N - (4- (2,4-dihydroxyphenyl) -1,3-thiazol-2-yl) -2-methylpropanamide

Structural formula
General
Surname	N - [4- (2,4-dihydroxyphenyl) -1,3-thiazol-2-yl] -2-methylpropanamide
other names	ISOBUTYLAMIDO THIAZOLYL RESORCINOL ( INCI ) ; Thiamidol;
Molecular formula	C 13 H 14 N 2 O 3 S
External identifiers / databases
EC number	807-621-3
ECHA InfoCard	100.235.348
PubChem	71543007
ChemSpider	45891877
Wikidata	Q27285652
properties
Molar mass	278.33 g · mol -1
safety instructions
H and P phrases	H: 317-411
	P: ?
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

N - [4- (2,4-Dihydroxyphenyl) -1,3-thiazol-2-yl] -2-methylpropanamide (name protected by Beiersdorf: Thiamidol ) is a chemical compound thatinhibitshuman tyrosinase . Tyrosinase is an enzyme that is involved in the formation of the body's own skin pigment , melanin .

The substance developed and patented by Beiersdorf is used externally on the skin. It is supposed to reduce pigment spots and prevent them from reappearing.

background

A hyperpigmentation ( melasma ), so that the excessive presence of melanin in the skin, by an increased production of melanin in the melanocytes caused. UV radiation from the sun activates melanocyte activity in the skin. A punctual, excessive presence of melanin in the skin shows up in brown pigment spots.

Different forms of hyperpigmentation are, for example, lentigines ( age spots ) or post-inflammatory (i.e., occurring after inflammation of the skin) hyperpigmentation. They show different clinical features, such as: B. Duration or place of occurrence. There are several ways to treat hyperpigmentation, but most of them are very gross, such as: B. chemical peels or laser therapies .

development

The rate of melanin formation is determined by the activity of the enzyme tyrosinase . Tyrosinase is therefore a primary target for the suppression of hyperpigmentation. Numerous tyrosinase inhibitors have already been identified, several of which have shown no clinical efficacy, since development was carried out using mycotic tyrosinase from Agaricus bisporus (mTyr, “mushroom tyrosinase”) as the target structure. The use of a recombinant human tyrosinase (hTyr) as a target structure in connection with a screening of 50,000 compounds led to the identification of resorcinylthiazoles as particularly effective inhibitors of human tyrosinase, including thiamidol with a mean inhibitory concentration (IC ₅₀ ) of 1.1 μmol / L. In comparison, the IC ₅₀ compared to hTyr is significantly higher for other substances that are also used for skin lightening , such as 4-butylresorcinol (21 μmol / L), kojic acid (500 μmol / L) or hydroquinone and arbutin (> 4000 μmol / L). Fungal tyrosinase (mTyr) was only weakly inhibited by thiamidol, the IC ₅₀ was 108 μmol / L.

In melanocyte cultures, thiamidol strongly, but reversibly, inhibited melanin production, whereas hydroquinone, which also causes skin lightening, irreversibly inhibited melanogenesis.

Web links

New study data on the effectiveness of thiazolylresorcinol derivatives on hyperpigmentation of the skin , summary of the lecture by L. Kolbe (Beiersdorf) on the occasion of the 23rd annual meeting of the Society for Dermopharmacy in March 2019 (PDF)

Individual evidence

↑ Entry on ISOBUTYLAMIDO THIAZOLYL RESORCINOL in the CosIng database of the EU Commission, accessed on January 7, 2020.
↑ Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of N- [4- (2,4-dihydroxyphenyl) -1,3-thiazol-2-yl] -2-methylpropanamide in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA) is shown, which is derived from a self-classification by the distributor , accessed on July 7, 2020.
↑ Information on the Union trademark number 017162439 in the register of the German Patent and Trademark Office (DPMA)
↑ Craig Arrowitz, Andrea M. Schoelermann, Tobias Mann, Lily I. Jiang, Teresa Weber, Ludger Kolbe: Effective Tyrosinase Inhibition by Thiamidol Results in Significant Improvement of Mild to Moderate Melasma . In: Journal of Investigative Dermatology . tape 139 , no. 8 , August 2019, p. 1691–1698 , doi : 10.1016 / j.jid.2019.02.013 .
↑ ^a ^b ^c ^d Tobias Mann, Wolfram Gerwat, Jan Batzer, Kerstin Eggers, Cathrin Scherner, Horst Wenck, Franz Stäb, Vincent J. Hearing, Klaus-Heinrich Röhm, Ludger Kolbe: Inhibition of Human Tyrosinase Requires Molecular Motifs Distinctively Different From Mushroom Tyrosinase. Journal of Investigative Dermatology, Volume 138 (2018), pp. 1601-1608, doi: 10.1016 / j.jid.2018.01.019 .

[CosIng-1] Entry on ISOBUTYLAMIDO THIAZOLYL RESORCINOL in the CosIng database of the EU Commission, accessed on January 7, 2020.

[2] Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of N- [4- (2,4-dihydroxyphenyl) -1,3-thiazol-2-yl] -2-methylpropanamide in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA) is shown, which is derived from a self-classification by the distributor , accessed on July 7, 2020.

[3] Information on the Union trademark number 017162439 in the register of the German Patent and Trademark Office (DPMA)

[4] Craig Arrowitz, Andrea M. Schoelermann, Tobias Mann, Lily I. Jiang, Teresa Weber, Ludger Kolbe: Effective Tyrosinase Inhibition by Thiamidol Results in Significant Improvement of Mild to Moderate Melasma . In: Journal of Investigative Dermatology . tape 139 , no. 8 , August 2019, p. 1691–1698 , doi : 10.1016 / j.jid.2019.02.013 .

[mann2018-5] Tobias Mann, Wolfram Gerwat, Jan Batzer, Kerstin Eggers, Cathrin Scherner, Horst Wenck, Franz Stäb, Vincent J. Hearing, Klaus-Heinrich Röhm, Ludger Kolbe: Inhibition of Human Tyrosinase Requires Molecular Motifs Distinctively Different From Mushroom Tyrosinase. Journal of Investigative Dermatology, Volume 138 (2018), pp. 1601-1608, doi: 10.1016 / j.jid.2018.01.019 .