title: 9H-Carbazole-1-carboxamides as potent and selective JAK2 inhibitors.
abstract: The discovery, synthesis, and characterization of 9H-carbazole-1-carboxamides as potent and selective ATP-competitive inhibitors of Janus kinase 2 (JAK2) are discussed. Optimization for JAK family selectivity led to compounds 14 and 21, with greater than 45-fold selectivity for JAK2 over all other members of the JAK kinase family.
authors.affiliation: Bristol-Myers Squibb Co., 5 Research Parkway, Wallingford, CT 06492-1951, USA. Electronic address: Kurt.Zimmermann@bms.com.
authors.forename: Kurt
authors.initials: K
authors.lastname: Zimmermann
authors.affiliation: Bristol-Myers Squibb Co., 5 Research Parkway, Wallingford, CT 06492-1951, USA.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Sang
authors.affiliation: Bristol-Myers Squibb Co., 5 Research Parkway, Wallingford, CT 06492-1951, USA.
authors.forename: Harold A
authors.initials: HA
authors.lastname: Mastalerz
authors.affiliation: Bristol-Myers Squibb Co., 5 Research Parkway, Wallingford, CT 06492-1951, USA.
authors.forename: Walter L
authors.initials: WL
authors.lastname: Johnson
authors.affiliation: Bristol-Myers Squibb Co., 5 Research Parkway, Wallingford, CT 06492-1951, USA.
authors.forename: Guifen
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Bristol-Myers Squibb Co., Province Line Rd., Princeton, NJ 08540-4000, USA.
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Bristol-Myers Squibb Co., Province Line Rd., Princeton, NJ 08540-4000, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Batt
authors.affiliation: Bristol-Myers Squibb Co., Province Line Rd., Princeton, NJ 08540-4000, USA.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Lombardo
authors.affiliation: Bristol-Myers Squibb Co., 5 Research Parkway, Wallingford, CT 06492-1951, USA.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Vyas
authors.affiliation: Bristol-Myers Squibb Co., Province Line Rd., Princeton, NJ 08540-4000, USA.
authors.forename: George L
authors.initials: GL
authors.lastname: Trainor
authors.affiliation: Bristol-Myers Squibb Co., Province Line Rd., Princeton, NJ 08540-4000, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Tokarski
authors.affiliation: Bristol-Myers Squibb Co., Province Line Rd., Princeton, NJ 08540-4000, USA.
authors.forename: Matthew V
authors.initials: MV
authors.lastname: Lorenzi
authors.affiliation: Bristol-Myers Squibb Co., Province Line Rd., Princeton, NJ 08540-4000, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: You
authors.affiliation: Bristol-Myers Squibb Co., Province Line Rd., Princeton, NJ 08540-4000, USA.
authors.forename: Marco M
authors.initials: MM
authors.lastname: Gottardis
authors.affiliation: Bristol-Myers Squibb Co., Province Line Rd., Princeton, NJ 08540-4000, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lippy
authors.affiliation: Bristol-Myers Squibb Co., Province Line Rd., Princeton, NJ 08540-4000, USA.
authors.forename: Javed
authors.initials: J
authors.lastname: Khan
authors.affiliation: Bristol-Myers Squibb Co., Province Line Rd., Princeton, NJ 08540-4000, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Sack
authors.affiliation: Bristol-Myers Squibb Co., Province Line Rd., Princeton, NJ 08540-4000, USA.
authors.forename: Ashok V
authors.initials: AV
authors.lastname: Purandare
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D002227:Carbazoles / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D006801:Humans; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D002227:Carbazoles; D047428:Protein Kinase Inhibitors; C041514:carbazole; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053616:Janus Kinase 3
keywords: JAK; JAK family selectivity; JAK1; JAK2; JAK3; Myeloproliferative disorders; Myeloproliferative neoplasms; TYK2