title: The synthesis and SAR of 2-amino-pyrrolo[2,3-d]pyrimidines: a new class of Aurora-A kinase inhibitors.
abstract: A new class of Aurora-A inhibitors have been identified based on the 2-amino-pyrrolo[2,3-d]pyrimidine scaffold. Here, we describe the synthesis and SAR of this novel series. We report compounds which exhibit nanomolar activity in the Aurora-A biochemical assay and are able to inhibit tumor cell proliferation. This study culminates in compound 30, an inhibitor with potent activity against Aurora A (IC50=0.008 microM), anti-proliferative activity against several tumor cell lines and induces polyploidy in H460 cells.
authors.affiliation: Johnson and Johnson, PRDUS, LLC, Spring House, PA 19477, USA. kevinjmoriarty@comcast.net
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Moriarty
authors.forename: Holly K
authors.initials: HK
authors.lastname: Koblish
authors.forename: Thomas
authors.initials: T
authors.lastname: Garrabrant
authors.forename: Jahanvi
authors.initials: J
authors.lastname: Maisuria
authors.forename: Ehab
authors.initials: E
authors.lastname: Khalil
authors.forename: Farah
authors.initials: F
authors.lastname: Ali
authors.forename: Ioanna P
authors.initials: IP
authors.lastname: Petrounia
authors.forename: Carl S
authors.initials: CS
authors.lastname: Crysler
authors.forename: Anna C
authors.initials: AC
authors.lastname: Maroney
authors.forename: Dana L
authors.initials: DL
authors.lastname: Johnson
authors.forename: Robert A
authors.initials: RA
authors.lastname: Galemmo
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D064127:Aurora Kinases; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D011123:Polyploidy; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases