Orally bioavailable pyridine and pyrimidine-based Factor XIa inhibitors: Discovery of the methyl N-phenyl carbamate P2 prime group

Corte, James R.; Fang, Tianan; Pinto, Donald J. P.; Orwat, Michael J.; Rendina, Alan R.; Luettgen, Joseph M.; Rossi, Karen A.; Wei, Anzhi; Ramamurthy, Vidhyashankar; Myers, Jr., Joseph E.; Sheriff, Steven; Narayanan, Rangaraj; Harper, Timothy W.; Zheng, Joanna J.; Li, Yi-Xin; Seiffert, Dietmar A.; Wexler, Ruth R.; Quan, Mimi L.

doi:10.1016/j.bmc.2016.03.062

Title: Orally bioavailable pyridine and pyrimidine-based Factor XIa inhibitors: Discovery of the methyl N-phenyl carbamate P2 prime group

Journal Article · Sun May 01 00:00:00 EDT 2016 · Bioorganic and Medicinal Chemistry

DOI:https://doi.org/10.1016/j.bmc.2016.03.062· OSTI ID:1358846

Corte, James R.; Fang, Tianan; Pinto, Donald J. P.; Orwat, Michael J.; Rendina, Alan R.; Luettgen, Joseph M.; Rossi, Karen A.; Wei, Anzhi; Ramamurthy, Vidhyashankar; Myers, Jr., Joseph E.; Sheriff, Steven; Narayanan, Rangaraj; Harper, Timothy W.; Zheng, Joanna J.; Li, Yi-Xin; Seiffert, Dietmar A.; Wexler, Ruth R.; Quan, Mimi L.

View Accepted Manuscript (Publisher)

Cite

Export

Save

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1358846

Journal Information:: Bioorganic and Medicinal Chemistry, Journal Name: Bioorganic and Medicinal Chemistry Vol. 24 Journal Issue: 10; ISSN 0968-0896

Publisher:: ElsevierCopyright Statement

Country of Publication:: United Kingdom

Language:: English

Citation Metrics:

Cited by: 19 works

Citation information provided by
Web of Science

References (50)

Phenylimidazoles as Potent and Selective Inhibitors of Coagulation Factor XIa with in Vivo Antithrombotic Activity Hangeland, Jon J.; Friends, Todd J.; Rossi, Karen A. Journal of Medicinal Chemistry, Vol. 57, Issue 23 https://doi.org/10.1021/jm5010607	journal	November 2014
A facile synthesis of statine and analogs by reduction of .beta.-keto esters derived from Boc-protected amino acids. HPLC analyses of their enantiomeric purity Maibaum, Juergen; Rich, Daniel H. The Journal of Organic Chemistry, Vol. 53, Issue 4 https://doi.org/10.1021/jo00239a035	journal	February 1988
Reduced incidence of ischemic stroke in patients with severe factor XI deficiency Salomon, Ophira; Steinberg, David M.; Koren-Morag, Nira Blood, Vol. 111, Issue 8 https://doi.org/10.1182/blood-2007-10-120139	journal	April 2008
Factor XI contributes to thrombus propagation on injured neointima of the rabbit iliac artery Yamashita, A.; Nishihira, K.; Kitazawa, T. Journal of Thrombosis and Haemostasis, Vol. 4, Issue 7 https://doi.org/10.1111/j.1538-7836.2006.01973.x	journal	July 2006
Synthesis of (2R)-1-(4-Chloro-2-pyridyl)-2-(2-pyridyl)ethylamine: A Selective Oxime Reduction and Crystallization-Induced Asymmetric Transformation Negi, Shigeto; Matsukura, Masayuki; Mizuno, Masanori Synthesis, Vol. 1996, Issue 08 https://doi.org/10.1055/s-1996-4325	journal	August 1996
Preparation of primary amines and 2-azetidinones via N-(trimethylsilyl)imines Hart, David J.; Kanai, Kenichi; Thomas, Dudley G. The Journal of Organic Chemistry, Vol. 48, Issue 3 https://doi.org/10.1021/jo00151a002	journal	February 1983
On the fast translation functions for molecular replacement Navaza, J.; Vernoslova, E. Acta Crystallographica Section A Foundations of Crystallography, Vol. 51, Issue 4 https://doi.org/10.1107/S0108767394011335	journal	July 1995
Design, Synthesis, and Biological Evaluation of Peptidomimetic Inhibitors of Factor XIa as Novel Anticoagulants Lin, Jian; Deng, Hongfeng; Jin, Lei Journal of Medicinal Chemistry, Vol. 49, Issue 26 https://doi.org/10.1021/jm060978s	journal	December 2006
Refinement of severely incomplete structures with maximum likelihood in BUSTER–TNT Blanc, E.; Roversi, P.; Vonrhein, C. Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12 https://doi.org/10.1107/S0907444904016427	journal	November 2004
Reversal of diastereoselection in the addition of Grignard reagents to chiral 2-pyridyl tert-butyl (Ellman) sulfinimines Kuduk, Scott D.; DiPardo, Robert M.; Chang, Ronald K. Tetrahedron Letters, Vol. 45, Issue 35 https://doi.org/10.1016/j.tetlet.2004.07.003	journal	August 2004
FXI Is Essential for Thrombus Formation Following FeCl3-Induced Injury of the Carotid Artery in the Mouse Rosen, Elliot; Gailani, Dave; Castellino, Francis Thrombosis and Haemostasis, Vol. 87, Issue 04 https://doi.org/10.1055/s-0037-1613081	journal	January 2002
How good are my data and what is the resolution? Evans, Philip R.; Murshudov, Garib N. Acta Crystallographica Section D Biological Crystallography, Vol. 69, Issue 7 https://doi.org/10.1107/S0907444913000061	journal	June 2013
Inhibition of the intrinsic coagulation pathway factor XI by antisense oligonucleotides: a novel antithrombotic strategy with lowered bleeding risk Zhang, Hong; Löwenberg, Ester C.; Crosby, Jeffrey R. Blood, Vol. 116, Issue 22 https://doi.org/10.1182/blood-2010-04-277798	journal	November 2010
Clavatadine A, A Natural Product with Selective Recognition and Irreversible Inhibition of Factor XIa ^† Buchanan, Malcolm S.; Carroll, Anthony R.; Wessling, Deborah Journal of Medicinal Chemistry, Vol. 51, Issue 12 https://doi.org/10.1021/jm800314b	journal	June 2008
Patients with severe factor XI deficiency have a reduced incidence of deep-vein thrombosis Salomon, Ophira; Steinberg, David; Zucker, Michal Thrombosis and Haemostasis, Vol. 105, Issue 02 https://doi.org/10.1160/TH10-05-0307	journal	January 2011
Synthesis, Properties, and Reactions of 1 H -Indazol-3-ols and 1,2-Dihydro-3 H -indazol-3-ones Baiocchi, Leandro; Corsi, Giorgio; Palazzo, Giuseppe Synthesis, Vol. 1978, Issue 09 https://doi.org/10.1055/s-1978-24840	journal	January 1978
Discovery and Evaluation of Potent P ₁ Aryl Heterocycle-Based Thrombin Inhibitors Young, Mary Beth; Barrow, James C.; Glass, Kristen L. Journal of Medicinal Chemistry, Vol. 47, Issue 12 https://doi.org/10.1021/jm030303e	journal	June 2004
The CCP4 suite programs for protein crystallography Acta Crystallographica Section D Biological Crystallography, Vol. 50, Issue 5, p. 760-763 https://doi.org/10.1107/S0907444994003112	journal	September 1994
Novel one-pot cyclization of ortho substituted benzonitriles to 3-amino-1,2-benzisoxazoles Palermo, M. G. Tetrahedron Letters, Vol. 37, Issue 17 https://doi.org/10.1016/0040-4039(96)00425-X	journal	April 1996
Stereoselective synthesis of a novel pseudopeptide hapten for the generation of hydrolytic catalytic antibodies Rodriguez, Ana Chiva; Ramos, Anna Picó; Hawkes, Geoffrey E. Tetrahedron: Asymmetry, Vol. 15, Issue 12 https://doi.org/10.1016/j.tetasy.2004.05.005	journal	June 2004
Integration, scaling, space-group assignment and post-refinement Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 133-144 https://doi.org/10.1107/S0907444909047374	journal	January 2010
XDS Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2 https://doi.org/10.1107/S0907444909047337	journal	January 2010
Antithrombotic Effect of Antisense Factor XI Oligonucleotide Treatment in Primates Crosby, Jeffrey R.; Marzec, Ulla; Revenko, Alexey S. Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 33, Issue 7 https://doi.org/10.1161/ATVBAHA.113.301282	journal	July 2013
Large scale synthesis of 4-ethylpyrimidine Butters, M. Journal of Heterocyclic Chemistry, Vol. 29, Issue 5 https://doi.org/10.1002/jhet.5570290554	journal	August 1992
Antithrombotic and hemostatic effects of a small molecule factor XIa inhibitor in rats Schumacher, William A.; Seiler, Steven E.; Steinbacher, Thomas E. European Journal of Pharmacology, Vol. 570, Issue 1-3 https://doi.org/10.1016/j.ejphar.2007.05.043	journal	September 2007
Factor XI as a target for antithrombotic therapy Bane, Charles E.; Gailani, David Drug Discovery Today, Vol. 19, Issue 9 https://doi.org/10.1016/j.drudis.2014.05.018	journal	September 2014
Bacterial translation inhibitors, 1-acylindazol-3-ols as anthranilic acid mimics Stiff, Cory; Graber, David R.; Thorarensen, Atli Bioorganic & Medicinal Chemistry Letters, Vol. 18, Issue 23 https://doi.org/10.1016/j.bmcl.2007.08.041	journal	December 2008
High Levels of Coagulation Factor XI as a Risk Factor for Venous Thrombosis Meijers, Joost C. M.; Tekelenburg, Winnie L. H.; Bouma, Bonno N. New England Journal of Medicine, Vol. 342, Issue 10 https://doi.org/10.1056/NEJM200003093421004	journal	March 2000
Design and synthesis of macrocyclic indoles targeting blood coagulation cascade Factor XIa Hanessian, Stephen; Larsson, Andreas; Fex, Tomas Bioorganic & Medicinal Chemistry Letters, Vol. 20, Issue 23 https://doi.org/10.1016/j.bmcl.2010.09.141	journal	December 2010
Discovery of 1-(4-Methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro- 1 H -pyrazolo[3,4- c ]pyridine-3-carboxamide (Apixaban, BMS-562247), a Highly Potent, Selective, Efficacious, and Orally Bioavailable Inhibitor of Blood Coagulation Factor Xa Pinto, Donald J. P.; Orwat, Michael J.; Koch, Stephanie Journal of Medicinal Chemistry, Vol. 50, Issue 22 https://doi.org/10.1021/jm070245n	journal	November 2007
Synthesis and in vitro biological evaluation of aryl boronic acids as potential inhibitors of factor XIa Lazarova, Tsvetelina I.; Jin, Lei; Rynkiewicz, Michael Bioorganic & Medicinal Chemistry Letters, Vol. 16, Issue 19 https://doi.org/10.1016/j.bmcl.2006.07.043	journal	October 2006
Prevention of vascular graft occlusion and thrombus-associated thrombin generation by inhibition of factor XI Tucker, Erik I.; Marzec, Ulla M.; White, Tara C. Blood, Vol. 113, Issue 4 https://doi.org/10.1182/blood-2008-06-163675	journal	January 2009
Application of Fragment Screening and Fragment Linking to the Discovery of Novel Thrombin Inhibitors Howard, Nigel; Abell, Chris; Blakemore, Wendy Journal of Medicinal Chemistry, Vol. 49, Issue 4 https://doi.org/10.1021/jm050850v	journal	January 2006
Allosteric Modification of Factor XIa Functional Activity upon Binding to Polyanions ^† Sinha, Dipali; Badellino, Karen O.; Marcinkiewicz, Mariola Biochemistry, Vol. 43, Issue 23 https://doi.org/10.1021/bi049808c	journal	June 2004
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
AMoRe : an automated package for molecular replacement Navaza, J. Acta Crystallographica Section A Foundations of Crystallography, Vol. 50, Issue 2 https://doi.org/10.1107/S0108767393007597	journal	March 1994
Silyl-Mediated Halogen/Halogen Displacement in Pyridines and Other Heterocycles Schlosser, Manfred; Cottet, Fabrice European Journal of Organic Chemistry, Vol. 2002, Issue 24 https://doi.org/10.1002/1099-0690(200212)2002:24<4181::AID-EJOC4181>3.0.CO;2-M	journal	December 2002
Synthesis, SAR exploration, and X-ray crystal structures of factor XIa inhibitors containing an α-ketothiazole arginine Deng, Hongfeng; Bannister, Thomas D.; Jin, Lei Bioorganic & Medicinal Chemistry Letters, Vol. 16, Issue 11 https://doi.org/10.1016/j.bmcl.2006.02.052	journal	June 2006
Structure-based design of inhibitors of coagulation factor XIa with novel P1 moieties Pinto, Donald J. P.; Smallheer, Joanne M.; Corte, James R. Bioorganic & Medicinal Chemistry Letters, Vol. 25, Issue 7 https://doi.org/10.1016/j.bmcl.2015.01.028	journal	April 2015
Tetrahydroquinoline Derivatives as Potent and Selective Factor XIa Inhibitors Quan, Mimi L.; Wong, Pancras C.; Wang, Cailan Journal of Medicinal Chemistry, Vol. 57, Issue 3 https://doi.org/10.1021/jm401670x	journal	January 2014
Effects of factor IX or factor XI deficiency on ferric chloride-induced carotid artery occlusion in mice: Thrombosis in FIX- and FXI-deficient mice Wang, X.; Cheng, Q.; Xu, L. Journal of Thrombosis and Haemostasis, Vol. 3, Issue 4 https://doi.org/10.1111/j.1538-7836.2005.01236.x	journal	February 2005
Factor XI–dependence of surface- and tissue factor–initiated thrombus propagation in primates Gruber, András; Hanson, Stephen R. Blood, Vol. 102, Issue 3 https://doi.org/10.1182/blood-2003-01-0324	journal	August 2003
Inherited factor XI deficiency confers no protection against acute myocardial infarction Salomon, O.; Steinberg, D. M.; Dardik, R. Journal of Thrombosis and Haemostasis, Vol. 1, Issue 4 https://doi.org/10.1046/j.1538-7836.2003.00195.x	journal	April 2003
Factor XI Antisense Oligonucleotide for Prevention of Venous Thrombosis Büller, Harry R.; Bethune, Claudette; Bhanot, Sanjay New England Journal of Medicine, Vol. 372, Issue 3 https://doi.org/10.1056/NEJMoa1405760	journal	January 2015
In vitro, antithrombotic and bleeding time studies of BMS-654457, a small-molecule, reversible and direct inhibitor of factor XIa Wong, Pancras C.; Quan, Mimi L.; Watson, Carol A. Journal of Thrombosis and Thrombolysis, Vol. 40, Issue 4 https://doi.org/10.1007/s11239-015-1258-7	journal	August 2015
Effects of factor XI deficiency on ferric chloride-induced vena cava thrombosis in mice Wang, X.; Smith, P. L.; Hsu, M-Y. Journal of Thrombosis and Haemostasis, Vol. 4, Issue 9 https://doi.org/10.1111/j.1538-7836.2006.02093.x	journal	September 2006
Levels of intrinsic coagulation factors and the risk of myocardial infarction among men: opposite and synergistic effects of factors XI and XII Doggen, Carine J. M.; Rosendaal, Frits R.; Meijers, Joost C. M. Blood, Vol. 108, Issue 13 https://doi.org/10.1182/blood-2005-12-023697	journal	December 2006
Designing Allosteric Inhibitors of Factor XIa. Lessons from the Interactions of Sulfated Pentagalloylglucopyranosides Al-Horani, Rami A.; Desai, Umesh R. Journal of Medicinal Chemistry, Vol. 57, Issue 11 https://doi.org/10.1021/jm500311e	journal	December 2013
Pyridine and pyridinone-based factor XIa inhibitors Corte, James R.; Fang, Tianan; Hangeland, Jon J. Bioorganic & Medicinal Chemistry Letters, Vol. 25, Issue 4 https://doi.org/10.1016/j.bmcl.2014.12.050	journal	February 2015
A small-molecule factor XIa inhibitor produces antithrombotic efficacy with minimal bleeding time prolongation in rabbits Wong, Pancras C.; Crain, Earl J.; Watson, Carol A. Journal of Thrombosis and Thrombolysis, Vol. 32, Issue 2 https://doi.org/10.1007/s11239-011-0599-0	journal	May 2011

Similar Records

Orally bioavailable pyridine and pyrimidine-based Factor XIa inhibitors: Discovery of the methyl N-phenyl carbamate P2 prime group

Journal Article · Sun May 01 00:00:00 EDT 2016 · Bioorganic and Medicinal Chemistry · OSTI ID:1358846

Corte, James R.; Fang, Tianan; Pinto, Donald J. P.; +15 more

Discovery of Potent and Orally Bioavailable Pyridine N-Oxide-Based Factor XIa Inhibitors through Exp

Journal Article · Fri Jul 01 00:00:00 EDT 2022 · J. Med. Chem. · OSTI ID:1358846

Xu, Guozhang; Liu, Zhijie; Wang, Xinkang; +22 more

Discovery of 1-(4-Methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro- 1H-pyrazolo[3,4-c]pyridine-3-carboxamide (Apixaban, BMS-562247), a Highly Potent, Selective, Efficacious, and Orally Bioavailable Inhibitor of Blood Coagulation Factor Xa

Journal Article · Mon Mar 08 00:00:00 EST 2010 · J. Med. Chem. · OSTI ID:1358846

Pinto, Donald J.P.; Orwat, Michael J; Koch, Stephanie; +11 more

Title: Orally bioavailable pyridine and pyrimidine-based Factor XIa inhibitors: Discovery of the methyl N-phenyl carbamate P2 prime group

Citation Formats

References (50)

Similar Records

Related Subjects