remibrutinib   Click here for help

GtoPdb Ligand ID: 10457

Synonyms: compound 25 [PMID: 32083858] | example 6 [WO2015079417A1] | LOU-064 | LOU064 | LOU064-NXA | NVP-LOU064-NXA
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Remibrutinib (LOU064) is one of the examples claimed in Novartis' patent WO2015079417A1 [2], for novel amino pyrimidine derivatives that act as Bruton's tyrosine kinase (BTK) inhibitors and which claims their potential to treat autoimmune disorders, inflammatory/allergic diseases, transplant rejection and cancers of hematopoietic origin or solid tumours. The formal chemical name (LOU064; remibrutinib) to structure disclosure was published in February 2020 [1]. LOU064 is a covalent BTK inhibitor that binds the inactive conformation of the enzyme. This improves its selectivity compared to currently marketed covalent BTK inhibitors, and renders it more suitable for use in non-oncology indications.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 2
Rotatable bonds 11
Topological polar surface area 110.44
Molecular weight 507.21
XLogP 4.1
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES C=CC(=O)N(CCOc1c(N)ncnc1c1cc(F)cc(c1C)NC(=O)c1ccc(cc1F)C1CC1)C
Isomeric SMILES C=CC(=O)N(CCOc1c(N)ncnc1c1cc(F)cc(c1C)NC(=O)c1ccc(cc1F)C1CC1)C
InChI InChI=1S/C27H27F2N5O3/c1-4-23(35)34(3)9-10-37-25-24(31-14-32-26(25)30)20-12-18(28)13-22(15(20)2)33-27(36)19-8-7-17(11-21(19)29)16-5-6-16/h4,7-8,11-14,16H,1,5-6,9-10H2,2-3H3,(H,33,36)(H2,30,31,32)
InChI Key CUABMPOJOBCXJI-UHFFFAOYSA-N
References
1. Angst D, Gessier F, Janser P, Vulpetti A, Wälchli R, Beerli C, Littlewood-Evans A, Dawson J, Nuesslein-Hildesheim B, Wieczorek G et al.. (2020)
Discovery of LOU064 (Remibrutinib), a Potent and Highly Selective Covalent Inhibitor of Bruton's Tyrosine Kinase.
J Med Chem, 63 (10): 5102-5118. [PMID:32083858]
2. Angst D, Gessier F, Vulpetti A. (2015)
Novel amino pyrimidine derivatives.
Patent number: WO2015079417A1. Assignee: Novartis Ag. Priority date: 29/11/2013. Publication date: 04/06/2015.
3. Huth F, Schiller H, Jin Y, Poller B, Schuhler C, Weis W, Woessner R, Drollmann A, End P. (2022)
Novel Bruton's Tyrosine Kinase inhibitor remibrutinib: Drug-drug interaction potential as a victim of CYP3A4 inhibitors based on clinical data and PBPK modeling.
Clin Transl Sci, 15 (1): 118-129. [PMID:34432364]
4. Kaul M, End P, Cabanski M, Schuhler C, Jakab A, Kistowska M, Kinhikar A, Maiolica A, Sinn A, Fuhr R et al.. (2021)
Remibrutinib (LOU064): A selective potent oral BTK inhibitor with promising clinical safety and pharmacodynamics in a randomized phase I trial.
Clin Transl Sci, 14 (5): 1756-1768. [PMID:33834628]
5. Maurer M, Berger W, Giménez-Arnau A, Hayama K, Jain V, Reich A, Haemmerle S, Lheritier K, Walsh P, Xia S et al.. (2022)
Remibrutinib, a novel BTK inhibitor, demonstrates promising efficacy and safety in chronic spontaneous urticaria.
J Allergy Clin Immunol, 150 (6): 1498-1506.e2. [PMID:36096203]
6. Novartis. 
Novartis data show rapid and effective disease activity control with remibrutinib (LOU064) in patients with chronic spontaneous urticaria.
Accessed on 04/10/2021. Modified on 04/10/2021. www.novartis.com/news, https://www.novartis.com/news/media-releases/novartis-data-show-rapid-and-effective-disease-activity-control-remibrutinib-lou064-patients-chronic-spontaneous-urticaria