Novel synthesis of 19-nor-vitamin D compounds

Perlman, Kato L.; Swenson, Rolf E.; Paaren, Herbert E.; Schnoes, Heinrich K.; DeLuca, Hector F.

doi:10.1016/0040-4039(91)80559-o

Cited by 99 publications

(49 citation statements)

References 15 publications

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“…Inhibition of clonal proliferation was evaluated in leukemia HL-60, breast cancer MCF-7, prostate PC-3 and LNCaP cell lines [14]. The results were compared with those obtained for 1 and summarized in Table 2.e 2 Significant separations of the immunomodulatory activity from hypercalcemic effects (MTD) were observed.…”

Section: Immunomodulatory Activity and Iinhibi-tion Of Cancer Cell CLmentioning

confidence: 99%

“…The program benefited from our previous findings that biological activities could be enhanced, and the metabolic deactivation retarded, by introduction of a 23-double or triple bond, replacement of the C-25 geminal methyl groups with trifluoromethyl moieties and insertion of a 16-ene function. To broaden the basis of structure-activity relationships, we made liberal use of DeLuca's 19-nor modification [14] of the A-ring as shown in the following Scheme.…”

Section: Introductionmentioning

confidence: 99%

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C-20 Cyclopropyl Vitamin D3 Analogs

Uskoković¹,

Manchand²,

Marczak³

et al. 2006

CTMC

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The formal C-20 methylation of 1,25-dihydroxy vitamin D3 (calcitriol) and bridging of two methyl groups produces spiro[cyclopropane-1, 20'-calcitriol], colloquially referred to as C-20 cyclopropylcalcitriol, which is much more active in MLR for suppression of interferon-gamma release than calcitriol, and hypercalcemia in mice is elicited at a ten-fold lower dose when compared to calcitriol. Introduction of the Delta16,17-double bond, modification of the side chain by 23-unsaturation and replacement of the methyl groups at C-26 and C-27 with trifluoromethyl moieties create a highly active series of vitamin D analogs. As previously observed in the calcitriol series, the presence of the C-16 double bond in the cyclopropyl analogs also arrests metabolic side-chain oxidation in the at the C-24 oxo level in UMR 106 cells. The enhanced biological activity is ascribed, at least in part, to the improved resistance toward metabolic degradation.

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Section: Immunomodulatory Activity and Iinhibi-tion Of Cancer Cell CLmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

C-20 Cyclopropyl Vitamin D3 Analogs

Uskoković¹,

Manchand²,

Marczak³

et al. 2006

CTMC

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“…Ligand Pharmaceuticals identified the nonsecosteroidal activators of VDR upon screening of a compound library in cells, which were transfected with a reporter construct that contained a vitamin-Dresponsive element of the CYP24 promoter [57] (Table 76.12). A bis-phenyl derivative, LG190090, was characterized that was able to transactivate the reporter construct in a VDR-dependent manner (1000-fold less potent than 1,25(OH) 2 …”

Section: Non-secosteroidal Compoundsmentioning

confidence: 99%

“…Three different parts can be distinguished in the structure of 1,25(OH) 2 D 3 : a central rigid CD-bicyclic ring portion to which are connected at C-17 the flexible side chain and at C-8 the flexible seco-B,A-ring system. Many scientists focused on the introduction of chemical modifications into these flexible parts of the secosteroidal structure of 1,25(OH) 2 D 3 such as elongation, unsaturation, epimerization of the side chain or alterations of the A-ring such as the successful 19-nor modification which resulted in a 10-fold decreased calcemic activity of 1,25(OH) 2 D 3 [2,3]. Next to the introduction of structural modifications in the side chain or the A-ring, an extensive study of the structureefunction relationship was performed focusing on the least-studied CD-ring region.…”

Section: Introductionmentioning

confidence: 99%

Analogs of Calcitriol

et al. 2011

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“…2D-ASMA of these compounds was studied in comparison with the natural hormone (1) and the closely related 19-norvitamin D analog, 2MD (2) [19]. 19-Norvitamin D derivatives [19][20][21][22], which were first developed by DeLuca's group, are versatile analogs of vitamin D that are chemically stable and also easy to synthesized. …”

Section: Introductionmentioning

confidence: 99%