Calcipotriene CAS 112965-21-6
Introduction：Basic information about Calcipotriene CAS 112965-21-6, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Calcipotriene Basic information
| Product Name: | Calcipotriene |
| Synonyms: | 5z,7e,22e,24s)--bet;9,10-secochola-5,7,10(19),22-tetraene-1,3,24-triol,24-cyclopropyl-,(1-alpha,3;dovonex;mc903;CALCIPOTRIOL,CALCIPOTRIENE;Calciptriol, MC-903, Daivonex, Dovonex, Psorcutan;(1S,3S,5Z)-5-[(2E)-2-[(1R,3aR,7aR)-1-[(E,2S)-5-Cyclopropyl-5-hydroxy-pent-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidene-cyclohexane-1,3-diol;Calcipotriene |
| CAS: | 112965-21-6 |
| MF: | C27H40O3 |
| MW: | 412.6 |
| EINECS: | 601-218-4 |
| Product Categories: | Isotope Labelled Compounds;Intermediates & Fine Chemicals;Pharmaceuticals;API;chemical |
| Mol File: | 112965-21-6.mol |
Calcipotriene Chemical Properties
| Melting point | 166-168°C |
| Boiling point | 582.0±50.0 °C(Predicted) |
| density | 1.12±0.1 g/cm3(Predicted) |
| storage temp. | Desiccate at -20°C |
| solubility | DMSO: soluble15mg/mL, clear |
| form | powder |
| pka | 14.29±0.20(Predicted) |
| color | White to off-white |
| Stability: | Light and Temperature Sensitive, Light And Temperature Sensitive |
| InChIKey | LWQQLNNNIPYSNX-HCHVWAPNSA-N |
| SMILES | [C@@H]1(O)C/C(=C/C=C2\CCC[C@@]3(C)[C@@]\2([H])CC[C@@H]3[C@H](C)/C=C/[C@H](C2CC2)O)/C(=C)[C@@H](O)C1 |
| CAS DataBase Reference | 112965-21-6(CAS DataBase Reference) |
Safety Information
| Hazard Codes | Xi |
| Risk Statements | 36/37/38 |
| Safety Statements | 26 |
| RIDADR | UN 2811 6.1 / PGIII |
| WGK Germany | 3 |
| HS Code | 2906195000 |
| Storage Class | 6.1A - Combustible acute toxic Cat. 1 and 2 very toxic hazardous materials |
| Hazard Classifications | Acute Tox. 1 Dermal Acute Tox. 2 Oral Eye Irrit. 2 Repr. 2 Skin Sens. 1B STOT RE 1 |
| Toxicity | dog,LD50,skin,> 1500ug/kg (1.5mg/kg),BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)MUSCULOSKELETAL: OTHER CHANGESGASTROINTESTINAL: NAUSEA OR VOMITING,Journal of Toxicological Sciences. Vol. 21(Suppl, |
| Description | Calcipotriene also known as Calcipotriol, is a topical vitaminD3 derivative effective in the treatment of psoriasis vulgaris. The drug acts by binding to vitamin D3 receptors in the skin keratinocytes, producing an elevation in cell differentiation and a reduction in cell proliferation. Although its efficacy is comparable to calcitriol, calcipotriol exhibits at least 100 times less effect on calcium metabolism in rats. |
| Chemical Properties | White Crystalline Solid |
| Originator | Leo Denmark (Denmark) |
| Uses | Calcipotriene is an antipsoriatic that is a vitamin D3 analogue with low calcemic activity. It works by regulating the production and growth of skin cells. In the United States, this drug was first marketed under the trade name Dovonex and is used mainly for the treatment of psoriasis. It is one of the most effective non glucocorticoid topical drugs for the treatment of localized psoriasis.This drug has many off-label applications that are alternative therapies for many dermatologic diseases. |
| Indications | Calcipotriene (Dovonex), a synthetic vitamin D3 derivative,is indicated for the treatment of moderate plaquepsoriasis. Its mechanism of action is unknown, althoughit competes for calcitriol receptors on keratinocytes andnormalizes differentiation. It also has a variety of immunomodulatoryeffects in the skin. Although the drugcan cause local irritation, the most serious toxicities arehypercalciuria and hypercalcemia, which are usually reversible. |
| Definition | ChEBI: Calcipotriol is a seco-cholestane that is 26,27-cyclo-9,10-secocholesta-5,7,10,22-tetraene carrying additional hydroxy substituents at positions 1, 3 and 24. It is used (as its hydrate) in combination with betamethasone dipropionate, a corticosteroid, for the topical treatment of plaque psoriasis in adult patients. It has a role as a drug allergen and an antipsoriatic. It is a member of cyclopropanes, a secondary alcohol, a triol, a hydroxy seco-steroid and a seco-cholestane. |
| Preparation | A convergent approach for the total synthesis of calcipotriol (brand name: Dovonex), a proven Vitamin D analog used for the treatment of psoriasis, and medicinally relevant synthetic analogs is described. A Synthesis of calcipotriol via a Key Electroreductive Cross-coupling Approach Calcipotriol is currently the most successful VitD analog and is prescribed for the treatment of psoriasis, an autoimmune skin disease. |
| Manufacturing Process | (1S,3R)-Bis-(t-butyldimethylsilyloxy)-(20S)-formyl-9,10-secopregna(5E,7E,10(19))triene (Calverley Tetrahedron 43.4609 (1967) and (cyclopropyl)(tri-phenylphoshoranylidene)ketone are stirred in dimethyl sulfoxide undernitrogen. The reaction mixture is then diluted at room temperature with ethylacetate and washed with common salt solution. The organic phase is dried onsodium sulfate and filtered. After removal of the solvent, the residue is filteredwith toluene through silica gel. Evaporation of the solvent and gradientchromatography (toluene/hexane (1:1)-toluene) of the residue on silica gelyield (5E,7E,22E),(1S,3R)-1,3-bis-(t-butyldimethylsilyloxy)-24-cyclopropyl-9,10-secochola-5,7,10(19),22-tetraene-24-one. (5E,7E,22E),(1S,3R)-1,3-Bis-(t-butyldimethylsilyloxy)-24-cyclopropyl-9,10-secochola-5,7,10(19),22-tetraene-24-one in tetrahydrofuran and methanol aremixed with a 0.4 M methanol CeCl3·7H2O solution. Sodium borohydride isadded by portions under nitrogen with ice cooling. The suspension is stirredwith ice cooling and then put into ice/common salt solution. The aqueousphase is extracted with ethyl acetate, the organic phase is washed neutralwith water and dried on sodium sulfate. Filtration and removal of the solventyield oil. By chromatography on silica gel with ethyl acetate/hexane (1:9). The(5E,7E,22E),(1S,3R,24S)-1,3-bis-(t-butyldimethylsilyloxy)-24-cyclopropyl-9,10-secochola-5,7,10(19),22-tetraene-24-ol is obtained. (5E,7E,22E),(1S,3R,24S)-1,3-Bis-(t-butyldimethylsilyloxy)-24-cyclopropyl-9,10-secochola-5,7,10(19),22-tetraene-24-ol is dissolved in toluene and afteraddition of anthracene and 1 drop of triethylamine it is radiated at roomtemperature with a high pressure mercury vapor lamp (Heraeus TQ 150)through Pyrex glass. The reaction mixture is concentrated by evaporation andthe residue a mixture of (5Z,7E,22E),(1S,3R,24S)-1,3-bis-(t-butyldimethylsilyloxy)-24-cyclopropyl-9,10-secochola-5,7,10(19),22-tetraene-24-ol and anthracene - is directly reacted with tetrabutylammonium fluoride. (5Z,7E,22E),(1S,3R,24S)-1,3-Bis-(t-butyldimethylsilyloxy)-24-cyclopropyl-9,10-secochola-5,7,10(19),22-tetraene-24-ol in tetrahydrofuran is kept with a1 M solution of tetrabutylammonium fluoride in tetrahydrofuran undernitrogen. For working up, the cooled reaction mixture is poured into coldsodium bicarbonate solution and then extracted with ethyl acetate. Afterdrying of the organic phase on sodium sulfate, filtration and evaporation ofthe solvent yields a resin-like residue. Chromatography on silica gel with ethylacetate/hexane (2:1) yields (5Z,7E,22E),(1S,3R,24S)-24-cyclopropyl-9,10-secochola-5,7,10(19),22-tetraene-1,3,24-triol. |
| Brand name | Dovonex (Leo);Daivonex. |
| Therapeutic Function | Antipsoriatic |
| Biological Activity | Vitamin D 3 analog that displays minimal effects on calcium homeostasis. Regulates cell differentiation and proliferation; exhibits antiproliferative activity against human HL-60, HL60/MX2, MCF-7, T47D, SCC-25 and mouse WEHI-3 cancer cell lines. |
| Biochem/physiol Actions | Calcipotriol, a synthetic derivative of calcitriol or Vitamin D, is used in the treatment of psoriasis and marketed under the trade name Dovonex. It has comparable affinity with calcitriol (Vit. D) for the Vitamin D receptor (VDR), while being less than 1% as active as the calcitriol in regulating calcium metabolism. VDR belongs to the steroid/thyroid receptor superfamily, and is found on the cells of many different tissues including the thyroid, bone, kindney, and T cells of the immune system. Binding of calcipotriol to the VDR modulates the T cells gene transcription of cell differentiation and proliferation-related genes. |
| Pharmacology | Calcipotriene (Dovonex) enhances the effectiveness of ultraviolet B(UVB) but also increases photosensitivity in UVB-treated patients. Ultravioletlight, 6% salicylic acid, 12% lactic acid, hydrocortisone valerate 0.2% ointment,and tazarotene (Tazorac) gel degrade calcipotriene (Dovonex). Halobetasolointment and 5% tar gel are compatible with Calcipotriene (Dovonex).A British study found calcipotriene (Dovonex) to be safe and effective in apediatric population over the age of 3, although it is not approved by the FDA. |
| Side effects | Possible side effects include: severe burning, stinging, skin rash, or other irritation after applying the medicine; worsening of your skin condition; high calcium levels--confusion, tiredness, nausea, vomiting, loss of appetite, constipation, increased thirst or urination, weight loss; mild skin irritation; skin rash; itching. |
| storage | Store at -20°C |
Calcipotriene Preparation Products And Raw materials
| Raw materials | Selenium dioxide-->tert-Butyldimethylsilyl chloride-->4-METHYLMORPHOLINE-4-OXIDE SOLUTION-->Tetrabutylammonium fluoride-->Anthracene-->Cyclopropylmagnesium bromide-->Triethylamine-->Sodium borohydride-->CERIUM(III) CHLORIDE-->PHOSPHINE OXIDE, [2-[3,5-BIS [[(1,1-DIMETHYLETHYL) DIMETHYLSILY]OXY]-2-METHYLENECYCLOHEXYLIDENE]ETHYL]DIPHENYL-,[3S-(1Z,3A,5B0)]-->(1S,4R,E)-4-((1R,3aS,7aR,E)-4-((Z)-2-((3S,5R)-3,5-bis((tert-butyldiMethylsilyl)oxy)-2-Methylenecyclohexylidene)ethylidene)-7a-Methyloctahydro-1H-inden-1-yl)-1-cyclopropylpent-2-en-1-ol-->(5E)-Calcipotriene |
| Preparation Products | 24R-Calcipotriol |
