906673-24-3 Usage
Description
5-(4-cyanophenoxy)-2,3-dihydro-1-hydroxy-2,1-benzoxaborole, also known as AN2728, is a boron-based, topical anti-inflammatory agent that selectively inhibits phosphodiesterase 4 (PDE4), an enzyme involved in the conversion of cAMP into AMP, which signals for downstream inflammatory events. It is designed to enable effective penetration of the drug through human skin and rapid clearance to limit systemic circulation.
Uses
Used in Pharmaceutical Industry:
AN2728 is used as an anti-inflammatory agent for the treatment of mild to moderate atopic dermatitis (AD) in patients aged two years and older. It is being studied for its potent activity both in vitro and in vivo, and its ability to suppress the release of proinflammatory cytokines such as TNF-α, IL-2, INF-γ, IL-5, and IL-10.
Used in Inflammatory Research:
AN2728 is used as a research tool to study the inhibitory activity of PDE4 and cytokine release, providing insights into the development of new anti-inflammatory drugs and therapies.
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.
Synthesis
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.
Check Digit Verification of cas no
The CAS Registry Mumber 906673-24-3 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 9,0,6,6,7 and 3 respectively; the second part has 2 digits, 2 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 906673-24:
(8*9)+(7*0)+(6*6)+(5*6)+(4*7)+(3*3)+(2*2)+(1*4)=183
183 % 10 = 3
So 906673-24-3 is a valid CAS Registry Number.
906673-24-3Relevant articles and documents
Preparation method of crisaborole key intermediate
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Paragraph 0084-0089, (2021/08/07)
The invention discloses a method for preparing a crisaborole key intermediate with a structure as shown in a formula I. A synthetic route of the method is as shown in the specification, and the method specifically comprises the following steps: (1) reacting m-hydroxyl benzaldehyde-glycol acetal (II) with an iodine source in the presence of a catalyst to generate an iodinated product III; (2) in the presence of alkali, condensing III and a compound IV to generate V; and (3) in an inert gas atmosphere, carrying out a Miyaura boronation reaction between the compound V and the compound IV under the action of a catalyst to generate a compound VII, which does not need to be further purified, and removing the protection group under the action of acid to obtain a compound I, namely the crisaborole key intermediate. The method has the characteristics of cheap and easily available raw materials, low EHS risk of the used reagent and the synthesis process, simple and convenient separation and purification operation, suitability for industrial production and the like.
Preparation method of benzoxaborole compound
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, (2021/07/17)
The invention discloses a preparation method of a benzoxaborole compound. The preparation method comprises the following steps: (1) reacting raw materials containing halogenated hydrocarbon and boric acid ester under an alkaline condition, acidifying and hydrolyzing to obtain an intermediate VI; and (2) reacting a raw material containing the intermediate VI with halogenated cyanophenyl to obtain the benzoxaborole compound. The raw materials are low in price, the preparation cost of the benzoxaborole compound is reduced, the steps of protection and de-protection of organic groups are not needed in the preparation process, the reaction process is simplified, and yield reduction caused by group protection is avoided; and meanwhile, the method is mild in reaction condition, low in equipment requirement and easy for large-scale industrial production.
Preparation method of crisaborole
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, (2021/05/01)
The invention provides a preparation method of crisaborole. More specifically, 5-bromophthalide is used as an initial raw material, and is subjected to etherification, hydrolysis, hydroxyl protection, condensation reaction, photoreaction boronation and cyclization to obtain the crisaborole. The preparation method has the advantages of readily available raw materials, mild reaction conditions, avoidance of metal catalysis and harsh conditions due to adoption of photoreaction for boronizing, low cost, convenience in operation and suitability for industrial production.