Difamilast

Product Name: Difamilast
CAS No.: 937782-05-3
Chemical Name: Difamilast
Synonyms: OPA15406);Difamilast;Difa Misite;Difamilast (OPA-15406;Difamilast 937782-05-3;Difamilast, 10 mM in DMSO;N-((2-(4-(difluoromethoxy)-3-isopropoxyphenyl)oxazol-4-yl)methyl)-2-ethoxybenzamide;N-[[2-[4-(Difluoromethoxy)-3-(1-methylethoxy)phenyl]-4-oxazolyl]methyl]-2-ethoxybenzamide;N-[[2-[4-(difluoromethoxy)-3-propan-2-yloxyphenyl]-1,3-oxazol-4-yl]methyl]-2-ethoxybenzamide;Benzamide, N-[[2-[4-(difluoromethoxy)-3-(1-methylethoxy)phenyl]-4-oxazolyl]methyl]-2-ethoxy-
CBNumber: CB64694667
Molecular Formula: C23H24F2N2O5
Formula Weight: 446.44
MOL File: 937782-05-3.mol

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Difamilast Property

Density: 1.223±0.06 g/cm3(Predicted)
storage temp.: Store at -20°C
solubility: DMSO : 100 mg/mL (223.99 mM; Need ultrasonic)
pka: 13.12±0.46(Predicted)
form: Solid
color: White to off-white
InChI: InChI=1S/C23H24F2N2O5/c1-4-29-18-8-6-5-7-17(18)21(28)26-12-16-13-30-22(27-16)15-9-10-19(32-23(24)25)20(11-15)31-14(2)3/h5-11,13-14,23H,4,12H2,1-3H3,(H,26,28)
InChIKey: VFBILHPIHUPBPZ-UHFFFAOYSA-N
SMILES: C(NCC1=COC(C2=CC=C(OC(F)F)C(OC(C)C)=C2)=N1)(=O)C1=CC=CC=C1OCC

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Hazard and Precautionary Statements (GHS)

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N-Bromosuccinimide Price

ChemScene

Product number: CS-0039262
Product name: Difamilast
Purity: 99.20%
Packaging: 5mg
Price: $500
Updated: 2021/12/16

ChemScene

Product number: CS-0039262
Product name: Difamilast
Purity: 99.20%
Packaging: 10mg
Price: $850
Updated: 2021/12/16

ChemScene

Product number: CS-0039262
Product name: Difamilast
Purity: 99.20%
Packaging: 25mg
Price: $1800
Updated: 2021/12/16

ChemScene

Product number: CS-0039262
Product name: Difamilast
Purity: 99.20%
Packaging: 50mg
Price: $3000
Updated: 2021/12/16

ChemScene

Product number: CS-0039262
Product name: Difamilast
Purity: 99.20%
Packaging: 100mg
Price: $4600
Updated: 2021/12/16

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Difamilast Chemical Properties,Usage,Production

Uses

Difamilast (OPA-15406) is a topical, selective and nonsteroidal phosphodiesterase-4 (PDE4) inhibitor with particularly efficient inhibition of subtype B (IC50=11.2 nM). Difamilast can be used for the research of mild to moderate atopic dermatitis (AD)[1][2][3].

brand name

Moizerto

Biological Activity

Difamilast is a novel atopic dermatitis drug candidate discovered by Otsuka that has phosphodiesterase 4 (PDE4) inhibitory activity.

Mechanism of action

Difamilast works by inhibiting the activity of the PDE4 enzyme, thereby reducing the degradation of intracellular cyclic adenosine monophosphate (cAMP). cAMP is an intracellular signaling molecule that regulates a variety of cellular functions, including inhibiting inflammatory responses. By increasing cAMP levels, Difamilast helps reduce the production of inflammatory cytokines and relieves symptoms of atopic dermatitis.

Synthesis

The synthesis of difamilast (15) begins with the monobenzylated protocatechuic acid ethyl ester 15.1. Phenol 15.1 is first converted to the corresponding isopropyl ether and then debenzylated under palladium-catalyzed hydrogenation to produce the phenol intermediate 15.3. Difluoromethylation of 15.3 is accomplished by the addition of sodium chlorodifluoroacetate 15.4 at elevated temperature in the presence of potassium carbonate. The decarboxylation C-O bond formation reaction is likely to occur via a difluorocarbene process. The difluoromethylated product is treated with acid and then hydrolyzed in an alkaline medium to produce the benzoic acid derivative 15.5. The benzoic acid 15.5 is then converted to the benzamide 15.6 via the benzimide intermediate. The benzamide 15.6 is condensed with 1-ethoxy-3-chloroacetone 15.7 to produce the oxazole derivative, which is then saponified and recrystallized from 50% aqueous methanol to produce the alcohol 15.8.

Conversion of oxazole alcohol 15.8 to difamilast (15). First, alcohol 15.8 was converted to bromide 15.9 via an activation-displacement process, passing through a mesylate intermediate. Then, the alkyl bromide 15.9 was treated with potassium oxalimide to introduce the nitrogen center via an SN2-type displacement. Methylamine-mediated oxalimide deprotection and subsequent salt formation steps generated the amine 15.11 as a hydrochloride in a total yield of 69% over three steps. Finally, the hydrochloride 15.11 was treated with aqueous sodium carbonate to generate the free amine, which was subjected to an amide bond formation reaction with 2-ethoxybenzoic acid 15.12 and recrystallized from water and ethanol to give Difamilast (15).

in vitro

Difamilast has particularly efficient inhibition of subtype B (IC50=11.2 nM). It (OPA-15406) improves skin condition in relevant animal models of AD.

in vivo

Difamilast has particularly efficient inhibition of subtype B (IC50=11.2 nM). It (OPA-15406) improves skin condition in relevant animal models of AD.

in vivo

OPA-1540 improves skin condition in relevant animal models of AD^[1].

IC 50

PDE4B: 11.2 nM (IC₅₀)

References

[1] Hanifin JM, et, al. OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD): A phase-II randomized, double-blind, placebo-con DOI:10.1016/j.jaad.2016.04.001
[2] Ahluwalia J, et, al. Phosphodiesterase 4 Inhibitor Therapies for Atopic Dermatitis: Progress and Outlook. Drugs. 2017 Sep;77(13):1389-1397. DOI:10.1007/s40265-017-0784-3
[3] Soeberdt M, et, al. Small molecule drugs for the treatment of pruritus in patients with atopic dermatitis. Eur J Pharmacol. 2020 Aug 15;881:173242. DOI:10.1016/j.ejphar.2020.173242

Difamilast Preparation Products And Raw materials

Raw materials

Preparation Products

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Difamilast Suppliers

China 45 United States 1 Global 46

Bayee Biotech (Anqing) Co., Ltd.

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937782-05-3, DifamilastRelated Search:

Difamilast 937782-05-3

Difamilast (OPA-15406

OPA15406)

Benzamide, N-[[2-[4-(difluoromethoxy)-3-(1-methylethoxy)phenyl]-4-oxazolyl]methyl]-2-ethoxy-

N-[[2-[4-(difluoromethoxy)-3-propan-2-yloxyphenyl]-1,3-oxazol-4-yl]methyl]-2-ethoxybenzamide

Difamilast,PDE4,OPA 15406,Inhibitor,atopic,phosphodiesterase-4,OPA15406,Phosphodiesterase (PDE),OPA-15406,dermatitis,subtype,inhibit

Difamilast

N-((2-(4-(difluoromethoxy)-3-isopropoxyphenyl)oxazol-4-yl)methyl)-2-ethoxybenzamide

Difamilast, 10 mM in DMSO

N-[[2-[4-(Difluoromethoxy)-3-(1-methylethoxy)phenyl]-4-oxazolyl]methyl]-2-ethoxybenzamide

Difa Misite

937782-05-3

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