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
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
N-Bromosuccinimide Price
- Product number
- CS-0039262
- Product name
- Difamilast
- Purity
- 99.20%
- Packaging
- 5mg
- Price
- $500
- Updated
- 2021/12/16
- Product number
- CS-0039262
- Product name
- Difamilast
- Purity
- 99.20%
- Packaging
- 10mg
- Price
- $850
- Updated
- 2021/12/16
- Product number
- CS-0039262
- Product name
- Difamilast
- Purity
- 99.20%
- Packaging
- 25mg
- Price
- $1800
- Updated
- 2021/12/16
- Product number
- CS-0039262
- Product name
- Difamilast
- Purity
- 99.20%
- Packaging
- 50mg
- Price
- $3000
- Updated
- 2021/12/16
- Product number
- CS-0039262
- Product name
- Difamilast
- Purity
- 99.20%
- Packaging
- 100mg
- Price
- $4600
- Updated
- 2021/12/16
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
Difamilast Suppliers
- Tel
- 0556-5032306 18917961636
- wtx@bayeebio.com
- Country
- China
- ProdList
- 239
- Advantage
- 61
- Tel
- 0551-68933033 13956024211
- Fax
- 0551-68935833
- trchem@163.com
- Country
- China
- ProdList
- 98
- Advantage
- 58
- Tel
- 025-83697070
- Fax
- +86-25-83453306
- info@chemlin.com.cn
- Country
- China
- ProdList
- 16075
- Advantage
- 64
- Tel
- 0371-55932928 18937192232
- Fax
- 0086-0371-55932928
- 1282296214@qq.com
- Country
- China
- ProdList
- 498
- Advantage
- 55
- Tel
- 18149758185
- sales-cpd@caerulumpharma.com
- Country
- China
- ProdList
- 3506
- Advantage
- 58
- Tel
- 021-52996696，15000506266 15000506266
- Fax
- +86-21-52996696
- Country
- China
- ProdList
- 4769
- Advantage
- 55
- Tel
- 13770809694
- Fax
- +86 25 56203983
- googlexu_0114@sina.com
- Country
- China
- ProdList
- 990
- Advantage
- 58
- Tel
- 086-0519-83990708 18915800124
- Fax
- 0519-83990708
- info@pbpharm.com
- Country
- China
- ProdList
- 487
- Advantage
- 55
- Tel
- 021-QQ：65489617 15618227136
- Fax
- 21-5161 9052
- Sales@ATKchemical.com
- Country
- China
- ProdList
- 9125
- Advantage
- 58
- Tel
- 027-59402396 13419635609
- Fax
- 027-83989310
- 13419635609@163.com
- Country
- China
- ProdList
- 1991
- Advantage
- 55
- Tel
- 027-83778876 13667159345
- Fax
- 027-83778876
- 13667159345@163.com
- Country
- China
- ProdList
- 1997
- Advantage
- 55
- Tel
- 025-83221260
- Fax
- 02583221260
- renqing401@163.com
- Country
- China
- ProdList
- 267
- Advantage
- 55
- Tel
- 027-027-83778875 15807197853
- Fax
- 027-83991220
- 15807197853@163.com
- Country
- China
- ProdList
- 3931
- Advantage
- 58
- Tel
- 021-021-13773155751 19975051755
- 260924549@qq.com
- Country
- China
- ProdList
- 10524
- Advantage
- 58
- Tel
- 13912903754
- info@becaspharma.com
- Country
- China
- ProdList
- 2763
- Advantage
- 58
- Tel
- 027-68897569 18120462897
- Fax
- 027-68897569
- fiona@yuanmengbio.com
- Country
- China
- ProdList
- 4657
- Advantage
- 58
- Tel
- 027-59102966 18717199209
- Fax
- 027-59379337
- 2853877583@qq.com
- Country
- China
- ProdList
- 2715
- Advantage
- 58
- Tel
- 400-1647117 13681763483
- product02@bidepharm.com
- Country
- China
- ProdList
- 59936
- Advantage
- 58
- Tel
- 133-3998-5473 13339985473
- C13339985473@163.com
- Country
- China
- ProdList
- 4991
- Advantage
- 58
- Tel
- 4008200310
- marketing@tsbiochem.com
- Country
- China
- ProdList
- 24961
- Advantage
- 58
- Tel
- 027-59105166; 13125137732
- 2853863890@qq.com
- Country
- China
- ProdList
- 2987
- Advantage
- 58
- Tel
- 0371-53399770 18037166334
- 2853031800@qq.com
- Country
- China
- ProdList
- 5891
- Advantage
- 58
- Tel
- 0533-6092686 13371592196
- ddliu@bio-polar.cn
- Country
- China
- ProdList
- 2229
- Advantage
- 58
- Tel
- 25-8690-7345 18651693585
- zfx@farmasino.com
- Country
- China
- ProdList
- 136
- Advantage
- 58
- Tel
- 029-029-81123119 17391733320
- 1021@dideu.com
- Country
- China
- ProdList
- 9995
- Advantage
- 58
- Tel
- 025-025-66113011 18626450290
- cb5@aikonchem.com
- Country
- China
- ProdList
- 10358
- Advantage
- 58
- Tel
- 021-54306202 18917919676
- info@hanhongsci.com
- Country
- China
- ProdList
- 29995
- Advantage
- 58
- Tel
- 18860950986
- tangmanman@lebangpharma.com
- Country
- China
- ProdList
- 650
- Advantage
- 58
- Tel
- 025-85560043 15850508050
- Fax
- 025-85563444
- cindy.huang@synzest.com
- Country
- China
- ProdList
- 12000
- Advantage
- 58
- Tel
- 18024082417
- market@ubiochem.com
- Country
- China
- ProdList
- 9835
- Advantage
- 58
- Tel
- 028-81700200 13308200041
- 2851167782@qq.com
- Country
- China
- ProdList
- 11146
- Advantage
- 58
- Tel
- 400-821-026
- Sales@sangon.com
- Country
- China
- ProdList
- 6710
- Advantage
- 58
- Tel
- 18118984557; 18118984557
- 753016615@qq.com
- Country
- China
- ProdList
- 472
- Advantage
- 58
- Tel
- 800-364-9897
- sales@caymanchem.com
- Country
- China
- ProdList
- 6838
- Advantage
- 58
- Tel
- 18274875143 18932421294
- 18932421294@163.com
- Country
- China
- ProdList
- 38
- Advantage
- 58
- Tel
- 021-58003085 18817202306
- Fax
- QQ1060196522
- quhs@neutanpharma.com
- Country
- China
- ProdList
- 182
- Advantage
- 58
- Tel
- +86-0533-2185556 +8615965530500
- nickzhang@hangyubiotech.com
- Country
- China
- ProdList
- 8510
- Advantage
- 58
- Tel
- +undefined86-15223382610
- info@jooe.com
- Country
- China
- ProdList
- 6208
- Advantage
- 58
- Tel
- +86-0551-68665055 +86-+86-18616906106
- sales@trywchem.com
- Country
- China
- ProdList
- 183
- Advantage
- 58
- Tel
- +86-057181025280; +8617767106207
- Fax
- 0571-85806285
- sales@molcore.com
- Country
- China
- ProdList
- 49734
- Advantage
- 58
- Tel
- +86-19189228086 +8618858568638
- wuzhouding@huihecrop.com
- Country
- China
- ProdList
- 886
- Advantage
- 58
- Tel
- --
- Fax
- --
- info@neobioscience.com
- Country
- CHINA
- ProdList
- 6207
- Advantage
- 58
- Tel
- --
- Fax
- --
- goldg@gzbr.com.cn
- Country
- China
- ProdList
- 74
- Advantage
- 38
- Tel
- --
- Fax
- --
- chenjw@absin.cn
- Country
- CHINA
- ProdList
- 6208
- Advantage
- 58
- Tel
- --
- Fax
- --
- Proteintech-CN@ptglab.com
- Country
- CHINA
- ProdList
- 6290
- Advantage
- 58