JNJ-7777120

Chemical compound

JNJ-7777120
Clinical data


Other names	1-[(5-chloro-1H-indol-2-yl)carbonyl]-4-methylpiperazine
Identifiers
IUPAC name 5-chloro-2-[(4-methylpiperazin-1-yl)carbonyl]-1H-indole
CAS Number	459168-41-3^Y
PubChem CID	4908365
IUPHAR/BPS	1278
ChemSpider	4090750^N
UNII	4H1AU2V37X
ChEMBL	ChEMBL129198^N
CompTox Dashboard (EPA)	DTXSID20963461
ECHA InfoCard	100.164.683
Chemical and physical data
Formula	C₁₄H₁₆ClN₃O
Molar mass	277.75 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES C3CN(C)CCN3C(=O)c(cc1c2)[nH]c1ccc2Cl
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^N Key:HUQJRYMLJBBEDO-UHFFFAOYSA-N^N
^NY (what is this?) (verify)

JNJ-7777120 was a drug being developed by Johnson & Johnson Pharmaceutical Research & Development which acts as a potent and selective antagonist at the histamine H₄ receptor.^[1] It has anti-inflammatory effects,^[2] and has been demonstrated to be superior to traditional (H1) antihistamines in the treatment of pruritus (itching).^[3] The drug was abandoned because of its short in vivo half-life and hypoadrenocorticism toxicity in rats and dogs, that prevented advancing it into clinical studies.^[4]

References

^ Jiang W, Lim HD, Zhang M, et al. (July 2008). "Cloning and pharmacological characterization of the dog histamine H(4) receptor". Eur. J. Pharmacol. 592 (1–3): 26–32. doi:10.1016/j.ejphar.2008.06.095. PMID 18639542.
^ Thurmond RL, Desai PJ, Dunford PJ, Fung-Leung WP, Hofstra CL, Jiang W, Nguyen S, Riley JP, Sun S, Williams KN, Edwards JP, Karlsson L (Apr 2004). "A potent and selective histamine H4 receptor antagonist with anti-inflammatory properties". Journal of Pharmacology and Experimental Therapeutics. 309 (1): 404–13. doi:10.1124/jpet.103.061754. PMID 14722321. S2CID 8396875.
^ Dunford PJ, Williams KN, Desai PJ, Karlsson L, McQueen D, Thurmond RL (Jan 2007). "Histamine H4 receptor antagonists are superior to traditional antihistamines in the attenuation of experimental pruritus". Journal of Allergy and Clinical Immunology. 119 (1): 176–83. doi:10.1016/j.jaci.2006.08.034. PMID 17208599.
^ Thurmond RL, Venable J, Savall B, La D, Snook S, Dunford PJ, Edwards JP (2017). "Clinical Development of Histamine H4 Receptor Antagonists". Histamine and Histamine Receptors in Health and Disease. Handbook of Experimental Pharmacology. Vol. 241. pp. 301–320. doi:10.1007/164_2016_130. ISBN 978-3-319-58192-7. PMID 28233185.

Histamine receptor modulators

H₁

Agonists	2-Pyridylethylamine Betahistine Histamine HTMT L-Histidine UR-AK49
Antagonists	First-generation: 4-Methyldiphenhydramine Alimemazine Antazoline Azatadine Bamipine Benzatropine (benztropine) Bepotastine Bromazine Brompheniramine Buclizine Captodiame Carbinoxamine Chlorcyclizine Chloropyramine Chlorothen Chlorphenamine Chlorphenoxamine Cinnarizine Clemastine Clobenzepam Clocinizine Cloperastine Cyclizine Cyproheptadine Dacemazine Decloxizine Deptropine Dexbrompheniramine Dexchlorpheniramine Dimenhydrinate Dimetindene Diphenhydramine Diphenylpyraline Doxylamine Embramine Etodroxizine Etybenzatropine (ethylbenztropine) Etymemazine Fenethazine Flunarizine Histapyrrodine Homochlorcyclizine Hydroxyethylpromethazine Hydroxyzine Isopromethazine Isothipendyl Meclozine Medrylamine Mepyramine (pyrilamine) Mequitazine Methafurylene Methapyrilene Methdilazine Moxastine Orphenadrine Oxatomide Oxomemazine Perlapine Phenindamine Pheniramine Phenyltoloxamine Pimethixene Piperoxan Pipoxizine Promethazine Propiomazine Pyrrobutamine Talastine Thenalidine Thenyldiamine Thiazinamium Thonzylamine Tolpropamine Tripelennamine Triprolidine Second/third-generation: Acrivastine Alinastine Astemizole Azelastine Bamirastine Barmastine Bepiastine Bepotastine Bilastine Cabastinen Carebastine Cetirizine Clemastine Clemizole Clobenztropine Desloratadine Dorastine Ebastine Efletirizine Emedastine Epinastine Fexofenadine Flezelastine Ketotifen Latrepirdine Levocabastine Levocetirizine Linetastine Loratadine Mapinastine Mebhydrolin Mizolastine Moxastine Noberastine Octastine Olopatadine Perastine Pibaxizine Piclopastine Quifenadine (phencarol) Rocastine Rupatadine Setastine Sequifenadine (bicarphen) Talastine Temelastine Terfenadine Vapitadine Zepastine Others: Atypical antipsychotics (e.g., aripiprazole, asenapine, brexpiprazole, brilaroxazine, clozapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone, zotepine) Phenylpiperazine antidepressants (e.g., hydroxynefazodone, nefazodone, trazodone, triazoledione) Tetracyclic antidepressants (e.g., amoxapine, loxapine, maprotiline, mianserin, mirtazapine, oxaprotiline) Tricyclic antidepressants (e.g., amitriptyline, butriptyline, clomipramine, desipramine, dosulepin (dothiepin), doxepin, imipramine, iprindole, lofepramine, nortriptyline, protriptyline, trimipramine) Typical antipsychotics (e.g., chlorpromazine, flupenthixol, fluphenazine, loxapine, perphenazine, prochlorperazine, thioridazine, thiothixene) Unknown/unsorted: Azanator Belarizine Elbanizine Flotrenizine GSK1004723 Napactadine Tagorizine Trelnarizine Trenizine

Agonists

Antagonists

First-generation: 4-Methyldiphenhydramine
Alimemazine
Antazoline
Azatadine
Bamipine
Benzatropine (benztropine)
Bepotastine
Bromazine
Brompheniramine
Buclizine
Captodiame
Carbinoxamine
Chlorcyclizine
Chloropyramine
Chlorothen
Chlorphenamine
Chlorphenoxamine
Cinnarizine
Clemastine
Clobenzepam
Clocinizine
Cloperastine
Cyclizine
Cyproheptadine
Dacemazine
Decloxizine
Deptropine
Dexbrompheniramine
Dexchlorpheniramine
Dimenhydrinate
Dimetindene
Diphenhydramine
Diphenylpyraline
Doxylamine
Embramine
Etodroxizine
Etybenzatropine (ethylbenztropine)
Etymemazine
Fenethazine
Flunarizine
Histapyrrodine
Homochlorcyclizine
Hydroxyethylpromethazine
Hydroxyzine
Isopromethazine
Isothipendyl
Meclozine
Medrylamine
Mepyramine (pyrilamine)
Mequitazine
Methafurylene
Methapyrilene
Methdilazine
Moxastine
Orphenadrine
Oxatomide
Oxomemazine
Perlapine
Phenindamine
Pheniramine
Phenyltoloxamine
Pimethixene
Piperoxan
Pipoxizine
Promethazine
Propiomazine
Pyrrobutamine
Talastine
Thenalidine
Thenyldiamine
Thiazinamium
Thonzylamine
Tolpropamine
Tripelennamine
Triprolidine

Second/third-generation: Acrivastine
Alinastine
Astemizole
Azelastine
Bamirastine
Barmastine
Bepiastine
Bepotastine
Bilastine
Cabastinen
Carebastine
Cetirizine
Clemastine
Clemizole
Clobenztropine
Desloratadine
Dorastine
Ebastine
Efletirizine
Emedastine
Epinastine
Fexofenadine
Flezelastine
Ketotifen
Latrepirdine
Levocabastine
Levocetirizine
Linetastine
Loratadine
Mapinastine
Mebhydrolin
Mizolastine
Moxastine
Noberastine
Octastine
Olopatadine
Perastine
Pibaxizine
Piclopastine
Quifenadine (phencarol)
Rocastine
Rupatadine
Setastine
Sequifenadine (bicarphen)
Talastine
Temelastine
Terfenadine
Vapitadine
Zepastine

Others: Atypical antipsychotics (e.g., aripiprazole, asenapine, brexpiprazole, brilaroxazine, clozapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone, zotepine)
Phenylpiperazine antidepressants (e.g., hydroxynefazodone, nefazodone, trazodone, triazoledione)
Tetracyclic antidepressants (e.g., amoxapine, loxapine, maprotiline, mianserin, mirtazapine, oxaprotiline)
Tricyclic antidepressants (e.g., amitriptyline, butriptyline, clomipramine, desipramine, dosulepin (dothiepin), doxepin, imipramine, iprindole, lofepramine, nortriptyline, protriptyline, trimipramine)
Typical antipsychotics (e.g., chlorpromazine, flupenthixol, fluphenazine, loxapine, perphenazine, prochlorperazine, thioridazine, thiothixene)

Unknown/unsorted: Azanator
Belarizine
Elbanizine
Flotrenizine
GSK1004723
Napactadine
Tagorizine
Trelnarizine
Trenizine

H₂

Agonists	Amthamine Betazole Dimaprit Histamine HTMT Impromidine L-Histidine UR-AK49
Antagonists	Bisfentidine Burimamide Cimetidine Dalcotidine Donetidine Ebrotidine Etintidine Famotidine Isolamtidine Lafutidine Lamtidine Lavoltidine (loxtidine) Lupitidine Metiamide Mifentidine Niperotidine Nizatidine Osutidine Oxmetidine Pibutidine Quisultazine (quisultidine) Ramixotidine Ranitidine Roxatidine Sufotidine Tiotidine Tuvatidine Venritidine Xaltidine Zolantidine

H₃

Agonists	α-Methylhistamine Cipralisant Histamine Imetit Immepip Immethridine L-Histidine Methimepip Proxyfan
Antagonists	A-349821 A-423579 ABT-239 ABT-652 AZD5213 Bavisant Betahistine Burimamide Ciproxifan Clobenpropit Conessine Enerisant GSK-189254 Impentamine Iodophenpropit Irdabisant JNJ-5207852 NNC 38-1049 PF-03654746 Pitolisant SCH-79687 Thioperamide VUF-5681

H₄

Agonists	4-Methylhistamine α-Methylhistamine Histamine L-Histidine OUP-16 VUF-8430
Antagonists	JNJ-7777120 Mianserin Seliforant Thioperamide Toreforant VUF-6002

See also: Receptor/signaling modulators; Monoamine metabolism modulators; Monoamine reuptake inhibitors

v t e Piperazines
Simple piperazines (no additional rings)	Aminoethylpiperazine Diethylcarbamazine HEPPS Midafotel Piperazine PIPES
Phenylpiperazines	2C-B-PP 3,4-CFP Acaprazine Antrafenine Aripiprazole Batoprazine Bifeprunox BRL-15,572 Ciprofloxacin CSP-2503 Dapiprazole DCPP DMPP Diphenylpiperazine Dropropizine EGIS-12,233 Elopiprazole Eltoprazine Enpiprazole Ensaculin Etoperidone Flesinoxan Fluanisone Flibanserin Fluprazine Itraconazole Ketoconazole Levodropropizine Lorpiprazole mCPP Mefway MeOPP Mepiprazole Naftopidil Naluzotan Naphthylpiperazine Nefazodone Niaprazine Oxypertine Pardoprunox pCPP pFPP Posaconazole S-14,506 S-14,671 S-15,535 SB-258,585 SB-271,046 SB-357,134 SB-399,885 Sonepiprazole TFMPP Tolpiprazole Trazodone Urapidil Vesnarinone Vilazodone Vortioxetine WAY-100,135 WAY-100,635
Benzylpiperazines	2C-B-BZP 3-Methylbenzylpiperazine Befuraline Bifeprunox Buclizine BZP Chlorbenzoxamine DBZP Fipexide Imatinib MBZP MDBZP Meclozine Methoxypiperamide NSI-189 Piberaline Piribedil RN-1747 Sunifiram Trimetazidine Vesnarinone
Diphenylalkylpiperazines (benzhydrylalkylpiperazines)	AD-1211 Almitrine Amperozide BRL-15,572 Buclizine BW373U86 Cetirizine Chlorbenzoxamine Chlorcyclizine Cinnarizine Clocinizine Cyclizine DBL-583 Diphenpipenol Diphenylmethylpiperazine Dotarizine DPI-221 DPI-287 DPI-3290 GBR-12,783 GBR-12,935 GBR-13,069 GBR-13,098 GBR-13,119 Hydroxyzine Lidoflazine Manidipine Meclozine MT-45 Oxatomide SNC-80 Vanoxerine
Pyrimidinylpiperazines	Buspirone Dasatinib Eptapirone Gepirone Ipsapirone Piribedil Prazitone Pyrimidinylpiperazine Revospirone Tandospirone Tirilazad Trimazosin Umespirone Zalospirone
Pyridinylpiperazines	Atevirdine Azaperone Delavirdine Mirtazapine ORG-12962 Pyridinylpiperazine
Benzo(iso)thiazolyl piperazines	Lurasidone Perospirone Revospirone Tiospirone Ziprasidone
Tricyclics (piperazine attached via side chain)	Amoxapine Clopenthixol Clorotepine Clozapine Cyanothepin Doclothepin Docloxythepin Flupentixol Fluphenazine Isofloxythepin Loxapine Meperathiepin Metitepine Octomethothepin Olanzapine Opipramol Oxyclothepin Oxyprothepin Peradithiepin Perathiepin Perazine Perphenazine Pirenzepine Prochlorperazine Thiethylperazine Thiothixene Trifluoperazine Trifluthepin Zuclopenthixol
Others/Uncategorized	6-Nitroquipazine AP-238 Azimilide Bucinnazine Cinepazet Cinepazic acid Cinepazide CPD-1 Cyclohexylpiperazine EGIS-7625 Hexocyclium Indinavir JNJ-7777120 Lodenafil MK-212 Mirodenafil PB-28 Quipazine Ranolazine SA-4503 Sildenafil Tadalafil Vardenafil VUF-6002 WY-46824 Zipeprol