title: Synthesis and biological evaluation of novel cryptophycin analogs with modification in the beta-alanine region.
abstract: Structure modification of the beta-alanine region (fragment C) of the potent antimitotic agent cryptophycin was investigated. This includes: (1) introduction of substituents at the previously unsubstituted C7 position of the macrolide ring and (2) replacement of the (2R)-3-amino-2-methyl-propanoic acid (beta-alanine) with various (1)-amino acids to give the corresponding 15-membered unnatural cryptophycin analogs.
authors.affiliation: Lilly Research Laboratories, Indianapolis, IN 46285, USA.
authors.forename: C
authors.initials: C
authors.lastname: Shih
authors.forename: L S
authors.initials: LS
authors.lastname: Gossett
authors.forename: J M
authors.initials: JM
authors.lastname: Gruber
authors.forename: C S
authors.initials: CS
authors.lastname: Grossman
authors.forename: S L
authors.initials: SL
authors.lastname: Andis
authors.forename: R M
authors.initials: RM
authors.lastname: Schultz
authors.forename: J F
authors.initials: JF
authors.lastname: Worzalla
authors.forename: T H
authors.initials: TH
authors.lastname: Corbett
authors.forename: J T
authors.initials: JT
authors.lastname: Metz
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy; D003110:Colonic Neoplasms / Q000188:drug therapy; D047630:Depsipeptides; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology*; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D015091:beta-Alanine / Q000737:chemistry*