Design, synthesis and biological evaluation of novel 2-alkylidene 19-norcalcitriol analogs.
Bioorg Chem
; 101: 104013, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32629275
ABSTRACT
Continuing our studies aimed at A-ring modified vitamin D compounds, we designed novel 19-norcalcitriol derivatives bearing at C-2 pegylated chains of different lengths. The terminal fragments of these substituents contain hydroxyls or moieties possessing nitrogen and/or sulfur atoms capable of transition metal ions complexation. Also, two conjugate-type platinum(II) complexes of 19-norcalcitriol were obtained in which l-methionine served as chelating moiety. The convergent synthesis of the target 19-norcalcitriol analogs involved several steps with the crucial one being condensation of A-ring phosphine oxide and the known Grundmann ketone by Wittig-Horner reaction. Further elaboration of the 2-alkylidene substituent provided all final compounds which were then tested to determine their affinity for the vitamin D receptor and cytotoxic activity.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Calcitriol
/
Desenho de Fármacos
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article