Literature DB >> 26288682

Structure-Based Design of Selective Janus Kinase 2 Imidazo[4,5-d]pyrrolo[2,3-b]pyridine Inhibitors.

Amy C Hart1, Gretchen M Schroeder1, Honghe Wan1, James Grebinski1, Jennifer Inghrim1, James Kempson1, Junqing Guo1, William J Pitts1, John S Tokarski1, John S Sack1, Javed A Khan1, Jonathan Lippy1, Matthew V Lorenzi1, Dan You1, Theresa McDevitt1, Ragini Vuppugalla1, Yueping Zhang1, Louis J Lombardo1, George L Trainor1, Ashok V Purandare1.   

Abstract

Early hit to lead work on a pyrrolopyridine chemotype provided access to compounds with biochemical and cellular potency against Janus kinase 2 (JAK2). Structure-based drug design along the extended hinge region of JAK2 led to the identification of an important H-bond interaction with the side chain of Tyr 931, which improved JAK family selectivity. The 4,5-dimethyl thiazole analogue 18 demonstrated high levels of JAK family selectivity and was identified as a promising lead for the program.

Entities:  

Keywords:  Janus kinase 2 (JAK2); Kinase; myeloproliferative neoplasms; structure-based drug design (SBDD); thiazole

Year:  2015        PMID： 26288682      PMCID： PMC4538451          DOI： 10.1021/acsmedchemlett.5b00225

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  12 in total

Review 1.  A role for JAK2 mutations in myeloproliferative diseases.

Authors:  Kelly J Morgan; D Gary Gilliland
Journal:  Annu Rev Med       Date:  2008       Impact factor: 13.739

2.  Synthesis, initial SAR and biological evaluation of 1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-amine derived inhibitors of IkappaB kinase.

Authors:  James Kempson; Junqing Guo; Jagabandhu Das; Robert V Moquin; Steven H Spergel; Scott H Watterson; Charles M Langevine; Alaric J Dyckman; Mark Pattoli; James R Burke; Xiaoxia Yang; Kathleen M Gillooly; Kim W McIntyre; Laishun Chen; John H Dodd; Murray McKinnon; Joel C Barrish; William J Pitts
Journal:  Bioorg Med Chem Lett       Date:  2009-04-05       Impact factor: 2.823

3.  Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis.

Authors:  Francisco Cervantes; Alessandro M Vannucchi; Jean-Jacques Kiladjian; Haifa Kathrin Al-Ali; Andres Sirulnik; Viktoriya Stalbovskaya; Mari McQuitty; Deborah S Hunter; Richard S Levy; Francesco Passamonti; Tiziano Barbui; Giovanni Barosi; Claire N Harrison; Laurent Knoops; Heinz Gisslinger
Journal:  Blood       Date:  2013-10-30       Impact factor: 22.113

Review 4.  Investigational Janus kinase inhibitors.

Authors:  Constantine S Tam; Srdan Verstovsek
Journal:  Expert Opin Investig Drugs       Date:  2013-02-23       Impact factor: 6.206

5.  A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera.

Authors:  Chloé James; Valérie Ugo; Jean-Pierre Le Couédic; Judith Staerk; François Delhommeau; Catherine Lacout; Loïc Garçon; Hana Raslova; Roland Berger; Annelise Bennaceur-Griscelli; Jean Luc Villeval; Stefan N Constantinescu; Nicole Casadevall; William Vainchenker
Journal:  Nature       Date:  2005-04-28       Impact factor: 49.962

6.  Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis.

Authors:  Ross L Levine; Martha Wadleigh; Jan Cools; Benjamin L Ebert; Gerlinde Wernig; Brian J P Huntly; Titus J Boggon; Iwona Wlodarska; Jennifer J Clark; Sandra Moore; Jennifer Adelsperger; Sumin Koo; Jeffrey C Lee; Stacey Gabriel; Thomas Mercher; Alan D'Andrea; Stefan Fröhling; Konstanze Döhner; Peter Marynen; Peter Vandenberghe; Ruben A Mesa; Ayalew Tefferi; James D Griffin; Michael J Eck; William R Sellers; Matthew Meyerson; Todd R Golub; Stephanie J Lee; D Gary Gilliland
Journal:  Cancer Cell       Date:  2005-04       Impact factor: 31.743

7.  Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders.

Authors:  E Joanna Baxter; Linda M Scott; Peter J Campbell; Clare East; Nasios Fourouclas; Soheila Swanton; George S Vassiliou; Anthony J Bench; Elaine M Boyd; Natasha Curtin; Mike A Scott; Wendy N Erber; Anthony R Green
Journal:  Lancet       Date:  2005 Mar 19-25       Impact factor: 79.321

8.  A Survey of the Role of Noncovalent Sulfur Interactions in Drug Design.

Authors:  Brett R Beno; Kap-Sun Yeung; Michael D Bartberger; Lewis D Pennington; Nicholas A Meanwell
Journal:  J Med Chem       Date:  2015-03-03       Impact factor: 7.446

9.  A gain-of-function mutation of JAK2 in myeloproliferative disorders.

Authors:  Robert Kralovics; Francesco Passamonti; Andreas S Buser; Soon-Siong Teo; Ralph Tiedt; Jakob R Passweg; Andre Tichelli; Mario Cazzola; Radek C Skoda
Journal:  N Engl J Med       Date:  2005-04-28       Impact factor: 91.245

10.  Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms.

Authors:  Alfonso Quintás-Cardama; Kris Vaddi; Phillip Liu; Taghi Manshouri; Jun Li; Peggy A Scherle; Eian Caulder; Xiaoming Wen; Yanlong Li; Paul Waeltz; Mark Rupar; Timothy Burn; Yvonne Lo; Jennifer Kelley; Maryanne Covington; Stacey Shepard; James D Rodgers; Patrick Haley; Hagop Kantarjian; Jordan S Fridman; Srdan Verstovsek
Journal:  Blood       Date:  2010-02-03       Impact factor: 22.113
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  4 in total

1.  Understanding the structural features of JAK2 inhibitors: a combined 3D-QSAR, DFT and molecular dynamics study.

Authors:  Sathya Babu; Santhosh Kumar Nagarajan; Thirumurthy Madhavan
Journal:  Mol Divers       Date:  2019-01-07       Impact factor: 2.943

2.  Discovery of a Highly Selective JAK2 Inhibitor, BMS-911543, for the Treatment of Myeloproliferative Neoplasms.

Authors:  Honghe Wan; Gretchen M Schroeder; Amy C Hart; Jennifer Inghrim; James Grebinski; John S Tokarski; Matthew V Lorenzi; Dan You; Theresa Mcdevitt; Becky Penhallow; Ragini Vuppugalla; Yueping Zhang; Xiaomei Gu; Ramaswamy Iyer; Louis J Lombardo; George L Trainor; Stefan Ruepp; Jonathan Lippy; Yuval Blat; John S Sack; Javed A Khan; Kevin Stefanski; Bogdan Sleczka; Arvind Mathur; Jung-Hui Sun; Michael K Wong; Dauh-Rurng Wu; Peng Li; Anuradha Gupta; P N Arunachalam; Bala Pragalathan; Sankara Narayanan; Nanjundaswamy K C; Prakasam Kuppusamy; Ashok V Purandare
Journal:  ACS Med Chem Lett       Date:  2015-07-12       Impact factor: 4.345

3.  Discovery of novel JAK2 and EGFR inhibitors from a series of thiazole-based chalcone derivatives.

Authors:  Kamonpan Sanachai; Thitinan Aiebchun; Panupong Mahalapbutr; Supaphorn Seetaha; Lueacha Tabtimmai; Phornphimon Maitarad; Iakovos Xenikakis; Athina Geronikaki; Kiattawee Choowongkomon; Thanyada Rungrotmongkol
Journal:  RSC Med Chem       Date:  2021-02-26

4.  A Novel Naphthoquinone-Coumarin Hybrid That Inhibits BCR-ABL1-STAT5 Oncogenic Pathway and Reduces Survival in Imatinib-Resistant Chronic Myelogenous Leukemia Cells.

Authors:  Patricia Martín-Rodríguez; Borja Guerra; Idaira Hueso-Falcón; Haidee Aranda-Tavío; Juan Díaz-Chico; José Quintana; Francisco Estévez; Bonifacio Díaz-Chico; Angel Amesty; Ana Estévez-Braun; Leandro Fernández-Pérez
Journal:  Front Pharmacol       Date:  2019-01-09       Impact factor: 5.810
  4 in total

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