title: Synthesis and stereochemical effects of pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines as EGFR and ErbB-2 inhibitors.
abstract: A novel class of pyrrolidinyl-acetyleneic thieno[3,2-d]pyrimidines has been identified which potently inhibit the EGFR and ErbB-2 receptor tyrosine kinases. Synthetic modifications of the pyrrolidine carbamate moiety result in a range of effects on enzyme and cellular potency. In addition, the impact of the absolute stereochemical configuration on cellular potency and oral mouse pharmacokinetics is described.
authors.affiliation: Department of Oncology Medicinal Chemistry, GlaxoSmithKline, Research Triangle Park, NC 27709, USA. Kirk.L.Stevens@GSK.com
authors.forename: Kirk L
authors.initials: KL
authors.lastname: Stevens
authors.forename: Krystal J
authors.initials: KJ
authors.lastname: Alligood
authors.forename: Jennifer G Badiang
authors.initials: JG
authors.lastname: Alberti
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Caferro
authors.forename: Stanley D
authors.initials: SD
authors.lastname: Chamberlain
authors.forename: Scott H
authors.initials: SH
authors.lastname: Dickerson
authors.forename: Hamilton D
authors.initials: HD
authors.lastname: Dickson
authors.forename: Holly K
authors.initials: HK
authors.lastname: Emerson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Griffin
authors.forename: Robert D
authors.initials: RD
authors.lastname: Hubbard
authors.forename: Barry R
authors.initials: BR
authors.lastname: Keith
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mullin
authors.forename: Kimberly G
authors.initials: KG
authors.lastname: Petrov
authors.forename: Roseanne M
authors.initials: RM
authors.lastname: Gerding
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Reno
authors.forename: Tara R
authors.initials: TR
authors.lastname: Rheault
authors.forename: David W
authors.initials: DW
authors.lastname: Rusnak
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Sammond
authors.forename: Stephon C
authors.initials: SC
authors.lastname: Smith
authors.forename: David E
authors.initials: DE
authors.lastname: Uehling
authors.forename: Alex G
authors.initials: AG
authors.lastname: Waterson
authors.forename: Edgar R
authors.initials: ER
authors.lastname: Wood
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D051379:Mice; D010599:Pharmacokinetics; D011743:Pyrimidines / Q000138:chemical synthesis / Q000494:pharmacology*; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; D011743:Pyrimidines; D011759:Pyrrolidines; D018719:Erb-b2 Receptor Tyrosine Kinases; C032519:pyrrolidine