83805-11-2

Basic information

• Product Name: FALECALCITRIOL
• Synonyms: FALECALCITRIOL;(+)-(5Z,7E)-26,26,26,27,27,27-Hexafluoro-9,10-secocholesta-5,7,10(19)-triene-1α,3β,25-triol;26,26,26,27,27,27-Hexafluoro-1,25-dihydroxyvitamin D3;9,10-Secocholesta-5,7,10(19)-triene-1,3,25-triol, 26,26,26,27,27,27-hexafluoro-, (1α,3β,5Z,7E)-;Flocalcitriol;Flocalcitrol;Fulstan;Hornel
• CAS NO: 83805-11-2
• Molecular Formula: C₂₇H₃₈F₆O₃
• Molecular Weight: 524.58
• Product Categories: Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 83805-11-2.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 576.9 °C at 760 mmHg
• Flash Point: 302.7 °C
• Appearance: /
• Density: 1.24 g/cm³
• Vapor Pressure: 1.03E-15mmHg at 25°C
• Refractive Index: 1.504
• CAS DataBase Reference: FALECALCITRIOL(CAS DataBase Reference)
• NIST Chemistry Reference: FALECALCITRIOL(83805-11-2)
• EPA Substance Registry System: FALECALCITRIOL(83805-11-2)

Safety Data

• Hazardous Substances Data: 83805-11-2(Hazardous Substances Data)

Usage

Description

Falecalcitriol, previously known as flocalcitrol, was launched by several codevelopers in Japan for the treatment of secondary hyperthyroidism (SHPT). This hexafluorinated analog of 1α,25-dihydroxyvitamin D3 (calcitriol), the hormonally active form of vitamin D3, can be obtained by several different synthetic routes from a conveniently protected cholestenol, a key step being an aldol reaction with hexafluoroacetone. Falecalcitriol is several times more active than 1,25(OH)2D3 in regulating the proliferation of parathyroid cells and parathyroid hormone (PTH) synthesis that are believed to be mediated through binding to VDR, a nuclear receptor for vitamin D; furthermore, it was proposed that a bioactive 23S-hydroxylated metabolite, resistant to further metabolism, contributes to the retention of an active compound for longer in cells and so, to significantly lengthen the duration of action. In a comparative clinical study conducted in hemodialysis patients with moderate to severe SHPT, falecalcitriol was found to be more active than alfacalcidol in suppressing parathyroid hormone without triggering hypercalcemia.

Originator

University of Wisconsin (US)

Uses

Hexafluorinated analog of Calcitriol (C144500). A more potent therapeutic agent for secondary hyperparathyroidism.

Brand name

Hornel, Fulstan

Hazard

A poison by ingestion.

InChI:InChI=1/C27H38F6O3/c1-16(6-4-13-25(36,26(28,29)30)27(31,32)33)21-10-11-22-18(7-5-12-24(21,22)3)8-9-19-14-20(34)15-23(35)17(19)2/h8-9,16,20-23,34-36H,2,4-7,10-15H2,1,3H3/b18-8+,19-9-/t16-,20-,21-,22+,23+,24-/m1/s1

Upstream product

• 163392-53-8 (5Z,7E)-(1S,3R)-1,3-bis[(t-butyldimethylsilyl)oxy]-26,26,26,27,27,27-hexafluoro-25-methoxymethoxy-9,10-seco-5,7,10⁽¹⁹⁾-cholestatriene 
• 143884-26-8 (5Z,7E,20R)-1α,3β-bis<(tert-butyldimethylsilyl)oxy>-20-formylmethyl-9,10-seco-5,7,10(19)-pregnatriene 
• 167893-02-9 1α,3β-bis[(t-butyldimethylsilyl)oxy]-26,26,26,27,27,27-hexafluoro-9,10-secocholesta-5(Z),7(E),10(19)-trien-23(R),25-diol 
• 167893-00-7 1α,3β-bis[(t-butyldimethylsilyl)oxy]-26,26,26,27,27,27-hexafluoro-23-oxo-9,10-secocholesta-5(Z),7(E),10(19)-trien-25-ol 
• 167892-99-1 1α,3β-bis[(t-butyldimethylsilyl)oxy]-20(S)-(n-propyl-23-oxo)-9,10-secopregna-5(Z),7(E),10(19)-triene 
• 85382-46-3 25,26,27-trisnorcholest-5-ene-1α,3β,24-triol 1,3-diacetate 
• 117467-20-6 (R)-4-((8S,9S,10R,13R,14S,17R)-3-Hydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)-pentanoic acid methyl ester 
• 85382-50-9 1α,3β,25-thihydroxy-26,26,26,27,27,27-hexafluorocholest-5-ene-24-yl phenyl sulfone 1,3-bis(triethylsilyl) ether 
• 85382-52-1 26,26,26,27,27,27-hexafluoro-1α,3β,25-triacetoxycholest-5,7-diene 
• 85382-51-0 1α,25-dihydroxy-26,26,26,27,27,27-hexafluorocholesterol triacetate 
• 89084-29-7 (1S,3R,8S,9S,10R,13R,14S,17R)-17-((R)-4-Benzenesulfonyl-6,6,6-trifluoro-5-hydroxy-1-methyl-5-trifluoromethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-1,3-diol 
• 89084-28-6 Acetic acid (1S,3R,8S,9S,10R,13R,14S,17R)-3-acetoxy-10,13-dimethyl-17-[(R)-1-methyl-4-(toluene-4-sulfonyloxy)-butyl]-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-1-yl ester 
• 85382-49-6 25,26,27-trisnor-1α,3β-bistriethylsiloxycholest-5-ene-24-yl phenyl sulfone 
• 85382-48-5 25,26,27-trisnor-1α,3β-diacetoxycholest-5-ene-24-yl phenyl sulfone 

Downstream Products

• 210907-40-7 (6Z)-(1R,3R)-26,26,26,27,27,27-hexafluoro-9,10-seco-5(10),6,8-cholestatriene-1β,3β,25-triol 
• 210907-37-2 (6Z)-(3R)-26,26,26,27,27,27-hexafluoro-9,10-seco-5⁽¹⁰⁾,6,8-cholestatriene-3,25-diol-1-one 

Relevant articles and documents

Synthesis and biological evaluations of A-ring isomers of 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3

The activated vitamin D3 derivative 26,27-F6-1α,25(OH)2D3 (2a), its three A-ring diastereomers (2b, 2c, 2d), and 5,6-trans isomer (2e) were prepared. Two analogues (2b, 2c) of these isomers were synthesized by a palladium catalyzed coupling reaction using vinyl bromide 5 and enynes (6a, 6b), which were derived from readily commercially available 2S-(+)-glycidyl p-toluenesulfonate 7, as a common starting material. Competitive vitamin D receptor (VDR) binding affinities of these diastereomers of 2a were evaluated. Interestingly, the stereochemical effects at C-1,3 of 2a were considerably more moderate than those of 1α,25(OH)2D3 (1). In particular, isomerization at the 5,6-double bond of 2a only slightly reduced VDR affinity, whereas 5,6-trans-1α,25(OH)2D3 had a significantly lower binding affinity than 1. Copyright (C) 2000 Elsevier Science Ltd.

Immunosuppressive agents

The invention relates to pharmaceutical compositions comprising at least one Vitamin D derivative and a method of using the pharmaceutical compositions in suppressing immune responses.