JNJ-7777120

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H16ClN3O
Molecular Weight	277.749
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1CCN(CC1)C(=O)C2=CC3=CC(Cl)=CC=C3N2

InChI

InChIKey=HUQJRYMLJBBEDO-UHFFFAOYSA-N

InChI=1S/C14H16ClN3O/c1-17-4-6-18(7-5-17)14(19)13-9-10-8-11(15)2-3-12(10)16-13/h2-3,8-9,16H,4-7H2,1H3

HIDE SMILES / InChI

Molecular Formula	C14H16ClN3O
Molecular Weight	277.749
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://adisinsight.springer.com/drugs/800022618
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/14722321 | https://www.ncbi.nlm.nih.gov/pubmed/17275092

1-[(5-chloro-1H-indol-2-yl)carbonyl]-4-methylpiperazine (JNJ 7777120) is the first selective antagonist of the histamine H4 receptor. Johnson & Johnson Pharmaceutical Research and Development is developing JNJ 7777120 for the treatment of inflammatory disorders. JNJ 7777120 demonstrates efficacy as anti-inflammatory agents in vivo. JNJ 7777120 have shown promising activity in down-regulating immune responses in a range of animal disease models including acute inflammation, hapten-mediated colitis, allergic airway inflammation (e.g. allergic rhinitis), colitis, allergic pruritis and atopic dermatitis.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Histamine H4 receptor 20 Target ID: CHEMBL3759 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14722321	Antagonist 2849		4.5 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Allergic rhinitis 104 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26003849	Primary	Basic research	Unknown Approved Use Unknown
Dermatitis 10 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22897580 https://www.ncbi.nlm.nih.gov/pubmed/22686688	Primary	Basic research	Unknown Approved Use Unknown
Pruritus 31 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21689731	Primary	Basic research	Unknown Approved Use Unknown
Colitis 7 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16213481	Primary	Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Deletion and down-regulation of HRH4 gene in gastric carcinomas: a potential correlation with tumor progression.	2012	22363581
Histamine H4 receptor antagonism diminishes existing airway inflammation and dysfunction via modulation of Th2 cytokines.	2010-06-24	20573261
[Effect of histamine H4 receptor and its antagonist on allergic rhinitis in rats].	2010-06	21055325
Molecular determinants of ligand binding to H4R species variants.	2010-05	20103609
The histamine H4 receptor mediates inflammation and pruritus in Th2-dependent dermal inflammation.	2010-04	19907432
Histamine stimulates human lung fibroblast migration.	2010-04	19851834
Does the histamine H4 receptor have a pro- or anti-inflammatory role in murine bronchial asthma?	2010	20215812
Interactions of histamine H1-receptor agonists and antagonists with the human histamine H4-receptor.	2009-11	19720730
The histamine H receptor as a new target for treatment of canine inflammatory skin diseases.	2009-10	20178494
Expression of histamine H4 receptor in human epidermal tissues and attenuation of experimental pruritus using H4 receptor antagonist.	2009-10	19652466
A new generation of anti-histamines: Histamine H4 receptor antagonists on their way to the clinic.	2009-09	19736622
Effect of histamine H4 receptor antagonist on allergic rhinitis in mice.	2009-06	19275949
The histamine H4 receptor antagonist JNJ7777120 induces increases in the histamine content of the rat conjunctiva.	2009-06	19184344
Histamine H4 receptor antagonism reduces hapten-induced scratching behaviour but not inflammation.	2009-01	18647342
Histamine H4 receptors modulate dendritic cell migration through skin--immunomodulatory role of histamine.	2008-10	18782117
Phenylalanine 169 in the second extracellular loop of the human histamine H4 receptor is responsible for the difference in agonist binding between human and mouse H4 receptors.	2008-10	18635748
Cloning and pharmacological characterization of the dog histamine H4 receptor.	2008-09-11	18639542
Histamine H(4) receptors regulate ACTH release in AtT-20 cells.	2008-06-10	18439995
Activation mechanism of the human histamine H4 receptor--an explicit membrane molecular dynamics simulation study.	2008-06	18572901
Binding mode analysis and enrichment studies on homology models of the human histamine H4 receptor.	2008-05	17900762
Histamine receptor H4R-selective ligands influence the STAT6 Transcription Activation Domain (TAD) and the DNA-binding.	2008	18345495
Histamine downregulates monocyte CCL2 production through the histamine H4 receptor.	2007-08	17507084
Antiinflammatory and antinociceptive effects of the selective histamine H4-receptor antagonists JNJ7777120 and VUF6002 in a rat model of carrageenan-induced acute inflammation.	2007-06-01	17382315
The histamine H(4) receptor: a novel modulator of inflammatory and immune disorders.	2007-03	17275092
Histamine H4 receptor antagonists are superior to traditional antihistamines in the attenuation of experimental pruritus.	2007-01	17208599
Role of histamine H3 and H4 receptors in mechanical hyperalgesia following peripheral nerve injury.	2007	18401194
Characterization of the histamine H4 receptor binding site. Part 1. Synthesis and pharmacological evaluation of dibenzodiazepine derivatives.	2006-07-27	16854056
The histamine H4 receptor mediates allergic airway inflammation by regulating the activation of CD4+ T cells.	2006-06-01	16709868
Inhibitory effects of histamine H4 receptor antagonists on experimental colitis in the rat.	2005-10-17	16213481
Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist.	2005-09	15947036
Synthesis and structure-activity relationships of indole and benzimidazole piperazines as histamine H(4) receptor antagonists.	2004-11-01	15454206
A potent and selective histamine H4 receptor antagonist with anti-inflammatory properties.	2004-04	14722321

Patents

Sample Use Guides

In Vivo Use Guide

JNJ7777120 (5mg/kg i.p.) significantly suppressed nasal symptoms and the number of coughs in ovalbumin-induced allergic rhinitis in guinea pigs. JNJ7777120 was administered orally at 10 mg/kg to mice, rats, and dogs and intravenously at 1 mg/kg in dogs and 3 mg/kg in rats. LC/MS analysis was used to quantitate the plasma levels. After oral administration, JNJ 7777120 had an absolute oral availability of 22 to 100% and an oral half-life of 1 to 2 h depending on the species.

Route of Administration: Other

In Vitro Use Guide

The IC50 for inhibition of the histamine-induced chemotaxis assay was 40 nM using 10 μM histamine, showing that JNJ 7777120 is a very potent antagonist of the H4 receptor in mouse bone marrow-derived mast cells

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:57:29 GMT 2025` Edited by `admin` on `Mon Mar 31 18:57:29 GMT 2025`
Record UNII	4H1AU2V37X
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

1-((5-CHLORO-1H-INDOL-2-YL)CARBONYL)-4-METHYLPIPERAZINE

Preferred Name

English

JNJ-7777120

Common Name

English

Code System Code Type Description

PUBCHEM

4908365