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
A potent and selective histamine H4 receptor antagonist with anti-inflammatory properties.	2004 Apr	14722321
Synthesis and structure-activity relationships of indole and benzimidazole piperazines as histamine H(4) receptor antagonists.	2004 Nov 1	15454206
Histamine downregulates monocyte CCL2 production through the histamine H4 receptor.	2007 Aug	17507084
Interactions of histamine H1-receptor agonists and antagonists with the human histamine H4-receptor.	2009 Nov	19720730
The histamine H receptor as a new target for treatment of canine inflammatory skin diseases.	2009 Oct	20178494
Expression of histamine H4 receptor in human epidermal tissues and attenuation of experimental pruritus using H4 receptor antagonist.	2009 Oct	19652466
A new generation of anti-histamines: Histamine H4 receptor antagonists on their way to the clinic.	2009 Sep	19736622
Does the histamine H4 receptor have a pro- or anti-inflammatory role in murine bronchial asthma?	2010	20215812
[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