Design and efficient synthesis of new stable 1alpha,25-dihydroxy-19-norvitamin D3 analogues containing amide bond.
The design and synthesis of new 1alpha,25-dihydroxy-19-norvitamin D(3) analogues 3a-c, which have an amide bond in the molecule instead of the diene, are described. The A-ring moiety was constructed by a (3S,5S)-3,5-dihydroxypiperidine derivative (9, 11, or 13) prepared from D-mannose, and a CD-ring carboxylic acid 16 was synthesized from Grundmann's ketone. Coupling those parts gave desired 3a-c in good yield. This strategy can be applied in combinatorial chemistry; therefore, those compounds would be applicable as useful tools in the development of new drugs.
Suhara
Yoshitomo
Y
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan.
Kittaka
Atsushi
A
Ono
Keiichiro
K
Kurihara
Masaaki
M
Fujishima
Toshie
T
Yoshida
Akihiro
A
Takayama
Hiroaki
H
D000577:Amides / Q000138:chemical synthesis; D001665:Binding Sites; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D015195:Drug Design; D008958:Models, Molecular; D018167:Receptors, Calcitriol / Q000737:chemistry; D013329:Structure-Activity Relationship
D000577:Amides; D018167:Receptors, Calcitriol; C083610:1,25-dihydroxy-19-norvitamin D3; D002117:Calcitriol