Acitretin CAS 55079-83-9
Introduction：Basic information about Acitretin CAS 55079-83-9, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Acitretin Basic information
| Product Name: | Acitretin |
| Synonyms: | (all-e)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraen;9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid;(ALL-E)-9-(4-METHOXY-2,3,6-TRIMETHYLPHENYL)-3,7-DIMETHYL-2,4,6,8-NONATETRAENOIC ACID;ACITRETIN;SORIATANE;NEOTIGASON;Neotigason, Soriatane;Acritretin |
| CAS: | 55079-83-9 |
| MF: | C21H26O3 |
| MW: | 326.43 |
| EINECS: | 259-474-4 |
| Product Categories: | Inhibitors;API;Aromatics;Soriatane;Active Pharmaceutical Ingredients;Various Metabolites and Impurities;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;Retinoids;Intracellular receptor |
| Mol File: | 55079-83-9.mol |
Acitretin Chemical Properties
| Melting point | 228-230°C |
| Boiling point | 404.46°C (rough estimate) |
| density | 1.1348 (rough estimate) |
| refractive index | 1.4700 (estimate) |
| storage temp. | -20°C |
| solubility | Practically insoluble in water, sparingly soluble in tetrahydrofuran, slightly soluble in acetone and in ethanol (96 per cent), very slightly soluble in cyclohexane. |
| pka | 4.72±0.33(Predicted) |
| form | powder |
| color | Light yellow to yellow |
| λmax | 352nm(MeOH)(lit.) |
| Merck | 14,112 |
| Stability: | LIGHT SENSITIVE |
| InChI | InChI=1S/C21H26O3/c1-14(8-7-9-15(2)12-21(22)23)10-11-19-16(3)13-20(24-6)18(5)17(19)4/h7-13H,1-6H3,(H,22,23)/b9-7+,11-10+,14-8+,15-12+ |
| InChIKey | IHUNBGSDBOWDMA-AQFIFDHZSA-N |
| SMILES | C(O)(=O)/C=C(\C)/C=C/C=C(\C)/C=C/C1=C(C)C=C(OC)C(C)=C1C |
| CAS DataBase Reference | 55079-83-9(CAS DataBase Reference) |
Safety Information
| Hazard Codes | T,N |
| Risk Statements | 61-36/38-50/53 |
| Safety Statements | 53-26-45-60-61-37/39 |
| RIDADR | UN 3077 9/PG 3 |
| WGK Germany | 3 |
| RTECS | RA8460000 |
| F | 8-10-21 |
| HazardClass | 9 |
| PackingGroup | III |
| HS Code | 2918992090 |
| Storage Class | 6.1C - Combustible, acute toxic Cat.3 toxic compounds or compounds which causing chronic effects |
| Hazard Classifications | Aquatic Acute 1 Aquatic Chronic 1 Eye Irrit. 2 Repr. 1B Skin Irrit. 2 |
| Hazardous Substances Data | 55079-83-9(Hazardous Substances Data) |
| Toxicity | LD50 i.p. in mice (mg/kg): >4000 (1 day), 700 (10 days), 700 (20 days) (Bollag, 1978) |
| Description | Acitretin is the free acid form of etretinate useful in the treatment of severe psoriasis and other disorders of keratinization. Although the two compounds have virtually the same efficacy and teratogenic side-effects, acitretin is advantageous for child-bearing women, as its shorter half-life reduces the necessary contraception period from two years to only one month after treatment ceases. |
| Chemical Properties | Crystalline Solid |
| Originator | Hoffmann-La Roche (Switzerland) |
| Uses | A synthetic retinoid which is the major metabolite of etretinate (E938000). |
| Uses | antipsoriatic;binds to nuclear receptors that regulate gene transcription |
| Uses | Acitretin, a retinoid that binds to nuclear receptors and regulates gene expression, is a potent activator of the α-secretase ADAM10 gene expression and apoptosis inducer via the CD95 signalling pathway. Acitretin is a systemic retinoid drug used in the treatment of severe psoriasis. |
| Indications | Unlike isotretinoin, acitretin (Soriatane) is not primarilysebosuppressive. Rather, it promotes normalizationof dysregulated keratinocyte proliferative activity in theepidermis and is also antiinflammatory. Oral absorptionis optimal when acitretin is taken with a fatty meal; peaklevels are reached approximately 3 hours after ingestion,while steady-state plasma levels are achieved afterapproximately 3 weeks of daily dosing. The mean terminalelimination half-life of the parent compound is 49hours. However, when consumed with ethanol, acitretinmay be transesterified to form etretinate, a retinoid thatis stored in adipose tissue, resulting in a much longerhalf-life (3–4 months or longer). |
| Definition | ChEBI: All-trans-acitretin is an acitretin, a retinoid and an alpha,beta-unsaturated monocarboxylic acid. It has a role as a keratolytic drug. |
| Manufacturing Process | 228 g of 5-(4-methoxy-2,3,6-trimethyl-phenyl)-3-methyl-penta-2,4-diene-1-triphenylphosphonium bromide was added under nitrogen to 910 ml ofdimethylformamide and treated at 5-10°C within 20 min. with 17.5 g of asuspension of sodium hydride (about 50% by weight) in mineral oil. Themixture was stirred for 1 hour at about 10°C, then 61.8 g of 3-formylcrotonicacid butyl ester was added dropwise at 5-8°C, a mixture was heated for 2hours at 65°C, subsequently introduced into 8 L of ice-water, then was added300 g of sodium chloride, and the mixture thoroughly extracted with a total18 L of hexane. The extract was washed 5 times with 1 L of methanol/water(6:4 parts by volume) each time and 2 times with 1.5 L water each time,dried over sodium sulphate and evaporated under reduced pressure to leave9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-nona-2,4,6,8-tetraen-1-oicacid butyl ester, m.p. 80-81°C. 125.8 g of this ester was introduced into 2 L of abs. ethanol and treated witha solution of 125.6 g of hydroxide in 195 ml of water. The mixture was heated to boiling under nitrogen gassing for 30 minutes, then cooled, introduced into10 L of ice-water and, after the addition of about 240 ml of conc. hydrochloricacid (pH 2-4), thoroughly extracted with total 9 L methylene chloride. Extractis washed with about 6 L water to neutrality, dried over calcium chloride andevaporated under reduced pressure. The residue is taken up in 700 ml ofhexane. The precipitated 9-(4-methoxy-2,3,6-trimethyl-phenyl)-3,7-dimethylnona-2,4,6,8-tetraen-1-oic acid melts at 228-230°C. |
| Brand name | Soriatane (Connetics);Neotigason (r) 10;Neotigason roche 10 mg;Neotigason sauter kapsein 25 mg. |
| Therapeutic Function | Antipsoriatic |
| World Health Organization (WHO) | Acitretin, a retinol derivative, was introduced in 1989 for thetreatment of severe psoriasis. By the end of 1990, acitretin was confirmed to bemetabolized in part to etretinate. Marketing authorization was suspendedtemporarily in France while the product information was modified to conform to therecommendations issued by the Committee for Proprietary Medicinal Products ofthe European Communities. Acitretin remains registered in several countries. Seealso WHO comment for etretinate. |
| General Description | Pharmaceutical secondary standards for application in quality control, provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards. Acitretin is a major metabolite of etretinate and belongs to the class of retinoid and is typically used for treating psoriasis. Acitretin inhibits excessive cell growth and keratinisation which are the major symptoms of psoriasis, therefore reducing plaque formation and scaling. |
| Biochem/physiol Actions | Synthetic retinoid that is a metabolite of etretinate. Preferentially binds to cellular retinoic acid binding proteins (CRABPs). |
| Mechanism of action | Acitretin(Soriatane) is a synthetic derivative of vitamin A that is particularly effective intreating the pustular and erythrodermic forms of psoriasis. It is the main metaboliteof etretinate; ingestion of alcohol with acitretin increases the amount of detectableetretinate. It is accumulated in fatty tissue with a prolonged elimination half-life ofapproximately 120 days. Most patients show improvement within 2 to 4 weeks,although some patients may need as long as 6 months of therapy before a responseis noted. |
| Pharmacology | Like other systemic retinoids, acitretin is a seriousteratogen and should not be prescribed for women ofchildbearing potential unless no acceptable alternativeis available and the patient has acknowledged in writingthat she understands the need to use two effectiveforms of contraception during therapy and for 3 yearsfollowing discontinuation of therapy. Because of themuch longer half-life of etretinate, which may beformed when ethanol is ingested with acitretin, femalepatients of childbearing potential must also agree not toingest alcohol during treatment and for 2 months followingits discontinuation. Other toxicities are similarto those of isotretinoin; they include cutaneous irritationand inflammation, bone and joint pain, hyperlipidemia,hepatic enzyme elevation, and tendinous andligamentous calcifications.Alopecia (hair loss) may alsooccur in some patients. |
| Clinical Use | Acitretin is most useful for the treatment of severepsoriasis, particularly the pustular and erythrodermicvariants. Psoriatic nail changes and arthritis also may respond.Combining the drug with ultraviolet light therapy(Re-UVB, in the case of ultraviolet B radiation, orRe-PUVA, with psoralen plus ultraviolet A radiation)permits the use of lower doses of both acitretin and ultravioletradiation. Other conditions for which the drugmay be especially useful include congenital and acquiredhyperkeratotic disorders, such as the ichthyosesand palmoplantar keratodermas, and severe lichenplanus. |
| Side effects | Side effects are dose dependent and include elevation of triglycerides,hepatitis, hair loss, thinning of the nails, cheilitis, xerosis, and stickiness ofthe skin. Gemfibrozil (300 mg b.i.d.) corrects elevated lipid levels on thistherapy. |
| Veterinary Drugs and Treatments | Acitretin may be useful in the treatment of canine lamellar ichthyosis,solar-inducedprecancerous lesions in Dalmatians or bullTerriers, actinic keratoses, squamous cell carcinomas,and intracutaneouscornifying epitheliomas (multiple keratoacanthomas). While the drug has provided effective treatment of idiopathicseborrhea (particularly in cocker spaniels), it is not effective in treatingthe ceruminous otitis that may also be present. Results havebeen disappointingin treating idiopathic seborrheas seen in bassethounds and West Highland terriers. Acitretin’s usage in cats is very limited, but etretinate has shownsome usefulness in treating paraneoplasticactinic keratosis, solarinducedsquamous cell carcinoma and Bowen’s Disease in thisspecies. |
| target | HIV | gp120/CD4 |
| Drug interactions | Potentially hazardous interactions with other drugs Alcohol: increased risk of teratogenicity in women. Antibacterials: possibly increased risk of benign intracranial hypertension with tetracyclines - avoid concomitant use. Anticoagulants: possible antagonism of the anticoagulant effect of coumarins. Cytotoxics: increased concentration of methotrexate (also increased risk of hepatotoxicity) - avoid concomitant use. Vitamin A: risk of hypervitaminosis - avoid concomitant use. |
| Metabolism | Acitretin is metabolised by isomerisation into its 13-cis isomer (cis acitretin), which is also a teratogen, by glucuronidation and cleavage of the side chain. Acitretin is excreted entirely in the form of its metabolites, in approximately equal parts via the kidneys and the bile. |
Acitretin Preparation Products And Raw materials
| Raw materials | Triethyl orthoformate-->Phosphoric acid-->Ethoxyethyne-->TOLUALDEHYDES-->THREE METHYL BENZENE-->3-Formyl crotonic acid butyl ester-->Sodium hydride-->Triphenylphosphine hydrobromide |
