Crisaborole

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Achtung

• Gefahrenhinweise

  H315：Verursacht Hautreizungen.

  H319：Verursacht schwere Augenreizung.

  H335：Kann die Atemwege reizen.

• Sicherheit

  P261：Einatmen von Staub vermeiden.

  P301+P310：BEI VERSCHLUCKEN: Sofort GIFTINFORMATIONSZENTRUM/Arzt/... (geeignete Stelle für medizinische Notfallversorgung vom Hersteller/Lieferanten anzugeben) anrufen.

  P305+P351+P338：BEI KONTAKT MIT DEN AUGEN: Einige Minuten lang behutsam mit Wasser spülen. Eventuell vorhandene Kontaktlinsen nach Möglichkeit entfernen. Weiter spülen.

  P311：GIFTINFORMATIONSZENTRUM/Arzt anrufen.

Crisaborole Chemische Eigenschaften,Einsatz,Produktion Methoden

• Beschreibung

  Crisaborole is a phosphodiesterase- 4 (PDE4) inhibitor that was approved by FDA on December 14, 2016 as Eucrisa, a topical treatment of for mild to moderate atopic dermatitis (AD) in patients aged two years and older. The drug, which was developed by Anacor Pharmaceuticals and later acquired and marketed by Pfizer, is delivered as a 2% ointment, which is applied topically. Its structure contains a boron atom, which facilitates skin penetration and binding to the bimetal center of the phosphodiesterase 4 enzyme. The unique employment of boron within the chemical structure of the drug is designed to enable selective engagement of PDE4 (an enzyme involved in the conversion of cAMP into AMP, which signals for downstream inflammatory events), effective penetration of the drug through human skin, and rapid clearance to limit systemic circulation.

• Verwenden

  A series of phenoxy benzoxaboroles were synthesized and screened for their inhibitory activity against PDE4 and cytokine release. 5-(4-Cyanophenoxy)-2,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2728) showed potent activity both in vitro and in vivo. AN2728 is being studied as an anti-inflammatory agent.

• Definition

  ChEBI: Crisaborole is a member of the class of benzoxaboroles that is 5-hydroxy-1,3-dihydro-2,1-benzoxaborole in which the phenolic hydrogen has been replaced by a 4-cyanophenyl group. A phosphodiesterase 4 inhibitor that is used for treatment of mild to moderate atopic dermatitis in children and adults. It has a role as a phosphodiesterase IV inhibitor, an antipsoriatic and a non-steroidal anti-inflammatory drug. It is a benzoxaborole, an aromatic ether and a nitrile. ?

• Biochem/physiol Actions

  Crisaborole is a non-steroidal anti-inflammatory phosphodiesterase 4 (PDE4) inhibitor. Crisaborole has an IC50 value of 490 nM for PDE4 with similar IC50 values for release of cytokines TNF-α, IL-2, and IFN-γ, and shows little inhibition against other PDE isozymes. Crisaborole has been approved as a topical treatment for atopic dermatitis.

• Nebenwirkungen

  EUCRISA may cause side effects.
  Allergic reactions. EUCRISA may cause allergic reactions at or near the application site. These can be serious and may include hives, itching, swelling, and redness.
  www.eucrisa.com

• Synthese

  Several disclosures describing synthetic approaches to ethereal boron-containing anti-inflammatory compounds have been published by Anacor. Commercially available bromobenzaldehyde 134 was protected as the corresponding acetal upon subjection to warm ethylene glycol in the presence of catalytic p-toluenesulfonic acid. This was followed by nucleophilic aromatic substitution involving 4-fluorobenzonitrile and subsequent acetal deprotection to furnish diaryl ether 136. Although multiple approaches to crisaborole have been reported from this intermediate diaryl ether 136, the published literature approach involves the following sequence: reduction of the aldehyde with sodium borohydride followed by THP protection to furnish bromobenzene 137, which then underwent lithium-halogen exchange prior to quenching with triisopropyl borate and acidification to arrive at crisaborole (XIII). Alternatively, patents from Anacor describe a general approach employing a Miyaura coupling of 136, enabling the installation of the corresponding pincacol borane, which could then be exposed to reduction conditions using sodium borohydride followed by boric acid wash, aqueous workup, and lyophilization to furnish XIII.

  

• Mode of action

  Crisaborole is a Phosphodiesterase 4 Inhibitor. The mechanism of action of crisaborole is as a Phosphodiesterase 4 Inhibitor.

Crisaborole Upstream-Materialien And Downstream Produkte

Crisaborole Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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