Tazarotene

Base Information

• Chemical Name: Tazarotene
• CAS No.: 118292-40-3
• Molecular Formula: C21H21NO2S
• Molecular Weight: 351.469
• Hs Code.: 2942000000
• European Community (EC) Number: 601-516-4
• UNII: 81BDR9Y8PS
• DSSTox Substance ID: DTXSID5046691
• Nikkaji Number: J679.813F
• Wikipedia: Tazarotene
• Wikidata: Q3981685
• NCI Thesaurus Code: C29487
• RXCUI: 83947
• Pharos Ligand ID: PVZSWAXQMF34
• Metabolomics Workbench ID: 43090
• ChEMBL ID: CHEMBL1657
• Mol file: 118292-40-3.mol

Synonyms:AGN 190168;AGN-190168;ethyl 6-(2-(4,4-dimethylthiochroman-6-yl)ethynyl)nicotinate;tazarotene;Tazorac

Chemical Property of Tazarotene

Chemical Property:

• Appearance/Colour: White solid
• Vapor Pressure: 4.03E-10mmHg at 25°C
• Melting Point: 97-98 °C
• Refractive Index: 1.624
• Boiling Point: 499.8 °C at 760 mmHg
• PKA: 0.04±0.29(Predicted)
• Flash Point: 256.1 °C
• PSA: 64.49000
• Density: 1.22 g/cm³
• LogP: 4.43150
• Storage Temp.: Store at +4°C
• Solubility.: DMSO: >15mg/mL
• XLogP3: 4.9
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 5
• Exact Mass: 351.12930009
• Heavy Atom Count: 25
• Complexity: 547

Purity/Quality:

99% ^*data from raw suppliers

Tazarotene ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCOC(=O)C1=CN=C(C=C1)C#CC2=CC3=C(C=C2)SCCC3(C)C
• Recent ClinicalTrials: Tazarotene 0.045% Lotion for Treating PIE and PIH in Subjects With Acne
• Recent EU Clinical Trials: A Phase 4 (Phase 2 in European Union), Open-Label, Multicenter Study Evaluating the Absorption and Systemic Pharmacokinetics and HPA Axis Suppression Potential of Topically Applied IDP-118 Lotion in Pediatric Subjects with Moderate to Severe Plaque Psoriasis
• Description: Tazarotene belongs to a third generation prescription topical retinoid. It is marketed in different forms including cream (brand name: Avage), foam (brand name: Fabuir) and gel (brand name: Tazorac). It is mainly used for the treatment of psoriasis, acne, and sun damaged skin. The detailed mechanisms of action of Tazarotene are still unclear. It is converted to its active form, the cognate carboxylic acid of tazarotene (AGN 190299) in vivo through rapid de-esterification in animals and man. AGN 190299 is capable of binding to all the three members of the retinoic acid receptor (RAR) family: RARα, RARβ, and RARγ with relative selectivity for RARβ, and RARγ. This process may further modify gene expression. However, it is unclear whether this is related to its mode of action. Common side effects associated with it include worsening of acne, desquamation, burning/stinging, erythema and pruritus increased sensitivity to sunlight, dry skin, itchiness, redness, skin pain rash and skin discoloration. In most cases, these side effects are mild and can remarkable decrease after the first 2–4 weeks. Tazarotene should not be used in the following cases: patients are allergic to it; patients are pregnant; patients have a sunburn; patients are taking photo-sensitive drugs such as thiazides and tetracycline.
• Uses: An acetylenic retinoid prodrug converted to the active metabolite, Tazarotenic acid, with selective affinity for retinoic acid receptors RAR?and RAR. Antiacne; antipsoriatic. Used in treatment of photodamaged skin Tazarotene is a prescription topical retinoid sold as a cream or gel. This medication is approved for treatment of psoriasis, acne, and sun damaged skin (photodamage). It is commonly sold in two concentrations: 0.05% and 0.1%. In addition to tretinoin, wh anticholelithic Used to treat psoriasis, acne and sun damaged skin.
• Indications: Like other retinoids, tazarotene (Tazorac) acts by binding to RARs and altering gene expression. Tazarotene appears to be particularly selective for the retinoid receptors RAR-β and RAR-γ, but the clinical significance of this observation is unknown.
• Therapeutic Function: Keratolytic
• Clinical Use: In the United States, tazarotene has been approved for topical treatment of psoriasis (involving up to 20% body surface area) and mild to moderate facial acne. Application site burning, stinging, and desquamation are common side effects, especially with acne. Tazarotene is contraindicated in women who are pregnant.

Technology Process of Tazarotene

There total 15 articles about Tazarotene 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: 86.3%

4,4-dimethylbenzothiopyran-6-ylacetylene + 6-chloro-3-pyridinecarboxylic acid ethyl ester (49608-01-7) → tazarotene (118292-40-3)

Guidance literature:

With palladium on activated charcoal; potassium acetate; triphenylphosphine; In N,N-dimethyl-formamide; at 80 ℃; for 5h; Temperature; Reagent/catalyst; Solvent; Inert atmosphere;

Reference yield: 60.0%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + 6-chloro-3-pyridinecarboxylic acid ethyl ester (49608-01-7) → tazarotene (118292-40-3)

Guidance literature:

6-chloro-3-pyridinecarboxylic acid ethyl ester; With potassium carbonate; triphenylphosphine; 5%-palladium/activated carbon; In toluene; at 45 - 50 ℃;

(4,4-dimethylthiochroman-6-yl)acetylene; copper(l) iodide; In toluene; at 45 - 115 ℃; Product distribution / selectivity;

Reference yield: 59.0%

6-[2-(4,4-dimethylthiochroman-6yl)ethynyl]nicotinic acid ethyl ester S-oxide → tazarotene (118292-40-3)

Guidance literature:

With N,N-dimethyl-formamide; phosphorus trichloride; at -20 ℃; for 1h;

upstream raw materials:

(4,4-dimethylthiochroman-6-yl)acetylene

6-chloro-3-pyridinecarboxylic acid ethyl ester

ethanol

6-[2-(4,4-dimethylthiochroman-6-yl)ethynyl]nicotinic acid

Downstream raw materials:

6-[2-(4,4-dimethylthiochroman-6-yl)ethynyl]nicotinic acid

(R)-6-(2-(2-benzoyloxy-4,4-dimethylthiochroman-6-yl)ethynyl)nicotinic acid ethyl ester

(S)-6-(2-(2-benzoyloxy-4,4-dimethylthiochroman-6-yl)ethynyl)nicotinic acid ethyl ester

6-(2-(2-benzoyloxy-4,4-dimethylthiochroman-6-yl)ethynyl)nicotinic acid ethyl ester

Refernces

Quantitative method for determination of 3,3-dimethylallyl bromide genotoxic impurity in Tazarotene drug substance by GC-MS

10.1002/sscp.202000009

The study presents a highly sensitive gas chromatography-mass spectrometry (GC-MS) quantitative method for determining 3,3-dimethylallyl bromide, a genotoxic impurity, in tazarotene drug substance. 3,3-Dimethylallyl bromide is a raw material used in the preparation of tazarotene, and it is a key genotoxic alert that needs to be controlled in the drug substance. The researchers validated the method according to the International Conference for Harmonization Q2 (R1) guideline. They used a DB-1 column for separation and selected ions with m/z values of 148, 150, and 69 for mass spectrometry detection. The limit of detection (LOD) and limit of quantitation (LOQ) for 3,3-dimethylallyl bromide were established at 0.7 and 2.1 ppm, respectively. The method demonstrated good precision, accuracy, linearity, and robustness, making it suitable for the quantification of 3,3-dimethylallyl bromide at low levels in tazarotene drug substance, which is crucial for ensuring the safety and quality of the pharmaceutical product.