title: Phosphate prodrugs of PD154075.
abstract: In the preparation of phosphate prodrugs of PD154075, several strategies of linking a phosphate group to the indole moiety were studied. A novel linker, p-hydroxymethylbenzoyloxymethoxycarbonyl, was discovered to provide the phosphate prodrug of PD154075 (compound 9) with significantly increased aqueous solubility, sufficient stability in aqueous solution and good bio-reconversion in vivo.
authors.affiliation: Chemical Development, Parke-Davis Pharmaceutical Research, Arbor, MI 48105, USA. zhijian.zhu@wl.com
authors.forename: Z
authors.initials: Z
authors.lastname: Zhu
authors.forename: H G
authors.initials: HG
authors.lastname: Chen
authors.forename: O P
authors.initials: OP
authors.lastname: Goel
authors.forename: O H
authors.initials: OH
authors.lastname: Chan
authors.forename: L A
authors.initials: LA
authors.lastname: Stilgenbauer
authors.forename: B H
authors.initials: BH
authors.lastname: Stewart
mesh_terms: D000818:Animals; D004355:Drug Stability; D007211:Indoles / Q000737:chemistry; D008297:Male; D010755:Organophosphates / Q000138:chemical synthesis* / Q000378:metabolism*; D010710:Phosphates / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
chemical_list: C413742:2-benzofuranylmethoxycarboyl-alpha-methyl-1'-((4-(phosphoryloxymethyl)benzoyl)methoxycarbonyl)tryptophan-N-(1-phenylethyl)amide; D007211:Indoles; D010755:Organophosphates; D010710:Phosphates; D011355:Prodrugs; D014364:Tryptophan; C089683:PD 154075