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 2778		4.5 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Allergic rhinitis 100 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 29 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
		252160038
Synthesis and structure-activity relationships of indole and benzimidazole piperazines as histamine H(4) receptor antagonists.	2004 Nov 1	15454206
Characterization of the histamine H4 receptor binding site. Part 1. Synthesis and pharmacological evaluation of dibenzodiazepine derivatives.	2006 Jul 27	16854056
Antiinflammatory and antinociceptive effects of the selective histamine H4-receptor antagonists JNJ7777120 and VUF6002 in a rat model of carrageenan-induced acute inflammation.	2007 Jun 1	17382315
Activation mechanism of the human histamine H4 receptor--an explicit membrane molecular dynamics simulation study.	2008 Jun	18572901
Binding mode analysis and enrichment studies on homology models of the human histamine H4 receptor.	2008 May	17900762
Histamine H4 receptors modulate dendritic cell migration through skin--immunomodulatory role of histamine.	2008 Oct	18782117
Effect of histamine H4 receptor antagonist on allergic rhinitis in mice.	2009 Jun	19275949
The histamine H4 receptor antagonist JNJ7777120 induces increases in the histamine content of the rat conjunctiva.	2009 Jun	19184344
Does the histamine H4 receptor have a pro- or anti-inflammatory role in murine bronchial asthma?	2010	20215812
Histamine stimulates human lung fibroblast migration.	2010 Apr	19851834
[Effect of histamine H4 receptor and its antagonist on allergic rhinitis in rats].	2010 Jun	21055325
Histamine H4 receptor antagonism diminishes existing airway inflammation and dysfunction via modulation of Th2 cytokines.	2010 Jun 24	20573261
Molecular determinants of ligand binding to H4R species variants.	2010 May	20103609
Deletion and down-regulation of HRH4 gene in gastric carcinomas: a potential correlation with tumor progression.	2012	22363581

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 `Fri Dec 15 17:57:06 GMT 2023` Edited by `admin` on `Fri Dec 15 17:57:06 GMT 2023`
Record UNII	4H1AU2V37X
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

JNJ-7777120

Common Name

English

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

Systematic Name

English

Code System Code Type Description

PUBCHEM

4908365