TOREFORANT - Encyclopedia Information

Toreforant
Names

IUPAC name 5-(4,6-dimethyl-1H-benzimidazol-2-yl)-4-methyl-N-[3-(1-methylpiperidin-4-yl)propyl]pyrimidin-2-amine
Identifiers
CAS Number	952494-46-1
3D model ( JSmol)	Interactive image
ChEMBL	ChEMBL3301609
ChemSpider	31389942
DrugBank	DB12522
KEGG	D10735
PubChem CID	23650961
UNII	U6LA7G393X
InChI InChI=1S/C23H32N6/c1-15-12-16(2)21-20(13-15)27-22(28-21)19-14-25-23(26-17(19)3)24-9-5-6-18-7-10-29(4)11-8-18/h12-14,18H,5-11H2,1-4H3,(H,27,28)(H,24,25,26) Key: FCRFVPZAXGJLPW-UHFFFAOYSA-N
SMILES CC1=CC(=C2C(=C1)NC(=N2)C3=CN=C(N=C3C)NCCCC4CCN(CC4)C)C
Properties
Chemical formula	C₂₃H₃₂N₆
Molar mass	392.551 g·mol⁻¹
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Toreforant (JNJ-38518168) is an orally-dosed selective antagonist of the histamine H₄ receptor that has been studied for various health conditions. It is the successor of a number of H₄-selective compounds developed by Johnson & Johnson.^[1] Phase IIa clinical trials completed as recently as November 2018 continue to suggest that toreforant is safe.^[2]

As of the end of 2020, there is no regulator-approved H₄ antagonist. In U.S. Phase II clinical trials, toreforant, by itself, did not show efficacy against eosinophilic asthma.^[2] The drug did show at least partial efficacy against rheumatoid arthritis in patients who were nonresponsive to methotrexate.^[3] As the H₄ receptor is widely implicated in the regulation of inflammatory states, the potential uses for an H₄ antagonist remain significant.^[4]^[5]^[6]

References

^ 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.
^ ^a ^b Kollmeier AP, Barnathan ES, O'Brien C, Chen B, Xia Y, Zhou B, Loza MJ, Silkoff PE, Ge M, Thurmond RL (2018). "A phase 2a study of toreforant, a histamine H4 receptor antagonist, in eosinophilic asthma". Annals of Allergy, Asthma & Immunology. 121 (5): 568–574. doi: 10.1016/j.anai.2018.08.001. PMID 30102965. S2CID 51972933.
^ Thurmond RL, Greenspan A, Radziszewski W, Xu XL, Miao Y, Chen B, Ge T, Zhou B, Baker DG, Pavlova D, Ritchlin CT, Tanaka Y, Takeuchi T, Smolen JS (September 2016). "Toreforant, A Histamine H4 Receptor Antagonist, in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy: Results of 2 Phase II Studies". The Journal of Rheumatology. 43 (9): 1637–1642. doi: 10.3899/jrheum.160164. PMID 27422891. S2CID 46885520.
^ Saravanan C, Bharti SK, Jaggi S, Singh SK (February 2011). "Histamine H₄ receptor: a novel target for inflammation therapy". Mini Reviews in Medicinal Chemistry. 11 (2): 143–58. doi: 10.2174/138955711794519519. PMID 21222579.
^ 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.
^ Thangam EB, Jemima EA, Singh H, Baig MS, Khan M, Mathias CB, et al. (2018). "The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation: The Hunt for New Therapeutic Targets". Frontiers in Immunology. 9: 1873. doi: 10.3389/fimmu.2018.01873. PMC 6099187. PMID 30150993.

Histamine receptor modulators

H₁

Agonists

Antagonists

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)

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

This pharmacology-related article is a stub. You can help Wikipedia by expanding it.

Toreforant

Names
IUPAC name 5-(4,6-dimethyl-1H-benzimidazol-2-yl)-4-methyl-N-[3-(1-methylpiperidin-4-yl)propyl]pyrimidin-2-amine
Identifiers
CAS Number	952494-46-1
3D model ( JSmol)	Interactive image
ChEMBL	ChEMBL3301609
ChemSpider	31389942
DrugBank	DB12522
KEGG	D10735
PubChem CID	23650961
UNII	U6LA7G393X
InChI InChI=1S/C23H32N6/c1-15-12-16(2)21-20(13-15)27-22(28-21)19-14-25-23(26-17(19)3)24-9-5-6-18-7-10-29(4)11-8-18/h12-14,18H,5-11H2,1-4H3,(H,27,28)(H,24,25,26) Key: FCRFVPZAXGJLPW-UHFFFAOYSA-N
SMILES CC1=CC(=C2C(=C1)NC(=N2)C3=CN=C(N=C3C)NCCCC4CCN(CC4)C)C
Properties
Chemical formula	C₂₃H₃₂N₆
Molar mass	392.551 g·mol⁻¹
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Toreforant

Names

IUPAC name

5-(4,6-dimethyl-1H-benzimidazol-2-yl)-4-methyl-N-[3-(1-methylpiperidin-4-yl)propyl]pyrimidin-2-amine

Identifiers

CAS Number

952494-46-1

3D model ( JSmol)

Interactive image

ChEMBL

ChEMBL3301609

ChemSpider

31389942

DrugBank

DB12522

KEGG

D10735

PubChem CID

23650961

UNII

U6LA7G393X

InChI

InChI=1S/C23H32N6/c1-15-12-16(2)21-20(13-15)27-22(28-21)19-14-25-23(26-17(19)3)24-9-5-6-18-7-10-29(4)11-8-18/h12-14,18H,5-11H2,1-4H3,(H,27,28)(H,24,25,26)
Key: FCRFVPZAXGJLPW-UHFFFAOYSA-N

SMILES

CC1=CC(=C2C(=C1)NC(=N2)C3=CN=C(N=C3C)NCCCC4CCN(CC4)C)C

Properties

Chemical formula

C₂₃H₃₂N₆

Molar mass

392.551 g·mol⁻¹

Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Infobox references

References

^ 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.
^ ^a ^b Kollmeier AP, Barnathan ES, O'Brien C, Chen B, Xia Y, Zhou B, Loza MJ, Silkoff PE, Ge M, Thurmond RL (2018). "A phase 2a study of toreforant, a histamine H4 receptor antagonist, in eosinophilic asthma". Annals of Allergy, Asthma & Immunology. 121 (5): 568–574. doi: 10.1016/j.anai.2018.08.001. PMID 30102965. S2CID 51972933.
^ Thurmond RL, Greenspan A, Radziszewski W, Xu XL, Miao Y, Chen B, Ge T, Zhou B, Baker DG, Pavlova D, Ritchlin CT, Tanaka Y, Takeuchi T, Smolen JS (September 2016). "Toreforant, A Histamine H4 Receptor Antagonist, in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy: Results of 2 Phase II Studies". The Journal of Rheumatology. 43 (9): 1637–1642. doi: 10.3899/jrheum.160164. PMID 27422891. S2CID 46885520.
^ Saravanan C, Bharti SK, Jaggi S, Singh SK (February 2011). "Histamine H₄ receptor: a novel target for inflammation therapy". Mini Reviews in Medicinal Chemistry. 11 (2): 143–58. doi: 10.2174/138955711794519519. PMID 21222579.
^ 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.
^ Thangam EB, Jemima EA, Singh H, Baig MS, Khan M, Mathias CB, et al. (2018). "The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation: The Hunt for New Therapeutic Targets". Frontiers in Immunology. 9: 1873. doi: 10.3389/fimmu.2018.01873. PMC 6099187. PMID 30150993.

This pharmacology-related article is a stub. You can help Wikipedia by expanding it.

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