Synthesis and testing of 2alpha-modified 1alpha,25-dihydroxyvitamin D(3) analogues with a double side chain: marked cell differentiation activity

Yoshitomo Suhara; Atsushi Kittaka; Seishi Kishimoto; Martin J Calverley; Toshie Fujishima; Nozomi Saito; Takayuki Sugiura; Keizo Waku; Hiroaki Takayama

doi:10.1016/s0960-894x(02)00722-9

Synthesis and testing of 2alpha-modified 1alpha,25-dihydroxyvitamin D(3) analogues with a double side chain: marked cell differentiation activity

Bioorg Med Chem Lett. 2002 Nov 18;12(22):3255-8. doi: 10.1016/s0960-894x(02)00722-9.

Authors

Yoshitomo Suhara¹, Atsushi Kittaka, Seishi Kishimoto, Martin J Calverley, Toshie Fujishima, Nozomi Saito, Takayuki Sugiura, Keizo Waku, Hiroaki Takayama

Affiliation

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa, Japan.

PMID: 12392726
DOI: 10.1016/s0960-894x(02)00722-9

Abstract

The 2alpha-methyl-, 2alpha-(3-hydroxypropyl)-, and 2alpha-(3-hydroxypropoxy)-derivatives of the 'double side chain' analogue of 1alpha,25-dihydroxyvitamin D(3) were synthesized using Trost A-ring/CD-ring connective strategy. Regarding the requisite A-ring building blocks, a new, high yield and stereoselective route to the 2alpha-methyl compound starting from D-glucose was developed. All three new analogues showed potent HL-60 cancer cell differentiation activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkynes / chemistry
Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / pharmacology
Calcitriol / analogs & derivatives*
Calcitriol / chemical synthesis
Calcitriol / pharmacology
Cattle
Cell Differentiation / drug effects*
HL-60 Cells
Humans
Ligands
Receptors, Calcitriol / metabolism
Stereoisomerism
Structure-Activity Relationship

Substances

Alkynes
Antineoplastic Agents
Ligands
Receptors, Calcitriol
Calcitriol