. Nat Rev Drug Discov. 2005 Feb;4(2):107-20.
3 Combined histamine H1 and H3 receptor blockade produces nasal decongestion in an experimental model of nasal congestion. Am J Rhinol. 1999 Sep-Oct;13(5):391-9.
4 Clobenpropit analogs as dual activity ligands for the histamine H3 and H4 receptors: synthesis, pharmacological evaluation, and cross-target QSAR s... Bioorg Med Chem. 2009 Jun 1;17(11):3987-94.
5 The histamine H4 receptor is functionally expressed on T(H)2 cells. J Allergy Clin Immunol. 2009 Mar;123(3):619-25.
6 Challenges of drug discovery in novel target space. The discovery and evaluation of PF-3893787: a novel histamine H4 receptor antagonist. Bioorg Med Chem Lett. 2011 Nov 1;21(21):6596-602.
7 The histamine H4 receptor: from orphan to the clinic. Front Pharmacol. 2015; 6: 65.
8 Azines as histamine H4 receptor antagonists. Front Biosci (Schol Ed). 2012 Jan 1;4:967-87.
9 Role of histamine in short- and long-term effects of methamphetamine on the developing mouse brain. J Neurochem. 2008 Nov;107(4):976-86.
10 Synthesis and structure-activity relationships of N-aryl-piperidine derivatives as potent (partial) agonists for human histamine H3 receptor. Bioorg Med Chem. 2010 Jul 15;18(14):5441-8.
11 Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first pote... J Pharmacol Exp Ther. 2005 Sep;314(3):1310-21.
12 Comparison of human, mouse, rat, and guinea pig histamine H4 receptors reveals substantial pharmacological species variation. J Pharmacol Exp Ther. 2001 Oct;299(1):121-30.
13 Histamine excites neonatal rat sympathetic preganglionic neurons in vitro via activation of H1 receptors. J Neurophysiol. 2006 Apr;95(4):2492-500.
14 Discovery of novel human histamine H4 receptor ligands by large-scale structure-based virtual screening. J Med Chem. 2008 Jun 12;51(11):3145-53.
15 Cloning and pharmacological characterization of a fourth histamine receptor (H(4)) expressed in bone marrow. Mol Pharmacol. 2001 Mar;59(3):420-6.
16 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
17 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
18 Acute wake-promoting actions of JNJ-5207852, a novel, diamine-based H3 antagonist. Br J Pharmacol. 2004 Nov;143(5):649-61.
19 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
20 JNJ-39220675, a novel selective histamine H3 receptor antagonist, reduces the abuse-related effects of alcohol in rats. Psychopharmacology (Berl). 2011 Apr;214(4):829-41.
21 SAR110894, a potent histamine H receptor antagonist, displays procognitive effects in rodents. Pharmacol Biochem Behav. 2012 Aug;102(2):203-14.
22 Randomized clinical study of a histamine H3 receptor antagonist for the treatment of adults with attention-deficit hyperactivity disorder. CNS Drugs. 2012 May 1;26(5):421-34.
23 A randomized study of H3 antagonist ABT-288 in mild-to-moderate Alzheimer's dementia.J Alzheimers Dis.2014;42(3):959-71.
24 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032225)