Alitretinoin

Base Information

• Chemical Name: Alitretinoin
• CAS No.: 5300-03-8
• Molecular Formula: C₂₀H₂₈O₂
• Molecular Weight: 300.441
• Hs Code.: 29162090
• European Community (EC) Number: 610-929-9,691-439-2
• NSC Number: 659772
• UNII: 1UA8E65KDZ
• DSSTox Substance ID: DTXSID6040404
• Wikipedia: Alitretinoin
• Wikidata: Q3611854
• NCI Thesaurus Code: C1574
• RXCUI: 81864
• Pharos Ligand ID: AAMX7XXM488N
• Metabolomics Workbench ID: 29045
• ChEMBL ID: CHEMBL705
• Mol file: 5300-03-8.mol

Synonyms:9 cis Retinoic Acid;9-cis-retinoic acid;9cRA compound;alitretinoin;BAL4079;Panretin;Toctino

Chemical Property of Alitretinoin

Chemical Property:

• Appearance/Colour: Pale yellow solid
• Melting Point: 189-191 °C
• Boiling Point: 462.801 °C at 760 mmHg
• PKA: 4.73±0.33(Predicted)
• Flash Point: 350.596 °C
• PSA: 37.30000
• Density: 1.011 g/cm³
• LogP: 5.60260
• Storage Temp.: −20°C
• Sensitive.: Moisture & Light Sensitive
• Solubility.: Acetonitrile (Very Slightly), Chloroform (Slightly), DMSO (Slightly), Ethanol (
• Water Solubility.: Soluble in chloroform (50 mg/ml), DMSO (~25 mg/ml), ethanol (25 mg/ml), and acetone (25 mg/ml). Insoluble in water.
• XLogP3: 6.3
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 5
• Exact Mass: 300.208930132
• Heavy Atom Count: 22
• Complexity: 567

Purity/Quality:

98% ^*data from raw suppliers

9-cis Retinoic Acid ^*data from reagent suppliers

Safty Information:

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

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1=C(C(CCC1)(C)C)C=CC(=CC=CC(=CC(=O)O)C)C
• Isomeric SMILES: CC1=C(C(CCC1)(C)C)/C=C/C(=C\C=C\C(=C\C(=O)O)\C)/C
• Recent ClinicalTrials: Follow-up Efficacy and Safety of Alitretinoin in Severe Chronic Hand Dermatitis
• Recent EU Clinical Trials: A 24 week, randomised, assessor blinded, active-controlled, parallel group, phase 3, 2 arm trial to compare the efficacy and safety of delgocitinib cream 20 mg/g twice-daily with alitretinoin capsules once-daily in adult participants with severe chronic hand eczema
• Description: Alitretinoin was introduced in the US for the topical treatment of cutaneous lesions in patients with Kaposi's sarcoma (KS), the most frequent malignancy observed in AIDS patients. It is a derivative of 9-cis-retinoic acid (9- cis-RA) identified as an endogenous hormone in mammalian tissues. Alitretinoin binds to all isoforms of the intracellular retinoid X (RXR) and retinoid A (RAR) receptors thus inducing cell differentiation, increasing cell apoptosis and inhibiting cellular proliferation in experimental models of human cancer. In an international phase III trial in patients with KS, 42% of 82 patients treated with 0.1% gel formulation experienced complete or partial responses cf 7% for controls. Alitretinoin is the first topical therapy for KS and is expected to be a new option to its traditional management.
• Uses: 9-cis-Retinoic acid is a vitamin A analog that inhibits cell proliferation and induces cell differentiation. 9-cis-Retinoic acid is an inhibitor of Cox-2 and an activator of RAR α, RAR β, RAR γ and RXR. An endogenous retinoic acid isomer, which is capable of binding to both retinoic acid receptors (RAR) and retinoid X receptors (RXR). A biologically active ligand for members of the RAR and RXR subfamilies, implying that it may play a critical role in regulating retinoid-responsive pathways.
• Indications: Alitretinoin (Panretin) is a naturally occurring endogenous retinoid that binds to and activates all known retinoid receptors (both RARs and RXRs). It is approved for the topical treatment of cutaneous lesions of Kaposi’s sarcoma. Most patients have local irritation while using alitretinoin gel; however, the irritation rarely necessitates discontinuation of therapy.

Technology Process of Alitretinoin

There total 80 articles about Alitretinoin 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: 100.0%

ethyl (2E,4E,6Z,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoate (86708-67-0,24519-09-3) → 9-cis-retinoic acid (302-79-4,3555-80-4,4759-48-2,5300-03-8,5352-74-9,68070-34-8,68070-35-9,97950-17-9,98462-64-7,124510-04-9)

Guidance literature:

With potassium hydroxide; In ethanol;

DOI:10.1055/s-2001-14908

Reference yield: 98.0%

ethyl (2E,4E,6Z,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoate (86708-67-0,24519-09-3) + potassium hydroxide → 9-cis-retinoic acid (302-79-4,3555-80-4,4759-48-2,5300-03-8,5352-74-9,68070-34-8,68070-35-9,97950-17-9,98462-64-7,124510-04-9)

Guidance literature:

With water; In ethanol; at 50 ℃;

DOI:10.1039/b813760a

Reference yield: 83.0%

(2E,4E,6Z,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraenoic acid ethyl ester (24519-09-3) → 9-cis-retinoic acid (302-79-4,3555-80-4,4759-48-2,5300-03-8,5352-74-9,68070-34-8,68070-35-9,97950-17-9,98462-64-7,124510-04-9)

Guidance literature:

With potassium hydroxide; In ethanol; at 70 ℃; for 3h;

DOI:10.1021/jo952189g

upstream raw materials:

ethyl 3-methylbut-2-enoate

(2Z,4E)-3-methyl-5-[2,6,6-trimethylcyclohex-1-enyl]penta-2,4-dienal

9,13-di-cis-retinoic acid

diethyl 3-(ethoxycarbonyl)-3-methylprop-2-en-yl phosphate

Downstream raw materials:

9-cis-retinoic acid

retinoyl chloride

13-cis-retinoic acid

potassium all-trans-retinoate

Refernces

• 1、 Kahremany, Shirin,Sander, Christopher Lane,Tochtrop, Gregory P.,Kubas, Adam,Palczewski, Krzysztof. "Z -isomerization of retinoids through combination of monochromatic photoisomerization and metal catalysis". supporting information. p. 8125 - 8139. Retrieved 2019/09/19.
• 2、 -. "Stereospecific synthesis process for tretinoin compounds". Page/Page column 10; 11. . Retrieved 2014/09/29.