Tretinoin

Base Information

• Chemical Name: Tretinoin
• CAS No.: 302-79-4
• Deprecated CAS: 56573-65-0,7005-78-9,187175-63-9,7005-78-9
• Molecular Formula: C20H28O2
• Molecular Weight: 300.441
• Hs Code.: 29362100
• European Community (EC) Number: 206-129-0
• NSC Number: 759631,122758
• UNII: 5688UTC01R
• DSSTox Substance ID: DTXSID7021239
• Nikkaji Number: J1.313.469C,J2.378.058E,J494.243D,J528.606I,J623.910B,J690.379G,J1.518K,J646.157C,J646.158A,J970.183D
• Wikipedia: Tretinoin
• Wikidata: Q29417
• NCI Thesaurus Code: C900,C2398
• RXCUI: 10753
• Pharos Ligand ID: AAM7T1JPHW13
• Metabolomics Workbench ID: 29042
• ChEMBL ID: CHEMBL38
• Mol file: 302-79-4.mol

Synonyms:(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)nona-2,4,6,8-tetraenoate;all-trans-beta-Retinoic acid;Vitamin A acid;Tretinoine (French) (EINECS);Retin A;trans-Retinoic acid;all-trans-Vitamin A1 acid;Acide retinoique (French) (DSL);2,4, 6,8-Nonatetranoic acid, 3,7-dimethyl-9-(2,6, 6-trimethyl-1-cyclohexen-1-yl)-, (2E, 4E, 6E, 8E)-;all-trans-Retinoate;AGN 100335;Vitamin A acid sodium salt;Vitamin A1 acid, all-trans-;ATRA;Retin-A;Vesnaroid;Tretin M;all-(E)-Retinoic acid;Retinoic acid, sodium salt;beta-Retinoic acid;Cordes Vas;Aberel;Tretinoin, all-trans-;Retionic acid;Dermairol;Eudyna;Aknefug;Retinoate;all-trans-Retinoic acid;Retacnyl;Tretinoin (all-trans retinoic acid );Tretinoin USP26;

Chemical Property of Tretinoin

Chemical Property:

• Appearance/Colour: yellow-orange powder
• Vapor Pressure: 7.55E-10mmHg at 25°C
• Melting Point: 179-184 °C
• Refractive Index: 1.4800 (estimate)
• Boiling Point: 462.8 °C at 760 mmHg
• PKA: 4.73±0.33(Predicted)
• Flash Point: 350.6 °C
• PSA: 37.30000
• Density: 1.011 g/cm³
• LogP: 5.60260
• Storage Temp.: 2-8°C
• Sensitive.: Light Sensitive
• Solubility.: Practically insoluble in water, soluble in methylene chloride, slightly soluble in ethanol (96 per cent).
• 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%min ^*data from raw suppliers

Retinoic Acid ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T,Xn
• Hazard Codes: T,Xn,N
• Statements: 22-63-38-20/21/22-51/53
• Safety Statements: 53-26-36/37/39-45-36/37-61-24/25

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

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: Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial
• Recent EU Clinical Trials: Treatment of striae distensae with fractional radiofrequency and topical tretinoin: An intra-individual study with blinded outcome assessment
• Recent NIPH Clinical Trials: Clinical study on the safety and usefulness of Cyclodextrin inclusion welding Tretinoin for wrinkles and pigmentation of the skin
• Uses: (1) Applies to abnormal tyshiyongyupe of acne, fish phosphorus disease and abnormal psoriasis. (2) Resistance to abnormal skin drugs. (3) Tretinoin mainly affects the growth of bones and epithelial metabolism, can promote epithelial cell proliferation and updates, and can inhibit the proliferation and differentiation of keratinocytes, so hyperkeratosis can be back to normal. Therefore many complete or incomplete keratosis, hyperkeratosis of diseases have a certain therapeutic effect, treat a variety of skin diseases. Tretinoin is mainly used in the treatment of psoriasis, ichthyosis, follicular keratosis, acne, lichen planus, verrucous epidermal nevus, impetigo, vitiligo, lichen psoriasis, the face of pityriasis alba, etc. keratolytic, antiacne, antineoplastic antipruritic Physiological metabolite of vitamin A. Effects gene expression via nuclear retinoic acid receptors (RAR); mediates cellular growth and differentiation retinoic acid (tretinoin) is a vitamin A derivative. It has demonstrated an ability to alter collagen synthesis, increase dermal hyaluronic acid levels, and stimulate fibroblast growth and the extracellular matrix. It is used for keratinization disorders and for treating acne. Retinoic acid’s anti-aging effect has been convincingly documented and it is often used for treating the visible signs of aging, though these results can take approximately 6 months to be visible. It is associated with a number of adverse effects, including irritation, photosensitivity, skin dryness, redness, and peeling. It should also not be used while pregnant.
• Drug Interactions: Combined use with light-sensitive drugs may increase the risk of light sensitivity. Use with caution when combined with soap and other detergents, preparations containing keratolytic (such as benzoyl peroxide, thalidomide, salicylic acid, and sulfur), preparations containing ethanol, or isotretinoin, as this may worsen skin irritation and dryness. Combined use with cimetidine, cyclosporine, diltiazem, verapamil and ketoconazole may increase the blood concentration of this drug and lead to retinoic acid poisoning. Combined use with pentobarbital, phenobarbital and rifampicin may decrease the blood concentration of this drug. This drug will impact the hepatic cytochrome P450 enzyme system and change the blood concentration of this drug. Taking oryzanol, vitamin B1 or vitamin B6 while also taking this drug may alleviate or eliminate adverse effects of this drug, including headaches.
• Description: all-trans Retinoic acid is a metabolite of vitamin A and a ligand for retinoic acid receptors (RARs) with IC50 values of 9, 3, and 10 nM for RARα, RARβ, and RARγ, respectively, in radioligand binding assays. It induces expression of a luciferase reporter in COS-7 cells expressing RARα, RARβ, or RARγ (EC50s = 169, 9, and 2 nM, respectively). all-trans Retinoic acid (17 nmol) reduces papilloma formation induced by phorbol 12-myristate 13-acetate (TPA; ) in mice. It reduces bile duct proliferation, hydroxyproline levels, and liver inflammation in a rat model of α-naphthylisothiocyanate-induced chronic cholestasis and reduces plasma levels of alkaline phosphatase and bile salts in the Mdr2-/- mouse model of cholestasis. all-trans Retinoic acid also reduces hepatic fat accumulation, triglycerides, body weight, and serum glucose levels in mice with Western diet-induced obesity.
• Indications: Topical tretinoin (Retin-A, Renova, Avita), like isotretinoin, alters keratinization in the acroinfundibulum. In addition, it reverses certain premalignant and other histological changes associated with the photoaging changes that accompany chronic exposure to ultraviolet radiation. Topically applied tretinoin is indicated in comedogenic and papulopustular acne vulgaris, and its mild exfoliative effects make it sometimes useful in molluscum contagiosum, flat warts, and some ichthyotic disorders. It is often prescribed to lessen the clinical signs of photoaging (wrinkling and hyperpigmented macules).
• Clinical Use: The major toxic effect of tretinoin is erythema and irritation of the skin to which it is applied, especially if the skin is moist.This toxicity often decreases with continued therapy.
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: possibly increased risk of benign intracranial hypertension with tetracyclines - avoid. Antifungals: possible increased risk of tretinoin toxicity with fluconazole, ketoconazole and voriconazole. Vitamin A: risk of hypervitaminosis - avoid.

Technology Process of Tretinoin

There total 165 articles about Tretinoin 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

ethyl (all-E)-retinoate

5,8-epidioxy-5,8-dihydroretinoic acid

4-ethoxyretinoic acid

Refernces

• 1、 Cartier, Dominique,Valla, Alain,Labia, Roger,Le Guillou, Régis,Potier, Pierre. "A new one-pot synthesis of all E-retinoic acid via a new enaminodiester synthon". . p. 5789 - 5790. Retrieved 2003.
• 2、 Thibonnet, Jér?me,Abarbri, Mohamed,Duchêne, Alain,Parrain, Jean-Luc. "Stereoselective synthesis of all-trans-, (13Z)- and (9-nor)-retinoic acids via Stille reaction". . p. 141 - 143. Retrieved 1999.
• 3、 Allegrone, Gianna,Brenna, Elisabetta,Fronza, Giovanni,Fuganti, Claudio,Giovenzana, Tommaso,Malpezzi, Luciana,Barlocchi, Enrico,Pellegatta, Cesare. "Impurity analysis of retinoic acid samples". . p. 3528 - 3531. Retrieved 2005.
• 4、 -. "Synthesis method of new compounds Potassium all-trans retinoate and Potassium 9-cis retinoate.". Paragraph 0029-0030. . Retrieved 2021/07/07.
• 5、 -. "Preparation method of tretinoin". Paragraph 0020; 0029; 0031-0032; 0043; 0047; 0051. . Retrieved 2020/05/11.