JNJ-7777120 (PD010521, HUQJRYMLJBBEDO-UHFFFAOYSA-N)

General

Preferred name

JNJ-7777120

Synonyms

JNJ 7777120

JNJ7777120

[3H]JNJ 7777120

[³H]JNJ 7777120

P&D ID

PD010521

CAS

459168-41-3

Tags

available

biased GPCR ligand

drug candidate

Drug indication

Inflammation

Structure

PD010521

JNJ-7777120

RO5

277.1

HBA

HBD

LOGP

2.21

Structure formats

SMILES

CN1CCN(C(=O)c2cc3cc(Cl)ccc3[nH]2)CC1

InChI

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

InChIkey

HUQJRYMLJBBEDO-UHFFFAOYSA-N

MOL

JNJ-7777120 RDKit 2D 19 21 0 0 0 0 0 0 0 0999 V2000 -5.1962 -8.1073 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8971 -7.3573 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.8971 -5.8573 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -5.1073 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2990 -5.8573 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -5.1073 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2990 -5.8573 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -3.6073 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2135 -2.7256 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 2.5981 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2135 -2.7256 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.2990 -7.3573 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -8.1073 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 6 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 1 0 12 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 5 18 1 0 18 19 1 0 19 2 1 0 17 8 1 0 16 10 1 0 M END > <ID> PD010521 > <Name> JNJ-7777120

Description

(extracted from source data)

DESCRIPTION Selective H4 receptor antagonist (Tocriscreen Plus)

DESCRIPTION Highly potent and selective adenosine A3 receptor antagonist (Tocris Bioactive Compound Library)

DESCRIPTION JNJ-7777120 is the first potent and selective non-imidazole histamine H4 receptor antagonist with Ki of 4.5 nM, exhibits >1000-fold selectivity over the other histamin receptors. (BOC Sciences Bioactive Compounds)

Protein targets

8.3

7.85

HRH4 Histamine H4 receptor antagonist

BIOCHEM 195x

CELL-BASED 141.2x

6.01

4.33

HRH1 Histamine H1 receptor

5.97

HRH4 Histamine H4 receptor

5.47

5.7

HRH3 Histamine H3 receptor

Target pathways

G alpha (i) signalling events

R-HSA-418594

HRH4

G alpha (q) signalling events

R-HSA-416476

HRH1

Histamine receptors

R-HSA-390650

HRH3

HRH1

HRH4

References

2023 Treatment of allergy: Overview of synthetic anti-allergy small molecules in medicinal chemistry.

Zhang S, Liu Y et al. Eur J Med Chem

2020 UR-DEBa242: A Py-5-Labeled Fluorescent Multipurpose Probe for Investigations on the Histamine H3 and H4 Receptors.

Bartole E, Grätz L et al. J Med Chem

2019 Alkyl derivatives of 1,3,5-triazine as histamine H4 receptor ligands.

Łażewska D, Mogilski S et al. Bioorg Med Chem

2019 [3H]UR-DEBa176: A 2,4-Diaminopyrimidine-Type Radioligand Enabling Binding Studies at the Human, Mouse, and Rat Histamine H4 Receptors.

Bartole E, Littmann T et al. J Med Chem

2018 Biased Ligands of G Protein-Coupled Receptors (GPCRs): Structure-Functional Selectivity Relationships (SFSRs) and Therapeutic Potential.

Tan L, Yan W et al. J Med Chem

2018 Discovery of a Novel Highly Selective Histamine H4 Receptor Antagonist for the Treatment of Atopic Dermatitis.

Ko K, Kim HJ et al. J. Med. Chem.

2016 2,4-Diaminopyrimidines as dual ligands at the histamine H1 and H4 receptor-H1/H4-receptor selectivity.

Hammer SG, Gobleder S et al. Bioorg. Med. Chem. Lett.

2016 Conformational Restriction and Enantioseparation Increase Potency and Selectivity of Cyanoguanidine-Type Histamine H4 Receptor Agonists.

Geyer R, Nordemann U et al. J. Med. Chem.

2015 Diaminopyrimidines, diaminopyridines and diaminopyridazines as histamine H4 receptor modulators.

Savall BM, Meduna SP et al. Bioorg. Med. Chem. Lett.

2015 Functional Profiling of 2-Aminopyrimidine Histamine H4 Receptor Modulators.

Tichenor MS, Thurmond RL et al. J. Med. Chem.

2014 Discovery and SAR of 6-alkyl-2,4-diaminopyrimidines as histamine H₄ receptor antagonists.

Savall BM, Chavez F et al. J. Med. Chem.

2014 The effect of pK(a) on pyrimidine/pyridine-derived histamine H4 ligands.

Savall BM, Meduna SP et al. Bioorg. Med. Chem. Lett.

2014 Biased ligand modulation of seven transmembrane receptors (7TMRs): functional implications for drug discovery.

Correll CC, McKittrick BA. J. Med. Chem.

2013 Bispyrimidines as potent histamine H(4) receptor ligands: delineation of structure-activity relationships and detailed H(4) receptor binding mode.

Engelhardt H, Schultes S et al. J. Med. Chem.

2013 A novel series of histamine H4 receptor antagonists based on the pyrido[3,2-d]pyrimidine scaffold: comparison of hERG binding and target residence time with PF-3893787.

Andaloussi M, Lim HD et al. Bioorg. Med. Chem. Lett.

2013 Mapping histamine H4receptorligand binding modes

Schultes S, Nijmeijer S et al. MedChemComm

2012 Ligand based design of novel histamine H4 receptor antagonists; fragment optimization and analysis of binding kinetics.

Smits RA, Lim HD et al. Bioorg. Med. Chem. Lett.

2012 Synthesis of novel histamine H4 receptor antagonists.

Lane CA, Hay D et al. Bioorg. Med. Chem. Lett.

2012 Detailed structure-activity relationship of indolecarboxamides as H4 receptor ligands.

Engelhardt H, de Esch IJ et al. Eur. J. Med. Chem.

2011 Triamino pyrimidines and pyridines as histamine H(4) receptor modulators.

Meduna SP, Savall BM et al. Bioorg. Med. Chem. Lett.

2011 Mepyramine-JNJ7777120-hybrid compounds show high affinity to hH(1)R, but low affinity to hH(4)R.

Wagner E, Wittmann HJ et al. Bioorg. Med. Chem. Lett.

2011 Challenges of drug discovery in novel target space. The discovery and evaluation of PF-3893787: a novel histamine H4 receptor antagonist.

Mowbray CE, Bell AS et al. Bioorg. Med. Chem. Lett.

2011 Discovery of a series of potent and selective human H4 antagonists using ligand efficiency and libraries to explore structure-activity relationship (SAR).

Masood MA, Selby MD et al. Bioorg. Med. Chem. Lett.

2011 Molecular determinants of ligand binding modes in the histamine H(4) receptor: linking ligand-based three-dimensional quantitative structure-activity relationship (3D-QSAR) models to in silico guided receptor mutagenesis studies.

Istyastono EP, Nijmeijer S et al. J. Med. Chem.

2009 2,4-Diaminopyrimidines as histamine H4 receptor ligands--Scaffold optimization and pharmacological characterization.

Sander K, Kottke T et al. Bioorg. Med. Chem.

2009 Synthesis and structure-activity relationships of cyanoguanidine-type and structurally related histamine H4 receptor agonists.

Igel P, Geyer R et al. J. Med. Chem.

2008 Fragment based design of new H4 receptor-ligands with anti-inflammatory properties in vivo.

Smits RA, Lim HD et al. J. Med. Chem.

2008 Discovery of novel human histamine H4 receptor ligands by large-scale structure-based virtual screening.

Kiss R; Kiss B et al.

2008 Rotationally constrained 2,4-diamino-5,6-disubstituted pyrimidines: a new class of histamine H4 receptor antagonists with improved druglikeness and in vivo efficacy in pain and inflammation models.

Cowart MD, Altenbach RJ et al. J. Med. Chem.

2008 Structure-activity studies on a series of a 2-aminopyrimidine-containing histamine H4 receptor ligands.

Altenbach RJ, Adair RM et al. J. Med. Chem.

2008 cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain responses against carrageenan-induced hyperalgesia.

Liu H, Altenbach RJ et al. J. Med. Chem.

2008 Discovery of quinazolines as histamine H4 receptor inverse agonists using a scaffold hopping approach.

Smits RA, de Esch IJ et al. J. Med. Chem.

2006 Characterization of the histamine H4 receptor binding site. Part 1. Synthesis and pharmacological evaluation of dibenzodiazepine derivatives.

Smits RA, Lim HD et al. J. Med. Chem.

2005 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.

Lim HD, van Rijn RM et al. J Pharmacol Exp Ther

2005 Preparation and biological evaluation of indole, benzimidazole, and thienopyrrole piperazine carboxamides: potent human histamine h(4) antagonists.

Venable JD, Cai H et al. J. Med. Chem.

2004 A potent and selective histamine H4 receptor antagonist with anti-inflammatory properties.

Thurmond RL, Desai PJ et al. J Pharmacol Exp Ther

2004 Synthesis and structure-activity relationships of indole and benzimidazole piperazines as histamine H(4) receptor antagonists.

Terzioglu N, van Rijn RM et al. Bioorg Med Chem Lett

2004 STUDIES ON NOVEL NON-IMIDAZOLE HUMAN H4 RECEPTOR ANTAGONISTS USING GFA AND FREE-WILSON ANALYSIS

Pimple SR, Kelkar MA et al. Med Chem Res

2003 The first potent and selective non-imidazole human histamine H4 receptor antagonists.

Jablonowski JA; Grice CA et al.

BiasDB (dataset)

Compound Sets

AdooQ Bioactive Compound Library