title: Potent immunosuppressive C32-O-arylethyl ether derivatives of ascomycin with reduced toxicity.
abstract: The synthesis of C32-O-arylethyl ether derivatives of ascomycin that possess equivalent immunosuppressant activity but reduced toxicity, compared to FK-506, is described.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Armstrong
authors.forename: F
authors.initials: F
authors.lastname: Wong
authors.forename: M A
authors.initials: MA
authors.lastname: Holmes
authors.forename: P J
authors.initials: PJ
authors.lastname: Sinclair
authors.forename: M T
authors.initials: MT
authors.lastname: Goulet
authors.forename: F J
authors.initials: FJ
authors.lastname: Dumont
authors.forename: M J
authors.initials: MJ
authors.lastname: Staruch
authors.forename: S
authors.initials: S
authors.lastname: Koprak
authors.forename: L B
authors.initials: LB
authors.lastname: Peterson
authors.forename: R
authors.initials: R
authors.lastname: Rosa
authors.forename: M B
authors.initials: MB
authors.lastname: Wilusz
authors.forename: G J
authors.initials: GJ
authors.lastname: Wiederrecht
authors.forename: J G
authors.initials: JG
authors.lastname: Cryan
authors.forename: M J
authors.initials: MJ
authors.lastname: Wyvratt
authors.forename: W H
authors.initials: WH
authors.lastname: Parsons
mesh_terms: D000284:Administration, Oral; D000818:Animals; D065095:Calcineurin Inhibitors; D004353:Drug Evaluation, Preclinical; D007035:Hypothermia / Q000139:chemically induced; D020104:Immunophilins / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D020128:Inhibitory Concentration 50; D007275:Injections, Intravenous; D007674:Kidney Diseases / Q000139:chemically induced; D018942:Macrolides / Q000138:chemical synthesis* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D022021:Tacrolimus Binding Proteins; D018675:Toxicity Tests
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D018942:Macrolides; C058028:immunomycin; D022021:Tacrolimus Binding Proteins; D020104:Immunophilins; D016559:Tacrolimus