Isotretinoin

Base Information

• Chemical Name: Isotretinoin
• CAS No.: 4759-48-2
• Molecular Formula: C20H28O2
• Molecular Weight: 300.441
• Hs Code.: 29362100
• European Community (EC) Number: 225-296-0
• NSC Number: 758156
• UNII: EH28UP18IF
• DSSTox Substance ID: DTXSID4023177
• Nikkaji Number: J1.313.475H,J8.772F
• Wikipedia: Isotretinoin
• Wikidata: Q287029
• NCI Thesaurus Code: C603
• RXCUI: 6064
• Pharos Ligand ID: AAM1WQZXPL2C
• Metabolomics Workbench ID: 29044
• ChEMBL ID: CHEMBL547
• Mol file: 4759-48-2.mol

Synonyms:13 cis Retinoic Acid;13-cis-Retinoic Acid;Accutane;Isotretinoin;Isotretinoin Zinc Salt, 13 cis Isomer;Isotretinoin Zinc Salt, 13-cis-Isomer;Ro 4 3780;Ro 4-3780;Ro 43780;Roaccutane

Chemical Property of Isotretinoin

Chemical Property:

• Appearance/Colour: yellowish crystalline powder
• Vapor Pressure: 7.55E-10mmHg at 25°C
• Melting Point: 172-175 °C(lit.)
• Refractive Index: 1.4800 (estimate)
• Boiling Point: 462.8 °C at 760 mmHg
• PKA: 4.76±0.33(Predicted)
• Flash Point: 350.6 °C
• PSA: 37.30000
• Density: 1.011 g/cm³
• LogP: 5.60260
• Storage Temp.: −20°C
• Solubility.: Practically insoluble in water, soluble in methylene chloride, slightly soluble in ethanol (96 per cent). It is sensitive to air, heat and light, especially in solution. Carry out all operations as rapidly as possible and avoid exposure to actinic light; use freshly prepared solutions.
• Water Solubility.: insoluble
• 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

Isotretinoin ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T
• Hazard Codes: T
• Statements: 61-36/37/38-20/21/22
• Safety Statements: 53-26-36/37/39-45-37/39

MSDS Files:

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Dermatologic Agents
• 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: Effect of Systemic Isotretinoin on Serum Irisin Level in Acne Vulgaris Patients
• Recent EU Clinical Trials: A randomized, partially blinded, parallel study to evaluate the effects of nacystelyn in combination with isotretinoin in the treatment of recalcitrant acne vulgaris.
• Recent NIPH Clinical Trials: Phase 2b study of combined immunotherapy with dinutuximab, interleukin-2, and G-CSF for high risk neuroblastoma
• Uses: Isotretinoin is a vitamin A class drugs that It can rapidly and strongly inhibit the cell proliferation and differentiation process of skin glands cells. It has a high effect on severe nodular cystic acne. This product has a high gastrointestinal absorption, but invalid for topical administration. It is used for treating severe acnes which cannot be treated by other drugs. It also has some effects on treating cystic acne, the party of acne, rosacea, ichthyosis, follicular keratosis and pityriasis red hair and other skin diseases. isotretinoin is a retinoid derivative with improved bioavailability and percutaneous absorption for acne treatment products. Presently being studied in conjuction with the treatment of photoaged skin.
• Indications: 1. Isotretinoin should be the primary choice for treatment of refractory acne, especially for severe nodular, cystic, inflammatory acne patients to whom conventional therapy is ineffective. 2. Generalized Plana or verrucous epidermal dysplasia; 3. Skin disease of abnormal cornification; 4. Cutaneous lupus erythematosus; 5. lichen planus, atrophic lichen sclerosis. Isotretinoin (Accutane) alters keratinization in the acroinfundibulum of sebaceous glands and shrinks them, thereby reducing sebum excretion and comedogenesis. These features underlie its usefulness in acne vulgaris, since sebum secretion is a hallmark of acneprone skin. Furthermore, the drug has antiinflammatory activity.
• Drug Interactions: 1. Combination with warfarin can enhance the latter one’s effect. 2. Combination together with Avi A ester, vitamin A acetate or Vitamin A acid can increase the incidence and severity of adverse reactions. 3. Combination with methotrexate can increase the blood concentration of the latter one, and thus increasing the damage to the liver. 4. Combination with tetracycline can lead to brain and cause pseudo-tumor in brain and cause benigh hypertension. Clinical manifestations of hypertension are accompanied by headache, dizziness and visual disturbances. 5. Combination with carbamazepine results in decreased plasma concentrations of the latter one. 6. Combination with light-sensitive drugs increases the light-sensitive effect.
• Description: Isotretinoin is the 9-cis isomer of retinoic acid, a close relative of retinol, or vitamin A. It was originally developed to treat cystic acne, and today this is still its primary use despite several more modern applications of the drug, including a treatment for pancreatic and brain cancers. First shown to be an effective treatment for acne in 1982, its development stemmed from advances in knowledge of the effects of vitamin A to reduce or eliminate sebum production. Since that time, however, several instances of deleterious effects became well known, most notably birth defects arising from the use of isotretinoin.
• Therapeutic Function: Antiacne, Keratolytic
• Clinical Use: Isotretinoin is most useful for the treatment of severe recalcitrant nodular acne vulgaris. It may also be helpful in other disorders of keratinization, but it is not useful for psoriasis. High doses of isotretinoin (2mg/kg/day) are effective as cancer chemoprevention agents to reduce the frequency of cutaneous malignancies in patients at increased risk, such as those with xeroderma pigmentosum, an inherited disorder in which DNA repair is deficient, or in immunosuppressed patients.
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: possible increased risk of benign intracranial hypertension with tetracyclines - avoid. Antifungals: possible increased risk of toxicity with fluconazole, ketoconazole and voriconazole. Vitamins: increased risk of hypervitaminosis with vitamin A.

Technology Process of Isotretinoin

There total 157 articles about Isotretinoin 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

(2E,4E)-3-methyl-5-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4-pentadienal

11-cis,13-cis-12-carboxyretinoic acid

ethyl retinoate

Downstream raw materials:

9-cis-retinoic acid

all-(E)-retinoic and 13-(Z)-retinoic anhydride

13-cis-retinoyl chloride

13-(Z)-retinoic anhydride

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.