Acitretin

Base Information

• Chemical Name: Acitretin
• CAS No.: 55079-83-9
• Molecular Formula: C₂₁H₂₆O₃
• Molecular Weight: 326.436
• Hs Code.: 2918992090
• European Community (EC) Number: 259-474-4
• UNII: LCH760E9T7
• DSSTox Substance ID: DTXSID6022553
• Nikkaji Number: J23.289K,J261.795A
• Wikipedia: Acitretin
• Wikidata: Q341500
• NCI Thesaurus Code: C985
• RXCUI: 16818
• Pharos Ligand ID: KZFPFPZVL7XB
• Metabolomics Workbench ID: 144476
• ChEMBL ID: CHEMBL1131
• Mol file: 55079-83-9.mol

Synonyms:13-cis-Acitretin;Acitretin;Acitretin, (Z,E,E,E)-Isomer;Etretin;Isoacitretin;Isoetretin;Neotigason;Ro 10-1670;Ro 101670;Ro 13-7652;Ro 137652;Ro-10-1670;Ro-13-7652;Ro101670;Ro137652;Soriatane

Chemical Property of Acitretin

Chemical Property:

• Appearance/Colour: crystalline solid
• Vapor Pressure: 1.08E-11mmHg at 25°C
• Melting Point: 228-230 °C
• Refractive Index: 1.569
• Boiling Point: 521.3 °C at 760 mmHg
• PKA: 4.72±0.33(Predicted)
• Flash Point: 180.3 °C
• PSA: 46.53000
• Density: 1.051 g/cm³
• LogP: 5.16700
• Storage Temp.: 2-8°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.
• XLogP3: 6.1
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 6
• Exact Mass: 326.18819469
• Heavy Atom Count: 24
• Complexity: 539

Purity/Quality:

99.5% ^*data from raw suppliers

Acitretin ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T, N
• Hazard Codes: T,N
• Statements: 61-36/38-50/53
• Safety Statements: 53-26-45-60-61-37/39

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Dermatologic Agents
• Canonical SMILES: CC1=CC(=C(C(=C1C=CC(=CC=CC(=CC(=O)O)C)C)C)C)OC
• Isomeric SMILES: CC1=CC(=C(C(=C1/C=C/C(=C/C=C/C(=C/C(=O)O)/C)/C)C)C)OC
• Recent ClinicalTrials: Outcomes With Treatment and Withdraw of Secukinumab in Patients With Plaque Psoriasis
• Recent EU Clinical Trials: The induction of apoptosis by anti-psoriatic treatments
• 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.
• Uses: A synthetic retinoid which is the major metabolite of etretinate (E938000). antipsoriatic;binds to nuclear receptors that regulate gene transcription 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 primarily sebosuppressive. Rather, it promotes normalization of dysregulated keratinocyte proliferative activity in the epidermis and is also antiinflammatory. Oral absorption is optimal when acitretin is taken with a fatty meal; peak levels are reached approximately 3 hours after ingestion, while steady-state plasma levels are achieved after approximately 3 weeks of daily dosing. The mean terminal elimination half-life of the parent compound is 49 hours. However, when consumed with ethanol, acitretin may be transesterified to form etretinate, a retinoid that is stored in adipose tissue, resulting in a much longer half-life (3–4 months or longer).
• Therapeutic Function: Antipsoriatic
• Clinical Use: Acitretin is most useful for the treatment of severe psoriasis, particularly the pustular and erythrodermic variants. Psoriatic nail changes and arthritis also may respond. Combining the drug with ultraviolet light therapy (Re-UVB, in the case of ultraviolet B radiation, or Re-PUVA, with psoralen plus ultraviolet A radiation) permits the use of lower doses of both acitretin and ultraviolet radiation. Other conditions for which the drug may be especially useful include congenital and acquired hyperkeratotic disorders, such as the ichthyoses and palmoplantar keratodermas, and severe lichen planus.
• 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.

Technology Process of Acitretin

There total 27 articles about Acitretin which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 95.0%

13-cis-Acitretin (69427-46-9,1067630-53-8,419534-31-9) → acitretin (54757-46-9,69427-46-9,69427-47-0,55079-83-9,1067630-53-8,419534-31-9)

Guidance literature:

With iodine; In diethyl ether; benzene; at 20 ℃; for 8h;

Reference yield: 94.0%

3,7-dimethyl-7-hydroxy-9-(4-methoxy-2,3,6-trimethylphenyl)-nona-2,4,8-trienoic acid → acitretin (54757-46-9,69427-46-9,69427-47-0,55079-83-9,1067630-53-8,419534-31-9)

Guidance literature:

With iodine; toluene-4-sulfonic acid; 1.) methylene dichloride, reflux, 15 min; 2.) diethyl ether/benzene, rt, 7 h;

DOI:10.1016/0040-4020(95)00114-N

Reference yield: 88.5%

isobutyl ester of (all-E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoic acid → acitretin (54757-46-9,69427-46-9,69427-47-0,55079-83-9,1067630-53-8,419534-31-9)

Guidance literature:

With potassium hydroxide; In ethanol; for 0.75h; Heating;

DOI:10.1007/BF02218431

upstream raw materials:

13-cis-Acitretin

2-[(2E,4E,6E)-7-(4-Methoxy-2,3,6-trimethyl-phenyl)-1,5-dimethyl-hepta-2,4,6-trienylidene]-malonic acid

methyl ethyl β-methylglutaconate

5-(4-methoxy-2,3,6-trimethylphenyl)-3-methyl-2(E),4(E)-pentadien-1-al

Downstream raw materials:

13-cis-Acitretin

1-[9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoyl]imidazole

9-(4-methoxy-2,3,6-trimethyl-phenyl)-3,7-dimethyl-nona-2,4,6,8-tetraen-1-oic acid allyl ester

succinimidyl acitretinate

Refernces

• 1、 -. "Novel isomerization method of acitretin". Paragraph 0059-0070. . Retrieved 2018/10/19.
• 2、 -. "STEREOSPECIFIC SYNTHESIS PROCESS FOR TRETINOIN COMPOUNDS". Paragraph 0045; 0046. . Retrieved 2014/04/03.