Aminopyrazole Carboxamide Bruton's Tyrosine Kinase Inhibitors. Irreversible to Reversible Covalent Reactive Group Tuning

被引：26

作者：

Schnute, Mark E. ^{[1
]}

Benoit, Stephen E. ^{[2
]}

Buchler, Ingrid P. ^{[1
]}

Caspers, Nicole ^{[3
]}

Grapperhaus, Margaret L. ^{[4
]}

Han, Seungil ^{[3
]}

Hotchandani, Rajeev ^{[1
]}

Huang, Nelson ^{[1
]}

Hughes, Robert O. ^{[1
]}

Juba, Brian M. ^{[2
]}

Kim, Kyung-Hee ^{[1
]}

Liu, Erica ^{[2
]}

McCarthy, Erin ^{[2
]}

Messing, Dean ^{[1
]}

Miyashiro, Joy S. ^{[2
]}

Mohan, Shashi ^{[2
]}

O'Connel, Thomas N. ^{[3
]}

Ohren, Jeffrey F. ^{[3
]}

Parikh, Mihir D. ^{[3
]}

Schmidt, Michelle ^{[4
]}

Selness, Shaun R. ^{[4
]}

Spriner, John R. ^{[1
]}

Thanabal, Venkataraman ^{[3
]}

Trujillo, John I. ^{[3
]}

Walker, Daniel P. ^{[4
]}

Wan, Zhao-Kui ^{[1
]}

Withka, Jane M. ^{[3
]}

Wittwer, Arthur J. ^{[5
]}

Wood, Nancy L. ^{[2
]}

Xing, Li ^{[1
]}

Zapf, Christoph W. ^{[1
]}

Douhan, John, III ^{[2
]}

机构：

[1] Pfizer, Med Design, Cambridge, MA 02139 USA

[2] Pfizer, Inflammat & Immunol Res, Cambridge, MA 02139 USA

[3] Pfizer, Med Design, Groton, CT 06340 USA

[4] Pfizer, Med Chem, St Louis, MO 63017 USA

[5] Pfizer, Inflammat & Immunol Res, St Louis, MO 63017 USA

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2019年 / 10卷 / 01期

关键词：

BTK; EGFR; irreversible covalent inhibitor; reversible covalent inhibitor; X-LINKED AGAMMAGLOBULINEMIA; CATHEPSIN-K; POTENCY; PROTEIN; LUPUS; BTK; THERAPIES; DISCOVERY;

D O I：

10.1021/acsmedchemlett.8b00461

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Potent covalent inhibitors of Bruton's tyrosine kinase (BTK) based on an aminopyrazole carboxamide scaffold have been identified. Compared to acrylamide-based covalent reactive groups leading to irreversible protein adducts, cyanamide-based reversible-covalent inhibitors provided the highest combined BTK potency and EGFR selectivity. The cyanamide covalent mechanism with BTK was confirmed through enzyme kinetic, NMR, MS, and X-ray crystallographic studies. The lead cyanamide-based inhibitors demonstrated excellent kinome selectivity and rat pharmaco-kinetic properties.

引用

页码：80 / 85

页数：11

共 29 条

[1]

[Anonymous], 2015, CURR TOP MICROBIOL I, DOI DOI 10.1007/82_

[2] Acalabrutinib (ACP-196): A Covalent Bruton Tyrosine Kinase Inhibitor with a Differentiated Selectivity and In Vivo Potency Profile [J].

Barf, Tjeerd ;

Covey, Todd ;

Izumi, Raquel ;

van de Kar, Bas ;

Gulrajani, Michael ;

van Lith, Bart ;

van Hoek, Maaike ;

de Zwart, Edwin ;

Mittag, Diana ;

Demont, Dennis ;

Verkaik, Saskia ;

Krantz, Fanny ;

Pearson, Paul G. ;

Ulrich, Roger ;

Kaptein, Allard .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2017, 363 (02) :240-252

[3] Ability of Bruton's Tyrosine Kinase Inhibitors to Sequester Y551 and Prevent Phosphorylation Determines Potency for Inhibition of Fc Receptor but not B-Cell Receptor Signaling [J].

Bender, Andrew T. ;

Gardberg, Anna ;

Pereira, Albertina ;

Johnson, Theresa ;

Wu, Yin ;

Grenningloh, Roland ;

Head, Jared ;

Morandi, Federica ;

Haselmayer, Philipp ;

Liu-Bujalski, Lesley .

MOLECULAR PHARMACOLOGY, 2017, 91 (03) :208-219

[4] Response to Rituximab in Patients With Rheumatoid Arthritis in Different Compartments of the Immune System [J].

Boumans, Maria J. H. ;

Thurlings, Rogier M. ;

Gerlag, Danielle M. ;

Vos, Koen ;

Tak, Paul P. .

ARTHRITIS AND RHEUMATISM, 2011, 63 (11) :3187-3194

[5]

Bradshaw JM, 2015, NAT CHEM BIOL, V11, P525, DOI [10.1038/NCHEMBIO.1817, 10.1038/nchembio.1817]

[6] How Reactive Metabolites Induce an Immune Response That Sometimes Leads to an Idiosyncratic Drug Reaction [J].

Cho, Tiffany ;

Uetrecht, Jack .

CHEMICAL RESEARCH IN TOXICOLOGY, 2017, 30 (01) :295-314

[7]

CONLEY ME, 1985, J IMMUNOL, V134, P3070

[8] Discovery of GDC-0853: A Potent, Selective, and Noncovalent Bruton's Tyrosine Kinase Inhibitor in Early Clinical Development [J].

Crawford, James J. y ;

Johnson, Adam R. ;

Misner, Dinah L. ;

Belmont, Lisa D. ;

Castanedo, Georgette ;

Choy, Regina ;

Coraggio, Melis ;

Doug, Liming ;

Eigenbrot, Charles ;

Erickson, Rebecca ;

Ghilardi, Nico ;

Hau, Jonathan ;

Katewa, Arna ;

Kohli, Pawan Bir ;

Lee, Wendy ;

Lubach, Joseph W. ;

McKenzie, Brent S. ;

Ortwine, Daniel F. ;

Schutt, Leah ;

Tay, Suzanne ;

Wei, BinQing ;

Reif, Karin ;

Liu, Lichuan ;

Wong, Harvey ;

Young, Wendy B. .

JOURNAL OF MEDICINAL CHEMISTRY, 2018, 61 (06) :2227-2245

[9] The role of Bruton's tyrosine kinase in autoimmunity and implications for therapy [J].

Crofford, Leslie J. ;

Nyhoff, Lindsay E. ;

Sheehan, Jonathan H. ;

Kendall, Peggy L. .

EXPERT REVIEW OF CLINICAL IMMUNOLOGY, 2016, 12 (07) :763-773

[10] Novel and potent cyclic cyanamide-based cathepsin K inhibitors [J].

Deaton, DN ;

Hassell, AM ;

McFadyen, RB ;

Miller, AB ;

Miller, LR ;

Shewchuk, LM ;

Tavares, FX ;

Willard, DH ;

Wright, LL .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (07) :1815-1819

← 1 2 3 →