title: Discovery and characterization of the potent, selective and orally bioavailable MMP inhibitor ABT-770.
abstract: Modification of the biphenyl portion of MMP inhibitor 2a gave analogue 2i which is greater than 1000-fold selective against MMP-2 versus MMP-1. The stereospecific synthesis of both enantiomers of 2i was achieved beginning with (S)- or (R)-benzyl glycidyl ether. The (S)-enantiomer, 11 (ABT-770), is orally bioavailable and efficacious in an in vivo model of tumor growth.
authors: Cancer Research Area, Abbott Laboratories, Dept. 47J, Bldg. AP10, 100 Abbott Park Road, Abbott Park, IL 60064, USA. mike.curtin@abbott.com
authors: M L
authors: ML
authors: Curtin
authors: A S
authors: AS
authors: Florjancic
authors: H R
authors: HR
authors: Heyman
authors: M R
authors: MR
authors: Michaelides
authors: R B
authors: RB
authors: Garland
authors: J H
authors: JH
authors: Holms
authors: D H
authors: DH
authors: Steinman
authors: J F
authors: JF
authors: Dellaria
authors: J
authors: J
authors: Gong
authors: C K
authors: CK
authors: Wada
authors: Y
authors: Y
authors: Guo
authors: I B
authors: IB
authors: Elmore
authors: P
authors: P
authors: Tapang
authors: D H
authors: DH
authors: Albert
authors: T J
authors: TJ
authors: Magoc
authors: P A
authors: PA
authors: Marcotte
authors: J J
authors: JJ
authors: Bouska
authors: C L
authors: CL
authors: Goodfellow
authors: J L
authors: JL
authors: Bauch
authors: K C
authors: KC
authors: Marsh
authors: D W
authors: DW
authors: Morgan
authors: S K
authors: SK
authors: Davidsen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D001713:Biphenyl Compounds / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D002455:Cell Division / Q000187:drug effects; D004285:Dogs; D004791:Enzyme Inhibitors / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics; D006207:Half-Life; D000882:Haplorhini; D006877:Hydroxamic Acids / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D020128:Inhibitory Concentration 50; D007275:Injections, Intravenous; D061965:Matrix Metalloproteinase Inhibitors; D008657:Metabolic Clearance Rate; D009374:Neoplasms, Experimental / Q000188:drug therapy; D051381:Rats; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; C442959:ABT-770