174671-46-6

Basic information

• Product Name: 5-FLUOROBENZO[C][1,2]OXABOROL-1(3H)-OL
• Synonyms: 5-FLUOROBENZO[C][1,2]OXABOROL-1(3H)-OL;AN 2690;Tavaborole;5-Fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole;5-Fluoro-1,3-dihydro-2,1-benzoxaborol-1-ol;AN-2690(Tavaborole);Tavaborole(AN-2690);AN-269
• CAS NO: 174671-46-6
• Molecular Formula: C₇H₆BFO₂
• Molecular Weight: 151.93
• Mol File: 174671-46-6.mol
• Article Data: 19

Chemical Properties

• Melting Point: 120-122℃
• Boiling Point: 230.831 °C at 760 mmHg
• Flash Point: 93.404 °C
• Appearance: /
• Density: 1.288 g/cm³
• Storage Temp.: -20°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 6.81±0.20(Predicted)
• Stability: Hygroscopic
• CAS DataBase Reference: 5-FLUOROBENZO[C][1,2]OXABOROL-1(3H)-OL(CAS DataBase Reference)
• NIST Chemistry Reference: 5-FLUOROBENZO[C][1,2]OXABOROL-1(3H)-OL(174671-46-6)
• EPA Substance Registry System: 5-FLUOROBENZO[C][1,2]OXABOROL-1(3H)-OL(174671-46-6)

Safety Data

• Hazardous Substances Data: 174671-46-6(Hazardous Substances Data)

Usage

Description

Tavaborole (Kerydin?), discovered and developed by Anacor, was approved by the US FDA in July 2014. Tavaborole, topical solution, 5% is an oxaborole antifungal indicated for the treatment of onychomycosis of the toenails due to Trichophyton rubrum or Trichophyton mentagrophytes. The mechanism of action of tavaborole is inhibition of fungal protein synthesis, which inhibits an aminoacyl-transfer ribonucleic acid synthetase.

Uses

Tavaborole is a topical treatment of toenail onychomycosis.

Definition

ChEBI: A member of the class of benzoxaboroles that is 1,3-dihydro-1-hydroxy-2,1-benzoxaborole substituted at position 5 by a fluoro group. A topical antifungal agent used for the treatment of onychomycosis (fungal infection of the toenails and fingernails).

General Description

Tavaborole is a boron-based pharmaceutical agent. It has broad-spectrum oxaborole antifungal activity. Due to its low molecular weight, it facilitates maximal nail plate penetration than its predecessors.

Biochem/physiol Actions

Tavaborole (AN2690) is a potent antifungal that targets the post-transfer editing site of leucyl-tRNA synthetase (LeuRS). Tavaborole forms a covalent adduct with the 3′ adenosine of tRNA(leu) at the editing site of fungal, but not bacterial LeuRS, locking the enzyme in an inactive conformation. Tavaborole was recently approved for the treatment of onychomycosis of the toenail in adults.

Synthesis

Three syntheses of tavaborole (XXXII) have been reported. The 26.9 g scale approach started with 2-bromo-5-fluorophenyl methanol (257), which was treated with ethyl vinyl ether (258) to produce o-bromobenzyl alcohol derivative 259 in 82% yield. 259 was then converted into the corresponding phenylboronic acid, followed by the one-pot deprotection and spontaneous cyclization upon treatment with 6 M hydrochloric acid, delivering tavaborole (XXXII) in 43% yield.

in vitro

an2690 showed the most active against fungi and especially against the dermatophytes t. rubrum and t. mentagrophytes, the primary fungal pathogens causing onychomycosis. in addition, an2690 was identified as having a unique profile of in vitro antidermatophyte activity, maintenance of this activity in the presence of keratin, and exceedingly good penetration of human nails [1].

references

[1] baker sj, zhang yk, akama t, lau a, zhou h, hernandez v, mao w, alley mr, sanders v, plattner jj. discovery of a new boron-containing antifungal agent, 5-fluoro-1,3-dihydro-1-hydroxy-2,1- benzoxaborole (an2690), for the potential treatment of onychomycosis. j med chem. 2006;49(15):4447-50.[2] hui x, baker sj, wester rc, barbadillo s, cashmore ak, sanders v, hold km, akama t, zhang yk, plattner jj, maibach hi. in vitro penetration of a novel oxaborole antifungal (an2690) into the human nail plate. j pharm sci. 2007;96(10):2622-31.[3] markham a. tavaborole: first global approval. drugs. 2014;74(13):1555-8.

Upstream product

• 456-47-3 3-fluoro-benzenemethanol 
• 7732-18-5 water 
• 877264-43-2 (5-fluoro-2-iodophenyl)methanol 
• 1061223-45-7 (4-fluoro-2-(hydroxymethyl)phenyl)boronic acid 
• 5419-55-6 Triisopropyl borate 
• 943310-52-9 5-fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde 
• 452-63-1 2-Bromo-5-fluorotoluene 
• 139911-29-8 4-fluoro-2-methylphenylboronic acid 
• 13675-18-8 tetrahydroxydiboron 
• 202865-66-5 2-bromo-5-fluorobenzyl alcohol 
• 850567-57-6 2-(bromomethyl)-4-fluorophenylboronic acid pinacol ester 
• 651326-68-0 1-bromo-2-(1-ethoxyethoxymethyl)-4-fluorobenzene 
• 845301-93-1 2-bromo-5-fluoro-[1-(methoxymethoxy)methyl]benzene 

Downstream Products

• 1574699-66-3 1,1′-((2,3-dimethylbutane-2,3-diyl)bis(oxy))bis(5-fluoro-1,3-dihydrobenzo[c][1,2]oxaborole) 
• 1574699-68-5 1,1′-(propane-1,2-diylbis(oxy))bis(5-fluoro-1,3-dihydrobenzo[c][1,2]oxaborole) 

Relevant articles and documents

A combined experimental-computational study of benzoxaborole crystal structures

Benzoxaboroles are organoboron molecules which are gaining growing interest in different fields, notably for the development of new drugs. However, extensive characterization of these molecules in the solid state is still lacking. Here, questions related to the structure and spectroscopic signatures of crystalline benzoxaborole phases are thus addressed, using a combined experimental-computational approach. Two simple benzoxaboroles were studied: 1,3-dihydro-1-hydroxy-2,1-benzoxaborole (denoted as BBzx) and 5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole (also referred to as AN2690, a newly developed antifungal drug). First, the crystal structures of AN2690 and BBzx at room temperature are discussed, emphasizing the intermolecular interactions which play an important role in their formation. Then, results of IR and multinuclear (1H, 11B, 13C and 19F) solid state NMR characterization are presented, together with density functional theory (DFT) calculations which were carried out to assist in the interpretation of the spectra. Finally, the influence of polymorphism and anisotropic thermal expansion properties of the crystal structures on the NMR parameters of BBzx and AN2690 is discussed.

Benzoxaborole-1-alcohol compound and preparation method and application thereof

The invention belongs to the field of bactericides, and particularly relates to a benzoxaborole-1-alcohol compound and a preparation method and application thereof. The benzoxaborole-1-alcohol compound has good bactericidal activity, can effectively control tomato early blight, wheat scab, rice sheath blight disease, strawberry gray mold, apple blotch, cucumber anthracnose and other crop diseases,can produce excellent antibacterial effects at low concentration, and shows good selectivity. The compound is used as a leucyl-tRNA synthetase inhibitor, the evolution difference of aminoacyl-tRNA synthetase of germs and eukaryotes is utilized, and the compound has very high safety to non-target organisms while killing the germs and can be used as a bactericide in agriculture.

Preparation process of antifungal drug tavaborole

The invention relates to a preparation process of an antifungal drug tavaborole. The preparation process of the antifungal drug tavaborole comprises the following reaction steps: taking 2-bromo-5-fluorobenzaldehyde as a starting material, reacting the 2-bromo-5-fluorobenzaldehyde with pinacol borate in the presence of a palladium catalyst and a solvent to generate 2-pinacol boron-5-fluorobenzaldehyde (TAV-A), and carrying out reduction and ring closure to generate the product tavaborole. In aftertreatment, the PH value of a reaction solution is adjusted by using sig water, and then the tavaborole can be separated out. The preparation process is short in reaction steps, mild and safe in conditions, easy to operate and high in yield, is environmentally friendly, and is suitable for industrial production.