JNJ-54175446

JNJ-54175446
Legal status
Legal status	Investigational New Drug;
Identifiers
	IUPAC name (R)-(2-chloro-3-(trifluoromethyl)phenyl)(1-(5-fluoropyrimidin-2-yl)-4-methyl-6,7-dihydro-1H-[1,2,3]triazolo[4,5-c]pyridin-5(4H)-yl)methanone;
CAS Number	1627902-21-9;
PubChem CID	90409366;
Chemical and physical data
Formula	C18H13ClF4N6O
Molar mass	440.79 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[C@@H]1C2=C(CCN1C(=O)C3=C(C(=CC=C3)C(F)(F)F)Cl)N(N=N2)C4=NC=C(C=N4)F;
	InChI InChI=1S/C18H13ClF4N6O/c1-9-15-13(29(27-26-15)17-24-7-10(20)8-25-17)5-6-28(9)16(30)11-3-2-4-12(14(11)19)18(21,22)23/h2-4,7-9H,5-6H2,1H3/t9-/m1/s1; Key:CWFVVQFVGMFTBD-SECBINFHSA-N;

JNJ-54175446 is an investigational P2X7 receptor antagonist developed by Janssen Pharmaceuticals. It is hoped that the drug can reduce neuroinflammation and therefore treat psychiatric disorders such as major depressive disorder.^[1]^[2]^[3]^[4]^[5]^[6]

References

^ Recourt, Kasper; van der Aart, Jasper; Jacobs, Gabriel; de Kam, Marieke; Drevets, Wayne; van Nueten, Luc; Kanhai, Kawita; Siebenga, Pieter; Zuiker, Rob; Ravenstijn, Paulien; Timmers, Maarten; van Gerven, Joop; de Boer, Peter (September 2020). "Characterisation of the pharmacodynamic effects of the P2X7 receptor antagonist JNJ-54175446 using an oral dexamphetamine challenge model in healthy males in a randomised, double-blind, placebo-controlled, multiple ascending dose trial". Journal of Psychopharmacology. 34 (9): 1030–1042. doi:10.1177/0269881120914206. PMID 32248747. S2CID 214809417.
^ Timmers, Maarten; Ravenstijn, Paulien; Xi, Liwen; Triana-Baltzer, Gallen; Furey, Maura; Van Hemelryck, Sandy; Biewenga, Jeike; Ceusters, Marc; Bhattacharya, Anindya; van den Boer, Maarten; van Nueten, Luc; de Boer, Peter (December 2018). "Clinical pharmacokinetics, pharmacodynamics, safety, and tolerability of JNJ-54175446, a brain permeable P2X7 antagonist, in a randomised single-ascending dose study in healthy participants". Journal of Psychopharmacology. 32 (12): 1341–1350. doi:10.1177/0269881118800067. PMID 30260294. S2CID 52842478.
^ Bhattacharya, Anindya; Ceusters, Marc (January 2020). "Targeting neuroinflammation with brain penetrant P2X7 antagonists as novel therapeutics for neuropsychiatric disorders". Neuropsychopharmacology. 45 (1): 234–235. doi:10.1038/s41386-019-0502-9. ISSN 0893-133X. PMC 6879571. PMID 31477815.
^ Recourt, Kasper; de Boer, Peter; van der Ark, Peter; Benes, Heike; van Gerven, Joop M. A.; Ceusters, Marc; van Nueten, Luc; Drevets, Wayne C.; Bhatacharya, Anindya; Browning, Michael; Jacobs, Gabriel E. (24 July 2023). "Characterization of the central nervous system penetrant and selective purine P2X7 receptor antagonist JNJ-54175446 in patients with major depressive disorder". Translational Psychiatry. 13 (1): 266. doi:10.1038/s41398-023-02557-5. ISSN 2158-3188. PMC 10363543. PMID 37482560. S2CID 260114192.
^ Koole, Michel; Schmidt, Mark E.; Hijzen, Anja; Ravenstijn, Paulien; Vandermeulen, Corinne; Van Weehaeghe, Donatienne; Serdons, Kim; Celen, Sofie; Bormans, Guy; Ceusters, Marc; Zhang, Wei; Van Nueten, Luc; Kolb, Hartmuth; de Hoon, Jan; Van Laere, Koen (May 2019). "18 F-JNJ-64413739, a Novel PET Ligand for the P2X7 Ion Channel: Radiation Dosimetry, Kinetic Modeling, Test-Retest Variability, and Occupancy of the P2X7 Antagonist JNJ-54175446". Journal of Nuclear Medicine. 60 (5): 683–690. doi:10.2967/jnumed.118.216747. PMID 30262518. S2CID 52880797.
^ Xu, Yan; Miao, Xin; Ravenstijn, Paulien; Hijzen, Anja; Schmidt, Mark E.; Nandy, Partha; Zhou, Honghui (March 2020). "Translational Model-Informed Dose Selection for a Human Positron Emission Tomography Imaging Study of JNJ-54175446, a P2X7 Receptor Antagonist". Clinical and Translational Science. 13 (2): 309–317. doi:10.1111/cts.12711. PMC 7070800. PMID 31642608. S2CID 204850939.

[1] Recourt, Kasper; van der Aart, Jasper; Jacobs, Gabriel; de Kam, Marieke; Drevets, Wayne; van Nueten, Luc; Kanhai, Kawita; Siebenga, Pieter; Zuiker, Rob; Ravenstijn, Paulien; Timmers, Maarten; van Gerven, Joop; de Boer, Peter (September 2020). "Characterisation of the pharmacodynamic effects of the P2X7 receptor antagonist JNJ-54175446 using an oral dexamphetamine challenge model in healthy males in a randomised, double-blind, placebo-controlled, multiple ascending dose trial". Journal of Psychopharmacology. 34 (9): 1030–1042. doi:10.1177/0269881120914206. PMID 32248747. S2CID 214809417.

[2] Timmers, Maarten; Ravenstijn, Paulien; Xi, Liwen; Triana-Baltzer, Gallen; Furey, Maura; Van Hemelryck, Sandy; Biewenga, Jeike; Ceusters, Marc; Bhattacharya, Anindya; van den Boer, Maarten; van Nueten, Luc; de Boer, Peter (December 2018). "Clinical pharmacokinetics, pharmacodynamics, safety, and tolerability of JNJ-54175446, a brain permeable P2X7 antagonist, in a randomised single-ascending dose study in healthy participants". Journal of Psychopharmacology. 32 (12): 1341–1350. doi:10.1177/0269881118800067. PMID 30260294. S2CID 52842478.

[3] Bhattacharya, Anindya; Ceusters, Marc (January 2020). "Targeting neuroinflammation with brain penetrant P2X7 antagonists as novel therapeutics for neuropsychiatric disorders". Neuropsychopharmacology. 45 (1): 234–235. doi:10.1038/s41386-019-0502-9. ISSN 0893-133X. PMC 6879571. PMID 31477815.

[4] Recourt, Kasper; de Boer, Peter; van der Ark, Peter; Benes, Heike; van Gerven, Joop M. A.; Ceusters, Marc; van Nueten, Luc; Drevets, Wayne C.; Bhatacharya, Anindya; Browning, Michael; Jacobs, Gabriel E. (24 July 2023). "Characterization of the central nervous system penetrant and selective purine P2X7 receptor antagonist JNJ-54175446 in patients with major depressive disorder". Translational Psychiatry. 13 (1): 266. doi:10.1038/s41398-023-02557-5. ISSN 2158-3188. PMC 10363543. PMID 37482560. S2CID 260114192.

[5] Koole, Michel; Schmidt, Mark E.; Hijzen, Anja; Ravenstijn, Paulien; Vandermeulen, Corinne; Van Weehaeghe, Donatienne; Serdons, Kim; Celen, Sofie; Bormans, Guy; Ceusters, Marc; Zhang, Wei; Van Nueten, Luc; Kolb, Hartmuth; de Hoon, Jan; Van Laere, Koen (May 2019). "18 F-JNJ-64413739, a Novel PET Ligand for the P2X7 Ion Channel: Radiation Dosimetry, Kinetic Modeling, Test-Retest Variability, and Occupancy of the P2X7 Antagonist JNJ-54175446". Journal of Nuclear Medicine. 60 (5): 683–690. doi:10.2967/jnumed.118.216747. PMID 30262518. S2CID 52880797.

[6] Xu, Yan; Miao, Xin; Ravenstijn, Paulien; Hijzen, Anja; Schmidt, Mark E.; Nandy, Partha; Zhou, Honghui (March 2020). "Translational Model-Informed Dose Selection for a Human Positron Emission Tomography Imaging Study of JNJ-54175446, a P2X7 Receptor Antagonist". Clinical and Translational Science. 13 (2): 309–317. doi:10.1111/cts.12711. PMC 7070800. PMID 31642608. S2CID 204850939.

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[2]

[3]

[4]

[5]

[6]

See also

References