ethyl 6-[2-(4,4-dimethyl-3,4-dihydro-2H-1-benzothiopyran-6-yl)ethynyl]pyridine-3-carboxylate

• ChemBase ID: 678
• Molecular Formular: C21H21NO2S
• Molecular Mass: 351.46194
• Monoisotopic Mass: 351.12929992
• SMILES: S1CCC(c2c1ccc(c2)C#Cc1ncc(cc1)C(=O)OCC)(C)C
• Canonical SMILES: CCOC(=O)c1ccc(nc1)C#Cc1ccc2c(c1)C(C)(C)CCS2
• InChI: InChI=1S/C21H21NO2S/c1-4-24-20(23)16-7-9-17(22-14-16)8-5-15-6-10-19-18(13-15)21(2,3)11-12-25-19/h6-7,9-10,13-14H,4,11-12H2,1-3H3
• InChIKey: OGQICQVSFDPSEI-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: ethyl 6-[2-(4,4-dimethyl-3,4-dihydro-2H-1-benzothiopyran-6-yl)ethynyl]pyridine-3-carboxylate
• IUPAC Traditional name: tazarotene
• Brand Name: Tazarotene [USAN:INN]; Tazorac; Zorac
• Synonyms: Tazorac; Avage; Zora; Tazarotene(Avage); tazarotene; Tazarotene; Ethyl 6-((4,4-dimethylthiochroman-6-yl)ethynyl)nicotinate; 6-[2-(3,4-Dihydro-4,4-dimethyl-2H-1-benzothiopyran-6-yl)ethynyl]-3-pyridinecarboxylic Acid Ethyl Ester; AGN 190168; Zorac

Database IDs

• CAS Number: 118292-40-3
• PubChem SID: 160964141; 46508992
• PubChem CID: 5381

CALCULATED PROPERTIES

JChem

• H Acceptors: 2
• H Donor: 0
• LogD (pH = 5.5): 5.218718
• LogD (pH = 7.4): 5.2187405
• Log P: 5.2187405
• Molar Refractivity: 97.882 cm^3
• Polarizability: 39.30108 Å^3
• Polar Surface Area: 39.19 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 5.15
• LOG S: -5.67
• Solubility (Water): 7.50e-04 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; DMSO; Methanol; Soluble
• Apperance: Light Yellow Solid
• Melting Point: 103-105°C
• Hydrophobicity(logP): 5.6

Safety Information

• Storage Condition: -20°C; Refrigerator

Product Information

• Purity: 95+%; 97%
• Salt Data: Free Base

DETAILS

DrugBank - DB00799

• Drug Groups: approved; investigational
• Description: Tazarotene (marketed as Tazorac?, Avage? and Zorac?) 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). [Wikipedia]
• Indication: Used to treat psoriasis, acne and sun damaged skin (photodamage).
• Pharmacology: Tazarotene is a prodrug and a member of the acetylenic class of retinoids. Following topical application, tazarotene undergoes esterase hydrolysis to form its active metabolite, tazarotenic acid. When treating acne tazarotene may be taken in conjunction with an oral antibiotic. Tazarotene has been shown in peer-reviewed double blinded studies to reduce: mottling and hyperpigmentation, sallowness, fine wrinkling and coarse wrinkling in sun damaged skin. Histological studies have shown that long term (greater than 1 year) use of Tazarotene is associated with a significant reduction in atypical melanocytes and keratocytes - cells considered to be precursors of skin cancer. Some studies have shown long term use of Tazarotene to be associated with increased collagen production and better organization of skin collagen bundles.
• Toxicity: Excessive topical use may lead to marked redness, peeling, or discomfort. Oral ingestion of the drug may affect liver function causing hypertriglyceridemia. Other symptoms may include conjunctival irritation, hair loss, headache, edema, fatigue, dermatitis, nausea, and visual disturbances. Oral administration of this material to rats and rabbits at doses of 0.20 mg/kg/day (rabbits) and 0.25 mg/kg/day (rats) resulted in developmental toxicity. A no effect level of 0.05 mg/kg/day was established. Similar teratogenic effects have been reported for other retinoid compounds.
• Affected Organisms: Humans and other mammals
• Biotransformation: Undergoes esterase hydrolysis in skin to form its active metabolite, tazarotenic acid. Tazarotenic acid is further metabolized in skin and, after systemic absorption, hepatically metabolized to sulfoxides, sulfones, and other polar products for elimination.
• Absorption: Minimal systemic absorption of tazarotene occurs due to its rapid metabolism in the skin to the active metabolite, tazarotenic acid, which can be systemically absorbed and further metabolized. Gender had no influence on the systemic bioavailability of tazarotenic acid.
• Half Life: The half-life of the active form of the drug, tazarotenic acid, is approximately 18 hours in normal and psoriatic patients.
• Protein Binding: The active form of the drug, tazarotenic acid, is highly bound to plasma proteins (>99%).
• Elimination: Tazarotene and tazarotenic acid were metabolized to sulfoxides, sulfones and other polar metabolites which were eliminated through urinary and fecal pathways.
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Selleck Chemicals - S1569

Research Area: Inflammation
Biological Activity:
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, which has been associated with greater skin improvements with high concentrations, tazarotene and isotretinoin creams are also found to be effective for photodamage, but at the expense of skin irritation. More evidence is needed before any recommendations can be made on oral or topical polysaccharides or hydroxy acids. [1][2]

Toronto Research Chemicals - T010050

An acetylenic retinoid prodrug converted to the active metabolite, Tazarotenic acid, with selective affinity for retinoic acid receptors RARβ and RARγ. Antiacne; antipsoriatic. Used in treatment of photodamaged skin.

REFERENCES

• http://en.wikipedia.org/wiki/Tazarotene
• Tang-Liu, D.D.-S., et al.: Clin. Pharmacokinet., 37, 273 (1999)
• Roeder, A., et al.: Skin Pharmacol. Physiol., 17, 111 (1999)