evobrutinib   Click here for help

GtoPdb Ligand ID: 9752

Synonyms: A250 [WO2012170976] | M-2951 | M2951 | MSC 2364447 | MSC-2364447C | MSC2364447C
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Evobrutinib is a Bruton's tyrosine kinase Inhibitor discovered by Merck, that has clinical potential across multiple autoimmune conditions (including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis) [1]. it is an orally active, ootent, and highly selective inhibitor with a covalent binding mode. The chemical structure is claimed as A250 in patent WO2012170976 [3].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 93.37
Molecular weight 429.22
XLogP 4.11
No. Lipinski's rules broken 0
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Canonical SMILES C=CC(=O)N1CCC(CC1)CNc1ncnc(c1c1ccc(cc1)Oc1ccccc1)N
Isomeric SMILES C=CC(=O)N1CCC(CC1)CNc1ncnc(c1c1ccc(cc1)Oc1ccccc1)N
InChI InChI=1S/C25H27N5O2/c1-2-22(31)30-14-12-18(13-15-30)16-27-25-23(24(26)28-17-29-25)19-8-10-21(11-9-19)32-20-6-4-3-5-7-20/h2-11,17-18H,1,12-16H2,(H3,26,27,28,29)
1. Caldwell RD, Qiu H, Askew BC, Bender AT, Brugger N, Camps M, Dhanabal M, Dutt V, Eichhorn T, Gardberg AS et al.. (2019)
Discovery of Evobrutinib: An Oral, Potent, and Highly Selective, Covalent Bruton's Tyrosine Kinase (BTK) Inhibitor for the Treatment of Immunological Diseases.
J Med Chem, 62 (17): 7643-7655. [PMID:31368705]
2. Haselmayer P, Camps M, Liu-Bujalski L, Nguyen N, Morandi F, Head J, O'Mahony A, Zimmerli SC, Bruns L, Bender AT et al.. (2019)
Efficacy and Pharmacodynamic Modeling of the BTK Inhibitor Evobrutinib in Autoimmune Disease Models.
J Immunol, 202 (10): 2888-2906. [PMID:30988116]
3. Hodous B, Liu-Bujalski L, Jones R, Bankston D, Johnson TL, Mochalkin I, Nguyen N, Qiu H, Goutopoulos A, Brugger N. (2012)
Compositions and methods for the production of pyrimidine and pyridine compounds with btk inhibitory activity.
Patent number: WO2012170976. Assignee: Merck Patent Gmbh. Priority date: 10/06/2011. Publication date: 13/12/2012.
4. Montalban X, Arnold DL, Weber MS, Staikov I, Piasecka-Stryczynska K, Willmer J, Martin EC, Dangond F, Syed S, Wolinsky JS et al.. (2019)
Placebo-Controlled Trial of an Oral BTK Inhibitor in Multiple Sclerosis.
N Engl J Med, 380 (25): 2406-2417. [PMID:31075187]