Macrocyclic ketone analogues of halichondrin B.
Structurally simplified macrocyclic ketone analogues of halichondrin B were prepared by total synthesis and found to retain the potent cell growth inhibitory activity in vitro, stability in mouse serum, and in vivo efficacy of the natural product.
Zheng
Wanjun
W
Department of Medicinal Chemistry, Eisai Research Institute, 4 Corporate Drive, Andover, MA 01810, USA.
Seletsky
Boris M
BM
Palme
Monica H
MH
Lydon
Paul J
PJ
Singer
Lori A
LA
Chase
Charles E
CE
Lemelin
Charles A
CA
Shen
Yongchun
Y
Davis
Heather
H
Tremblay
Lynda
L
Towle
Murray J
MJ
Salvato
Kathleen A
KA
Wels
Bruce F
BF
Aalfs
Kimberley K
KK
Kishi
Yoshito
Y
Littlefield
Bruce A
BA
Yu
Melvin J
MJ
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004988:Ethers, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D047028:Macrocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018942:Macrolides; D051379:Mice; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D000095662:Polyether Polyketides
D004988:Ethers, Cyclic; D005663:Furans; D007659:Ketones; D047028:Macrocyclic Compounds; D018942:Macrolides; C070519:halichondrin B; D000095662:Polyether Polyketides; C490954:eribulin