Toreforant

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]

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
3D model (JSmol)
ChEMBL
ChemSpider
DrugBank
KEGG
UNII
  • 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
  • CC1=CC(=C2C(=C1)NC(=N2)C3=CN=C(N=C3C)NCCCC4CCN(CC4)C)C
Properties
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

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]

See also

References
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.


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